From The Associated Press:

Germs in the gut may help drive appetite, says new research into the link between obesity and bacteria.

Previous studies have shown that overweight people and normal-weight people harbor different types and amounts of microbes that naturally live in the intestine. To determine why, scientists are peering into mice.

Emory University researchers noticed that mice with an altered immune system were fatter than regular mice, and had a collection of disorders — high blood pressure, and cholesterol and insulin problems — called metabolic syndrome, often a precursor of heart disease and diabetes.

Everyone is born with a sterile digestive tract that within days is flooded with bacteria from first foods and the environment. Altered immunity in these mice meant somewhat different bacteria grew in their intestines than in normal rodents — driving bigger appetites, metabolic syndrome and a low-grade inflammation believed key to obesity’s illnesses, Emory associate pathology professor Andrew Gewirtz reported Thursday in the journal Science.

To prove it, Gewirtz transferred bacteria from the fat mice directly into the germ-free intestines of normal newborn mice — and those mice began eating more and developed inflammation and insulin problems.

Restrict access to food and the altered mice don’t gain weight, but still experienced the other symptoms, he noted.

“People are getting obese because they’re eating more, but it suggests the reason they’re eating more may not simply be that calories are cheap and available,” Gewirtz said. “The reason they’re eating more may be an increased appetite resulting from changes in intestinal bacteria.”

His next step is to study how gut bacteria changes in people having weight-loss surgery.

I read about this study months ago and it sounds interesting. What do you think?

I also recommend getting tested for food allergies if you have G.I problems or increased inflammation.

From USNews.com:

Think about your group of friends: Among them is surely someone who waxes enthusiastic about the Atkins diet, another who tried it but then regained the 10 lost pounds, someone else who found success with a low-fat, higher-carb regimen, and another who couldn’t stay on that for more than a week but swears by South Beach. The more science learns about the marvelous diversity among human beings—fueled by genetic, environmental, and other factors—the clearer it becomes that a one-size-fits-all approach to diet is bound to fail.

Indeed, the weight-loss industry has cottoned to the notion that one specific diet isn’t likely to work for everyone and is churning out eating plans based on what authors say is scientific evidence that taking your individual differences into account makes success more likely. One (The Metabolism Miracle, by dietitian Diane Kress) holds that the estimated quarter of U.S. adults with the high blood pressure, abdominal obesity, insulin resistance, and other symptoms known collectively as metabolic syndrome need a period of low-carb dieting to rest their “overworked pancreas and liver while shrinking fat cells,” then the “methodical” re-introduction of carbs. Another, the Women ‘ s Health Perfect Body Diet, offers two different eating plans keyed to your “carb tolerance.” Meantime, The GenoType Diet, by naturopathic physician Peter D’Adamo, uses blood type, fingerprint analysis, and leg length measurements, among other factors, to prescribe one of six diets based on a “unique genetic type.” And if you’ve got more extra cash than the $25 you’d spend on a book, various companies offer gene tests that they promise will identify the ideal mix of macronutrients (carbs, protein, and fat) and the exercise intensity that will most likely lead to weight loss.

Is there anything to the fancy formulas and rules? (T he GenoType Diet advises “Hunters,” who have a “heightened sense of fair play,” symmetrical bodies, and type O blood, to embrace beef tongue but spurn ham and kangaroo.) The bottom line remains that if you want to lose weight on a diet, you have to burn off more calories than you’re taking in. As the authors of a study that compared diets with different compositions of macronutrients— fat, protein, and carbs—wrote in the New England Journal of Medicine earlier this year: “These findings together point to behavioral factors rather than macronutrient metabolism as the main influences on weight loss.” They concluded that “any type of diet, when taught for the purpose of weight loss with enthusiasm and persistence, can be effective.” This line of evidence stretches back years, says George Bray, chief of the division of clinical obesity and metabolism at the Pennington Biomedical Research Center of Louisiana State University and an author of the NEJM study. There’s no evidence, he says, that substituting the same number of calories in fat for carbs is going to make you lose more weight or body fat.

But the hard part of dieting, as anyone who’s tried it can attest, is not so much finding an eating plan with the appropriate number of calories but following it. That means adopting a balanced diet that’s going to support your health, not just your weight loss, and that matches your preferences and lifestyle. Some of those preferences, and the rest of our eating habits, are surely influenced by genes.

[Read Can Mindful Eating Help You Lose Weight?]

For example, researchers have reported in the last year that genes predisposing people to obesity act in the brain to mediate behavior, rather than directly influencing metabolism. In other words, obese people are more likely to overeat. Satiety mechanisms are complex and involve multiple sensors, some of which detect one macronutrient better than the other two; there’s probably some genetic variation in the way each sensor operates, says Dale Schoeller, a professor at the University of Wisconsin-Madison who researches biochemical and molecular nutrition. So yes, it’s entirely possible that a carb-heavy breakfast can leave you hungry in two hours, while it keeps your neighbor full until noon. For someone else, it might be high-protein or high-fiber. (That doesn’t mean that anyone should entirely eliminate a macronutrient or prohibit otherwise healthy foods entirely unless there’s some medical reason for doing so.)

It’s not yet at all clear what determines the differences between dieters—although Jose Ordovas, director of the Nutrition and Genomics Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, is optimistic that the day will come. One aim of nutritional genomics is to discover how genes and food interact in order to prescribe diets that will better address individual predisposition to things like high cholesterol, osteoporosis, cancer, and diabetes as well as weight loss. “In the future, we’ll predict the risk of the individual, and from the beginning we’ll be able to put them on the kind of diet that will work for them,” he says. “So if we’re successful, the individual will know from day one that it’s going to work for him.”

But, he says, the gene tests on the market are not likely to help much in their current iterations. There’s a long road from identifying an association between a variation in a certain gene and the ability to thrive on a certain type of diet to translating the knowledge into anything useful. Associations are often found in small populations—say, among 69 obese Spaniards, those with a particular gene variation are less likely to lose body fat on a low-calorie diet—but don’t necessarily hold true for large populations. There’s plenty of promise in this area, says Ordovas, but much more comprehensive data is needed. “We have to be very careful,” he says. “We need to create a new science that’s solid and can’t be confused with snake oil.”

Proponents of using existing knowledge to prescribe personalized diets say that some information, albeit imperfect, is better than nothing. “We don’t have a good idea of how these individual gene variations interact, but we can integrate this information with what we know about health and family history to identify the best path to take in a very educated way,” says Colleen Fogarty Draper, a registered dietitian, nutritional genomics consultant, and founder of Nugenso Nutrition, a private nutrition consultation practice in the Boston area. She uses Inherent Health’s weight management test, based on the DNA taken from a cheek swab, to identify five key variations in genes regulating fat absorption and fat-cell formation, among others. The test is supposed to identify which diet and exercise pattern clients are most likely to respond to, although she says she’s careful to tell them that it’s not a definitive prediction. Even so, she says, there’s a psychological effect, too. “Once they see it on paper and see a test result, they’re more likely to comply,” she says. “It offers a little more inspiration.” (The investment of $149 undoubtedly helps, too.)

“We can’t define the perfect personalized diet,” says Ken Kornman, a dentist with a doctorate in microbiology and immunology who is founder and chief science officer of the Inherent brand’s parent company, Interleukin Genetics. “What we feel confident that we can do is to substantially improve upon the current random results that someone gets when they go on a diet.” The company recently announced the results of a small (100-person) unpublished study that suggests people who followed diets matched to their genotype using the company’s test lost more weight than those who weren’t correctly matched.

If you don’t want to pay for what might at this point turn out to be just an expensive bit of inspiration, how can you individualize your diet by yourself? First, focus on working on your total health, not just weight loss. Dietitians don’t advise simply eating 1,300 calories of whatever you want, whether it’s carrots or Coke, to lose extra pounds; while two foods may be equal in calories, they don’t necessarily offer the same nutritional value. Whatever mix of carbs, fat, and protein you end up with, it should consist primarily of what experts generally agree are the best-bang-for-the-calorie-buck foods: a balanced combination of lots of whole fruits and vegetables, whole grains rather than processed carbs, legumes, lean protein like fish, and “good” fats like omega-3 fatty acids and olive oil rather than saturated or trans-fats. That kind of diet is more likely to meet your nutritional needs and keep you satisfied. Fruits and vegetables are good at filling you up. On the other end of the caloric scale, nuts, for example, seem to promote weight loss, possibly because they are slowly digested and control hunger, says Schoeller.

If you’re diabetic or have another chronic disease, or are at high risk for one, you should talk with a nutritionist about special tweaks you may want to make to your diet—being sure you avoid saturated fat or excess sodium, for example, or, in the case of diabetes, picking foods that keep your blood sugar steady. (That’s what the Nutrisystem D plan does; it’s a low-calorie diet, but its foods have a low glycemic index, meaning they more slowly affect blood sugar levels, so dieters can manage their disease better.)

People with the metabolic syndrome are generally advised to lose weight by limiting calories and following a healthful diet rich in fruits and vegetables and low in unhealthful fats, rather than with any special carb-restriction regimen, says Maria Collazo-Clavell, an endocrinologist at the Mayo Clinic. (Dietitian Kress says she has unpublished data on nearly 4,000 patients showing that her diet for those with “Metabolism B,” as she calls metabolic syndrome, works better than the standard low-fat, calorie-controlled diet advice.)

If you’re generally healthy but just need to drop some weight, you might do some experimenting. Cassandra Forsythe, author of the Women ‘ s Health Perfect Body Diet, recommends eating a high-carb breakfast of a bagel and sugar-free jam one day and monitoring your mood, energy levels, and hunger throughout the morning. Then try a low-carb breakfast of scrambled eggs with feta, plus a small apple, the next. (Repeat to confirm the results.) She puts forth two different meal plans depending on which breakfast makes you feel better: one for the carb-energized, which includes about two more servings of carbs per day than the other, and one for the carb-sluggish, which substitutes about two servings of fat. Even if you don’t want to go to the trouble of a formal experiment, just pay attention to how you feel after different foods. Do you feel satisfied? Can you go about your day without obsessing over your next meal? “Think about what you do best with. Maybe you feel fuller after lentils and rice rather than chicken or fish,” says Forsythe.

Notice she didn’t mention choosing between four different types of Lunchables.Remember, whatever ratio of carbs, proteins, and fat you find works best for you, your diet should primarily be comprised of healthful whole foods. Sounds boring. Won’t sell many books. But at this point, it’s still the simplest and best route to success.

Check out the organwiseguys.com for keeping your kids healthy and active. There was a study done on the Amish people and how many calories they ingested in one day. The study found the average Amish person ingested close to 5,000 calories per day. Their diets were high in fat and complex carbs. The study also showed they had almost no obesity problem. Why? What's the difference from the rest of society? The only answer is they are all very physically active from early morning to when they go to sleep. Burn more than you take in and you will lose weight.

Check out the Organwiseguys.com to help answer how to solve the obesity problem. If you haven't seen The Organ Wise Guys on your PBS station call and recommend they start playing them.

Journal of Brachial Plexus and Peripheral Nerve Injury Volume 4

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Intraperitoneal Alpha-Lipoic Acid to prevent neural damage after crush injury to the rat sciatic nerve Senoglu, Mehmet Nacitarhan, Vedat Kurutas, Ergul Belge Senoglu, Nimet Altun, Idris Atli, Yalcin Ozbag, Davut info:doi/10.1186/1749-7221-4-22 info:pmid/19939272 Journal of Brachial Plexus and Peripheral Nerve Injury 2009, 4:22 2009-11-25 Journal of Brachial Plexus and Peripheral Nerve Injury 2009-11-25 4 1 Research article 22 -->Research article

Intraperitoneal Alpha-Lipoic Acid to prevent neural damage after crush injury to the rat sciatic nerve

Mehmet Senoglu¹

, Vedat Nacitarhan²

, Ergul Belge Kurutas³

, Nimet Senoglu⁴

, Idris Altun¹

, Yalcin Atli³

and Davut Ozbag⁵

¹  Department of Neurosurgery, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey

²  Department of Physical Medicine and Rehabilitation, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey

³  Department of Biochemistry, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey

⁴  Department of Anaesthesiology and Reanimation, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey

⁵  Department of Anatomy, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey

author email corresponding author email

Journal of Brachial Plexus and Peripheral Nerve Injury 2009, 4:22doi:10.1186/1749-7221-4-22

The electronic version of this article is the complete one and can be found online at: http://www.jbppni.com/content/4/1/22

Received:	1 September 2009
Accepted:	25 November 2009
Published:	25 November 2009

© 2009 Senoglu et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Crush injury to the sciatic nerve causes oxidative stress. Alfa Lipoic acid (a-LA) is a neuroprotective metabolic antioxidant. This study was designed to investigate the antioxidant effects of pretreatment with a-LA on the crush injury of rat sciatic nerve.

Methods

Forty rats were randomized into four groups. Group I and Group II received saline (2 ml, intraperitoneally) and a-LA (100 mg/kg, 2 ml, intraperitoneally) in the groups III and IV at the 24 and 1 hour prior to the crush injury. In groups II, III and IV, the left sciatic nerve was exposed and compressed for 60 seconds with a jeweler's forceps. In Group I (n = 10), the sciatic nerve was explored but not crushed. In all groups of rats, superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) levels were measured in samples of sciatic nerve tissue.

Results

Compared to Group I, Group II had significantly decreased tissue SOD and CAT activities and elevated MDA levels indicating crush injury (p < 0.05). In the a-LA treatment groups (groups III and IV), tissue CAT and SOD activities were significantly increased and MDA levels significantly decreased at the first hour (p < 0.05) and on the 3^rd day (p < 0.05). There was no significant difference between a-LA treatment groups (p > 0.05).

Conclusion

A-LA administered before crush injury of the sciatic nerve showed significant protective effects against crush injury by decreasing the oxidative stress. A-LA should be considered in the treatment of peripheral nerve injuries, but further studies are needed to explain the mechanism of its neuroprotective effects.

Introduction

The rat sciatic nerve is a well-established preparation for studying peripheral nerve injuries. Focal crush injury causes axonal interruption but preserves the connective sheaths (axonotmesis). As regards this type of injury, nerve regeneration is usually successful [1].

The increased formation of reactive oxygen species (ROS) and decreased antioxidant defense is defined as oxidative stress, which is widely recognized as an important feature of many diseases. Superoxide dismutase (SOD), and catalase (CAT) are cellular antioxidants, which protect cells from oxidative stress. Lipid peroxidation (LPO) is one of the most important expressions of oxidative stress induced by ROS. Malondialdehyde (MDA) is an indicator of lipid peroxidation, and increases in various diseases [2].

Alpha-Lipoic acid (a-LA) is a powerful lipophilic antioxidant in vitro and in vivo, which plays a pivotal role as cofactor in many mitochondrial reactions, readily absorbed from the diet and can easily cross the blood brain barrier [3].

It is known to act as scavenger of many reactive oxygen species and to interact with other antioxidants such vitamin C and vitamin E, resulting in their regeneration. Due to its antioxidant activity, a-LA has been proposed as a treatment for oxidative disorders of the nervous system that involve free radicals since it exerts a profound neuroprotective effect in experimental models of stroke, trauma, degenerative disorders of the CNS and diabetes [3].

Administration of a-LA to rodents has been demonstrated to reduce the damage that occurs after ischemia-reperfusion injuries in the cerebral cortex [3], heart [4,5] and peripheral nerve [6], and after injection of NMDA into the striatum [7]. However, to our knowledge, the effects of a-LA on crush injury have not been investigated in the English literature [3-7].

The increased formation of ROS and decreased antioxidant defense is defined as oxidative stress, which is widely recognized as an important feature of many diseases. SOD, and CAT are cellular antioxidants, which protect cells from oxidative stress. LPO is one of the most important expressions of oxidative stress induced by ROS. MDA is an indicator of lipid peroxidation, and increases in various diseases [2].

The purpose of this study was to investigate the effects of a-LA on sciatic nerve injury by measurement of SOD and CAT activities, as well as MDA level in sciatic nerve crush injury model in rats.

Materials and methods

Animals and Surgery

This prospective, experimental, sham-control study was performed in the animal laboratory of the Kahramanmaras Sutcu Imam University, Faculty of Medicine. Female Sprague-Dawley rats were obtained from Experimental Research Laboratory of Sutcu Imam University Faculty of Medicine. The experimental design was approved by the Ethics committee of KSU. Rats were fed with standard rat diet routinely, however they were deprived of food for 12 h prior to the first operation. All rats had free access to standard rat chow and tap water.

Forty adult female Sprague-Dawley rats (200-250 grams) were used in this study. Rats were randomly divided into four groups including one sham, one control and two treatment groups.

Group I - (Sham group) Normal adult female rats (Non-crush): Non-crush group, no intervention was made, simply sciatic nerve samples were taken.

Group II - (Control group) 60 seconds of sciatic crush was performed and then sciatic nerve samples were taken at the 1st hour.

Group III - Crush-a-LA group (1 hr): 100 mg/kg intraperitoneal a-LA injection was done 24 and 1 hour before crush injury. Sixty seconds of crush was performed. Sciatic nerve samples were taken at the 1st hour.

Group IV - Crush-a-LA group (3rd day): 100 mg/kg intraperitoneal a-LA injection was done 24 and 1 hour before crush injury. Sixty seconds of crush was performed. Sciatic nerve samples were taken on the 3rd day.

Groups I and II received saline (2 ml, intraperitoneally). However, groups III and IV received saline plus a-LA (100 mg/kg, 2 ml, intraperitoneally [MEDA Pharma GmbH & Co. KG]) [8] at 1 h and 24 h before the crush injury. We aimed to investigate the early effects of antioxidant therapy with a-LA. In Group I, sciatic nerve was explorated but not crushed. Sciatic nerve injury was induced in groups II, III and IV. Briefly stated, exploration was conducted under anesthesia with intraperitoneal pentobarbital (50 mg/kg), while body temperature was maintained by using a heating blanket at 35-37°C. The sciatic nerve was exposed in the mid-gluteal region through biceps muscle dissection under an operating microscope, crushed by a #4 Jeweler's forceps at the mid-point for 60 seconds, then unclamped. The site of crush was marked with a 5-0 suture tied in surrounding muscle. The operated animals were allowed and survived. The nerves were re-exposed under the operating microscope one hour later in groups I, II and III, and 3 days later in Group IV and the nerve tissue was harvested. One-centimeter-long sciatic nerve segments centered on the lesion site points were collected for biochemical analyses. No prophylactic antibiotics were given. The experimental model was very well tolerated. No animal died during the operations.

Preparation of tissue homogenates

Tissue samples were immediately excised, weighed, perfused with 1.15% ice-cold KCl, minced, then homogenized in five volumes (w/v) of the same solution, using a Heidolph 50110 R2R0 homogenizer. Antioxidant enzymes and MDA assays were performed on the supernatant preparation in a Sorvall RC-2B centrifugation of the homogenate at 14.000 rpm for 30 min at +4°C.

Evaluation of biochemical parameters

CAT activities were determined by measuring the decrease in hydrogen peroxide concentration at 230 nm by the method of Beutler [9]. Assay medium consisted of 1 M Tris HCl-5 mM Na₂EDTA buffer solution (pH 8.0), 1.0 M phosphate buffer solution (pH 7.0), and 10 mM H₂O₂. CAT activity was expressed as U/mg protein.

SOD activity was measured according to the method described by Fridovich [10]. This method employs xanthine and xanthine oxidase to generate superoxide radicals which react with p-iodonitrotetrazolium violet (INT) to form a red formazan dye which was measured at 505 nm. Assay medium consisted of the 0.01 M phosphate buffer, CAPS (3-cyclohexilamino-1-propanesulfonicacid) buffer solution (50 mM CAPS, 0.94 mM EDTA, saturated NaOH) with pH 10.2, solution of substrate (0.05 mM xanthine, 0.025 mM INT) and 80 U/L xanthine oxidase. SOD activity was expressed as U/mg protein.

LPO level in the tissue samples was expressed as MDA. It was measured according to procedure of Ohkawa et al [11]. The reaction mixture contained 0.1 ml of sample, 0.2 ml of 8.1% sodium dodecyl sulphate (SDS), 1.5 ml of 20% acetic acid and 1.5 ml of 0.8% aqueous solution of TBA. The mixture pH was adjusted to 3.5 and volume was finally made up to 4.0 ml with distilled water and 5.0 ml of the mixture of n-butanol and pyridine (15:1, v/v) were added. The mixture was shaken vigorously. After centrifugation at 4000 rpm for 10 min, the absorbance of the organic layer was measured at 532 nm. The results of MDA were expressed as nmol/mg protein.

Assay of Protein levels

The protein concentration of the tissue was measured in digital Spectronic-20 spectrophotometer by the method of Lowry [12].

Statistical analysis

All variables were expressed as medians, mean ± standard deviation with the range. Data were analyzed using Mann-Whitney U-test. Differences were considered significant when the probability was less than 0.05. All data were entered and processed by an SPSS 9.05 for Windows statistical package.

Results

Oxidative parameter results are presented in Table 1. Results of the antioxidants levels in all groups are presented in Figures 1, 2, 3.

Figure 1. Sciatic nerve MDA (nmol/mg protein) levels in all groups.

Figure 2. Sciatic nerve CAT (U/mg protein) levels in all groups.

Figure 3. Sciatic nerve SOD (U/mg protein) levels in all groups.

Table 1. The activities of antioxidant enzymes and MDA levels in four groups.

Compared with sham group (Group I), tissue SOD and CAT activities decreased and MDA level elevated significantly in the control group (Group II), which indicated crush injury (p < 0.05). After a-LA treatment tissue SOD and CAT activities increased and MDA level decreased significantly, at the first hour (Group III, p < 0.05) and on the 3^rd day (Group IV, p < 0.05). However, there were no significant differences between treatment groups (Groups III and IV, p > 0.05).

Discussion

In the present study, we investigated antioxidant effects of a-LA on sciatic nerve which was subjected to 60 seconds of crush injury, based on differences observed in biochemical parameters measured. We observed that a-LA had antioxidant effects on injured sciatic nerve and these effects were similar at the first hour and on the 3^rd day.

The pathophysiology of the crush injury has not been fully understood, and it has been debated whether the ischemia, secondary to compression, or the mechanical deformation of nerve fibers per se is the more significant etiologic factor [13].

Nerve injury may depend on the length of time of crush insult. During a pilot study of our research, we showed that especially 60-second compression caused injury in sciatic nerve. After the injury due to the tissue destruction, free oxygen radicals increase and cause tissue damage [14,15].

Normal cell functions and integrity of cell structures may be broken via considerable reactivity of ROS. The organism has enzymatic (e.g. superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (e.g. vitamin C, vitamin E) antioxidant mechanisms that work as scavengers for the harmful ROS. Radical-scavenging antioxidants are consumed by the increased free radical activity. Oxidative stress can be defined as an increase in oxidants and/or a decrease in antioxidant capacity. Although determination of either oxidants or antioxidant components alone may give information about the oxidative stress, determination of oxidants along with antioxidants is more useful in this context. Therefore, oxidants and antioxidant capacity should be measured simultaneously to assess oxidative stress more accurately. In addition, the total plasma LPO level, as an indicator of oxidative stress, reflects the redox balance between oxidation and anti-oxidation. In addition, excess amounts of ROS generated in inflamed tissues can cause injury to host cells and also induce DNA damage and mutations [16]. And, oxidative DNA damage has been suggested to play an important role in the development of cancer [17]. In several studies, increase in oxidative components or decrease in antioxidants or both have been reported in subjects with either acute or chronic various diseases [18-21].

Antioxidant activity is a relative concept: it depends on the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid, protein). To control oxidative processes, biological systems have been equipped with several antioxidant mechanisms. Antioxidant enzymes such as SOD and CAT are concerned with the removal of superoxide anion and peroxide. An imbalance between oxidative and antioxidative processes results in oxidative stress. Drugs can intervene in oxidative processes as antioxidants and delay or prevent their damaging effects. A-LA acid is an example of an existing drug therapeutic effect of which has been related to its antioxidant activity. Many experimental results show that both lipoic acid and Dihydrolipoic acid (DHLA) can improve the antioxidant capacity of tissue against different forms of oxidative stress. Hence, some physicians started to administer lipoic acid to patients with liver cirrhosis, mushroom poisoning, heavy metal intoxication and diabetic polyneuropathy [22].

The SOD-CAT system provides the first defense against oxygen toxicity. SOD catalyzes the dismutation of the superoxide anion radical to water and hydrogen peroxide, which is detoxified by the CAT activity. Usually a simultaneous induction response in the activities of SOD and CAT is observed when an exogen antioxidant is applied [23]. In the present study, the activities of SOD and CAT were also found to be high in sciatic tissue of rats in groups III and IV. The activity of SOD was reported to be higher in various diseases by several workers [19,21] indicating high production of superoxide anion radical. Since CAT levels were detected high in sciatic tissue of rats in groups III and IV, this may be attributed to high production of peroxide radicals. Increased SOD and CAT activities in in those groups may be a response against oxidative stress.

The extent of LPO is determined by the balance between the production of oxidants and the removal and scavenging of those oxidants by antioxidants. Therefore, lipid peroxidation has been extensively used as a marker of oxidative stress [24]. Antioxidants are potential candidates for prevention or treatment of oxidative damage and free radical injury [5,25].

In this study, tissue MDA levels increased and CAT and SOD activities decreased significantly in the control group compared with sham group showing crush injury. After a-LA treatment, groups III and IV had significantly higher tissue SOD and CAT activities and lower MDA levels than control group showing antioxidative effects. However, these antioxidant effects were similar in treatment groups (groups III and IV) showing that preventive antioxidant effects of a-LA took place in the early phase. This finding was concordant with the finding of decreased oxidative injury (i.e. decreased MDA levels in nerve tissue) seen in pretreated groups, which was confirmed by biochemical parameters. Oxidative stress is a mechanism of nerve injury but likely not the major mechanism, and that therapeutic strategy for neuroprotection from crush injury should not be based on antioxidants alone.

Further clinical and laboratory investigations focusing on specific mechanism of antioxidant effects of a-LA, and its therapeutic effects in peripheral nerve injury is warranted.

Abbreviations

SOD: superoxide dismutase; CAT: catalase; MDA: malondialdehyde; a-LA: Alfa Lipoic acid; CNS: Central Nervous System; ROS: reactive oxygen species; LPO: Lipid peroxidation; DHLA: Dihydrolipoic acid.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

MS and NS designed the study and drafted the manuscript. MS and IA performed experimental operations. EBK, YA and DO had specimen collection of this experimental study. VN and performed the statistical analysis. All authors read and approved the final manuscript.

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Alpha lipoic acid can be purchased at nutritional stores and is a very potent natural anti-oxidant. There are plenty of studies backing up the neuroprotective properties of this supplement. It also helps with detoxifying the cells and liver. Many Emergency rooms give this via. I.V for drug over dose.

From NutraIngredients.com:

Supplements of the omega-3 fatty acid DHA (docosahexaenoic acid) may alter the function of the brain associated with working memory, according to results of a new study with healthy boys.

Scientists from the University of Cincinnati showed for the first time using neuro-imaging that supplementation with DHA alters the functional activity in cortical attention networks in humans.

“The present findings add to an emerging body of evidence from preclinical and clinical imaging studies that suggest that dietary DHA intake is a robust modulator of functional cortical activity,” wrote lead author Robert McNamara in the American Journal of Clinical Nutrition.

European support

The study follows hot on the heels of, and vindicates, backing from the European Food Safety Authority (EFSA) for DHA-related brain and eye health claims for infants.

EFSA’s Panel on Dietetic Products, Nutrition and Allergies (NDA) said DHA (docosahexaenoic acid) levels of 100mg of per day were appropriate for 7-24 month-old infants along with 200mg per day for pregnant and lactating women.

The DHA claims relating to brain health stated: “DHA intake can contribute to normal brain development of the foetus, infant and young children”

Another shorter chain, omega-3 fatty acid, ALA (alpha linolenic acid), was affirmed as important for the normal brain development of children up to the age of 18 but no levels were specified.

Study details

While there is a growing body of evidence linking DHA to cognitive function, Dr McNamara and his co-workers note that it is unkown how DHA supplementation may affect functional cortical activity in humans. In order to fill this knowledge gap, they recruited 33 health boys aged between 8 and 10 and randomly assigned them to receive one of two doses of DHA (400 or 1200 mg per day, Martek Biosciences) or placebo for eight weeks.

Brain activation patterns were measured using functional magnetic resonance imaging (fMRI) during a test of sustained attention (playing video games). The results showed that DHA levels in the membrane of red blood cells (erythrocytes ) increased by 47 and 70 per cent in the low and high dose DHA group, while the placebo groups experienced an 11 per cent drop in DHA levels.

The “main finding” from the fMRI data was an indication of significant increases in the activation of the dorsolateral prefrontal cortex part of the brain in the DHA groups – an area of the brain associated with working memory. Changes in other parts of the brain, including the occipital cortex (the visual processing centre) and the cerebellar cortex (plays a role in motor control) were observed.

“These findings suggest that this imaging paradigm could be useful for elucidating neurobiological mechanisms underlying deficits in cortical activity in psychiatric disorders associated with DHA deficiencies, including ADHD and major depression,” wrote the researchers.

Another Great article about Omega 3 Fatty Acids and childhood development.

I know I'm always linking research articles to how the Brain functions but that's what I do! Anyway, the reason people who are bored die earlier is do to the brain not being stimulated enough. There are three things the neurons in the brain need to survive: Oxygen, Glucose, and activation aka stimulus. If any of the three are missing you will have cell death. You may be asking the question than why are these people dieing of heart attacks? Through neuroresearch scientists have found the left side of your brain controls the hearts rhythm and speed. The right side of the brain controls the speed only. If someone is having a left sided brain issue they can have Tachycardia(speeding up of the heart)and arrhythmia(heart beat is irregular). This is the worse case scenario. If the right side of brain is having difficulty firing you will only get tachycardia. When the brain is bored or under stimulated you have slow neuronal death. So stop reading my ramblings and go get some exercise!

From contracostatimes.com:

In her 88 years, Florence Siegel has learned how to relax: A glass of red wine. A crisp copy of The New York Times, if she can wrest it from her husband. Some classical music, preferably Bach. And every night like clockwork, she lifts a pipe to her lips and smokes marijuana.
Long a fixture among young people, use of the country%u2019s most popular illicit drug is now growing among the AARP set, as the massive generation of baby boomers who came of age in the 1960s and %u201970s grows older.

The number of people aged 50 and older reporting marijuana use in the prior year went up from 1.9 percent to 2.9 percent from 2002 to 2008, according to surveys from the Substance Abuse and Mental Health Services Administration.

The rise was most dramatic among 55- to 59-year-olds, whose reported marijuana use more than tripled from 1.6 percent in 2002 to 5.1 percent.

Observers expect further increases as 78 million boomers born between 1945 and 1964 age. For many boomers, the drug never held the stigma it did for previous generations, and they tried it decades ago.

Some have used it ever since, while others are revisiting the habit in retirement, either for recreation or as a way to cope with the aches and pains of aging.

Siegel walks with a cane and has arthritis in her back and legs. She finds marijuana has helped her sleep better than pills ever did. And she can%u2019t figure out why everyone her age isn%u2019t sharing a joint, too.

%u201CThey%u2019re missing

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a lot of fun and a lot of relief,%u201D she said.
Politically, advocates for legalizing marijuana say the number of older users could represent an important shift in their decades-long push to change the laws.

%u201CFor the longest time, our political opponents were older Americans who were not familiar with marijuana and had lived through the %u2018Reefer Madness%u2019 mentality and they considered marijuana a very dangerous drug,%u201D said Keith Stroup, the founder and lawyer of NORML, a marijuana advocacy group.

%u201CNow, whether they resume the habit of smoking or whether they simply understand that it%u2019s no big deal and that it shouldn%u2019t be a crime, in large numbers they%u2019re on our side of the issue.%u201D

Each night, 66-year-old Stroup says he sits down to the evening news, pours himself a glass of wine and rolls a joint. He%u2019s used the drug since he was a freshman at Georgetown, but many older adults are revisiting marijuana after years away.

%u201CThe kids are grown, they%u2019re out of school, you%u2019ve got time on your hands and frankly it%u2019s a time when you can really enjoy marijuana,%u201D Stroup said. %u201CFood tastes better, music sounds better, sex is more enjoyable.%u201D

The drug is credited with relieving many problems of aging: aches and pains, glaucoma, macular degeneration, and so on. Patients in 14 states enjoy medical marijuana laws, but those elsewhere buy or grow the drug illegally to ease their conditions.

Among them is Perry Parks, 67, of Rockingham, N.C., a retired Army pilot who suffered crippling pain from degenerative disc disease and arthritis. He had tried all sorts of drugs, from Vioxx to epidural steroids, but found little success. About two years ago he turned to marijuana, which he first had tried in college, and was amazed how well it worked for the pain.

%u201CI realized I could get by without the narcotics,%u201D Parks said, referring to prescription painkillers. %u201CI am essentially pain free.%u201D

But there%u2019s also the risk that health problems already faced by older people can be exacerbated by regular marijuana use.

Older users could be at risk for falls if they become dizzy, smoking it increases the risk of heart disease and it can cause cognitive impairment, said Dr. William Dale, chief of geriatrics and palliative medicine at the University of Chicago Medical Center.

He said he%u2019d caution against using it even if a patient cites benefits.

%u201CThere are other better ways to achieve the same effects,%u201D he said.

Pete Delany, director of applied studies at the Substance Abuse and Mental Health Services Administration, said boomers%u2019 drug use defied stereotypes, but is important to address.

%u201CWhen you think about people who are 50 and older you don%u2019t generally think of them as using illicit drugs%u2014the occasional Hunter Thompson or the kind of hippie dippie guy that gets a lot of press maybe,%u201D he said. %u201CAs a nation, it%u2019s important to us to say, %u2018It%u2019s not just young people using drugs it%u2019s older people using drugs.%u2019%u201D

In conversations, older marijuana users often say they smoke in less social settings than when they were younger, frequently preferring to enjoy the drug privately. They say the quality (and price) of the drug has increased substantially since their youth and they aren%u2019t as paranoid about using it.

Dennis Day, a 61-year-old attorney in Columbus, Ohio, said when he used to get high, he wore dark glasses to disguise his red eyes, feared talking to people on the street and worried about encountering police. With age, he says, any drawbacks to the drug have disappeared.

%u201CMy eyes no longer turn red, I no longer get the munchies,%u201D Day said. %u201CThe primary drawbacks to me now are legal.%u201D

Siegel bucks the trend as someone who was well into her 50s before she tried pot for the first time. She can muster only one frustration with the drug.

%u201CI never learned how to roll a joint,%u201D she said. %u201CIt%u2019s just a big nuisance. It%u2019s much easier to fill a pipe.%u201D