Hyperlipidemias: Asia

Shiomi M, Fan J. · Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Hyogo, Japan. · Curr Opin Lipidol. · Pubmed #18957890 No free full text.

Abstract: PURPOSE OF REVIEW: Use of suitable animal models is essential for investigation of the mechanisms underlying cardiac events and development of the therapeutic strategies; however, ideal animal models that can recapitulate human coronary atherosclerosis and subsequent acute myocardial infarction are still lacking. In this article, we review the insights learned from myocardial infarction-prone Watanabe heritable hyperlipidemic (designated as WHHLMI) rabbits and discuss the possibility of using this model for the study of human acute coronary syndromes. RECENT FINDINGS: The vulnerable plaques of human coronary arteries are histologically characterized by a large lipid core and a thin fibrous cap with inflammatory cells. Recent studies have revealed that inflammatory cells and inflammatory mediators (such as cytokines and matrix metalloproteinases) play an important role in the plaque rupture. SUMMARY: We developed the WHHLMI rabbit that shows spontaneous myocardial infarction caused by coronary atherosclerosis. The coronary lesions of WHHLMI rabbits have features of fatty streaks, fibrous plaques, and fibroatheromatous plaques. Some plaques contain a lipid core and a thin fibrous cap similar to human vulnerable plaques. In spite of this, the plaque rupture is not observed in WHHLMI rabbits, suggesting that other additional factors such as mechanical stress are required to trigger the rupture. WHHLMI rabbits may become an important means for elucidating the possible mechanisms of plaque rupture by exposing the plaques to additional risk factors beyond hyperlipidemia.

Hishida T. · Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nizuho-ku, Nagoya City, Japan. · Yakugaku Zasshi. · Pubmed #17202793 links to  free full text

This publication has no abstract.

Mattar M, Obeid O. · Department of Nutrition and Food Science, American University of Beirut. · Nutr Health. · Pubmed #19326719 No free full text.

Abstract: Hypertriglyceridemia, regarded as one of the independent clinical markers of metabolic syndrome, is a frequently observed disorder that has been shown to be common in the Arab region. Epidemiologic and clinical trials demonstrated that omega-3 fatty acids have the potential to reduce the incidence of cardiovascular disease (CVD); one of the mechanisms by which this effect is achieved is through reducing plasma triglyceride levels. There is strong scientific evidence from human trials that omega-3 fatty acids from either fish or fish oil supplements significantly reduce blood triglyceride levels and these benefits appear to be dose-dependent. The active ingredients of fish oils include the long chain fatty acids EPA and DHA. The ideal amount of omega-3 fatty acid that should be incorporated into the diet without provoking detrimental effects on other lipid components such as decreasing HDL-C and/or increasing LDL-C has not yet been elucidated. Presently, a prescription form of omega-3 fatty acid has been approved by the United States Food and Drug Administration (USFDA) as an adjunct to the diet for the treatment of very high triglyceride levels (> or = 500 mg/dl) in adults. Patients with hypertriglyceridemia have been shown to respond well to the use of omega-3 fatty acids even when used in conjunction with statins where greater improvements in the lipid profile were found as compared to treatment with statins alone. A determinant of the responsiveness to fish oil could be attributed to the ApoE genotype of individuals.

Doi K, Ishida K. · Nippon Institute for Biological Science, Shin-Machi, Ome, Tokyo 198-0024, Japan. · J Toxicol Sci. · Pubmed #19182431 links to  free full text

Abstract: Certain disease conditions can modify drug-induced toxicities, which, in turn, may cause a medication-related health crisis. Therefore, preclinical investigations into the alterations in drug-induced toxicities using appropriate disease animal models are very important. This paper reviews the reported data related to the effects of diabetes and hypertriglyceridemia, common lifestyle-related diseases in a modern society, on acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity in rats and mice. It has generally been reported that diabetes protects rats and mice from APAP-induced hepatotoxicity and there are several reports that help to speculate on the effects of diabetes on APAP-induced nephrotoxicity. In fructose-induced hypertriglyceridemic rats, hepatotoxicity of APAP becomes apparently less severe, whereas nephrotoxicity of APAP becomes significantly more severe. The mechanisms of alteration of APAP-induced hepatorenal toxicity under diabetic and hypertriglyceridemic conditions are also discussed in this paper.

Tripathi YB. · Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. · Recent Pat Inflamm Allergy Drug Discov. · Pubmed #19149746 No free full text.

