Motherhealth Caregivers Bay Area In-Home Care Hollistic

Home made health cures from the pros

1. When diarrhea strikes his family, Gannady Raskin, MD, ND, dean of the School of Naturopathic Medicine at Bastyr University, cures it with herbal concoctions. “Tea made from pomegranate skin will help an upset stomach,” he says. Set aside the leftovers of your next purchase; you can store dried skin for up to 6 months. Then steep a tablespoon’s worth in a cup of boiling water for 3 to 4 minutes. Oak bark (available at health food stores) works, too: Boil for 3 minutes, let sit for half an hour, and then strain. Both recipes are rich in tannins, which help the body produce mucus to line the stomach and lessen irritation. Drink 2 tablespoons, 4 to 6 times a day.

2. If you suspect food poisoning, couple black tea with a few pieces of burned toast, says Georgianna Donadio, PhD, director of the National Institute of Whole Health, a holistic certification program for medical professionals. “The tannic acid in tea and charcoal in the toast will neutralize the toxins and help you get much better very quickly.” Burned rice on the pan, made into a warm drink works too.
3. In the early stages of cold or flu, try this recipe from Brian Berman, MD, director of the Center for Integrative Medicine at the University of Maryland School of Medicine: Place a whole unpeeled grapefruit, sectioned into four pieces, in a pot and cover with water; heat to just under a boil. Stir and add a tablespoon of honey, and drink the whole mixture like tea. “The simmering releases immune boosters from the grapefruit into the water–vitamin C and flavonoids hidden between the rind and the fruit,” he says. “The concoction packs more punch than store-bought grapefruit juice, plus the warmth eases a sore throat.” To beef up your body’s healing response, he swears by liquid olive leaf extract, available at health food stores. Studies suggest that its antiviral qualities can help treat cold and flu bugs. “You end up getting rid of mucus sooner, and it helps your immune system fight back as well,” Dr. Berman says. Vit C and zinc losenges work too.

4. Itchy scalp, sunburn or any skin disorder in mouth or any body part, use aloe vera.

5. Congestion and bronchitis call for an oldie but a goodie, says Woodson Merrell, MD, an assistant clinical professor of medicine at Columbia University College of Physicians and Surgeons: medicated vapor rub. Applied to the chest, it helps stuffed-up sufferers breathe easier, but Dr. Merrell prefers a cleaner approach: Boil a pot of water, let it cool for about 1 minute, and then mix in a teaspoon of vapor rub. Lean over it with your head about a foot from the steam. Use a towel over your head to make a tent, and inhale for 5 minutes. Yes for massage with vapor rub not only on chest and back but also on feet.

6. You can soothe a toothache with cloves; the old-fashioned remedy really works, says Jack Dillenberg, DDS, dean of the Arizona School of Dentistry & Oral Health. But today, not everyone has the spice handy, so he recommends eugenol–clove extract–available at your pharmacy. Soak a cotton ball and place it directly on the tooth for several minutes, and the pain should subside until you can get to a dentist. Tea tree mouth wash works too.

7. Recurring fever blisters (you might know them as cold sores) can’t be completely cured–but they can be treated, and outbreaks prevented, with the amino acid L-lysine, found in ointments or tablets in health food stores, says Paul Horowitz, MD, medical director of the Legacy Pediatric Clinics at Emanuel Children’s Hospital in Portland, OR. If you’re among the 60 to 90% of Americans who carry the herpesvirus that causes blisters, start taking 1,000 mg three times a day with meals as soon as you feel an outbreak coming on. (The supplement may not be safe for those with high cholesterol, heart disease, or high triglycerides.)

8. After a hard workout, Declan Connolly, PhD, a professor of exercise science at the University of Vermont, drinks a bottle of tart cherry juice; he studied its antioxidant and anti-inflammatory abilities and concluded that it helps sore muscles recover. “Though you may feel fine initially after a workout, your tissues suffer tiny tears and swelling,” he says. “Tart cherries contain higher amounts of anthocyanins–antioxidants that help repair damage–than sweet cherries and most other fruits or vegetables.” Dr. Connolly tested the brand CherryPharm, available to consumers and athletes at CherryPharm.com. You can also find other brands of 100% tart cherry juice or juice concentrate in natural food supermarkets or health food stores.

9. Write your home made recipes here…..

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Collected by
Connie Dello Buono

Connie Dello Buono ; motherhealth@gmail.com

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Bacterial signal can flip the macrophage ‘engine’ from oxidative phosphorylation to glycolysis; a New Inflammatory “Danger” Signal for chronic inflammation

When you drive a car, sometimes it’s fine to just chug along. But if there’s a threat you might suddenly have to take action to get out of trouble. Could it be similar for front-line immune cells called macrophages when an infection tries to take hold?
A new study suggests that unthreatened macrophages tick over on one form of core metabolism, oxidative phosphorylation. But throw a bacterial threat into the mix and that metabolism switches over to a form called aerobic glycolysis, and you see an inflammatory response.

Prof Luke O’Neill from Trinity College Dublin likens the switch to what happens in a hybrid car when it changes from using electricity as a source of energy to burning petrol instead. And he and colleagues have just mapped out how a bacterial signal can flip the macrophage ‘engine’ from oxidative phosphorylation to glycolysis.

Co-author Prof Cormac Taylor, from University College Dublin, agrees that the study highlights the links between biochemical pathways that we typically associate with metabolism, immunity and disease. “What has become really important recently is the recognition of the key role of cross-talk between the pathways regulating metabolism, inflammation and tumor development,” he says. “And this is one of the clearest examples where there is a direct interface between inflammation and the type of metabolism we see in cancer.”

You could extend that hybrid-car analogy even further. Macrophages in the blood have the job of ‘sensing’ potential threats such as bacteria and then engulfing them. So perhaps they are like hybrid police cars, keeping watch and responding when there’s a threat.
The study found that if you expose macrophages to lipopolysaccharide – a signal of bacterial threat – the LPS binds to a toll-like receptor on the surface of the macrophage. This is an early signal of trouble, much like the message coming in over the police radio.

Then the core metabolism in the macrophage changes from oxidative phosphorylation to glycolysis, the equivalent of putting the boot down and switching the energy source in the hybrid engine.

“If there’s a bacterial invader threatening an infection, then you want the macrophages to become active, this is a good thing,” says O’Neill, who is Director of the Trinity Biomedical Sciences Institute.
As well as the switch to glycolysis, you also see an inflammatory response, and O’Neill believes they have found an important cog in the mechanism: succinate.

“When macrophages make that switch there is also a rise in the metabolite succinate, and this acts as a danger signal that turns on the pro-inflammatory cytokine interleukin-1ss,” he explains.
Succinate also appears to alter the shapes of several proteins in the macrophages, though it’s not known exactly what effect this has – there is plenty yet to discover. “I would anticipate that these proteins are activated through this succinylation process, but that is something we are going to look at now,” says O’Neill.

In other words, succinate seems to act as the police car’s siren, spreading the news that a response is needed and triggering it in the form of inflammation.

Of course this activation and inflammation can be helpful when there’s a threat to fight off. But too much of an inflammatory response is not such good news: if it runs on for too long you can get chronic inflammation, or if the response is overzealous, it can result in potentially life-threatening sepsis.

So the researchers also looked at ways to reduce the inflammation, and found that they were able to inhibit interleukin-1ss expression in the model by interfering with the switch to glycolysis.
They were also able to tone down the inflammatory response with an anti-epilepsy medication called vigabatrin. “We tried that because the drug interferes with a pathway by which the macrophages are making succinate,” explains O’Neill. “And we saw that the drug protected mice from a serious immune reaction called sepsis.”

Dampening down the macrophage’s ability to respond might not be such a great idea for people in good health, but being able to cut the inflammatory ramp-up could point to new treatments for acute and chronic inflammatory conditions, according to O’Neill. “It’s very exciting because we now have a new way to interfere with the production of interleukin-1, which is implicated in several conditions, including diabetes,” he says.

The findings could also offer insight on the relationship between inflammation and cancer, he adds, because glycolytic metabolism is also seen in tumor cells – the Warburg effect – and cancer and inflammation go hand in glove. “There is a parallel here, the same peculiar metabolism is kicking off in tumors as we see in macrophages,” says O’Neill.

Reference: Tannahill et al., Succinate is an inflammatory signal that induces IL-1? through HIF-1?. Nature. 2013 Mar 24. doi: 10.1038/nature11986
Image: Denis Klein
Follow Scientific American on Twitter @SciAm and @SciamBlogs.
Visit ScientificAmerican.com for the latest in science, health and technology news.
© 2013 ScientificAmerican.com. All rights reserved.

About
Sepsis: blood poisoning
Glycolysis is the process in which one glucose molecule is broken down to form two molecules of pyruvic acid. The glycolysis process is a multistep metabolic pathway that occurs in the cytoplasm of animal cells, plant cells, and the cells of microorganisms. At least six enzymes operate in the metabolic pathway.
oxidative phosphorylation the formation of high-energy phosphate bonds by phosphorylation of ADP to ATP coupled to the transfer of electrons from reduced coenzymes to molecular oxygen via the electron transport chain; it occurs in the mitochondria.

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Aside from feeding your brain, use your memory.
Use your brain or lose it. Learn new skills. If today’s jobs are either in computers or medical, learn new skills.

Connie Dello Buono

Prevent vascular disease, manage inflammation, get GYV health caps to boost ATP cells performance and speedy repair of your body, email connie to get the caps and join in spreading the benefits with extra income for you at motherhealth@gmail.com and text 408-854-1883

I love you mom

Mother you have embraced me from the moment I was born.
Ensuring that I don’t get hungry, cold or unattended, you are always at my side.
As if your world stopped, you gave all your attention to me.
Giving me breastmilk, massage when I’m sick and taking care of my daily needs.
Now that I’m a teen, you are kind of overdoing it by calling my cell all the time, it seems.
But, I must admit I missed your voice.
For you are always there for me.
I love you mom.

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by
Connie Dello Buono

Connie Dello Buono ; motherhealth@gmail.com

Stem cell transplant for nerve cells, memory and learning brain cells; GABA and cholinergic neurons

For the first time, human embryonic stem cells have been transformed into nerve cells that helped mice regain the ability to learn and remember.
A study at UW-Madison is the first to show that human stem cells can successfully implant themselves in the brain and then heal neurological deficits, says senior author Su-Chun Zhang, a professor of neuroscience and neurology.

Brain repair through cell replacement is a Holy Grail of stem cell transplant, and the two cell types are both critical to brain function, Zhang says. “Cholinergic neurons are involved in Alzheimer’s and Down syndrome, but GABA neurons are involved in many additional disorders, including schizophrenia, epilepsy, depression and addiction.”Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine. “These two neuron types are involved in many kinds of human behavior, emotions, learning, memory, addiction and many other psychiatric issues,” says Zhang.

The human embryonic stem cells were cultured in the lab, using chemicals that are known to promote development into nerve cells — a field that Zhang has helped pioneer for 15 years. The mice were a special strain that do not reject transplants from other species.
After the transplant, the mice scored significantly better on common tests of learning and memory in mice. For example, they were more adept in the water maze test, which challenged them to remember the location of a hidden platform in a pool.

The study began with deliberate damage to a part of the brain that is involved in learning and memory.
Three measures were critical to success, says Zhang: location, timing and purity. “Developing brain cells get their signals from the tissue that they reside in, and the location in the brain we chose directed these cells to form both GABA and cholinergic neurons.”
The initial destruction was in an area called the medial septum, which connects to the hippocampus by GABA and cholinergic neurons. “This circuitry is fundamental to our ability to learn and remember,” says Zhang.

