Kynurenine Tryptophan Cycle in Addiction

February 16, 2015

Kynurenine Tryptophan Cycle in Addiction

The immune system is an important part of normal body functioning. It is constantly modulating a balance between tolerance to non-harmful antigens and responsiveness to some pathogens. The process that facilitates tolerance is not known. However, recent studies show that this tolerance is due to tryptophan catabolism via the kynurenine metabolic pathway. The breakdown of tryptophan requires several enzymes which. These enzymes are found in various cells which includes those of the immune system.

Some of these enzymes involved in the breakdown of tryptophan produced through activation of the immune system. This process involves among others limitation of enzymes that are present in the dendritic cells and macrophages, 3-dioxygenase and indoleamine 2. Recent studies have shown that inhibition of these enzymes can result in the body rejecting allogeneic fetuses. This means that breakdown of tryptophan is necessary in immune tolerance aspects.

Some theories have been invented to try and explain how catabolism of tryptophan facilitates tolerance to drugs like alcohol. One such theory holds it that breakdown of tryptophan ends up suppressing proliferation of T cells by greatly reducing the supply of this amino acid that is critical in body processes. The other theory states that the down streaming of the metabolites involved in catabolism of tryptophan act as suppressors of some immune cells mainly through mechanisms of pro-apoptotic processes.

Kynurenine Tryptophan Cycle

What is tryptophan?

It is an amino acid that is required by all processes of the body for the synthesis of proteins and other body metabolic functions. Tryptophan is synthesized mainly from molecules like phosphoenolpyruvate that are present in bacteria, plants and fungi. Such organisms activate the tryptophan throughout the food chain. Animals are incapable of synthesizing this amino acid and because of this it must be taken in the diet in form of proteins which are then broken down into the respective amino acids in the digestive tract. The tryptophan that results from diet is deposited in the liver via the hepatic portal system. The protein that is not broken down in the liver enters into any of the two metabolic processes.

Because animals are incapable of synthesizing tryptophan, they must take it in the form of proteins, which are then hydrolyzed into the constituent amino acids in the digestive system. Dietary tryptophan is delivered to the liver through the hepatic portal system, and that portion which is not used for protein synthesis in the liver can then follow one of two basic metabolic fates.

In the first place, the protein that does not undergo synthesis can enter into the blood stream to later be used for synthesis of proteins and other cell functions in the body. Secondly, it can undergo degradation in the liver via a number of steps of metabolism which is basically referred to as the kynurenine pathway. Besides being a building block for proteins in the body, tryptophan also acts as the only source of substrate used for the production of important molecules in the body. Tryptophan is used in the gut and nervous system for serotonin synthesis and on the other hand pineal gland is useful in melatonin synthesis. In case the content of niacin in the body is not enough to carry out metabolic processes, tryptophan come in to facilitate cellular cofactor synthesis and nicotinamide adenine dinucleotide (NAD +) synthesis. NAD + synthesis as research shows take place mostly in the liver.

The kynurenine pathway

The kynurenine pathway results from proteins that are not synthesized in the liver. The enzymatic reactions take place proceeding from tryptophan. The main intermediates of the metabolic system include quinolinate, 3-hydroxyanthranilate and kynurenine. A catabolic reaction is completed in the liver and this result in the total oxidation of the amino acid tryptophan and in the process carbon dioxide and adenosine triphosphate are produced.

Tryptophan metabolism and addiction

The three stages that take place in the kynurenine pathway include an intial stage that involves tryptophan being broken down into kynurenine. The second stage starts from the produced kynurenine all the way to production of quinolinate. The final stage of the process involves enzymes that translate into total oxidation. The other processes that occurs within the three major processes picolinate production, kynuretic acid synthesis and synthesis of NAD +.

Most cells in the body have some of the enzymes that are involved in the kynurenine pathway. However, only hepatocytes have been shown to contain each and every enzyme that is used in every stage of the kynurenine pathway. Since the liver is the only tissue in the body that contains all thes enzymes of the pathway, the liver then acts as the major site in which NAD + is synthesized from tryptophan. Diet and intake of certain substances like alcohol can affect the flow of metabolisms in the kynurenine pathway. For more information about this topic visit www.awaremednetwork.com. At AwareMed you will also find other health and awareness tips that will benefit you.

Kynurenine Tryptophan Cycle in Addiction

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GABA Metabolism in the CNS in Addiction

February 14, 2015

GABA Metabolism in the CNS in Addiction

What is GABA?

Known as Gamma-Amino Butyric acid, it is an amino acid that performs functions of neurotransmitters in the brain.it is the most abundant neurotransmitters occurring in the central nervous system (CNS).it acts as an inhibitor of transmissions in the brain thus in the process calming down activities in the nervous system. It is found as a supplement in which it acts as a natural tranquilizer. It has been shown to increase levels of human growth hormones thus is very popular among body builders.

The Neurotransmitters Question

The brain is made up of millions of cells. Communication takes place from one brain region to another through neurotransmitters. Neurons are individual cells of the nerves that make up the nervous system. They serve as the wiring for the body to transmit information form one region to another. The electrical signals generated are transported through the neurons as a single impulse. Ones the impulses reaches the end of the neurons, it is transmitted to the other cell through neurotransmitters.

The central nervous system consists of the spinal cord and the brain. The two consist of neurotransmitters which pass from one end of the neuron to another. The peripheral nervous system which is made up of nerves that run to the rest of the body. The nerves transmit chemical signals from one neuron t adjacent gland cells and muscles.

GABA and glutamate are the most abundantly occurring neurotransmitters in the nervous system. The two are in abundance in the cerebral cortex which is the region where interpretation of sensation takes place and thinking occurs. The ending of the neurons are made up of sac like structures which are filled with neurotransmitters.

GABA

When the chemical and electrical signals reach the end of the neurons, they trigger the sacs to release neurotransmitters to act as a bridge between one nerve cell and another. The spaces called synapses act as a bridge through which signals pass to the other cells. On reaching the other neuron, the neurotransmitters attach to the cell receptors. This triggers the electric impulse to move from the end of the nerve cell neuron to the other cell completing the message transmission and triggering and effect.

Role of GABA In the Brain

It is formed in the cells of the brain from glutamate. GABA acts as an inhibitory neurotransmitter which simply means that it blocks nerve impulses in the brain. On the other hand, glutamate from which GABA is formed is an excitatory neurotransmitter. When it binds to cells adjacent to it, it activates them to send impulses throughout the brain from one cell to another. GABA instead of telling the brain to activate and send impulses, it tells it he opposite. It stimulates the brain not to send nerve impulses from one cell to another.

In the absence of GABA nerve cells tend to activate more often sending signals regularly. Disorders associated with anxiety such as headaches, addiction, panic attacks, Parkinson syndrome, cognitive impairment and seizures are all linked to low activity of GABA.

It naturally hinders nerve impulses transmission from one cell to another. It brings about a calming effect in the process. The best way to understand the significance of GABA is by understanding the effects of caffeine on the brain. Caffeine acts as an inhibitor of the release of GABA. When the levels of GABA are low in the brain, more nerve transmissions take place. This leads to the sensational feeling that one gets when they takes coffee. This feeling is as a result of activity of glutamate with less GABA.

The reason why, caffeine does this is simply because other molecules tend to bind with the neurons near the site where GABA binds with these neurons. This is exactly the way that basic tranquilizers like barbiturates and Benzodiazepines work. They increase the effects of GABA in the body which in turns inhibits the transmission of nerves.

GABA Metabolism

It is synthesized in a metabolic path known as the GABA shunt. The first step in GABA formation uses a-ketoglutarate that is formed from metabolism of glucose in the Kreb’s cycle. Afterwards a-ketoglutarate is processed by a-oxoglutarate to form glutamate. In the final process, the glutamate undergoes decarboxylation to form GABA through the glutamic acid decarboxylase enzyme. Like other neurotransmitters, GABA is stored in the synaptic vesicles of the brain and is only released when depolarization of the presynaptic membrane takes place.

GABA

GABA and Addiction

Alcohol consumption leads to loss of coordination of the motors as well as sedation as other high levels of inhibitory transmitters do. Studies therefore show that GABA effects contribute to some effects of alcohol in the brain. Past studies show that, GABA as an inhibitory neurotransmitter is affected by alcohol consumption. Continuous alcohol consumption leading to addiction lead to decline in GABA receptors found in the brain and his reduces the ability of the neurotransmitter t bind with cell receptors.

In this case, the body is forced to find ways to compensate for the declined levels of GABA neurotransmitters. These effects are responsible for brain function changes that lead to things like dependence and alcohol tolerance. When one withdraws from alcohol, the stimulating effects on the neurotransmitter disappear. The body has very few GABA receptors needed to balance the effects of excitatory neurotransmitters. Because of this the brain has too many excitatory nerve signals being transmitted. This translates to psychological and physical effects of alcohol addiction and withdrawal.