Abstract: Since hyperlipidemia, inflammation and obesity are closely related to atherosclerosis, therefore management of these factors together would be beneficial for overall treatment approach for atherosclerosis. Although, Indian system of medicine, especially Ayurveda has several medicinal plants with proven beneficial claims towards these pathological conditions, but most of them lack enough experimental data. BHUx is a novel polyherbal formulation, consisting of 5 medicinal plants namely Termenalia arjuna, Strychnox nux vomica, Boswellia serrata, Commiphora mukul, and Semecarpus anacardium, which have history of clinical use as single or in other combinations, but these plant fractions were never tried collectively in this ratio as in BHUx, which has been found to be effective on all the etiological factors, together. In this paper, antioxidant, anti-inflammatory, hypo-lipidemic, anti-proliferative properties of BHUx have been studied on several experimental models based on chemical tests, cell culture, in vitro models, and in vivo experiments with normal and transgenic animals. A separate pre-clinical toxicity study has also been carried out to prove its safety margin in therapeutic doses. Further, clinical trail of BHUx is under way, before it comes to market for public use as functional food to maintain healthy heart. This article also review some patent related to the field.

Khan FY, Ibrahim W. · Department of Medicine, Hamad General Hospital, Doha, Qatar. · Curr Clin Pharmacol. · Pubmed #19149497 No free full text.

Abstract: We report a case of rosuvastatin induced rhabdomyolysis in a low risk patient, who presented with five-day history of generalized muscle pain, weakness and easy fatigability associated with passing dark urine. Initial investigations showed creatinine 140micromol/L, creatine kinase (CK) 4566 U/L and serum myoglobin 2694 ng/ml with a significant increase in urine myoglobin. Although there were no obvious risk factors, the patient was diagnosed with rosuvastatin induced rhabdomyolysis. The drug was stopped on the first day of admission and the patient was initiated on intravenous fluid with cautious monitoring of serum electrolytes. On the following days the level of creatine kinase and serum myoglobin returned toward normal and consequently he was discharged without statins but on dietary therapy. On follow-up evaluation, the patient was symptom free his serum creatinine was 106micromol/L, whereas his LDL cholesterol was 2.1mmol/L. The rosuvastatin induced rhabdomyolysis is discussed and the danger of its use in low risk patients is emphasized.

Ichinose A. · Department of Molecular Patho-Biochemistry and Patho-Biology on Blood and Circulation, Yamagata University School of Medicine, 2-2-2 lIida-nishi, Yamagata 990-9585, Japan. · Brain Nerve. · Pubmed #19069164 No free full text.

Abstract: Prothrombotic and proatherogenic risk factors, including elevated lipoprotein (a), predispose an individual to initial and recurrent ischemic stroke. An increased plasma level of lipoprotein (a), over 25-30 mg/dL, is called hyperlipoprotein (a)-emia, and is largely determined by genetic polymorphisms in apolipoprotein (a). Apolipoprotein (a) is a major protein component of lipoprotein (a), and is connected with apolipoprotein B-100 of low density lipoprotein. The size of apolipoprotein (a) and concentration of lipoprotein (a) vary widely among individuals as well as between ethnic groups. The size of apolipoprotein (a) and plasma concentrations of lipoprotein (a) are inversely related. Accordingly, the number of tandemly repeated structures, named kringle-4 domains, determines the size of apolipoprotein (a), and consequently the plasma lipoprotein (a) level. In addition, the efficiency of apolipoprotein (a) gene expression is a determinant of lipoprotein (a) concentrations, since lipoprotein (a) levels vary more than 200-fold even among the individuals having the same apolipoprotein (a) size. First, we identified haplotypes in the 5'-promoter region of the apolipoprotein (a) gene as a regulating factor of plasma lipoprotein (a) levels. Second, a pentanucleotide repeat polymorphism upstream of the promoter region was also reported to affect plasma lipoprotein (a) levels. Third, two functional single nucleotide polymorphisms were identified in a distal enhancer region situated approximately 20 kb from the apolipoprotein (a) gene. Finally, several polymorphisms were identified in the kringle-4 domains, and found to influence plasma lipoprotein (a) levels as well as the lysine/fibrin-binding function. Since lower molecular weight forms of apolipoprotein (a) are closely associated with the incidence of ischemic stroke, both high plasma concentrations of lipoprotein (a) and small sizes (i. e., number of kringle-4 repeats in the gene) of apolipoprotein (a) are risk factors for the development of atherothrombosis.

Kuroki A, Akizawa T. · Department of Nephrology, Showa University, School of Medicine. · Nippon Rinsho. · Pubmed #18788403 No free full text.