The transplanted cells, however, were placed in the hippocampus — a vital memory center — at the other end of those memory circuits. After the transferred cells were implanted, in response to chemical directions from the brain, they started to specialize and connect to the appropriate cells in the hippocampus.
The study is the first to show that human stem cells can successfully implant themselves in the brain and then heal neurological deficits
The process is akin to removing a section of telephone cable, Zhang says. If you can find the correct route, you could wire the replacement from either end.
For the study, published in the current issue of Nature Biotechnology, Zhang and first author Yan Liu, a postdoctoral associate at the Waisman Center on campus, chemically directed the human embryonic stem cells to begin differentiation into neural cells, and then injected those intermediate cells. Ushering the cells through partial specialization prevented the formation of unwanted cell types in the mice.

Ensuring that nearly all of the transplanted cells became neural cells was critical, Zhang says. “That means you are able to predict what the progeny will be, and for any future use in therapy, you reduce the chance of injecting stem cells that could form tumors. In many other transplant experiments, injecting early progenitor cells resulted in masses of cells — tumors. This didn’t happen in our case because the transplanted cells are pure and committed to a particular fate so that they do not generate anything else. We need to be sure we do not inject the seeds of cancer.”
Though tantalizing, stem-cell therapy is unlikely to be the immediate benefit, Zhang notes that “for many psychiatric disorders, you don’t know which part of the brain has gone wrong.” The new study, he says, is more likely to see immediate application in creating models for drug screening and discovery.

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Use your brain or lose it. Learn new skills. If today’s jobs are either in computers or medical, learn new skills.
For example at this beta site, new skills in online ad and traffic generation can be learned:

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Long-term stress higher among elderly men than in women as shown in hair samples from Dutch study

The Dutch study concluded that elevated long-term cortisol levels are associated with a history of cardiovascular disease. The increased cardiovascular risk we found is equivalent to the effect of traditional cardiovascular risk factors, suggesting that long-term elevated cortisol may be an important cardiovascular risk factor.

Stress is associated with an increased incidence of cardiovascular disease. The impact of chronic stress on cardiovascular risk has been studied by measuring cortisol in serum and saliva, which are measurements of only 1 time point. These studies yielded inconclusive results. The measurement of cortisol in scalp hair is a novel method that provides the opportunity to measure long-term cortisol exposure. Our aim was to study whether long-term cortisol levels, measured in scalp hair, are associated with cardiovascular diseases.

A group of 283 community-dwelling elderly participants were randomly selected from a large population-based cohort study (median age, 75 y; range, 65–85 y). Cortisol was measured in 3-cm hair segments, corresponding roughly with a period of 3 months. Self-reported data concerning coronary heart disease, stroke, peripheral arterial disease, diabetes mellitus, and other chronic non-cardiovascular diseases were collected.

Results: Hair cortisol levels were significantly lower in women than in men (21.0 vs 26.3 pg/mg hair). High hair cortisol levels were associated with an increased cardiovascular risk (odds ratio, 2.7) and an increased risk of type 2 diabetes mellitus (odds ratio, 3.2). There were no associations between hair cortisol levels and non-cardiovascular diseases.

Copyright © 2013 by The Endocrine Society
Laura Manenschijn, Erasmus MC, Department of Internal Medicine, Room Ee-542, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: l.manenschijn@erasmusmc.nl.

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Connie Dello Buono ; motherhealth@gmail.com

Acute myocardial infarction; imbalance during ischemia-reperfusion ; mitochondrial energy adaption in cancer, obesity and metabolic disorders

Acute myocardial infarction is characterized by changes in biochemical properties during ischemia and reperfusion. The heart can survive a short period of ischemia by reducing myocardial contractility, increasing glucose uptake, and switching metabolism to glycolysis.
However, considering that the heart is one of the most energy-demanding tissues in the body, sustained oxygen and nutrient deprivation results in irreversible damage. Thus, reperfusion of the ischemic heart is a prerequisite for survival.

Paradoxically, reperfusion can further increase the myocardial damage that occurs during ischemia. The severity of reperfusion injury depends on the duration of the preceding ischemia and the effectiveness of blood flow during reperfusion. Several lines of evidence demonstrate that reperfusion injury is directly associated with cardiac mitochondrial dysfunction and increased ROS and RNS generation.

An imbalance of oxidants and antioxidants resulting in increased levels of ROS, RNS, or both can result in damage to lipids, proteins, carbohydrates, and DNA.
ROS are oxygen radicals generated in the body due to exposure from polluted air

Hearse et al. noted that reperfusion of isolated hearts after ischemia resulted in abrupt cardiomyocyte death. Following this paper, several studies showed that ischemia reperfusion is associated with a burst of H2O2, O2•;−, NO•, and ONOO−, but the exact mechanism of their generation is debated.
Although some ROS may be generated by NADPH oxidase and xanthine oxidase, it is likely that complexes I and III of the mitochondrial respiratory chain are the main sources of ROS during myocardial ischemia reperfusion.

In fact, studies using mitochondrial respiratory inhibitors show that the electron leak along the oxidative phosphorylation most likely occurs at the Fe-S centers of complex I and at some components of complex III.
During the early stages of reperfusion, ROS generation levels increase drastically. Interestingly, low amounts of ROS generated by mitochondria during brief and intermittent episodes of ischemia, termed ischemic preconditioning, significantly protect the heart against prolonged ischemia.

About
Dietary antioxidants are substances that have been shown to decrease the effects of ROS and RNS in humans.
Redox (reduction-oxidation) reactions include all chemical reactions in which atoms have their oxidation state changed. This can be either a simple redox process, such as the oxidation of carbon to yield carbon dioxide (CO2) or the reduction of carbon by hydrogen to yield methane (CH4), or a complex process such as the oxidation of glucose (C6H12O6) in the human body through a series of complex electron transfer processes.

Redox reactions are concerned with the transfer of electrons between species. The term comes from the two concepts of reduction and oxidation. It can be explained in simple terms:
• Oxidation is the loss of electrons or an increase in oxidation state by a molecule, atom, or ion.
• Reduction is the gain of electrons or a decrease in oxidation state by a molecule, atom, or ion.

Although oxidation reactions are commonly associated with the formation of oxides from oxygen molecules, these are only specific examples of a more general concept of reactions involving electron transfer.

Redox reactions, or oxidation-reduction reactions, have a number of similarities to acid–base reactions. Like acid–base reactions, redox reactions are a matched set, that is, there cannot be an oxidation reaction without a reduction reaction happening simultaneously. The oxidation alone and the reduction alone are each called a half-reaction, because two half-reactions always occur together to form a whole reaction. When writing half-reactions, the gained or lost electrons are typically included explicitly in order that the half-reaction be balanced with respect to electric charge.

TABLE 1 Examples of Reactive Oxygen and Nitrogen Species
Name Formula Comments
Superoxide O2- An oxygen-centered radical. Has limited reactivity.
Hydroxyl OH• A highly reactive oxygen-centered radical. Very reactive indeed: Attacks all molecules in the human body.
Peroxyl, alkoxyl RO2•, RO• Oxygen-centered radicals formed (among other routes) during the breakdown of organic peroxides.
Oxides of nitrogen NO•, NO2• Nitric oxide (NO•) is formed in vivo from the amino acid L-arginine. Nitrogen dioxide (NO2•) is made when NO reacts with O2 and is found in polluted air and smoke from burning organic materials (e.g., cigarette smoke).

SOURCE: Adapted from Halliwell, 1996, with permission; © International Life Sciences Institute, Washington, D.C.

About
Mitochondrial function is fundamental to metabolic homeostasis. In addition to converting the nutrient flux into the energy molecule ATP, the mitochondria generate intermediates for biosynthesis and reactive oxygen species (ROS) that serve as a secondary messenger to mediate signal transduction and metabolism.
Alterations of mitochondrial function, dynamics, and biogenesis have been observed in various metabolic disorders, including aging, cancer, diabetes, and obesity. However, the mechanisms responsible for mitochondrial changes and the pathways leading to metabolic disorders remain to be defined.
In the last few years, tremendous efforts have been devoted to addressing these complex questions and led to a significant progress. In a timely manner, the Forum on Mitochondria and Metabolic Homeostasis intends to document the latest findings in both the original research article and review articles, with the focus on addressing three major complex issues:
(1) mitochondria and mitochondrial oxidants in aging—the oxidant theory (including mitochondrial ROS) being revisited by a hyperfunction hypothesis and a novel role of SMRT in mitochondrion-mediated aging process being discussed;
(2) impaired mitochondrial capacity (e.g., fatty acid oxidation and oxidative phosphorylation [OXPHOS] for ATP synthesis) and plasticity (e.g., the response to endocrine and metabolic challenges, and to calorie restriction) in diabetes and obesity;
(3) mitochondrial energy adaption in cancer progression—a new view being provided for H+-ATP synthase in regulating cell cycle and proliferation by mediating mitochondrial OXPHOS, oxidant production, and cell death signaling.
It is anticipated that this timely Forum will advance our understanding of mitochondrial dysfunction in metabolic disorders.
Antioxidants. Redox Signal. 00, 000–000.

Measurement of Quantities in Foods
In order to meet the definition of a dietary antioxidant proposed here, the dietary intakes of the nutrient or food component must be able to be calculated from available national databases. These databases include the U.S. Department of Agriculture’s National Nutrient Databank, the Canadian Nutrient File, and other databases that contain a nationally representative sample of foods commonly eaten in the United States or Canada and that report concentrations for the antioxidant of interest and others. It is recognized that limitations exist in the use of food composition databases to accurately estimate intakes.
Decreased Adverse Effects of Some ROS and RNS
In order to meet the definition of a dietary antioxidant proposed here, the nutrient or food component must decrease the adverse effects of some ROS and RNS (see Table 1 for examples of ROS and RNS). An explanation of the biochemical and physiological mechanisms of these adverse effects follows.
Role of ROS and RNS in Health and Disease
ROS and RNS are produced metabolically by the body. It has been estimated that about 1 to 3 percent of the oxygen we utilize goes to make ROS. In addition, exposure to UV radiation or to air pollutants such as cigarette smoke (which contains oxidants) or ozone can cause the body to increase the levels of reactive radical species.

ROS is a collective term that includes several oxygen radicals—superoxide (O2•-) and its protonated form, hydroperoxyl (HO2•), hydroxyl (OH•), peroxyl (RO2•), alkoxyl (RO•)—and nonradicals—hydrogen peroxide (H2O2), hypochlorous acid (HOCl), ozone (O3), and singlet oxygen (O2)—that are oxidizing agents or are easily converted into radicals. RNS includes nitric oxide (NO•), peroxynitrite (ONOO-), and peroxynitrous acid (ONOOH).
Various compounds in the human body generate free radicals in their metabolism. Examples are catecholamines and compounds found in the mitochondrial electron-transport chain.
In addition, activated phagocytes produce ROS as one of the defense mechanisms they use to kill microbes. Thus, in this situation, ROS are used by the body as a defense mechanism against infection.
An imbalance of oxidants and antioxidants resulting in increased levels of ROS, RNS, or both can result in damage to lipids, proteins, carbohydrates, and DNA.
A considerable body of biological evidence shows that ROS and RNS can damage cells and other body components and could in theory contribute to dysfunction and disease states.
It has been postulated that oxidative damage caused by increased levels of production of ROS or RNS may contribute to the development of many chronic diseases, including age-related eye disease, atherosclerosis, cancer, coronary heart disease, diabetes, inflammatory bowel disease, neurodegenerative diseases, respiratory disease, and rheumatoid arthritis.

Antioxidant Mechanisms
The mechanisms of antioxidant action for decreasing the adverse effects of ROS or RNS are varied. They include (1) decreasing ROS or RNS formation; (2) binding metal ions needed for catalysis of ROS generation; (3) scavenging ROS, RNS, or their precursors; (4) up-regulating endogenous antioxidant enzyme defenses; (5) repairing oxidative damage to biomolecules, such as glutathione peroxidases or specific DNA glycosylases; and (6) influencing and up-regulating repair enzymes.
Some antioxidants remove free radicals by reacting directly with them in a noncatalytic manner before the radicals react with other cell components. For example, vitamin E inhibits lipid peroxidation by scavenging radical intermediates in the radical chain reaction with polyunsaturated fatty acids.
The effectiveness of each dietary antioxidant depends on which ROS or RNS is being scavenged, how and where they are generated, the accessibility of the antioxidants to this site, and what target of damage, or oxidizable substrate, is involved.
Antioxidant defense mechanisms include not only low-molecular-weight compounds, but also some antioxidant defense systems in the human body that are enzymatic, such as: (1) superoxide dismutase enzymes, which remove superoxide (O2•-) by accelerating its conversion to H2O2 and O2; (2) glutathione peroxidases, which convert H2O2 to water and O2 and which convert various hydroperoxides to harmless compounds; and (3) catalase, which converts H2O2 to water and O2 but only functions at relatively high concentrations of the ROS.

Connie Dello Buono ; motherhealth@gmail.com

Acute ischemic stroke, symptoms and scoring using TCM

TCM Syndrome and Scoring of Risks for Stroke

Select the above link.

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Connie Dello Buono ; motherhealth@gmail.com

Effect of egg white fermentation with lactobacilli on IgE binding ability of egg white proteins; reducing egg allergy by fermentation

The study demonstrated the potential of reducing egg allergy by fermentation of egg white with L. delbrueckii subsp. delbrueckii.
Egg allergy, afflicting around 1.6% to 3.2% of the total children population, is the second most common food allergy among infants and young children. The objective of the study was to determine if lactobacilli fermentation could reduce the IgE binding ability of egg white.

Acidification of egg white to pH6.0 and supplementation of tryptone are necessary to grow lactobacilli in egg white. Cell counts of Lactobacillus sanfranciscensis and Lactobacillus sakei were not affected up to 96h of incubation, while that of Lactobacillus delbrueckii subsp. delbrueckii decreased rapidly at the first 24h of incubation, increased to its inoculated level at 48h, and then leveled off afterwards.

The pH of fermented egg white was reduced to 5 after 48h of incubation with L. sanfranciscensis and/or L. sakei, and after 72h incubation with L. delbrueckii subsp. delbrueckii.
Among three strains studied, only L. delbrueckii subsp. delbrueckii fermented egg white showed 50% reduction in IgE binding ability. No obvious protein degradation in fermented egg white proteins was detected by SDS-PAGE.

The reduction of egg white IgE binding ability was attributed to ovomucoid, the dominant egg allergen, as shown the change of molecular weight analyzed by MALDI-TOF-MS, reduction of intensity of FITC labeled ovomucoid after fermentation, and the change of intensity of glycopeptides containing core+4HexNAc and core+3HexNAc.

Sen Li , Marina Offengenden , Messele Fentabil , Michael G. Gänzle , Jianping Wu. JOURNAL OF MIDWIFERY & WOMEN’S HEALTH, 20131526-9523. June 2013. Food Research International, Volume 52, Issue 1

High cost of cancer drugs; lung cancer story

High Cost Cancer Drugs

Cancer drugs constitute the second biggest category of drugs in the United States behind cholesterol-lowering medicines, and accounted for $17.8 billion of total prescription drug sales of $286.5 billion in 2007, according to IMS Health, a health care information company. Spending on drugs for cancer grew 14 percent last year, faster than for all but three other diseases.

I am voting for Bernie Sanders to lower the cost of drugs.

Connie’s comments: When my dad was diagnosed with lung cancer in 2002, last stage and was given 3 months to live, we opted for no chemotherapy and radiation.
In the comfort of his home, he used two oxygen tanks, caregiving from family members, juiced green papaya and other healing ways. He lived for 9 more months.
During my research when we found out about the cancer, some studies reported that Vit C and amino acid Lycine are beneficial in early stage of lung cancer.
My father worked in copper and nickel mines for about 10 yrs, car mechanic for 10 yrs and 2 yrs in asbestos work environment. He also smoked for 20 yrs, started it when he was only 20 yrs old. He had tuberculosis which was treated with drugs and cured 20 yrs before he died. Ten years before he died, he had quit smoking.
Without the CAT scan, we would never have found out about his lung cancer. He had chronic back pain and coughing for more than 15 yrs before he died of lung cancer. He wished to live long but we cannot afford the meds and was too late to discover his lung cancer.

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Collected by
Connie Dello Buono

Connie Dello Buono ; motherhealth@gmail.com

Call for live-in caregivers for homebound bayarea seniors at 408-854-1883

Autism Awareness

Autism Awareness by Dr Andrew Levison

Click the link above to view the article on Autism. Your brain has the power to heal and regenerate.

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Collected by
Connie Dello Buono
Connie Dello Buono ; motherhealth@gmail.com

Have a cell phone, computer and car: 10,000 sales, direct marketing work available (remote)

You strive constantly to serve the welfare of others, by devotion to selfless work to attain the supreme goal in life, with purpose and prosperity. Wise work for those business owners, working in big or small cities surrounded by positive and happy people. The product and service is in the travel industry, going to be a trillion dollar industry and the company is a 7-yr old direct marketing company with $400M in gross sales last year and the 6^th fastest growing direct marketing company with unique travel and vacation package service solutions.

You as a business owner, work within your hours and has the stamina and engine to work for the first 2 weeks with your own and the effort of a team of people. As a start up business owner, you will allocate time and money for cell phone, gas, food and miscellaneous (business cards, others estimated at $300).

If you are 18 yrs old or older, please email your resume to conniedbuono@gmail.com with available time for 30min phone interview, followed by 1 hr of training and availability to start immediately with coaching and job shadowing for 3 months or more. Bonus points (BMW car) for those who are people oriented and has connections in other countries such as Singapore, Europe, Latin America and other countries. Please ask the 3 most important questions that you may have to say yes to this job.

Have a blessed day.

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Know where your passion is. Whether in helping others generate more income thru ad traffic generation or computers/online skills, nutrition, travel savings or financial savings better than the bank, you choose your time wisely.

Use your brain or lose it. Learn new skills. If today’s jobs are either in computers or medical, learn new skills.
For example at this beta site, new skills in online ad and traffic generation can be learned:

http://addwallet.net/?id=clubalthea

Prevent rheumatoid arthritis with healthy immune system and good oral hygiene

Prevent rheumatoid arthritis with healthy immune system and good oral hygiene
• Smoking cessation
• Early diagnosis
• Fish oil (n3 fat – mainly EPA and DHA together 6 to 8 g/day)
• Strengthen immune system for those genetically susceptible host with triggers like smoking, many infective agents esp P gingivalis can cause oral cavity infection.

Fish Oil

An 18-month study was published in 2014 that evaluated how borage seed oil — rich in GLA — and fish oil rich fared against each other in treating patients with rheumatoid arthritis. It was discovered that all three groups (one taking fish oil, one taking borage oil and one taking a combination of the two) “exhibited significant reductions” in disease activity, and no therapy outperformed the others. For all three, “meaningful clinical responses” were the same after nine months. (11)

This is great news for both fish and borage oil when it comes to arthritis patients, but it’s critical to emphasize that the results were the same because taking too many supplements is simply a waste of money.

Another study also showed that omega-3 fish oil supplements worked just as well as NSAIDs in reducing arthritic pain and are a safer alternative to NSAIDs.

Illustration of pathways of genetics, inflammation, and infectious links between rheumatoid arthritis and periodontal diseases.

Arthritis – rheumatoid Causes

The exact causes of rheumatoid arthritis are unknown. Rheumatoid arthritis is most likely triggered by a combination of factors, including an abnormal autoimmune response, genetic susceptibility, and some environmental or biologic trigger, such as a viral infection or hormonal changes.

The Immune Response and Inflammatory Process

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body’s immune system, which fights infection and heals wounds and injuries:

• When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
• The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight any infections.
• In the process the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting off any bleeding blood vessel and initiating fiber-like patches to the tissue.
• Under normal conditions, the immune system has other special factors that control and limit this inflammatory process.

The Infection Fighters

Two important components of the immune system that play a role in the inflammation associated with rheumatoid arthritis are B cells and T cells, both of which belong to a family of immune cells called lymphocytes.
If the T cell recognizes an antigen as “non-self,” it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion.
For reasons that are still not completely understood, both the T cells and the B cells become overactive in patients with RA.
An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Genetic Factors

Genetic factors may play some role in RA either in terms of increasing susceptibility to developing the condition or by worsening the disease process but are clearly not the only important factors. The main genetic marker identified with rheumatoid arthritis is HLA (human leukocyte antigen).
A number of HLA genetic forms called HLA-DRB1 and HLA-DR4 alleles are referred to as the RA-shared epitope because of their association with rheumatoid arthritis. These genetic factors do not cause RA, but they may make the disease more severe once it has developed. Genetic variations in the HLA region may also predict drug treatment response to etanercept and the disease-modifying anti-rheumatic drug methotrexate.

Environmental Triggers – Infections

Although many bacteria and viruses have been studied, no single organism has been proven to be the primary trigger for the autoimmune response and subsequent damaging inflammation. Higher than average levels of antibodies that react with the common intestinal bacteria E. coli have appeared in the synovial fluid of people with RA. Some researchers think they may stimulate the immune system to prolong RA once the disease has been triggered by some other initial infection. Other potential triggers include Mycoplasma, parvovirus B19, retroviruses, mycobacteria, and Epstein-Barr virus.

Gingivitis, Gum Health Linked to Heart and Prostate Disorders

By Jim English

Periodontal disease is a chronic inflammatory disorder that causes gum tissues to pull away from the teeth, allowing bacteria to accumulate and triggering an inflammatory reaction that leads to the loss of bone tissues and teeth. In addition to the misery associated with the loss of one’s teeth, new research shows a positive link between the onset of periodontal disease and other chronic inflammatory disorders, including diabetes, cardiovascular disease, prostatitis and rheumatoid arthritis.
Periodontitis occurs when bacteria gather and form a “biofilm” that coats tooth surfaces at or below the gum line. These bacteria emit toxins that cause the body to mount an inflammatory response that, in turn, begins to eat away at gum tissues, leading to gingivitis. Eventually, if the source of inflammation is not brought under control, the process can result in the destruction of supportive bone structures (alveolar bone) that play a critical role in anchoring teeth firmly in place. As these retaining tissues break down, once-firm teeth become loose, leading to increasing inflammation, loss of bone and eventually requiring extraction.
Inflamed, bleeding gums and loss of teeth are only part of the damage. Gum disease is essentially an open wound that allows bacteria and their toxins to enter the body.
Inflamed, bleeding gums and the loss of teeth, however, are only a part of the potential damage arising from periodontal disease. Gum disease is essentially an open wound that allows bacteria and their toxins to enter the body and cause widespread damage. Research has established that advanced periodontal disease contributes to atherosclerosis, heart attack, stroke and diabetes. Conversely, diabetes, osteoporosis and osteoarthritis have been shown to contribute to periodontal disease.

Gum Health and Periodontitis

While periodontitis is recognized as the most common form of chronic infection and inflammation in humans, the number of people in the United States afflicted with periodontitis turns out to be significantly higher than was originally believed. In a recent National Health and Nutrition Examination Survey (NHANES) study, a full-mouth, comprehensive periodontal examination of over 450 adults over the age of 35 was compared with the results of earlier studies that relied on only a partial-mouth periodontal examination. The recent study shows that the previous partial-mouth study methodology may have underestimated the true incidence of periodontal disease by up to 50 percent.(1)
According to Samuel Low, DDS, MS, president of the American Academy of Periodontology, “This study shows that periodontal disease is a bigger problem than we all thought. It is a call to action for anyone who cares about his or her oral health. Given what we know about the relationship between gum disease and other diseases, taking care of your oral health isn’t just about a pretty smile. It has bigger implications for overall health, and is therefore a more significant public health problem.”
How ‘Jailbreaking’ Bacteria can Trigger Heart Disease
A growing body of research now links gum disease with the onset of heart disease, caused when plaque-causing bacteria from the mouth enter into the bloodstream and increase the risk of heart attack. According to Professor Howard Jenkinson of the University of Bristol, England, oral bacteria can wreak havoc if they are not kept in check by regular brushing and flossing. “Poor dental hygiene can lead to bleeding gums, providing bacteria with an escape route into the bloodstream, where they can initiate blood clots leading to heart disease,” he said.(2)

Streptococcus bacteria commonly live in the mouth, confined within communities termed “biofilms” that are responsible for causing tooth plaque and gum disease. Researchers have now shown that once let loose in the bloodstream, Streptococcus bacteria can use a protein, called PadA, as a weapon to force platelets in the blood to bind together and form clots.
Inducing blood clots is a selfish trick used by bacteria, Jenkinson points out. “When the platelets clump together they completely encase the bacteria. This provides a protective cover not only from the immune system, but also from antibiotics that might be used to treat infection,” he said. “Unfortunately, as well as helping out the bacteria, platelet clumping can cause small blood clots, growths on the heart valves (endocarditis), or inflammation of blood vessels that can block the blood supply to the heart and brain.”
Professor Jenkinson said the research highlights a very important public health message. “People need to be aware that, as well as keeping a check on their diet, blood pressure, cholesterol and fitness levels, they also need to maintain good dental hygiene to minimize their risk of heart problems.”

Periodontal Disease Linked to Prostatitis

In addition to contributing to development of heart disease, researchers from Case Western Reserve University School of Dental Medicine recently reported that initial results from a small sample shows that inflammation from gum disease and prostate problems just might be linked. In their paper, published in the official journal of the American Academy of Periodontology, the researchers described how they compared two unique markers for inflammation: Prostate-Specific Antigen (PSA), which is widely used to measure inflammation levels in prostate disease, and Clinical Attachment Level (CAL) of the gums and teeth, an indicator of periodontitis.
A PSA blood level of 4.0 ng/ml in the blood can be a sign of inflammation or malignancy, and patients with healthy prostate glands have lower than 4.0 ng/ml levels. A CAL number greater than 2.7 mm indicates periodontitis.

Like periodontitis, prostatitis also produces high inflammation levels. “Subjects with both high CAL levels and moderate to severe prostatitis have higher levels of PSA or inflammation,” stated Nabil Bissada, chair of the department of periodontics in the dental school. Bissada added that this might explain why PSA levels can be high in prostatitis, but sometimes cannot be explained by what is happening in the prostate glands. “It is something outside the prostate gland that is causing an inflammatory reaction,” he said. Because periodontitis has been linked to heart disease, diabetes and rheumatoid arthritis, the researchers felt a link might exist to prostate disease.
Thirty-five men from a sample of 150 patients qualified for their study, funded by the department of periodontology at the dental school. The participants were selected from patients with mild to severe prostatitis, who had undergone needle biopsies and were found to have inflammation and in some patients, malignancies.
The participants were divided into two groups: those with high PSA levels for moderate or severe prostatitis or a malignancy, and those with PSA levels below 4 ng/ml. All had not had dental work done for at least three months and were given an examination to measure the gum health. Looking at the results, the researchers from the dental school and the department of urology and the Institute of Pathology at the hospital found those with the most severe form of the prostatitis also showed signs for periodontitis.(3)

Polyunsaturated Fatty Acids may Reduce Periodontitis

In an article in the November issue of the Journal of the American Dietetic Association, researchers from Harvard Medical School and Harvard School of Public Health report that dietary intake of polyunsaturated fatty acids (PUFAs) like fish oil, known to have anti-inflammatory properties, shows promise for the effective treatment and prevention of periodontitis.
In a study involving over 9,000 adults, researchers found that omega-3 fatty acid intake, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were associated with reduced incidence of periodontitis. One of the study authors, Asghar Z. Naqvi commented, “To date, the treatment of periodontitis has primarily involved mechanical cleaning and local antibiotic application. Thus, a dietary therapy, if effective, might be a less expensive and safer method for the prevention and treatment of periodontitis.

Given the evidence indicating a role for omega-3 fatty acids in other chronic inflammatory conditions, it is possible that treating periodontitis with omega-3 fatty acids could have the added benefit of preventing other chronic diseases associated with inflammation, including stroke as well.”
In their paper the researchers reported an approximately 20 percent reduction in incidence of periodontitis in those consuming the highest amount of dietary DHA. The reduction correlated with EPA was smaller, while the correlation to LNA was not statistically significant. Foods that contain significant amounts of polyunsaturated fats include fatty fish like salmon, peanut butter and nuts.(4)

Periodontal health and systemic health

Given the increasing prevalence of periodontal disease and the growing body of research connecting periodontal health and systemic health, it is clearly essential to take steps to maintain healthy teeth and gums. According to Dr. Low, “Not only should you take good care of your periodontal health with daily tooth brushing and flossing, you should expect to get a comprehensive periodontal evaluation every year,” he advised. A dental professional, such as a periodontist, a specialist in the diagnosis, treatment and prevention of gum disease, will conduct the comprehensive exam to assess your periodontal disease status.
References
1. P. I. Eke, G. O. Thornton-Evans, L. Wei, W. S. Borgnakke, B. A. Dye. Accuracy of NHANES Periodontal Examination Protocols. Journal of Dental Research, 2010.
2. Society for General Microbiology (2010, September 5). ‘Jailbreak’ bacteria can trigger heart disease.
3. Joshi et al. Association Between Periodontal Disease and Prostate Specific Antigen Levels in Chronic Prostatitis Patients. Journal of Periodontology, 2010.
4. Asghar Z. Naqvi, Catherine Buettner, Russell S. Phillips, Roger B. Davis, Kenneth J. Mukamal. Omega-3 Fatty Acids and Periodontitis in US Adults. Journal of the American Dietetic Association, 2010; 110.

Obesity and rheumatic diseases

Abstract: A large body of evidence from clinical and experimental studies is aiding to understand the close relationships between obesity and rheumatic diseases. For instance, it is generally accepted that obesity contributes to the development of osteoarthritis by increasing mechanical load of the joints, at least in weight bearing joints. However, besides mechanical effects, recent studies demonstrated that white adipose tissue is able to secrete a plethora of soluble factors, called adipokines, which have a critical role in the development and progression of some rheumatic diseases such as osteoarthritis and rheumatoid arthritis. In this article, we summarize the recent findings on the interaction of certain adipokines with the two most common rheumatic diseases: osteoarthritis and rheumatoid arthritis.

Introduction

Up to the discovery of leptin in 1994 by Zhang et al. (1994), white adipose tissue (WAT) was considered only an energy storage tissue. In the recent years, WAT has been recognized to be a true endocrine organ, which is able to secrete a wide variety of factors termed adipokines (Hotamisligil et al., 1993; Fantuzzi, 2005). In addition to their metabolic activities recognized initially, these adipose-derived factors represent a new family of compounds that are also synthesized in other tissues, in addition to WAT, which could participate in several processes including inflammation and immunity (Otero et al., 2005; Tilg and Moschen, 2006; Lago et al., 2007).
Adipokines include a variety of pro-inflammatory factors with most of them being increased in obesity and appearing to contribute to the so-called “low-grade inflammatory state” in obese subjects. Inflammation in obesity is also closely related to a cluster of metabolic disorders including cardiovascular complications and autoimmune inflammatory diseases.
Apart from its metabolic activities, adipokines can be currently considered as key players of the complex network of soluble mediators involved in the pathophysiology of rheumatic diseases. Obesity, the condition that spurred the research on adipokines, has been considered a risk factor for developing osteoarthritis (OA) (Edwards et al., 2012; Vincent et al., 2012). It has been reported that obesity increases the incidence of OA, particularly in weight-bearing joints such as knees (Wluka et al., 2012), but the fact that obese subjects have an increased risk of OA in non-weight bearing joints such as hands (Yusuf et al., 2010; Grotle et al., 2008) reveals that soluble factors, adipokines indeed, are at play in the onset and progression of this rheumatic disease.
This review summarizes the current data concerning the involvement of certain adipokines in the two main rheumatic diseases, osteoarthritis and rheumatoid arthritis (RA).

Leptin

Leptin is a 16 kDa non-glycosylated hormone that is encoded by the obese (ob) gene, the murine homolog of human LEP gene (Zhang et al., 1994). Leptin exerts its biological actions through the activation of its OB-Rb long-form receptor isoform that is encoded by the gene diabetes (db) and belongs to the class 1 cytokine receptor superfamily. It is mainly produced by adipocytes, and its circulating levels are correlated with WAT mass. Mutation in either ob gene or the gene encoding the leptin receptor (the diabetes, or db gene), results in severe obesity. This hormone decreases food intake and increases energy consumption by acting on specific hypothalamic nuclei, inducing anorexigenic factors such as cocaine amphetamine related transcript (CART) and suppressing orexigenic neuropeptides such as neuropeptide Y (Ahima et al., 1996). Leptin levels are mostly dependent on the amount of body fat, but its synthesis is also regulated by inflammatory mediators (Gualillo et al., 2000).

Leptin and Osteoarthritis

It is increasingly evident that this hormone plays a key role in the OA pathophysiology; in fact serum leptin levels are increased in OA patients (de Boer et al., 2012). Some initial findings have suggested an anabolic role of this hormone in the cartilage (Dumond et al., 2003). But most studies revealed a catabolic role of leptin at cartilage level. For instance, our group demonstrated for the first time that, in cultured human and murine chondrocytes, type 2 nitric oxide synthase (NOS2) is synergistically activated by the combination of leptin plus interferon-γ. Next, we demonstrated that NOS2 activation by interleukin-1β (IL-1β) is increased by leptin via a mechanism involving JAK2, PI3K, and mitogen activated kinases (MEK1 and p38) (Otero et al., 2003; 2005). Nitric oxide (NO), which is induced by a wide range of pro-inflammatory cytokines, is a well-known pro-inflammatory mediator on joint cartilage, where it triggers chondrocyte phenotype loss, apoptosis, and activation of metalloproteinases (MMPs).
Recently, it has been demonstrated that leptin is able to a lso induce the expression of MMPs involved in OA cartilage damage, such as MMP-9 and MMP-13 (Toussirot et al., 2007). In fact, conditioned media from osteoarthritic infrapatellar fat pad, containing leptin, induce the synthesis of certain MMPs (Hui et al., 2012), demonstrating that the local production of leptin participates in the degradation processes occurred in the joints. More lines of evidence suggested that leptin, alone and in combination with IL-1β, up-regulates MMP-1 and MMP-3 production in human OA cartilage through the transcription factor NF-κB (nuclear factor κB), protein kinase C, and MAP kinase pathways. This adipokine is also correlated positively to MMP-1 and MMP-3 in synovial fluid (SF) from OA patients (Koskinen et al., 2011b). Moreover, recently leptin has been demonstrated to increase IL-8 production in human chondrocytes (Gomez et al., 2011). Bao et al. (2010) have defined that leptin enhanced both gene and protein levels of catabolic factors such as MMP-2 and MMP-9, while down-regulated the anabolic factors such as basic fibroblast growth factor (bFGF) in articular cartilage of rats. Additionally, the gene expression of ADAMTS-4 and -5 were markedly increased and a depletion of proteoglycan in articular cartilage was observed after treatment with leptin.
More recently, our group demonstrated that leptin per se is also able to increase the expression of vascular cell adhesion molecule-1 (VCAM-1), a relevant adhesion molecule involved in the recruitment and extravasation of leukocytes from circulating blood to inflamed joints (Conde et al., 2012).
Leptin also could contribute to abnormal osteoblast function in OA. In fact, the elevated production of leptin in OA abnormal subchondral osteoblast is correlated with the increased levels of ALP (alkaline phosphatase), OC (osteocalcin), collagen type I, and TGF-β1 (transforming growth factor β1), inducing a dysregulation of osteoblast function (Mutabaruka et al., 2010).
Leptin and leptin’s receptor expression levels were significantly increased in advanced OA cartilage and in SF (Vuolteenaho et al., 2012). Moreover, a very recent study showed that leptin bioactive levels are increased in SF from obese OA patients and SOCS-3 (a typically leptin-induced signaling suppressor in the cell) expression in cartilage is decreased in these patients compared with non-obese OA patients (Vuolteenaho et al., 2012).
Ku et al. (2009) have demonstrated a relationship of SF leptin concentrations with the radiographic severity of OA, suggesting a role of leptin as an effective marker for OA.
These results suggested that leptin might act as a pro-inflammatory factor on cartilage metabolism and exert a catabolic effect on OA joints. In recent studies, comparing the incidence rates of knee osteoarthritis between ob/ob and db/db mice and controls, no significant differences have been detected (Griffin et al., 2009). This recent finding suggested that obesity, per se, is not a sufficient condition to induce knee OA, whereas leptin is necessary in the development and progression of OA associated with obesity.
In fact, most studies support the role of the adipokines as a non-mechanical link between obesity and OA. In patients with clinical knee osteoarthritis, Berry et al. (2011) have demonstrated that leptin was significantly associated with increased levels of the bone formation biomarkers, such as osteocalcin and PINP, and reduced cartilage volume loss. In the same way, baseline expression of leptin receptors was associated with reduced levels of the cartilage formation biomarkers PIIANP, with increased cartilage defects score, and with increased cartilage volume loss. All these results were independent of age, sex, and body mass index.

Figure 1. Schematic representation of the most relevant effects of leptin and adiponectin in osteoarthritis and rheumatoid arthritis.
However, in other recent published papers, no association between leptin levels and hand OA progression or severity has been demonstrated (Massengale et al., 2012; Yusuf et al., 2011). To note, some authors found a correlation between leptin serum concentration and the intensity of chronic hand OA pain (Massengale et al., 2012) (Figure 1).

Leptin and Rheumatoid Arthritis

Together with other neuroendocrine signals, leptin seems to play a role in autoimmune diseases such as RA, but whether leptin can harm or protect joint structures in RA is still unclear. In patients with RA, circulating leptin levels have been described as either higher or unmodified in comparison to healthy controls (Otero et al., 2006; Toussirot et al., 2007). In RA patients, a fasting-induced fall in circulating leptin is associated with CD4+ lymphocyte hyporeactivity and increased IL-4 secretion (Fraser et al., 1999). Experimental antigen-induced arthritis is less severe in leptin-deficient ob/ob mice than in wild-type mice, whereas leptin-deficient mice and leptin-receptor-deficient mice exhibited a delayed resolution of the inflammatory process in zymosan-induced experimental arthritis. Notably, leptin decreased the severity of septic arthritis in wild-type mice. So, in the light of the present results it seems difficult to make an unambiguous conclusion about a potential role of leptin in RA (Bernotiene et al., 2006). Several studies have also demonstrated that there may exist a close dependence between the risk of aggressive course of RA and leptin levels (Lee et al., 2007; Targonska-Stepniak et al., 2008). In addition, a correlation among serum leptin, synovial fluid/serum leptin ratio, disease duration, and parameters of RA activity has been reported (Olama et al., 2012).
It is relevant to mention that current biologic treatments for RA, such as anti-TNF (tumor necrosis factor) therapies, do not directly modulate leptin levels (Derdemezis et al., 2009; Gonzalez-Gay et al., 2009; Popa et al., 2009).
Also, it is important to note the relevance of leptin in vitro. Many studies demonstrated the effect of this adipokine in different cell types present in the joint. Apart from the prominent activity of leptin in chondrocytes, which was demonstrated by our group and others (Conde et al., 2012; Otero et al., 2003; 2005; 2007), leptin has more recently been shown to also exert a pro-inflammatory effect on synovial fibroblasts. Leptin induced IL-8 production in synovial fibroblasts via a mechanism involving a canonical activation of the leptin receptor and NF-κB (Tong et al., 2008). To note, this effect was also demonstrated by our group in human chondrocytes (Gomez et al., 2011).
The action of leptin in RA is not only targeted to articular tissue, this adipokine also exerts direct modulatory effects on activation, proliferation, maturation, and production of inflammatory mediators in a variety of immune cells, including lymphocytes, natural killer cells, monocytes/macrophages, dendritic cells, neutrophils, and eosinophils (Lam and Lu, 2007).
In particular, it is known that leptin is able to modulate regulatory T cells (Treg) that are potent suppressors of autoimmunity. Matarese and colleagues have recently demonstrated that leptin secreted by adipocytes sustains T helper 1 (Th1) immunity by promoting effector T cell proliferation and by constraining Treg cell expansion (De Rosa et al., 2007). Weight loss, with concomitant reduction in leptin levels, induces a reduction in effector T cell proliferation and an increased expansion of Treg cells, leading to a down-regulation of Th1 immunity and cell-mediated autoimmune diseases associated with increased susceptibility to infections. On the contrary, an increase in adipocyte mass leads to high leptin secretion, which results in expansion of effector T cells and reduction of Treg cells. This fact determines an overall enhancement of the pro-inflammatory immunity and of T cell-mediated autoimmune disorders. Though, leptin can be considered as a link among immune tolerance, metabolic function, and autoimmunity and future strategies aimed at interfering with leptin signaling may represent innovative therapeutic tools for autoimmune disorders.
Very recently it has been demonstrated that leptin can activate mammalian target of rapamycin (mTOR) and regulate the proliferative capacity of regulatory T cells. This study suggests that the leptin-mTOR signaling pathway is an important link between host energy status and Treg cell activity. Authors conclude that oscillating mTOR activity is necessary for Treg cell activation and suggest that this might explain why Treg cells are unresponsive to TCR stimulation in vitro when high levels of leptin and nutrients may sustain mTOR activation (Procaccini et al., 2010; De Rosa et al., 2007). To note, both direct and indirect effects of leptin on the immune system have been described to account for the immune defects observed in leptin- and leptin-receptor-deficient rodents. Actually, Palmer et al. (2006) have also shown an indirect effect of leptin on the immune system, demonstrating that leptin receptor deficiency affects the immune system indirectly via changes in the systemic environment (Figure 1).

Adiponectin

Adiponectin, also known as GBP28, apM1, Acrp30, or AdipoQ, is a 244-residue protein that is produced mainly by WAT. Adiponectin has structural homology with collagens VIII and X and complement factor C1q, and it circulates in the blood in relatively large amounts in different molecular forms (Kadowaki and Yamauchi, 2005; Oh et al., 2007).
It increases fatty acid oxidation and reduces the synthesis of glucose in the liver. Ablation of the adiponectin gene has no dramatic effect on knockout mice on a normal diet, but when placed on a high fat/sucrose diet, they develop severe insulin resistance and exhibit lipid accumulation in muscles.
Circulating adiponectin levels tend to be low in morbidly obese patients and increase with weight loss (Kadowaki and Yamauchi, 2005; Oh et al., 2007).
Adiponectin acts via two receptors, one (AdipoR1) found predominantly in skeletal muscle and the other (AdipoR2) in liver. Transduction of the adiponectin signal by AdipoR1 and AdipoR2 involves the activation of AMPK, PPAR-α, PPAR-γ, and other signaling molecules (Kadowaki and Yamauchi, 2005).

Adiponectin and Osteoarthritis

Some findings indicate that adiponectin has a wide range of effects in pathologies involving inflammation, such as cardiovascular disease, endothelial dysfunction, type 2 diabetes, metabolic syndrome, and OA (Matsuzawa, 2006). In contrast to its previously described protective role in vascular diseases, there are some lines of evidence that show that adiponectin might act as a pro-inflammatory factor in joints, and it could be involved in matrix degradation.
Adiponectin-treated chondrocytes lead to the induction of NOS2, via a signaling pathway that involves PI3 kinase. Similarly, this adipokine also increases the production of IL-6, MMP-3, MMP-9, and MCP-1 in the same cell type (Lago et al., 2008). Recently, the induction of MMP-3 by adiponectin in chondrocytes was further confirmed, and it occurred, in part, through p38, AMPK, and NF-κB (Tong et al., 2011). In addition, Kang et al. (2010) have reported that collagenase-cleaved type II collagen neoepitope, a product of collagen type II degradation, was increased in supernatants of adiponectin-induced OA cartilage explants. Furthermore, it has been reported that adiponectin is able to induce the expression of IL-6 in human synovial fibroblasts (Tang et al., 2007).
Like leptin, adiponectin was recently described as a potent inductor of VCAM-1 in chondrocytes, even more than a classic pro-inflammatory cytokine as IL-1β. So, it is reasonable to describe a scenario in which this adipokine is able to perpetuate cartilage-degrading processes by inducing molecules responsible for monocyte and leukocyte infiltration to the joint.
In addition, the implication of adiponectin in OA pathogenesis is supported by clinical observations. It has been reported that plasma adiponectin levels were significantly higher in OA patients than in healthy controls (Laurberg et al., 2009). Actually, Filkova et al. (2009) found higher adiponectin serum levels in erosive OA patients compared with non-erosive OA patients. In the same way, Koskinen et al. (2011a) reported that serum adiponectin and adiponectin synthesis from OA cartilage are higher in patients with the radiologically most severe disease. Furthermore, these authors and others observed an association among adiponectin serum levels, OA biomarkers and local synovial inflammation (de Boer et al., 2012; Koskinen et al., 2011a). To note, adiponectin-leptin ratio was proposed as predictor of pain in OA patients (Gandhi et al., 2010), in fact this adipokine has been detected in OA synovial fluids correlating with aggrecan degradation (Hao et al., 2011).
Also, it is noteworthy that there was an increase in IL-6 and adiponectin production in infrapatellar fat pad (IFP) in knee osteoarthritis (Klein-Wieringa et al., 2011a; Ushiyama et al., 2003; Distel et al., 2009), showing that IFP could contribute to the local production of cytokines and adipokines. Taken together, these results suggest that adiponectin may be considered a potential molecule involved in joint disorders and matrix degradation.
However, the role of adiponectin in OA is controversial. There are some findings that show an inhibition of IL-1β-induced MMP-13 expression and up-regulation of tissue inhibitor of metallopreoteinase-2 (TIMP-2) mediated by adiponectin in chondrocytes (Chen et al., 2006). Moreover, in STR/Ort mice, an animal osteoarthritis model, the serum adiponectin levels are lower compared with control group (Uchida et al., 2009), suggesting a protective role for this adipokine in the development of the disease.
It is noteworthy that clinical data also support the fact that adiponectin could be a protective molecule against OA. A recent study revealed an inverse correlation between adiponectin and disease severity (Honsawek and Chayanupatkul, 2010). Moreover, it has been reported that patients with high adiponectin levels had a decreased risk for hand OA progression, suggesting that this adipokine may be a protective hormone against cartilage damage (Yusuf et al., 2011). Although, other recent studies showed that serum adiponectin levels were not associated with radiographic hand OA severity (Massengale et al., 2012) (Figure 1).

Adiponectin and Rheumatoid Arthritis

The potential role of adiponectin in rheumatoid arthritis has been actively investigated. Generally, low adiponectin levels have been associated with obesity, type 2 diabetes, atherosclerosis, and vessel inflammation. Moreover, in metabolic syndrome the role of adiponectin is clearly anti-inflammatory. On the other side, multiple studies described high adiponectin levels in patients with RA, and these levels correlate with severity of RA (Alkadi et al., 2011; Otero et al., 2006; Ebina et al., 2009). Several authors identified an association between serum adiponectin levels and radiographic damage in patients with RA (Klein-Wieringa et al., 2011b; Giles et al., 2009). These findings suggest that this adipokine may be a mediator of the paradoxical relationship between increasing adiposity and protection from radiographic damage in RA. In addition, other studies reveal that adiponectin is also related to erosive joint destruction in RA (Giles et al., 2011), and it has been described that this adipokine is associated with the pro-inflammatory cytokine IL-6 (Oranskiy et al., 2012; Ozgen et al., 2010).

At joint levels adiponectin might be pro-inflammatory

In contrast to its “protective” role against obesity and vascular diseases, at joint levels adiponectin might be pro-inflammatory. In synovial fibroblasts (SF), adiponectin induces IL-6 production and MMP-1, two of the main mediators of RA via the p38 MAPK pathway (Ehling et al., 2006). Similarly, IL-8 is induced by adiponectin through an intracellular pathway involving NF-κB (Gomez et al., 2011; Katano et al., 2009). In addition, adiponectin and IL-1β synergize in the induction of IL-6, IL-8, and prostaglandin E2 (PGE2) in RA synovial cells (Lee et al., 2012), suggesting that adiponectin and IL-1β may act synergistically in the induction of pro-inflammatory factors during RA progression.
Recent studies showed that adiponectin might also contribute to synovitis and joint destruction in RA by stimulating MMP-1, MMP-13, and vascular endothelial growth factor (VEGF) expression in synovial cells, surprisingly, more than conventional pro-inflammatory mediators (i.e., IL-1β) (Choi et al., 2009).

In addition, a study developed in RA synovial fibroblasts (RASFs) showed that adiponectin increases both cyclooxygenase-2 (COX-2) and membrane-associated PGE synthase-1 (mPGES-1) mRNA and protein expression, resulting in an increase in PGE2 production in a time and concentration-dependent manner (Kusunoki et al., 2010). This increase was inhibited by siRNA against adiponectin receptor (AdipoR1 and AdipoR2) or using inhibitors of specific proteins involved in adiponectin signal transduction (Kusunoki et al., 2010). Recently, Frommer et al. (2010) have confirmed the pro-inflammatory role of adiponectin in RA by demonstrating that this adipokine promotes inflammation through cytokine synthesis by the different cells present in the joint.

Also, it participates in the attraction of inflammatory cells to the synovium via chemokines synthesis and promoting matrix destruction due to the increased release of matrix metalloproteinases by chondrocytes. Moreover, the authors described that the different isoforms of adiponectin can induce the expression of different genes involved in the pathogenesis of RA (Frommer et al., 2012); these results suggest that adiponectin have detrimental effects in joint inflammatory diseases such as RA (Figure 1).

Other Adipokines in Osteoarthritis and Rheumatoid Arthritis – Chemerin

Chemerin, also known as tazarotene-induced gene 2 and retinoic acid receptor responder 2 (RARRES2), is a chemoattractant adipokine (Wittamer et al., 2003). It is secreted as an 18 kDa inactive proprotein and it is activated by posttranslational C-terminal cleavage (Wittamer et al., 2003). Chemerin acts via the G-coupled receptor chemokine-like receptor 1 (CMKLR1 or ChemR23) (Wittamer et al., 2003). Chemerin and its receptor are expressed mainly in adipose tissue (Bozaoglu et al., 2007), but also in, for instance, dendritic cells, and macrophages express chemerin receptor (Luangsay et al., 2009). ChemR23 is also expressed by endothelial cells, and it is up-regulated by pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 (Kaur et al., 2010).
Interestingly, chondrocytes express chemerin and its receptor (Berg et al., 2010; Conde et al., 2011), and IL-1β is able to increase chemerin expression (Conde et al., 2011). In the same way, Berg et al. (2010) have demonstrated that recombinant chemerin enhances the production of several pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), as well as different MMPs (MMP-1, MMP-2, MMP-3, MMP-8, and MMP-13) in human articular chondrocytes. These factors play a role in the degradation of the extracellular matrix, by causing a breakdown of the collagen and aggrecan framework, and result in the irreversible destruction of the cartilage in OA and RA. Moreover, these authors reported that recombinant chemerin phosphorylates p42/44 MAPK and Akt.
To note, chemerin was detected in synovial fluid from OA and RA patients (Eisinger et al., 2012; Huang et al., 2012), and the serum concentration of this adipokine was correlated with the disease severity in OA (Huang et al., 2012). Moreover, it has been reported that chemerin enhances the production of IL-6 and MMP-3 in fibroblast-like synoviocytes (Kaneko et al., 2011), suggesting a role for chemerin in the pathogenesis of RA. In addition, this adipokine stimulates the synthesis of CCL2 and TLR4 (Eisinger et al., 2012), and the authors postulated that chemerin develops certain functions in the relationship between innate immunity and joint inflammation.
Lipocalin 2. Lipocalin 2 (LCN2), also termed siderocalin, 24p3, uterocalin, and neutrophil gelatinase-associated lipocalin (NGAL), is a 25 kDa glycoprotein isolated from neutrophil granules although white adipose tissue (WAT) is thought to be the main source (Triebel et al., 1992). The LCN2 protein has been isolated as a 25 kDa monomer, as a 46 kDa homodimer, and in a covalent complex with MMP-9, and its cellular receptor, megalin (GP330), was described (Devireddy et al., 2001). LCN2 is involved in apoptosis of hematopoietic cells (Devireddy et al., 2001), transport of fatty acids and iron (Chu et al., 1998), modulation of inflammation (Cowland and Borregaard, 1997), among other processes.
LCN2 has recently been identified in chondrocytes (Owen et al., 2008). In these cells IL-1β, leptin, adiponectin, LPS, and dexamethasone act as potent modulators of LCN2 expression (Conde et al., 2011). LCN2 is likely to be involved in matrix degradation since it forms molecular complexes with MMP-9 (Gupta et al., 2007).
Recently, the group of Katano confirmed that the level of NGAL in SF was significantly higher in patients with RA than in those with osteoarthritis. Through proteome analysis Katano et al. (2009) have showed that GM-CSF may contribute to the pathogenesis of RA by the up-regulation of LCN2 in neutrophils, followed by induction of Cathepsin D, transitional endoplasmic reticulum ATPase (TERA), and transglutaminase 2 (tg2) in synoviocytes. These enzymes may contribute to the proliferation of synovial cells and infiltration of inflammatory cells inside the synovium.

Vaspin

Vaspin is a serpin (serine protease inhibitor) that was produced in the visceral adipose tissue (Hida et al., 2005). Interestingly, administration of vaspin to obese mice improved glucose tolerance and insulin sensitivity and reversed altered expression of genes that might promote insulin resistance. The induction of vaspin by adipose tissue might constitute a compensatory mechanism in response to obesity and its inflammatory complications.
With regard to rheumatic diseases, serum vaspin concentrations were increased in RA patients compared to healthy controls (Ozgen et al., 2010). Moreover, synovial fluid vaspin levels were significantly higher in RA patients compared to OA patients (Senolt et al., 2010).
Apelin. Apelin is a bioactive peptide that was originally identified as the endogenous ligand of the orphan G protein- coupled receptor APJ (Tatemoto et al., 1998). TNF increases apelin productions in both adipose tissue and blood plasma when administered to mice (Daviaud et al., 2006).
Hu et al. (2010) have suggested that apelin may play a catabolic role in cartilage metabolism. Apelin stimulates the proliferation of chondrocytes and significantly increases the mRNA expression of the catabolic factors MMP-1, MMP-3, MMP-9, and IL-1β in vitro. Intra-articular injection with apelin in vivo up-regulates the expression of MMP-3, MMP-9, and IL-1β in articular cartilage. By contrast, apelin treatment decreases the level of collagen II in the same tissue. In addition, after treatment with apelin, mRNA levels of ADAMTS-4 and ADAMTS-5 in articular cartilage are markedly increased and depletion of proteoglycan in articular cartilage was found.
Also, the same group reported that serum apelin levels were higher in OA patients compared with healthy controls (Hu et al., 2011). Moreover, this adipokine was present in the synovial fluid of these patients and correlated positively with disease activity (Hu et al., 2011). These results indicate that apelin could contribute to the development of OA.
Omentin. Omentin is a protein of 40 kDa secreted by omental adipose tissue and highly abundant in human plasma that had previously been identified as intelectin, a new type of Ca2+-dependent lectin with affinity to galactofuranosyl residues (which are constituents of pathogens and dominant immunogens) (Schaffler et al., 2005). So, it was suggested that a biological function of omentin/intelectin was the specific recognition of pathogens and bacterial components, playing an important role in the innate immune response to parasite infection (Gerwick et al., 2007). Moreover, several studies have shown that omentin gene expression is altered by inflammatory states and obesity (de Souza Batista et al., 2007).
Senolt et al. (2010) have found reduced levels of omentin in the synovial fluid of patients with RA compared with those with OA. In addition, it has been demonstrated that synovial fluid omentin concentrations were negatively correlated with the severity of the OA (Li et al., 2012; Xu et al., 2012), suggesting that this adipokine could serve as a biomarker for reflecting the severity of the disease.

Molecules secreted by adipose tissue could affect the joint structures in rheumatic diseases

The study of adipokines opened a new perspective of how molecules secreted by adipose tissue could affect the joint structures in rheumatic diseases. The relationship between obesity and rheumatic diseases such as OA has been considered just by a higher mechanical stress. However, the discovery of these adipose-derived factors demonstrated a metabolic relationship too. In the last several years there have been many studies trying to identify new adipokines and their signaling pathways, as well as, their actions in the different joint tissues.
All of the knowledge about these proteins could aid the development of new pharmacological treatments, for instance, the use of specific antibodies in a similar way to anti-TNF-α therapy. Also, with the data presented in this review we could conclude that adipokines might serve as biomarkers of the severity of certain rheumatic diseases.
This area of research is ongoing and more future research studies will be necessary to clarify the specific functions of adipokines in rheumatic diseases.
Acknowledgment
The work of O.G. and F.L. is funded by Instituto de Salud Carlos III and Xunta de Galicia (SERGAS) through a research-staff stabilization contract. O.G. is supported by Instituto de Salud Carlos III and Xunta de Galicia (grants PI11/01073 and 10CSA918029PR). F.L. is supported by Instituto de Salud Carlos III [grants PI11/00497 and REDINSCOR (RD06/0003/0016)]. This work was also partially supported by the RETICS Program, RD08/0075 (RIER) via Instituto de Salud Carlos III (ISCIII), within the VI NP of R+D+I 2008-2011 (OG). J.C. is a recipient of a fellowship from the Foundation IDIS-Ramón Dominguez. M.S. is a recipient of the “FPU” Program of the Spanish Ministry of Education. R.G. is a recipient of the “Sara Borrell Program” of the Spanish National Institute of Health “Carlos III.” V.L. is a recipient of a grant from Xunta de Galicia.
Resources
• http://www.niams.nih.gov — The National Institute of Arthritis and Musculoskeletal and Skin Diseases
• http://www.rheumatology.org — American College of Rheumatology
• http://www.arthritis.org — The Arthritis Foundation
• http://www.fda.gov/cder/drug/infopage/cox2 — FDA information on COX-2 inhibitors and NSAIDs
• http://www.clinicaltrials.gov — Find a clinical trial

Vitamin B5 – Panthothenate – for Schizophrenia

Vit B – Panthothenate – for schizophrenia

————————————-
Aside from feeding your brain, use your memory.
Use your brain or lose it. Learn new skills. If today’s jobs are either in computers or medical, learn new skills.
Connie Dello Buono ; motherhealth@gmail.com

Taste Of Beer Triggers Release Of Dopamine, happy neurotransmitter ; Cocaine bullies dopamine; MAO affects dopamine levels

Beer lift your spirits up

The taste of beer alone is enough to raise one’s spirits. The taste is linked with the release of dopamine, a neurotransmitter that controls the brain’s distribution of pleasure, according to a news study published in Neuropsychopharmacology.
“This is the first human demonstration that a stimulus that is reliably associated with alcohol association – that flavor alone, without any significant amount of alcohol – is able to induce a dopamine response,” said study author David Kareken.
The results were discovered by giving men a small gulp of their favorite beer and then scanning their brains. A scan revealed activity in the area of dopamine production. The amount of beer doled out was not large enough to change the subject’s blood-alcohol content level.
“This paper demonstrates that taste alone impacts on the brain functions associated with desire,” Peter Anderson, a professor of substance use, policy and practice at Newcastle University, U.K., said in a statement.
According to researchers, the study demonstrates that the smell of alcohol can cause relapses for addicts.
by RTT Staff Writer

Bananas

• Fruits like apples and bananas are excellent foods that trigger the release of dopamine. Bananas contain an amino acid called tyrosine which is the most important stimulant for the brain to produce dopamine. The brown spots on the banana contain the highest amount of dopamine. NaturalBuy.com explains that adding bananas to a diet may helps treat symptoms of depression. Apples contain an antioxidant called quercetin. Quercetin works to preserve dopamine levels in the body by protecting the dopamine cells from getting destroyed. Other fruits trigger the release of dopamine are blueberries, cranberries, prunes, and strawberries.
Proteins

Protein rich foods

Eating foods high in amino acids will trigger the release of dopamine. Proteins hold an amino acid called tyrosine which triggers the release of dopamine after entering the body. Dopamine is found in foods such as almonds, cheese, chicken, fish, and any other protein containing Omega 3 fatty acids. Dairy products such as cheese, milk, and yogurt contain protein. Black beans, chick peas, lima beans, and fava beans are all sources of rich protein foods that will help trigger dopamine. Eggs are a source of protein and contain choline, which is a vitamin that helps improve concentration and memory. Almonds are nuts loaded with protein but should be eaten in moderation because they can cause weight gain and headaches.

Chocolate

Chocolate contains phenylalanine, which is an essential amino acid that turns into tyrosine. The University of Maryland explains that tyrosine is a building block for the neurotransmitter that triggers dopamine. The stimulant in chocolate is in the cocoa and greater amounts of tyrosine are found in dark chocolate. In chocolate, the fat from the milk will also trigger dopamine because it’s a dairy product. Dark chocolate contains many antioxidants , however too much could harm the liver and cause weight gain. According to Chocolate.org, chocolate contains phenylalanine which is related to amino acids. Phenylalanine increases activity and has been proven to relieve depression in 60 percent of depressed patients.

Avoid Sugar

Foods high in sugar, cholesterol and saturated fats can lower your levels of dopamine. While these foods may produce a temporary feeling of satisfaction, they interfere with proper brain function and so the production of dopamine. Your eating habits closely correlate with your mood, so picking fresh fruits and vegetables and other foods with high nutritional value will not only keep you slimmer, it’ll keep your mood more balanced and you feeling better.

Dopamine and MAO

One of the neurotransmitters playing a major role in addiction is dopamine. Many of the concepts that apply to dopamine apply to other neurotransmitters as well.
As a chemical messenger, dopamine is similar to adrenaline. Dopamine affects brain processes that control movement, emotional response, and ability to experience pleasure and pain.
Regulation of dopamine plays a crucial role in our mental and physical health. Neurons containing the neurotransmitter dopamine are clustered in the midbrain in an area called the substantia nigra . In Parkinson’s disease, the dopamine- transmitting neurons in this area die. As a result, the brains of people with Parkinson’s disease contain almost no dopamine. To help relieve their symptoms, we give these people L-DOPA, a drug that can be converted in the brain to dopamine.

Drugs can stimulate or fail to stimulate dopamine receptors

Some drugs are known as dopamine agonists. These drugs bind to dopamine receptors in place of dopamine and directly stimulate those receptors. Some dopamine agonists are currently used to treat Parkinson’s disease. These drugs can stimulate dopamine receptors even in someone without dopamine neurons.
An example of agonist drug action
In contrast to dopamine agonists, dopamine antagonists are drugs that bind but don’t stimulate dopamine receptors. Antagonists can prevent or reverse the actions of dopamine by keeping dopamine from attaching to receptors.

Dopamine antagonists are traditionally used to treat schizophrenia and related mental disorders. A person with schizophrenia may have an overactive dopamine system. Dopamine antagonists can help regulate this system by “turning down” dopamine activity.

Cocaine

Cocaine and other drugs of abuse can alter dopamine function. Such drugs may have very different actions. The specific action depends on which dopamine receptors the drugs stimulate or block, and how well they mimic dopamine.
An example of antagonist drug action
Drugs can act directly or indirectly on dopamine receptors
Drugs such as cocaine and amphetamine produce their effects by changing the flow of neurotransmitters. These drugs are defined as indirect acting because they depend on the activity of neurons. In contrast, some drugs bypass neurotransmitters altogether and act directly on receptors. Such drugs are direct acting.
Use of these two types of drugs can lead to very different results in treating the same disease. As mentioned earlier, people with Parkinson’s disease lose neurons that contain dopamine. To compensate for this loss, the body produces more dopamine receptors on other neurons. Indirect agonists are not very effective in treating the disease since they depend on the presence of dopamine neurons. In contrast, direct agonists are more effective because they stimulate dopamine receptors even when dopamine neurons are missing.

MAO affects dopamine levels

Once returned to the sending neuron by the reuptake system, dopamine is subject to an enzyme named monoamine oxidase (MAO). MAO usually breaks down dopamine.
If no other factors were at work, MAO would keep the amount of “used” dopamine fairly low. However, dopamine taken back into the nerve ending can return to the vesicle for storage. Once inside the vesicle, dopamine is protected from MAO.

A drug named reserpine prevents the reuptake of dopamine and some other neurotransmitters. Administering reserpine causes dopamine to remain exposed within the cell and broken down by MAO. This profoundly reduces the available dopamine.
Changing the action of MAO can help us treat diseases that involve dopamine transmission. For instance, the drug deprenyl inhibits MAO. This increases the stores of dopamine and slows the progression of Parkinson’s disease. In higher doses, deprenyl enhances the effects of dopamine on behavior.
Interestingly, one form of MAO actually protects dopamine. This form of MAO, found in dopamine neurons, acts on substances in the neuron other than dopamine. Here MAO protects the “purity” of neurotransmission by breaking down other neurotransmitters. Inhibiting this form of MAO can increase levels of neurotransmitters such as serotonin, which seems to help people diagnosed with depression.
Drugs can also affect dopamine levels
Dopamine binds to its receptors quickly. This neurotransmitter is also quickly removed from its receptors as long as dopamine levels in the synapse are sufficiently high.
However, drugs can affect dopamine levels. Some drugs increase dopamine by preventing dopamine reuptake, leaving more dopamine in the synapse. An example is the widely abused stimulant drug, cocaine. Another is methylphenidate, used therapeutically to treat childhood hyperkinesis and symptoms of schizophrenia.
It’s interesting that amphetamine and cocaine produce affect behavior and heart function in similar ways. Furthermore, both drugs increase the amount of dopamine in the synapse. However, cocaine achieves this action by preventing dopamine reuptake, while amphetamine helps to release more dopamine. So, these drugs with similar effects produce their actions through entirely different processes. In turn, addiction to the two drugs may call for somewhat different types of treatment.

Neurons can become sensitized or desensitized to dopamine

One important aspect of drug addiction is how cells adapt to previous drug exposure.
For example, long-term treatment with dopamine antagonists increases the number of dopamine receptors. This happens as the nervous system tries to make up for less stimulation of the receptors by dopamine itself. Likewise, the receptors themselves become more sensitive to dopamine. Both are examples of the same process, called sensitization.
A type of sensitization.
An opposite effect occurs after dopamine or dopamine agonists repeatedly stimulate dopamine receptors. Here overstimulation decreases the number of receptors, and the remaining receptors become less sensitive to dopamine. This process is called desensitization.

Desensitization is better known as tolerance, where exposure to a drug causes less response than previously caused. Tolerance reflects the actions of the nervous system to maintain homeostasis -a constant degree of cell activity in spite of major changes in receptor stimulation. The nervous system maintains this constant level in an attempt to keep the body in a state of equilibrium, even when foreign chemicals are present.
Sensitization and desensitization do not take place only after long-term understimulation or overstimulation of dopamine receptors. Both sensitization and desensitization can occur after only a single exposure to a drug. In fact, they may develop within a few minutes.
A type of desensitization.
Disease and drugs can produce faulty sensitization
Sensitization or desensitization normally occur with drug exposure. However, addiction or mental illness can tamper with the reuptake system. This disrupts the normal levels of neurotransmitters in the brain and can lead to faulty desensitization or sensitization. If this happens in a region of the brain that serves emotion or motivation, the individual can suffer severe consequences.
Consider an example. Cocaine prevents dopamine reuptake by binding to proteins that normally transport dopamine. Not only does cocaine “bully” dopamine out of the way-it hangs on to the transport proteins much longer than dopamine does. As a result, more dopamine remains to stimulate neurons, which causes a prolonged feelings of pleasure and excitement. Amphetamine also increases dopamine levels. Again, the result is over-stimulation of these pleasure-pathway nerves in the brain.

Foods To Avoid When Taking Monoamine Oxidase Inhibitors

Q. Please review the dietary restrictions that should be observed when a patient is receiving monoamine oxidase inhibitor (MAOI) therapy?
R. Tyramine is an amino acid which is found in various foods, and is an indirect sympathomimetic that can cause a hypertensive reaction in patients receiving MAOI therapy.
Monoamine oxidase is found in the gastrointestinal tract and inactivates tyramine; when drugs prevent the catabolism of exogenous tyramine, this amino acid is absorbed and displaces norepinephrine from sympathetic nerve ending and epinephrine from the adrenal glands. If a sufficient amount of pressor amines are released, a patient may experience a severe occipital or temporal headache, diaphoresis, mydriasis, nuchal rigidity, palpitations, and the elevation of both diastolic and systolic blood pressure may ensue (Anon, 1989; Da Prada et al, 1988; Brown & Bryant, 1988).
On rare occasions, cardiac arrhythmias, cardiac failure, and intracerebral hemorrhage have developed in patients receiving MAOI therapy that did not observe dietary restrictions (Brown & Bryant, 1988).

Therefore, dietary restrictions are required for patients receiving MAOIs. Extensive dietary restrictions previously published were collected over a decade ago and due to changes in food processing and more reliable analytical methods, new recommendations have been published (Anon, 1989; McCabe, 1986).
The tyramine content of foods varies greatly due to the differences in processing, fermentation, ripening, degradation, or incidental contamination. Many foods contain small amounts of tyramine and the formation of large quantities of tyramine have been reported if products were aged, fermented, or left to spoil. Because the sequela from tyramine and MAOIs is dose-related, reactions can be minimized without total abstinence from tyramine-containing foods. Approximately 10 to 25 mg of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild reaction. Foods that normally contain low amounts of tyramine may become a risk if unusually large quantities are consumed or if spoilage has occurred (McCabe, 1986).
Three lists were compiled (foods to avoid, foods that may used in small quantities, and foods with insufficient evidence to restrict) to minimized the strict dietary restrictions that were previously used and improve compliance and safety of MAOI therapy. The foods to avoid list consists of foods with sufficient tyramine (in small or usual serving sizes) that would create a dangerous elevation in blood pressure and therefore should be avoided (McCabe, 1986).
________________________________________

Avoid Alcohol

ALCOHOLIC BEVERAGES – avoid Chianti wine and vermouth. Consumption of red, white, and port WINE in quantities less than 120 mL present little risk (Anon, 1989; Da Prada et al, 1988; McCabe, 1986). BEER and ALE should also be avoided (McCabe, 1986), however other investigators feel major domestic (US) brands of beer is safe in small quantities (1/2 cup or less than 120 mL) (Anon, 1989; Da Prada, 1988),
but imported beer should not be consumed unless a specific brand is known to be safe. WHISKEY and LIQUEURS such as Drambuie(R) and Chartreuse(R) have caused reactions. NONALCOHOLIC BEVERAGES (alcohol- free beer and wines) may contain tyramine and should be avoided (Anon, 1989; Stockley, 1993).
BANANA PEELS – a single case report implicates a BANANA as the causative agent, which involved the consumption of whole stewed green banana, including the peel. Ripe banana pulp contains 7 mcg/gram of tyramine compared to a peel which contains 65 mcg/gram and 700 mcg of tyramine and dopamine, respectively (McCabe, 1986).
BEAN CURD – fermented bean curd, fermented soya bean, soya bean pastes contain a significant amount of tyramine (Anon, 1989).
BROAD (FAVA) BEAN PODS – these beans contain dopa, not tyramine, which is metabolized to dopamine and may cause a pressor reaction and therefore should not be eaten particularly if overripe (McCabe, 1986; Anon, 1989; Brown & Bryant, 1988).
CHEESE – tyramine content cannot be predicted based on appearance, flavor, or variety and therefore should be avoided. CREAM CHEESE and COTTAGE CHEESE have no detectable level of tyramine (McCabe, 1986; Anon, 1989, Brown & Bryant, 1988).
FISH – fresh fish (Anon, 1989; McCabe, 1986) and vacuum- packed pickled fish or CAVIAR contain only small amounts of tyramine and are safe if consumed promptly or refrigerated for short periods; longer storage may be dangerous (Anon, 1989). Smoked, fermented, pickled (Herring) and otherwise aged fish, meat, or any spoiled food may contain high levels of tyramine and should be avoided (Anon, 1989; Brown & Bryant, 1988).
GINSENG – some preparations have resulted in a headache, tremulousness, and manic-like symptoms (Anon, 1989).
PROTEIN EXTRACTS – three brands of meat extract contained 95, 206, and 304 mcg/gram of tyramine and therefore meat extracts should be avoided (McCabe, 1986). Avoid liquid and powdered PROTEIN DIETARY SUPPLEMENTS (Anon, 1989).
MEAT, nonfresh or liver – no detectable levels identified in fresh chicken livers; high tyramine content found in spoiled or unfresh livers (McCabe, 1986). Fresh meat is safe, caution suggested in restaurants (Anon, 1989; Da Prada et al, 1988).
SAUSAGE, BOLOGNA, PEPPERONI and SALAMI contain large amounts of tyramine (Anon, 1989; Da Prada et al, 1988; McCabe, 1986). No detectable tyramine levels were identified in country CURED HAM (McCabe, 1986).
SAUERKRAUT – tyramine content has varied from 20 to 95 mcg/gram and should be avoided (McCabe, 1986).
SHRIMP PASTE – contain a large amount of tyramine (Anon, 1989).
SOUPS – should be avoided as protein extracts may be present; miso soup is prepared from fermented bean curd and contain tyramine in large amounts and should not be consumed (Anon, 1989).
YEAST, Brewer’s or extracts – yeast extracts (Marmite) which are spread on bread or mixed with water, Brewer’s yeast, or yeast vitamin supplements should not be consumed. Yeast used in baking is safe (Anon, 1989; Da Prada et al, 1988; McCabe, 1986).
The foods to use with caution list categorizes foods that have been reported to cause a hypertensive crisis if foods were consumed in large quantities, stored for prolong periods, or if contamination occurred. Small servings (1/2 cup, or less than 120 mL) of the following foods are not expected to pose a risk for patients on MAOI therapy (McCabe, 1986).

FOODS TO USE WITH CAUTION
(1/2 cup or less than 120 mL)
Alcoholic beverages – see under foods to avoid.
AVOCADOS – contain tyramine, particularly overripe (Anon, 1989) but may be used in small amounts if not overripened (McCabe, 1986).
CAFFEINE – contains a weak pressor agent, large amounts may cause a reaction (Anon, 1989).
CHOCOLATE – is safe to ingest for most patients, unless consumed in large amounts (Anon, 1989; McCabe, 1986).
DAIRY PRODUCTS – CREAM, SOUR CREAM, cottage cheese, cream cheese, YOGURT, or MILK should pose little risk unless prolonged storage or lack of sanitation standards exists (Anon, 1989; McCabe, 1986). Products should not be used if close to the expiration date (McCabe, 1986).
NUTS – large quantities of PEANUTS were implicated in a hypertensive reaction and headache. COCONUTS and BRAZIL NUTS have also been implicated, however no analysis of the tyramine content was performed (McCabe, 1986).
RASPBERRIES – contain tyramine and small amounts are expected to be safe (McCabe, 1986).
SOY SAUCE – has been reported to contain large amounts of tyramine and reactions have been reported with teriyaki (Anon, 1989), however analysis of soy sauce reveals a tyramine level of 1.76 mcg/mL and fermented meat may have contributed to the previously reported reactions (McCabe, 1986).
SPINACH, New Zealand prickly or hot weather – large amounts have resulted in a reaction (Anon, 1989; McCabe, 1986).
More than 200 foods contain tyramine in small quantities and have been implicated in reactions with MAOI therapy, however the majority of the previous reactions were due to the consumption of spoiled food. Evidence does not support the restriction of the following foods listed if the food is fresh (McCabe, 1986).
FOODS WITH INSUFFICIENT EVIDENCE FOR RESTRICTION (McCabe, 1986)
anchovies – cream cheese – raisins
beetroot – cucumbers – salad dressings
chips with vinegar – egg, boiled – snails
Coca Cola (R) – figs, canned – tomato juice
cockles – fish, canned – wild game
coffee – junket – worcestershire sauce
corn, sweet – mushrooms – yeast-leavened bread
cottage cheese – pineapple, fresh

Any protein FOOD, improperly stored or handled, can form pressor amines through protein breakdown. Chicken and beef liver, liver pate, and game generally contain high amine levels due to frequent mishandling. Game is often allowed to partially decompose as part of its preparation. Ayd (1986) reported that the freshness of the food is a key issue with MAOIs and that as long as foods are purchased from reputable shops and stored properly, the danger of a hypertensive crisis is minimal. Some foods should be avoided, the most dangerous being aged cheeses and yeast products used as food supplements (Gilman et al, 1985).
With appropriate dietary restrictions, the incidence of hypertensive crises has decreased to approximately 4% (Zisook, 1985). Treatment of a hypertensive reactions includes the=7F administration of phentolamine (Anon, 1989) 2.5 to 5 milligrams intravenously (slow) titrated against blood pressure (Zisook,=7F 1985; Lippman & Nash, 1990). One report has suggested that the use of sublingual nifedipine 10 milligrams was effective in treating 2 hypertensive reactions following the ingestion of a tyramine-containing food in a patient receiving MAOI therapy (Clary & Schweizerr, 1987). Chlorpromazine also has alpha-blocking properties and has been recommended as an agent for discretionary use (patient-initiated treatment) in the setting of dietary indiscretion (Lippman & Nash, 1990).
________________________________________
Conclusion
Dietary restrictions are required for individuals receiving monoamine oxidase inhibitor therapy to prevent a hypertensive crisis and other side effects.
The foods listed in the dietary restrictions have been categorized into those foods that must be avoided, foods that may be ingested in small quantities, and those foods that were previous implicated in reactions but upon analyses of fresh samples only a small tyramine content was identified and should be safe to consume if freshness is considered.
________________________________________

References:
1. Anon: Foods interacting with MAOI inhibitors. Med. Lett. Drug Ther. 1989; 31:11-12.
2. Ayd FJ: Diet and monoamine oxidase inhibitors (MAOIs): an update. Int. Drug Ther. Newsletter 1986; 21:19-20.
3. Brown CS & Bryant SG: Monoamine oxidase inhibitors: safety and efficacy issues. Drug Intell. Clinical Pharmacy 1988; 22:232-235.
4. Clary C & Schweizer E: Treatment of MAOI hypertensive crisis with sublingual nifedipine. Journal Clinical Psychiatry 1987; 48:249-250.
5. Da Prada M, Zurcher G, Wuthrich I et al: On tyramine, food, beverages and the reversible MAO inhibitor moclobemide. J. Neural Transm. 1988; 26(Suppl):31-56.
6. Gilman AG, Goodman LS & Rall TW et al (Ed): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 7th ed., Macmillan Publishing, New York, NY, 1985.
7. Lippman SB & Nash K: Monoamine oxidase inhibitor update. Potential adverse food and drug interactions. Drug Safety 1990; 5:195-204.
8. McCabe BJ: Dietary tyramine and other pressor amines in MAOI regimens: a review. J. Am. Diet Assoc. 1986; 86:1059-1064.
9. Stockley I: Alcohol-free beer not safe for MAOI patients. Pharm. J. 1993; 250:174. 10. Zisook S: A clinical overview of monoamine oxidase inhibitors. Psychosomatics 1985; 26:240-251.
AUTHOR INFORMATION:
Theodore G Tong, Pharm D/C Hansen
Assistant Clinical Professor of Pharmacy
University of California
San Franscisco, California 94143
10/79
Revised by DRUGDEX(R) Editorial Staff
Denver, Colorado 80204, 09/82
Revised by DRUGDEX(R) Editorial Staff, 09/83; 07/85;07/86; 09/89; 04/93; 01/94
(DC2763)
Stephen R. Saklad, Pharm.D. – saklad@uthscsa.edu
Psychiatric Pharmacy Program
The Univ Texas College of Pharmacy
(210) 567-8355 (Voice)
(210) 567-8328 (FAX)

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Connie Dello Buono

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High Cost Cancer Drugs

I am voting for Bernie Sanders to lower the cost of drugs.

Fish Oil

Arthritis – rheumatoid Causes

The Immune Response and Inflammatory Process

The Infection Fighters

Genetic Factors

Environmental Triggers – Infections

Gingivitis, Gum Health Linked to Heart and Prostate Disorders

Gum Health and Periodontitis

Periodontal Disease Linked to Prostatitis

Polyunsaturated Fatty Acids may Reduce Periodontitis

Periodontal health and systemic health

Obesity and rheumatic diseases

Introduction

Leptin

Leptin and Osteoarthritis

Leptin and Rheumatoid Arthritis

Adiponectin

Adiponectin and Osteoarthritis

Adiponectin and Rheumatoid Arthritis

At joint levels adiponectin might be pro-inflammatory

Other Adipokines in Osteoarthritis and Rheumatoid Arthritis – Chemerin

Vaspin

Molecules secreted by adipose tissue could affect the joint structures in rheumatic diseases

Beer lift your spirits up

Bananas

Protein rich foods

Chocolate

Avoid Sugar

Dopamine and MAO

Drugs can stimulate or fail to stimulate dopamine receptors

Cocaine

MAO affects dopamine levels

Neurons can become sensitized or desensitized to dopamine

Foods To Avoid When Taking Monoamine Oxidase Inhibitors

Avoid Alcohol