Dr. Dalal Akoury has years of experience with patients of addiction and other health conditions. This enables her to provide wise counsel to patients who may be going through certain health conditions. Many of these patients have gotten better and they now bear witness to her god works. To become part of this community and to receive regular health and awareness tips that will befit you, visit www.awaremednetwork.com today.

GABA Metabolism in the CNS in Addiction

NAC, the Cystine-Glutamate Antiporter and Addiction

February 5, 2015

NAC, the Cystine-Glutamate Antiporter and Addiction

Addiction is one complex problem faced by many. There is no limit to how many things people can get addicted to. If you cannot go a day without watching a movie, and then it gets to a point when you must slot in a couple of hours in your daily schedule to watch movies then that is your addiction.

If you keep getting those cravings for soda or sugary meals, you try to stay without them but the urge is so much that you only calm down after satisfying that thirst then that is an addiction.

Addiction can be good or bad. You can be addicted to work, you love your work that you can’t spend time away from your job. That is addiction. Such positive addictions too may be unhealthy. If you are addicted to work for instance, you will hardly spare time for other essential activities, such as being with your family.

Other forms of addiction often associated with the term, such as drug and substance abuse are detrimental to your health. A person who is addicted to alcohol for instance cannot live without it. Their lives often revolve around the liquor. The same applies to coke, cigarettes, marijuana and all other recreational drugs. The substance of addiction gets to dictate how you live your life.

the Cystine-Glutamate Antiporter

Facts about addiction

The habit is a problem. You have to first admit it in order to be able to get over it. An addict who finds it difficult to get over the problem may often be tempted to blame it on someone, or something else. But that is not a solution, acceptance is key.

Giving in to one’s yearnings is a matter of choice. At the beginning of any addiction you often see yourself in control of the situation. You are not forced to do anything, you just do it because you enjoy the act. With time though, this control diminishes and you become increasingly more vulnerable to the substance of your addiction.

You are in a position to drop your addictions by saying ‘no’ to the substance. This is the premise under which psychosocial support for addiction recovery is usually built. Through guidance one is offered a way out of their drug or substance habit. At such point, it is upon you to decide whether or not you are going to adopt a clean lifestyle.

NAC and Addiction

N-Acetyl L-Cysteine is a chemically changed version of the non-essential amino acids in the body. NAC works by purifying your body by removing harmful toxins. It is highly essential in recovery from drug addiction. alcohol and other drugs commonly abused cause a lot of damage to the liver, lungs, kidneys and other organs and this is likely to result in chronic ailments that are life threatening. This amino acid is essential as it protects cells from getting damaged in addition to its role in preserving functions of the liver.

It is a known precursor to Glutathione which is the most effective in destroying free radicals. The amino acid works to protect the brain and the liver from damages caused by toxins like alcohol, acidic mater, particles found in the air and cigarettes smoke. It also has other significant functions that are key to the wellbeing of an individual.

Among them, it helps the body to promote its burning of fat and aids the muscle building process. Studies also indicate that it can rid the body of copper by a chelating effect, and is used in the treatment of particular diseases including bronchitis, emphysema and certain respiratory problems among adults.

NAC plays a key role in the production of white blood cells necessary for body immunity. The white cells fight diseases that attack the body and help boost the natural immune response of the body. As such, the amino acid is essential for the defense of the body against disease attack. It further helps in insulin metabolism and functions, which is key to the body’s blood sugar regulation.

the Cystine-Glutamate Antiporter

Sources of NAC

N-Acetyl L-Cysteine can always be naturally manufactured by the body on its own. The high-protein foods such as eggs and meat are however potent dietary sources of this amino acid. Other good sources include foods such as broccoli, garlic, wheat, onions and red peppers.

Other sources that can be recommended for this important amino acid for those who are recovering from the damage caused by drug addiction include nutritional supplements found in a number of nutrition outlets in different continents. It is however important to seek recommendations form a physician since this product is largely unregulated and health consumers are likely to purchase a product that contains incorrect amount of ingredients recommended for the particular patient.

NAC, the Cystine-Glutamate Antiporter and Addiction

Circulating Stem Cells And Opiate Addiction

January 6, 2015

Deficit of Circulating Stem Cells-In Opiate Addiction Cause Major Illnesses in the Body

A new research has pointed out that deficit of circulating stem cells-in opiate addiction cause major illnesses in the body. This however is not much of a surprise since past researchers were able to discover the fact that slow cell growth and apoptosis were major reasons for the different capacities of addictive drugs. To people who have slow cell growth, the chances addiction is much higher of Couse within a shorter lifespan than those who had optimum cell growth levels.

Deficit of circulating stem cells-in opiate addiction cause major illnesses in the body The stem cell hypothesis of ageing suggests that ageing at the organismal level is reflected by impaired cell health at the cellular level including reduced function, reduced growth, increased senescence, and cell loss by apoptosis, necrosis. The often disorganized and disheveled body habitus of many drug addicts is well known, as is their predisposition to a variety of unusual disorders.

A rising body of knowledge suggests that disorders common in aged populations occur at an increased frequency in addicted populations as a result of stem cell deficiencies. Stem cells dysfunctions in addicts apply to:

Osteoporosis,
Neuropsychiatric disorders,
Depressed sperm counts,
Calcific arteriosclerosis,
Premature graying of the hair,
Severe mental disorders.

These problems have in common a failure in stem cell physiology. The high mortality accompanying chemical addictions is also well recognized.

New Research

Currently, the field of stem cell biology is mushrooming with many investigations centered on a host of prospective applications in regenerative medicine and including particularly bone marrow transplantation, tissue regeneration and immune and gene therapy. Several recent developments make these advances of particular interest to the field of addictive medicine particularly to its toxicology. Stem cells exist at low frequency in the peripheral circulating blood and may be quantitated there. Several methods have been recently described for the quantitation of various lines of stem and progenitor cells in peripheral blood, a tissue which is regularly accessed in routine clinical care. Secondly the endothelial progenitor cell has been said to be of enormous importance to the regeneration of the vasculature and has be noted to be a superior predictor of cardiovascular outcomes including mortality than commonly used classical cardiovascular risk factors. Similarly counts of the circulating osteoblastic progenitor cell have been shown to correlate with bone density studies. Finally the cellular theory of ageing suggests that stem cells and their health should be a special focus of ageing medicine and the deficits associated with ageing, and this has been confirmed by recent reports.

Given the importance of the circulating stem cells in the blood, it is therefore necessary to examine the peripheral blood for circulating stem cell numbers in addicted and control populations so as to find out the relationship between suppressed levels of the circulating stem cells and illnesses that are common in opiate addicts.

In a research that was done recently by substance abuse prevention policy it was found that patients who were addicted to opiates had decline in stem cells circulating in the peripheral blood appears to be three or four times as fast in addicts as in the general population.

In this research the patients were chosen from normal clinical primary care population. Medical patients were representative of those seen typically in primary care clinics. Opiate addicted patients were maintained on buprenorphine/naloxone combination and are gradually reduced. They were not in clinical withdrawal at any time. Blood was obtained with patient consent. Blood was drawn for standard clinical indications in the course of routine patient care. Peripheral venous blood was sampled from patients and processed fresh without storage by flow cytometry. Absolute lymphocyte counts were taken, and CD34+ CD45+ double positive cells were counted as haemopoietic stem cells (HSC’s), and CD34+ KDR+ (VEGFR2+) cells were denoted endothelial progenitor cells (EPC’s). Progenitor cells were standardized against the lymphocyte fraction as these were believed to be of the most appropriate nuclear cytoplasmic ratio.

Based on the data presented the decline in stem cells circulating in the peripheral blood appears to be three or four times as fast in addicts as in the general population. This therefore indicates that opiates addicts are more likely to suffer the symptoms of low circulating stem cells than those who are not addicted to opiates.

This research however was small but if these results are confirmed by other researches that are done on a much larger scope then they would have very significant potential implications for understanding the cumulative toxicology of indefinite maintenance therapies and programs both for opiate dependency and the notion presently widespread in medicinal chemistry, clinical, research funding and other circles that agonist medication is functionally superior to sustain patient compliance in the long term to antagonists. If confirmed the present results are likely to have far reaching implications for clinical practice and hence public policy, particularly as an increasing number of long acting depot preparations of antagonists are currently entering the marketplace.

Circulating Stem Cells This research as said earlier is a preliminary study and its researchers are still suggesting that further investigations be done for on-going research in this important field as it has significant future implications for drugs policy administrations and long term patient treatment development.

Finally drug addiction is effectively fought through integrative care. If you are battling with addiction and you need help call Dr. Dalal Akoury of AWAREmed Health and Wellness Center on (843) 213-1480 for help.

Deficit of Circulating Stem Cells-In Opiate Addiction Cause Major Illnesses in the Body

MicroRNA Quells Cocaine Craving

January 5, 2015

MicroRNA May Suppress Cocaine-Seeking Behavior

microRNA Currently there are very many people who are tripped in the use of drugs of abuse despite their life threatening effects. Drug addiction is a jail that many addicts find hard to evade. It is important to note that addicts do not use the drugs they abuse because they like using them, the honest truth however is that most addicts have tried to stop using their drugs of choice but they can’t just fight against their own craving. The cravings for drugs like cocaine that are known for their euphoric effects are one of the challenges that addicts face.

Typically, a person will use the drug once as an escapade to all the stress that he may be exposed to or as a result of mere curiosity having been misled by their peers that using cocaine is cool as they say it. However after getting the euphoric effects one is bound to go for more of this drug and this in the long run may result to cocaine addiction and even dependence. It has never been easy quitting the use of cocaine and many people even after going to rehab centers will still for the drug when exposed to triggers after they come back from the rehabs. It is this cocaine seeking behavior that is adopted by the addicts that makes it hard for them to quit. If this cocaine seeking behavior can be reduced then a person may win the fight against cocaine addiction easily.

The recent discovery by scientists that a minute snippet of genetic material called microRNA may suppress cocaine-seeking behavior presents hope to the medical fraternity as well as cocaine addicts. As a known fact the use of cocaine will cause both structural and functional alterations to the brains’ reward system. These changes cause a drift in the behavior of the users of cocaine. Through experiments and lab tests it has been found that these alterations results in increased drug-seeking behavior in both humans and rats. The desire to use cocaine become uncontainable hence overindulgence in drug use.

Just like with any other drugs of leisure, long-term use of cocaine will result in reduced response to the effects of cocaine which will force the user to use more of cocaine so as to achieve the sought euphoric feeling. After a long time of use of this drug the response will be lessened again and this will reduce the motivation of a user to continue using the drug. Researchers suspect that these differing influences may be why only about 15% of cocaine users ultimately lose control and compulsively seek the drug.

MicroRNAs are small pieces of RNA that don’t code for proteins but they regulate how much of a protein is made instead. Over the past decade, microRNAs have been linked to various cancers, degenerative disorders and other conditions. It was until recently that the contribution of these tiny molecules to drug use and addiction were brought under scrutiny.

Paul J. Kenny led study

In a research team that was led by Dr. Paul J. Kenny of the Scripps Research Institute in Jupiter, Florida, the team decided to explore how brain levels of specific microRNAs change when rats have extended or limited access to cocaine. The study was funded by NIH‘s National Institute on Drug Abuse (NIDA).

In the issue of Nature published on July 8, 2010, the scientists reported that rats given 6 hours of extended access to cocaine each day had markedly increased levels of a molecule called microRNA-212 in a particular brain region. The levels were nearly double those in rats with access to cocaine for an hour or less daily. The brain region, called the dorsal striatum, helps to regulate the development of habit formation.

After this discovery the researchers next tested the effects of elevated microRNA-212. The Researchers used a genetically altered virus to boost microRNA-212 expression in the dorsal striatum. A control group received an “empty” virus. When given extended access to cocaine, both groups predictably escalated their intake. But over time, cocaine intake plummeted in the rats with elevated microRNA-212. Cocaine consumption in this group continued to drop even as their exposure to the drug increased. Their cocaine intake became so low that they seemed to have a growing dislike for the drug.

To contrast the effects of this microRNA-212 in the brain, the researchers blocked the action of microRNA-212 in the brain and this led to sharp increase in cocaine intake and the rats began to self-administer the drug at exaggerated rates, similar to compulsive drug users. These results suggest that microRNA-212 may play an important role in preventing out-of-control drug use.

“The results of this study offer promise for the development of a totally new class of anti-addiction medications,” says Kenny. “Because we are beginning to map out how this specific microRNA works, we may be able to develop new compounds to manipulate the levels of microRNA-212 therapeutically with exquisite specificity, opening the possibility of new treatments for drug addiction.”

the fact that Cocaine consumption in the group of rate with elevated microRNA-212 continued to drop even as their exposure to the drug increased is a clear indication that that this minute component of genetic material may be used to quell the craving for cocaine in cocaine users. Dr. Dalal Akoury of AWAREmed Health and Wellness Center has dedicated her life to helping addicts restore their lives by use of integrative medicine. Call her on (843) 213-1480 for help.

MicroRNA May Suppress Cocaine-Seeking Behavior

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