Abstract: Intraglomerular hypertension, and glomerular hypertrophy, leading to glomerular scarring are suggested to have an effect on the progression in chronic kidney disease, unrelated to the initial cause of kidney injury. Tubulointerstitial disease is another factor, which may affect the prognosis. Strategies to prevent or minimize the progression of kidney disease consist of treating these disease-worsening mechanisms, including smoking cessation, treatment of hyperlipidemia, sodium and protein restriction, antihypertensive therapy, inhibition of renin-angiotensin-aldosterone system, and treatment of anemia. Studies in experimental animals and humans suggest that these therapies are effective to prevent the progression in chronic kidney disease and there are some evidences that these therapies have benefits in the patients with chronic kidney disease.

Chen ZY, Jiao R, Ma KY. · Food and Nutritional Sciences Programme, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, China. · J Agric Food Chem. · Pubmed #18778072 No free full text.

Abstract: Epidemiological studies have demonstrated that elevated levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the major risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) and a low ratio of TC to HDL-C are protective against CHD. A relationship between plasma TC and the risk of CHD is well established at concentrations above 240 mg/dL. In addition to the use of three main classes of cholesterol-lowering medications, including HMG-CoA reductase inhibitors, anion-exchange resins, and fibrates, a nutritionally balanced diet that reduces saturated fat and cholesterol intake has traditionally been the first goal of dietary therapy in lowering plasma TC. In recent years, nutraceuticals and functional foods have attracted much interest as possible alternative therapies for lowering plasma TC, especially for hypercholesterolemia patients, whose blood cholesterol level is marginally high (200-240 mg/dL) but not high enough to warrant the prescription of cholesterol-lowering medications. This review summarizes the findings of recent studies on the production, application, efficacy, and mechanisms of popular cholesterol-lowering nutraceuticals and functional foods.

Saruta T. · Keio University. · Nippon Rinsho. · Pubmed #18700540 No free full text.

Abstract: Mild hypertension is defined as blood pressure level of 140-159 mmHg systolic and/or 90-99 mmHg diastolic. The patients with blood pressure level of mild hypertension occupy about 60% of total hypertensive patients in Japan, and most of them are free of subjective symptoms except elevated blood pressure. However, some of the patients with mild hypertension develop cardiovascular events, since thay have occasionally cardiovascular damages on this level of blood pressure and several risk factors of cardiovascular diseases such as diabetes mellitus and hyperlipidemia.

Sarkar D, Latif SA, Aich J, Uddin SN. · Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh. mmcphysio · Mymensingh Med J. · Pubmed #18626463 No free full text.

Abstract: Antibodies specific to cholesterol was first reported in 1925. It may develop in the body naturally and it is believed that this antibody has a protective role against harmful forms of cholesterol, such as LDL & VLDL. An immunoglobulin protein, anticholesterol may be found in both circulation as well as digestive tract. Many studies have been done on anticholesterol antibody. Our immune system may produce anticholesterol antibodies in response to elevated levels of cholesterol rich particles, such as LDL & VLDL. It can be induced in animals by conjugating or incorporating the cholesterol antigen into a variety of structures. Immunization markedly decreases the risk of developing atherosclerosis. In comparison to non-tumorous normal subject, the antibody is found to be significantly higher in non-small cell lung cancer (NSCLC). Elevated anti-cholesterol antibodies might be applicable for the serodiagnosis of NSCLC. Some studies showed that LDL immunization induces T-cell dependent antibody formation that protects atherosclerosis. Origo Biosciences scientists had identified a dietary antibody to cholesterol. This protein, when ingested, binds to cholesterol in the human digestive tract and blocks its absorption into the bloodstream. These studies may lead to us to realize the importance of anticholesterol and to find the way for reduction of hypercholesterolemia and thereby reduction of morbidity and mortality.

Miura S, Saku K. · Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan. · Intern Med. · Pubmed #18591835 links to  free full text

Abstract: Niemann-Pick C1-like 1 (NPC1L1) has recently been identified and has been shown to have features of a plasma membrane transporter, including a secretion signal, 13 predicted transmembrane domains, extensive N-linked glycosylation sites and a sterol-sensing domain. It is highly expressed on the surface of absorptive jejunal enterocytes. NPC1L1 has been shown to be a direct target of ezetimibe, and an ezetimibe-sensitive pathway plays a role in intestinal cholesterol absorption. Ezetimibe-based therapy represents an exciting new area in the treatment of dyslipidemia.

Du XM, Irino N, Furusho N, Hayashi J, Shoyama Y. · Seiwa Pharmaceuticals Ltd., 1-12-15 Shiba-Daimon, Minato-ku, Tokyo, 105-8585, Japan. · Nat Med (Tokyo). · Pubmed #18404313 No free full text.

Abstract: The extract of Anoectochilus formosanus showed significant activity in decreasing the levels of the cytosolic enzymes LDH, GOT, and GPT, and the result demonstrated that A. formosanus possessed prominent hepatoprotective activity against CCl(4)-induced hepatotoxicity. