Wednesday, August 24, 2016

Overcome Infertility: What Exhibits Abnormal Cell Growth to Cause Infertility

Kyle J. Norton(Scholar and Master of Nutrients, all right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

                    Overcome Infertility 

Infertility is defined as inability of a couple to conceive after 12 months of unprotected sexual intercourse. It effects over 5 millions couple alone in the U. S. and many times more in the world. Because of unawareness of treatments, only 10% seeks help from professional specialist.

       What Exhibits Abnormal Cell Growth to Cause Infertility



1. Xanoestrogen
Xanoestrogen is also known as environment estrogen acts as estrogen. Accumulated of such toxins in the liver may block and interfere our body's reproductive normal functions including low sperm count, abnormal sperm production and movement.

2.Environment factors
Some people may not aware exposing themselves in certain chemical environment such as house building in previous dump site, living closed to some chemical processing site, etc. will interfere the body hormone production leading to reproductive abnormal function resulting in increasing the risk of birth defect, infertility and miscarriage.

4. Chemicals
Chemicals such as DDT, PCP and furans used in agriculture. freezer, etc. reduce the quality and lower the sperm count in men leading to infertility. In women, such chemicals may cause child defect and miscarriage.

5. Immune system
Malfunction of immune system caused by imbalance of our body qi and blood accordimg to traditional Chinese medicine (TCM) interferes with the reproductive process including the inflammation to cells which are vital involved in the processes of ovulation , preparation for implantation of a embryo ( malfunction of endometrial lining) and sperm quality ad quantity (Antibody attack his own sperm).

6. Occupations
Occupations which expose to high amount of hazardous chemicals, such as welder, steel processing may distort the normal processes of reproductive organs leading to eggs and sperm damaging such as low quality of egg and sperm and other reproductive diseases.
Pregnancy Miracle
Reverse Infertility And Get Pregnant Naturally
Using Holistic Ancient Chinese Medicine



Fatty Liver And Obesity Reversal, Using The Revolutionary Findings To Achieve Optimal Health And Loose Weight

Kyle J. Norton(Scholar and Master of Nutrients, all right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

According to Dr. Duncan Capicchiano in Naturopathic Medicine, Fatty Liver Disease is easy to treat and completely reversible in virtually every case  in years of his clinical practice
For more information of Fatty Liver And Obesity Reversal, Using The Revolutionary Findings To Achieve Optimal Health And Loose Weight, click Here
A. Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.

B. How to calculate your BMI index
BMI= weight (kg)/ height (m2)

C. Non-alcoholic Fatty Liver Disease is defined as a condition as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption. According to the study of "Nonalcoholic Fatty Liver Disease An Underrecognized Cause of Cryptogenic Cirrhosis" by Jeanne M. Clark, MD, MPH, Anna Mae Diehl, MD, posted in The Journals of the American Medical Association, researchers indicated in abstract that Cryptogenic cirrhosis is a common cause of liver-related morbidity and mortality in the United States. Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of cryptogenic cirrhosis.

D. How Obesity associates with Non-alcoholic Fatty Liver Disease
1, In atudy of "A new risk factor for the development of non-alcoholic fatty liver disease: HLA complex genes" by Celıkbılek M, Selçuk H, Yilmaz U., posted in PubMed, researchers indicated that To reduce the influence of possible confounding factors, we excluded diseases known to be associated with non-alcoholic fatty liver disease like obesity, diabetes mellitus, coronary artery disease, hyperlipidemia, and metabolic syndrome. Non-alcoholic fatty liver diseasewas diagnosed in 66 individuals (33 male, median age: 53.8 [range, 32-77 years]) by means of ultrasonography data, and 50 individuals, whose ultrasonography data did not show hepatosteatosis, comprised the control group (20 male, median age: 44.6 [range, 26-71 years]). Results: Human leukocyte antigen-B65 (28.8% vs 0%, p<0.001) and DQ5 (40.7% vs 16.1%, p<0.05) were found to be expressed significantly more in non-alcoholic fatty liver disease compared with controls. Serum alanine aminotransferase (27.1 IU/L vs 20 IU/L, p<0.05) was significantly higher in the study group. Conclusions: Our preliminary study suggests that human leukocyte antigen plays a role in the pathogenesis of non-alcoholic fatty liver disease; however, more studies are needed to clarify these data.

2. In a study of "Non-alcoholic steatohepatitis in children" by Nanda K., posted in PubMed, researchers indicated that Obesity has emerged as a significant new health problem in the pediatric population. Non-alcoholic steatohepatitis (NASH),..., A system of grading depending on degree of steatosis and/or inflammation and staging depending on the extent of fibrosis has also been proposed. Although there is no consensus for the treatment for NASH, effort needs to be made to prevent development of fibrosis, which results in cirrhosis and portal hypertension. Slow, consistent weight loss has been shown to be effective in childhood NAFLD, based on improvement of serum aminotransferases or liver sonogram. A low glycemic index diet has been shown to be more effective than a low fat diet in lowering BMI.

3. According to the study of "[Non-alcoholic fatty liver disease--new view]" [Article in Polish], by Raszeja-Wyszomirska J, Lawniczak M, Marlicz W, Miezyńska-Kurtycz J, Milkiewicz P., posted in PubMed, researchers found that The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others are under controlled trials or their effectiveness is low. NASH is not a common indication for liver transplantation because of the older age distribution of patients and high prevalence of comorbidity, related to metabolic syndrome. Recurence of NASH in the grafted liver is also a relatively frequent complication.

4. In a study of "Serotonin-receptor-3-antagonists improve obesity-associated fatty liver disease in mice" by Haub S, Ritze Y, Ladel I, Saum K, Hubert A, Spruss A, Trautwein C, Bischoff SC., posted in PubMed, researchers found that Palonosetron had similar effects as tropisetron regarding the reduction of liver fat and other parameters. Conclusions: Tropisetron and palonosetron are effective in attenuating NAFLD in a genetic mouse model of obesity. The effect likely involves the intestinal nervous system, resulting in a reduction of endotoxin influx into the liver and subsequently of liver inflammation and fat accumulation.

5. According to the study of "Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis" by Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palù G, Martines D., posted inPubMed, researchers found that HSCs isolated from ob/ob and db/db mice showed higher membrane CD14 mRNA levels and more pronounced lipopolysaccharide-induced proinflammatory and fibrogenic responses than HSCs from lean animals. In conclusion, genetically obese mice display enhanced intestinal permeability leading to increased portal endotoxemia that makes HSCs more sensitive to bacterial endotoxins. We suggest that in metabolic syndrome, patients may likewise have a greater intestinal mucosa permeability and increased lipopolysaccharide levels in portal blood that can contribute to the liver inflammatory damage.

6. in the abstract of study of "Animal models of steatohepatitis" by Koteish A, Mae Diehl A., posted in PubMed, researchers indicated that Animal models of hepatic steatosis and steatohepatitis have improved our understanding of the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Three models, genetically obese ob/ob mice, lipoatrophic mice and normal rats fed choline-deficient, methionine-restricted diets, have been particularly informative. All support the multiple 'hit' hypothesis for NAFLD pathogenesis that suggests that fatty livers are unusually vulnerable to oxidants and develop steatohepatitis when secondary insults generate sufficient oxidants to cause liver cell death and inflammation.

7. Etc.

E. Natural Treatments for Non-alcoholic Fatty Liver Disease
1. Hawthorn
Hawthorn is a shrubs and trees of the genus Crataegus, belonging to the family Rosaceae, native to temperate regions of the Northern Hemisphere in Europe, Asia and North America. The herb has been used in traditional medicine to treat heart disease and symptoms of heart diseases such as irregular heartbeat, high blood pressure, chest pain, hardening of the arteries, etc., circulatory disorders and respiratory illnesses.

Nonalcoholic fatty liver disease (NAFLD) is emerging as a widespread condition in US as approximate 30% of adult population are obese. Finding the natural treatments become for less or no side effects has become urgency in many scientific community including researchers in Universities. Alternative medicines for the treatment of NAFLD have been proven with many successful histories of controlling disease with no or less side effects, if compares to conventional treatment of the same. In a randomized controlled trials (RCTs) for the efficiency of traditional Chinese medicine (TCM) on the treatment of nonalcoholic fatty liver disease (NAFLD), Chinese herbal formulas have found to be effective in reducing the abnormality of alanine aminotransferase functions and fat accumulation in liver. Out of 246 kinds of Chinese herb, Hawthorn Fruit is found mostly in the list of many formulas. Of that reason, the herb may contain certain chemical constituents effectively in treatments of Nonalcoholic fatty liver disease (NAFLD).

2. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.. Curcumin is one of the natural phenols in the plant.

Turmeric has long been used in herbal medicine in treating diseases and today its curcuminoid, curcumin has attracted many interests from researchers in many parts of the world. Curcumin, as an antihyperlipidemic agents, has been found tolower the "bad cholesterol" low density lipoprotein (LDL), and increase high density lipoprotein (HDL) of which reduce the risk of fat accumulated in the tissues in the liver. Ecessive fat deposited in hepatocytes may cause metabolic imbalances, causing Non- alcoholic fatty liver diseases. In the support of the above, the water-soluble curcumin derivative was tested for its efficacy against steatohepatitis which is an inflammation of the liver with concurrent fat accumulation in liver, the derivative not only significantly alleviated fibrosis but also decreased the grade of liver steatosis.

3. Beeswax
Beeswax is a natural wax produced in the bee hive of honey bees of the genus Apis, containing mainly esters of fatty acids and many types of long chain alcohols.

Beeswax has been promoted as a healthy product for commercial profits in many parts of the world. Nonalcoholic fatty liver disease (NAFLD), as a result of abnormal function in fat accumulated in the liver. is associated with insulin resistance, liver fibrosis and cirrhosis, as a result of abnormal function in fat accumulated in the liver. D-002, a mixture of beeswax alcohols, in the study to test it efficacy in 50 NAFLD randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks, D-002 exhibited a normal liver echo pattern on ultrasonography, improved symptoms and reduced insulin levels. Of that result, D002, may be considered as a potential agent in treating Nonalcoholic fatty liverdisease (NAFLD).

4. Bernerine
Bernerine is a phytochemical found abundantly in root, bark, stem in plants of Berberis, including Oregon grape, barberry, tree turmeric, etc.
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc.
Non-alcoholic Fatty Liver Disease is defined as a condition of the fatty liver diseases as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption.

Sadly to say, Non alcoholic liver diseases has become most prevalence incidence to cause liver diseases because of uncontrolled diet with high in saturated fat. Conventional medication such as ameliorate, a cholesterol absorption inhibitor, is found to be effective in decreasing cholesterol absorption in the small intestine and ameliorated non-alcoholic fatty liver disease (NAFLD) pathology but with many side effects.
In herbal medicine, certain herbs have found to be effective not only in reducing the symptoms of non alcoholic, but also prevent the abnormal alanine aminotransferase functions and fat accumulation in liver.
Berberine and resveratrol, the phytochemical found abundantly in many vegetables and fruits as well herbs and herbal formulae such as Polygonum hypoleucum Ohwi, and Artemisia sacrorum Ledeb., and formulae including Yinchenhao Decoction (, YCHD), Qushi Huayu Decoction (, QSHYD), and Danning Tablet, were found not only to improve biochemical and histological change in nonalcoholic fatty liver disease, but also associated with inhibiting lipid accumulation through adenosine monophosphate-activated protein kinase activation or up regulating low-density lipoprotein receptor (LDLR) expression, alleviating lipid peroxidation, and reducing the production of inflammatory cytokines. In such instance, Berberine and resveratrol, may be considered as a potential treatment for nonalcoholic fatty liver disease in the future.

5. Weight Loss
Non alcoholic fatty liver diseases is widespread in Western world with no affirmative treatment. Most physicians suggested healthy diet with less in saturated and trans fat and reduction of patients' weight would be beneficial in management of the disease. As n-3 polyunsaturated fatty acids (PUFA)has been found to be effective in treating patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia with no adverse effects. In the study of the effect of weight reduction diet as an exclusive treatment for NAFLD, in 44 patients with NAFLD whom received a diet including a 500 to 1000 kcal per day intake reduction as30% fat, 15% protein, and 55% carbohydrate for six months, reduction of body weight, waist circumference and decrease diastolic blood pressure are significant. Total cholesterol, LDL, triglyceride, ALT, AST, GGT and CK18-M30 levels were significantly decreased as well. Of these result, weight reduction diet should be considered as a therapy in managing non alcoholic liver disease.
6. Bastard Teak (Premna tomentosa)
Bastard Teak (Premna tomentosa) is Indian ayurvedic medicine used widely in the treatment of liver disorder.

The prevalence of non alcoholic of liver disease is worrisome to Western world as it not only effects the organs donors, but also increase the medical cost in the future. AS well known, the liver is the first live of defense in detoxifying toxin accumulated in the body, and healthy liver is associated with a balanced diet that includes nutrients and herbs that support a healthy liver. In the study of the extracts from theayurvedic plant, Premna tomentosa (PT), pretreatment of (750 mg/kg, orally) for 15 days and then induced with hepatotoxicity by AA (640 mg/kg, intraperitoneally) in animals, was found to significantly inhibit induced alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids, serum lipoproteins, and lipid-metabolizing enzymes, as well as to exert a beneficial effect against liverinjury-induced membrane damage. Of that result, the extract may be considered for human trial for it efficacy in treating liver disorder, including Non alcoholic fatty disease.

7. Antioxidants
A free radical is any atom or molecule that has a single unpaired electron in an outer shell and highly reactive to react with other cell, which in turn, causes oxidative damage to the enzymes, other protein, unsaturated fatty acid, phospho-lipids, DNA and RNA, etc., leading to aging of the organisms, as a result of widespread damage due to set of a chain reaction auto-catalytically after attacking the lipid bilayers of the cell walls.
Non-alcoholic Fatty Liver Disease is defined as a condition of the fatty liver diseases as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption.

Antioxidants have been found to assist the body in selfrepairment of the cell damage caused by oxidative stress in balancing of the electrons. Oxidative stress is found to cause hepatic damage in patients with acute and chronic hepatitis B virus (HBV) infection and these imbalances in some researches were found to be associated in patients with Non alcoholic fatty liver disease (NAFLD). In a prospective study of 29 patients with NAFLD, 25 diseased controls with chronic viral hepatitis, and 23 healthy controls, lipid peroxidation are significantly increased among patients with NAFLD compared to healthy subjects, but there were no significant correlation between histological grading or staging and levels of pro and antioxidants. This study demonstrate that oxidative may be considered as a potential cause in managing patients with Non alcoholic fatty disease.

8. Phytochemicals Triterpenoid
Triterpenoid is a various unsaturated hydrocarbons, found in essential oils and oleoresins of plants, including Ilex hainanensis Merr.

Progression of nonalcoholic steatohepatitis (NASH) to Non alcoholic liver disease is inevitable if left untreated. Ilex hainanensis Merr. is the Chinese herb used to treat for hypertension, dyslipidemia and inflammation in Traditional Chinese Medicine (TCMs) and may be a potential medicine to treat Non alcoholic fatty disease. In the study to test the effect of Triterpenoid-rich fraction (TP) from Ilex hainanensis Merr. on NAFLD with Male Sprague-Dawley (SD) rats fed a normal diet (control) or high fat diet (NAFLD model), after 4 weeks, the high fat diet group was orally administrated TF (250 mg/kg) for another two weeks. TP not only improves the symptoms of the subjects, but also decreases the levels of triglyceride , total cholesterol, low-density lipoprotein cholesterol, abnormality of lipid accumulation , levels of inflammation and infection and apoptosis response in the liver. Of these results, TF is found to be effective in protecting liver against NAFLD by regulating lipids metabolism and alleviating insulin resistance, inflammation and oxidative stress. 

9. Mu Dan Pi or Dan Pi (Cortex Moutan Radicis)
Mu Dan Pi or Dan Pi (Cortex Moutan Radicis) is also known as peony. The acrid, bitter and mild cool herb has been used in TCM as anti micro organism, anti inflammatory agent and to enhance circulation and immune system, etc., as it clears heat and cools the blood, clears fire of yin deficiency, clear blood stasis and rid of clots, etc., by enhancing the functions of heart, liver and kidney channels.
Non-alcoholic Fatty Liver Disease is defined as a condition of the fatty liver diseases as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption.

Ingredients
1. Paeonol
2. Paeonoside
3. Paeonolide
4. Apiopaeonoside
5. Ozypaeoniflorin
6. Benzoylpaeoniflorin
7. Benzoyl-oxypaeoniflorin
8. Gallic aid
9. 1,23,4,6-pentagalloylglucose
10. Etc.

The benefits
Peony, a very popular Chinese herb is emerging as in many study for its Anti-inflammatory, anticoagulative , Anti-microbial and cytokine modulating effects, as well as properties as treatments of arthritis and asthma. In the study of the effects of peony in Non alcoholic liver disease caused by insulin resistance with Adult SD rats fed on high-fat-sugar-salt diet for 56 days, then divided randomly into nonalcoholic fatty liver model group, metformin group (0.2 g x kg(-1)) and total glucosides of paeony group. Oral administration of total glucosides of paeony group, hyperinsulinaemia and insulin resistence were resisted, the levels of free fatty acids (FFA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)] were decreased, HDL-C were increased, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE) were decreased and superoxide dismutase (SOD) were increased. The contents of malondialdehyde (MDA) were decreased. Of these result, researchers suggested that paeony may consist a potential effect in protecting liver function and modulate serum lipid for the fatty liver rats caused by insulin resistance.

Side Effects 
1, Do not use the herb in case of excessive menstruation, bleeding due to Yin deficiency
2. Do not use the herb in newborn, children, or if you are pregnant or breast feeding without first consulting with related field specialist
3. Etc.

10. Bay berry
Bay berry is a species of Myrica gale, genus Myrica, belonging to the family Myricaceae. Beside many nutrients, it also consists chemical constituents of Gallic acid, quercetin hexoside, quercetin deoxyhexoside, quercetin, anthocyanins, flavonols, and elllagitannins, etc.
Non-alcoholic Fatty Liver Disease is defined as a condition of the fatty liver diseases as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption.

The benefits
Bayberry juice is one of favorite drink among Chinese citizens. the fruits has been cultivated over 2000 years in Chinese literature for foods and medical use. Because of it recently found to contain certain chemicals with antioxidant effects, the fruits and its juice are being promoted as healthy products for commercial profits. In folk medicine, the fruit has been used in treating jaundice, painful and colitis, diarrhea, and nausea, etc.. Its main ingredient, anthocyanins, has been found to be effective in some studies for treating cardiovascular diseases and cancers. In a randomized, placebo-controlled, double-blind, crossover study of 44 participants (ages 18-25 y) given 250 mL of either bayberry juice or placebo twice daily for 4 wk, Bay berry juice is found to decrease inflammation and infection, liver cell apoptosis, and death of liver tissues as well as reduction of the risk of steatosis progreeion to cause NALFD. Of that results, researchers suggested that consumption of bayberry juice for a period of 4 wk can protect against NAFLD and its juice may be a candidate for potential prevention and treatment of Non acoholic fatty liver disease(NALFD).

The Side effects
1. Tannins found in bayberry may induce a drying effect on the skin and allergic effect in some patients
2. Bayberry may interactive with some prescription and non prescription medicine.
3. Etc.

11. Melatonin
Melatonin supplement, a synthetic product of the vertebrate pineal gland was sfound to have significantly broader actions including oncostatic effects (Blask et al., 2002), immunesystem stimulation (Guerrero & Reiter, 2002)and anti-inflammatory functions.
Non-alcoholic Fatty Liver Disease is defined as a condition of the fatty liver diseases as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption.

The benefits

In the study to investigate melatonin's preventive action in oxidative stress in a rat model with high fat diet-induced non-alcoholic fatty liver disease (NAFLD), Melatonin was ineffective in reverse the abnormal action of lipid accumulation and in enhancing normal lipidemic serum markers, but it enhanced the antioxidant effects by protecting the liver against the peroxidation and oxidative stress in liver tissue as well as a significant increasing of glutathione. 

12. Serum potassium
Dietary Minerals are the group of minerals essential for our body to sustain normal functions and physical health. 

In General, potassium is a very essential mineral to the human body for maintaining to build proteins and muscle, break down carbohydrates, maintain normal body growth and normal heart electricity,
Fatty liver disease is defined as a condition of accumulation of fat in the liver, including people who drink little or no alcohol (Non alcohol fatty disease) or who are excessive alcohol drinking (Alcohol fatty liver disease). The disease can even occurs after a short period of heavy drinking (acute alcoholic liver disease). More than 15 million people in the U.S. either abuse or overuse alcohol with fatty liver diseases with fat makes up 5-10 percent of liver weight.
Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of clinical conditions, actually representing an emerging disease of great clinical interest(4).

The benefits

Nonalcoholic fatty liver disease (NAFLD) are associated to increased risk of metabolic syndrome. In the study of in 8592 subjects with NAFLD (30·3%) and gradually decreased across serum potassium quartiles, to investigate the association of serum potassium with the risk of prevalent NAFLD. The result showed a significant relation between serum potassium level and NAFLD in women, younger subjects, those with insulin resistance and central obesity. Other in the study to investigate the association between NAFLD and primary aldosteronism (PA), and to identify determinants of NAFLD in this condition, showed that Serum potassium was lower in primary aldosteronism (PA) than in LREH patients with NAFLD (P < 0.001), while it was similar in PA and LREH patients without NAFLD.

According to Dr. Duncan Capicchiano in Naturopathic Medicine, Fatty Liver Disease is easy to treat and completely reversible in virtually every case 
For more information of  Fatty Liver And Obesity Reversal, Using The Revolutionary Findings To Achieve Optimal Health And Loose Weight, click Here

References
Hawthorn
(1) Methodologies for investigating natural medicines for the treatment of nonalcoholic fatty liver disease (NAFLD) by Kim MS, Kung S, Grewal T, Roufogalis BD.(PubMed)
(2) Traditional Chinese medicines benefit to nonalcoholic fatty liver disease: a systematic review and meta-analysis by Shi KQ, Fan YC, Liu WY, Li LF, Chen YP, Zheng MH.(PubMed)
 Turmeric
(1) Curcumin and liver disease.Vera-Ramirez L, Pérez-Lopez P, Varela-Lopez A, Ramirez-Tortosa M, Battino M, Quiles JL.(PubMed)
(2) [The effects of curcumin derivative on experimental steatohepatitis].[Article in Chinese] by Zeng CH, Zeng P, Deng YH, Shen N, Peng ML, Liu Q, Ren H.(PubMed)
Beeswax
(1) Beeswax (Wikipedia)
(2) Effects of D-002, a mixture of high molecular weight beeswax alcohols, on patients with nonalcoholic fatty liver disease by Illnait J, Rodríguez I, Mendoza S, Fernández Y, Mas R, Miranda M, Piñera J, Fernández JC, Mesa M, Fernández L, Carbajal D, Gámez R.(PubMed)
Bernerine
(1) Non-alcoholic fatty liver disease and liver transplantation: Outcomes and advances by Said A.(PubMed)
(2) The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial by Takeshita Y, Takamura T, Honda M, Kita Y, Zen Y, Kato KI, Misu H, Ota T, Nakamura M, Yamada K, Sunagozaka H, Arai K, Yamashita T, Mizukoshi E, Kaneko S.(PubMed)
Weight Loss
(1) How Much Weight Loss is Effective on Nonalcoholic Fatty Liver Disease? by Ghaemi A, Taleban FA, Hekmatdoost A, Rafiei A, Hosseini V, Amiri Z, Homayounfar R, Fakheri H.(PubMed)
(2) Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia by Zhu FS, Liu S, Chen XM, Huang ZG, Zhang DW.(PubMed)
Bastard Teak (Premna tomentosa)
(1) Assessment of the protective potential of Premna tomentosa (L. Verbenaceae) extract on lipid profile and lipid-metabolizing enzymes in acetaminophen-intoxicated rats by Devi KP, Sreepriya M, Balakrishna K, Veluchamy G, Devaki T.(PubMed)
(2) Protective effect of Premna tomentosa (L. Verbenaceae) extract on membrane-bound phosphatases and inorganic cations transport in acetaminophen-induced hepatotoxicity rats, by Devi KP, Sreepriya M, Balakrishna K, Devaki T.(PubMed)
Antioxidants
(1) Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD) by Madan K, Bhardwaj P, Thareja S, Gupta SD, Saraya A.(PubMed)
(2) [Investigation of oxidative stress and antioxidant defense in patients with hepatitis B virus infection and the effect of interferon-alpha plus lamivudine combination therapy on oxidative stress].[Article in Turkish. by Acar A, Görenek L, Aydin A, Eyigün CP, Eken A, Sayal A, Pahsa A.(PubMed)
Phytochemicals Triterpenoid
(1) Pharmacokinetic study of major bioactive components in rats after oral administration of extract of Ilex hainanensis by high-performance liquid chromatography/electrospray ionization mass spectrometry by Jie Yanga, 1, Fang Lva, 1, Xiao-qing Chenb, Wei-xi Cuia, Li-hong Chenc, Xiao-dong Wena, Qiang Wanga(Science direct)
(2) Triterpenoid-rich fraction from Ilex hainanensis Merr. attenuates non-alcoholic fatty liver disease induced by high fat diet in rats by Cui WX, Yang J, Chen XQ, Mao Q, Wei XL, Wen XD, Wang Q.(PubMed)
Mu Dan Pi or Dan Pi (Cortex Moutan Radicis)
(1) Chinese Herbs – Mu Dan Pi or Dan Pi (Cortex Moutan Radicis)
(2) [Effects of total glucosides of paeony on enhancing insulin sensitivity and antagonizing nonalcoholic fatty liver in rats].[Article in Chinese] by Zheng LY, Pan JQ, Lv JH.(PubMed)
Bay berry
(1) Chemical composition of clarified bayberry (Myrica rubra Sieb. et Zucc.) juice sediment by Fang Z, Zhang M, Tao G, Sun Y, Sun J.(PubMed)(2) One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans by Alvarez-Suarez JM1, Giampieri F2, Tulipani S3, Casoli T4, Di Stefano G5, González-Paramás AM6, Santos-Buelga C6, Busco F7, Quiles JL8, Cordero MD9, Bompadre S10, Mezzetti B11, Battino M12.(PubMed)
(3) Anthocyanins and their role in cancer prevention by Wang LS, Stoner GD.(PubMed)
(4) Effects of bayberry juice on inflammatory and apoptotic markers in young adults with features of non-alcoholic fatty liver disease by Guo H1, Zhong R2, Liu Y2, Jiang X3, Tang X3, Li Z3, Xia M4, Ling W3.(PubMed)
(5) Anaphylaxis and generalized urticaria from eating Chinese bayberry fruit by Wang HY, Gao ZS, Yang ZW, Shao JX, Zhao XZ, Dai Y, Van Ree R.(PubMed)
Melatonin
(1) Melatonin as an antioxidant: biochemical mechanisms andpathophysiological implications in humans (Acta, Biochimica, Polonica)
(2) Melatonin attenuates high fat diet-induced fatty liver disease in rats by Hatzis G, Ziakas P, Kavantzas N, Triantafyllou A, Sigalas P, Andreadou I, Ioannidis K, Chatzis S, Filis K, Papalampros A, Sigala F.(PubMed)
Serum potassium
(1) Low serum potassium level is associated with nonalcoholic fatty liver diseaseand its related metabolic disorders by Sun K, Lu J, Jiang Y, Xu M, Xu Y, Zhang J, Xu B, Sun J, Sun W, Ren C, Liu J, Wang W, Bi Y, Ning G.(PubMed)
(2) Nonalcoholic fatty liver disease in primary aldosteronism: a pilot study by Fallo F, Dalla Pozza A, Tecchio M, Tona F, Sonino N, Ermani M, Catena C, Bertello C, Mulatero P, Sabato N, Fabris B, Sechi LA.(PubMed)
(3) Review article: the diagnosis of non-alcoholic fatty liver disease -- availability and accuracy of non-invasive methods by Festi D, Schiumerini R, Marzi L, Di Biase AR, Mandolesi D, Montrone L, Scaioli E, Bonato G, Marchesini-Reggiani G, Colecchia A.(PubMed

Phytochemicals in Foods- The Effects of Thearubigins

Kyle J. Norton(Scholar and Master of Nutrients, all right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.


                                      Thearubigins




Thearubigins with reddish colour, is a phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), formed in tea leaves during fermentation.

Health Benefits
1. Tetanus toxin
In the elucidation of the mechanism of the protective effect of black tea extract'sthearubigin fraction against the action of tetanus toxin, found that thearubiginfraction mixed with tetanus toxin blocked the inhibitory effect of the toxin. Mixing iodinated toxin with thearubigin fraction inhibited the specific binding of [125I]tetanus toxin to the synaptosomal membrane preparation. The effects ofthearubigin fraction were dose-dependent, according to "A mechanism of thethearubigin fraction of black tea (Camellia sinensis) extract protecting against the effect of tetanus toxin" by Satoh E, Ishii T, Shimizu Y, Sawamura S, Nishimura M.(1)

2. Inflammatory bowel disease
in the examination of examine the protective effects of thearubigin, an anti-inflammatory and anti-oxidant beverage derivative, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, a model for inflammatory bowel disease, found that pretreatment of mice with thearubigin (40 mg kg(-1) day(-1), i.g. for 10 days) significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. Higher dose (100 mg kg(-1)) had comparable effects. This was associated with a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed colon as well as decreased serine protease activity. Thearubigin also reduced the levels of NO and O(2)(-) associated with the favourable expression of T-helper 1 cytokines and iNOS, according to "Thearubigin, the major polyphenol of black tea, ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis" by Maity S, Ukil A, Karmakar S, Datta N, Chaudhuri T, Vedasiromoni JR, Ganguly DK, Das PK.(2)

3. Prostate cancers
In the comparison of the anti-proliferative effect of black tea (Camellia sinensis) polyphenol, thearubigin (TR), alone or combined with the isoflavone genistein, on human prostate (PC-3) carcinoma cells, found that TR administered alone did not result in any alteration of cell growth. When combined with genistein, however, TR significantly inhibited cell growth and induced a G2/M phase cell cycle arrest in a dose dependent manner. These findings indicate the potential use of combined phytochemicals to provide protection against prostate cancer, according to "Synergistic effects of thearubigin and genistein on human prostate tumor cell (PC-3) growth via cell cycle arrest" by Sakamoto K.(3)

4. A375 melanoma cells
In the observation of observed the role of the three most important MAPK (ERK, JNK, and p38) in TF- and TR-induced apoptosis, found that TF and TR treatment induces a time-dependent increase in intracellular reactive oxygen species generation in A375 cells. Interestingly, treatment with the antioxidant N-acetyl cystein inhibits TF- and TR-induced JNK and p38 activation as well as induction of cell death in A375 cells. We also provide evidence demonstrating the critical role of apoptosis signal-regulating kinase 1 in TF- and TR-induced apoptosis in A375 cells, according to "Role of oxidation-triggered activation of JNK and p38 MAPK in black tea polyphenols induced apoptotic death of A375 cells" by Bhattacharya U, Halder B, Mukhopadhyay S, Giri AK.(4)

5. Anticlastogenic effects
In the investigation of potent antimutagenic and anticlastogenic effects of TF and TR in vitro in human cells in vitro, found that a significant decrease in both CA and MN were observed in the human lymphocyte cultures treated with either TF or TR pretreated with either B[a]P or AFB1 (250, 500, 1000 microg/ml) when compared with B[a]P or AFB1 treated cultures alone. TF shows more protective effects than TR in this in vitro system. These results indicate that both TF and TR have significant anticlastogenic effects in vitro in human lymphocytes, according to "Anticlastogenic effects of black tea polyphenols theaflavins and thearubigins in human lymphocytes in vitro" by Halder B, Pramanick S, Mukhopadhyay S, Giri AK.(5)

6. Antioxidative properties
In the review of the different issues and studies relating to composition, manufacturing, and antioxidative effects of black tea and its components in vitro as well as in vivo, found that Antioxidative properties of black tea are manifested by its ability to inhibit free radical generation, scavenge free radicals, and chelate transition metal ions. Black tea, as well as individual theaflavins, can influence activation of transcription factors such as NFkappaB or AP-1, according to "Antioxidative properties of black tea" by Łuczaj W, Skrzydlewska E.(6)

7. Hepatic and intestinal cytochrome P450 system
In the investigation of Theaflavins and theafulvins, a fraction of thearubigins, isolated from aqueous infusions of black tea, and their effects on the hepatic and intestinal cytochrome P450 system, found that treatment with theafulvins and theaflavins reduced the apoprotein levels. A single band in the cytochrome P450 region was evident when the intestinal microsomes were probed with antibodies to CYP4A1 but the level of expression was not affected by the treatment with the black tea polyphenols, according to "Hepatic and intestinal cytochrome P450 and conjugase activities in rats treated with black tea theafulvins and theaflavins" by Catterall F, McArdle NJ, Mitchell L, Papayanni A, Clifford MN, Ioannides C.(7)

8. Chronic myeloid leukemia
In the observation of the anticancer effect of black tea (BT) and its polyphenols theaflavin (TF) and thearubigin (TR) on U-937 cell line, a myeloid leukemic cell line and on leukemic cells isolated from peripheral blood of chronic myeloid leukemia (CML), found that BT, TF and TR. MTT assay showed growth inhibition of metabolically active cells and inhibition of DNA synthesis was observed by 3H-Thymidine incorporation after treatment with the compounds. In all cases TF and TR were more effective than BT, suggesting that these are possibly the active components in BT responsible for its antileukemic activity, according to "Studies with black tea and its constituents on leukemic cells and cell lines" by Das M, Chaudhuri T, Goswami SK, Murmu N, Gomes A, Mitra S, Besra SE, Sur P, Vedasiromoni JR.(8)

9. Oxidative stress
In the investigation of scavenging property of black tea and catechins, the major flavonols of tea-leaf, against damage by oxidative stress, found that Black tea extract in comparison to free catechins seemed to be a better protecting agent against various types of oxidative stress. Apparently, conversion of catechins to partially polymerized products such as theaflavin or thearubigin during 'fermentation' process for making black tea has no deleterious effect on its scavenging properties, according to "Protective role of black tea against oxidative damage of human red blood cells" by Halder J, Bhaduri AN.(9)

10. Antioxidative effects
In the study of the antioxidative activity of theaflavins (TFs) and thearubigin (TR) purified from the infusion of black tea leaves, using the tert-butyl hydroperoxide-induced lipid peroxidation of rat liver homogenates, found that activity of black tea was about as potent as that of green tea. These results suggest that black tea infusion containing TFs and TR could inhibit lipid peroxidation in biological conditions in the same way as green tea infusion containing epicatechins, according to "Antioxidative effects of black tea theaflavins and thearubiginon lipid peroxidation of rat liver homogenates induced by tert-butyl hydroperoxide" by Yoshino K, Hara Y, Sano M, Tomita I.(10)

11. Etc.

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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/12533914
(2) http://www.ncbi.nlm.nih.gov/pubmed/12787838
(3) http://www.ncbi.nlm.nih.gov/pubmed/10766429
(4) http://www.ncbi.nlm.nih.gov/pubmed/19594545
(5) http://www.ncbi.nlm.nih.gov/pubmed/16314069
(6) http://www.ncbi.nlm.nih.gov/pubmed/15850895
(7) http://www.ncbi.nlm.nih.gov/pubmed/12842182
(8) http://www.ncbi.nlm.nih.gov/pubmed/12636103
(9) http://www.ncbi.nlm.nih.gov/pubmed/9535765

Dietary Minerals Boron: The effects of Boron nutrition for brain and psychological function

Kyle J. Norton(Scholar, Master of Nutrients), all right reserved.
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

                                 Dietary Minerals 

Dietary Minerals are the group of minerals which is essential for our body to sustain normal functions and physical health.

                                      Boron

Boron, a vital trace mineral found abundantly in Almond, Red Apple, Apricots, Avocado, Banana, Red kidneyBeans, etc., is necessary for the normal growth and health of the body. Boric acid has antiseptic and antiviral activity. Its aqueous solutions have been used as mouth-washes, eye-drops, skin lotions and cosmetics.

     The effects of Boron nutrition for brain and psychological function

Certain stuies indicated that Boron (B) nutriture has been related to bone, mineral and lipid metabolism, energy utilization, and immune function. In the study to consider possible relationships between B nutriture and brain and psychological function, indicated that assessments of brain electrical activity in both animals and humans found that B deprivation results in decreased brain electrical activity similar to that observed in nonspecific malnutrition. Assessments of cognitive and psychomotor function in humans found that B deprivation results in poorer performance on tasks of motor speed and dexterity, attention, and short-term memory. However, little support was found for anecdotal reports that supplementation with physiologic amounts of B helps alleviate the somatic and psychological symptoms of menopause. Parallels between nutritional and toxicological effects of B on brain and psychological function are presented, and possible biological mechanisms for dietary effects are reviewed. Findings support the hypothesis that B nutriture is important for brain and psychological function in humans(8).

Overcome Infertility: What Exhibits Ovarian Condition To Cause Infertility

Kyle J. Norton(Scholar and Master of Nutrients, all right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

                    Overcome Infertility 

Infertility is defined as inability of a couple to conceive after 12 months of unprotected sexual intercourse. It effects over 5 millions couple alone in the U. S. and many times more in the world. Because of unawareness of treatments, only 10% seeks help from professional specialist.

       What Exhibits Ovarian Condition To Cause Infertility


1. Ovarian failure
Ovarian failure is a condition in which a women with age younger than 40 but she has experience the loss of ovarian function ( early menopause) as resulting of low levels of estrogen and high levels of FSH hormone.

2. Ovarian resistance
For what ever reason, some women's ovaries do not response to FSH stimulation leading to no developing follicle. sSome researchers believe it is caused deficiency of FSH and LH receptors in the ovaries or post receptor defect.

3. Ovarian dygenesis
It is caused by the extra X chromosome defective at birth leading to sterility.

4. Kallmann's syndrome
Kallmann's syndrome is a birth defect syndrome which causes malfunction of hypothalamus gland in secreting the gonadotropin-releasing hormone leading to delay of puberty.
a) In men, it causes low levels of testosterone resulting of small size penis, cryptorchism leading to infertility because of no sperm during ejaculation.
b) In women, it causes no menstrual period and no egg production.

5. Hyperthyroidism
A condition caused by over production of thyroid hormone in the body produces that interfere the production of estrogen causing inability of pituitary gland to trigger the production of LH then ovulation leading to infertility.

6. Cushing's syndrome
Cushing's syndrome is a condition in which too much cortisol hormone is produced by adrenal gland leading to lower sperm production in male and abnormal ovulation in women.
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Women Health: The Obesity and Anovulation Research and Studies of Body mass index-associated differences in response to ovulation induction with letrozole

Kyle J. Norton(Scholar, Master of Nutrients), all right reserved.
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Obesity is a medical condition of excess body fat accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.

You can calculate your BMI index BMI= weight (kg)/ height (m2)

The Studies of Body mass index-associated differences in response to ovulation induction with letrozole


In the study to o compare occurrence of pregnancy among obese (body mass index [BMI] ≥30) and nonobese (BMI <30), infertile women undergoing ovulationinduction with the aromatase inhibitor letrozole followed by intrauterine insemination (IUI), posted in PubMed, showed that 90 women underwent 180 letrozole-IUI cycles. Conception of pregnancy occurred in 10.4% and 18.2% of the BMI <30 and BMI ≥30 groups, respectively. Using BMI as a continuous variable showed a pregnancy odds ratio of 1.093 (confidence interval 1.008-1.184) for each unit increase in BMI. Incidence of miscarriage, multiple births, number of mature follicles, and presence of LH surge were similar between groups.

Most Common Diseases of 50 Plus: Thyroid Disease : Euthyroid sick syndrome as a result of Sepsis - The Complications

Kyle J. Norton(Scholar and Master of Nutrients, all right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.


                         Thyroid disease


Thyroid disease is defined as a condition of malfunction of thyroid. Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones.


             Euthyroid sick syndrome as a result of Sepsis

Sepsis is defined as a condition caused by chemicals released into the bloodstream to fight the infection trigger inflammation throughout the body as a result of severe infection(a)(b). according to the study by the University of Utah, sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis(c).

                                              The Complications

1. Impaired wound healing
Sepsis is one of the main causes for morbidity and mortality in hospitalized patients. Moreover, sepsis associated complications involving impaired wound healing are common(19).

2. Damage to Peripheral nerves and skeletal muscles
Among the critical illness myopathies, three main types have been identified: a non-necrotizing "cachectic" myopathy (critical illness myopathy in the strict sense), a myopathy with selective loss of myosin filaments ("thick filament myopathy") and an acute necrotizing myopathy of intensive care. Clinical manifestations of both critical illness myopathies and CIP include delayed weaning from the respirator, muscle weakness, and prolonging of the mobilization phase, according to the study by Ruprecht-Karls University, Heidelberg(20).

3. Organs failure
Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and the internal organs. Bacterial translocation may be a normal phenomenon occurring on frequent basis in healthy individuals without any deleterious consequences. But when the immune system is challenged extensively, it breaks down and results in septic complications at different sites away from the main focus. The factors released from the gut and carried in the mesenteric lymphatics but not in the portal blood are enough to cause multi-organ failure, according to Postgraduate Institute of Medical Education and Research(21).

4. Morbidity and mortality
Acute kidney injury (AKI) is a common and often catastrophic complication in hospitalized patients; however, the impact of AKI in surgical sepsis remains unknown. We used Risk, Injury, Failure, Loss, End stage (RIFLE) consensus criteria to define the incidence of AKI in surgical sepsis and characterize the impact of AKI on patient morbidity and mortality(22). Other study indicated that in patients with sepsis who are admitted to an ICU, cardiac troponin T elevations are independently associated with in-hospital and short-term mortality but not long-term mortality(23).

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Sources
(a) http://en.wikipedia.org/wiki/Sepsis
(b) http://www.mayoclinic.com/health/sepsis/DS01004
(c) http://www.ncbi.nlm.nih.gov/pubmed/24082613
(19) http://www.ncbi.nlm.nih.gov/pubmed/24086305
(20) http://www.ncbi.nlm.nih.gov/pubmed/11757954
(21) http://www.ncbi.nlm.nih.gov/pubmed/24064638
(22) http://www.ncbi.nlm.nih.gov/pubmed/24089113
(23) http://www.ncbi.nlm.nih.gov/pubmed/24083646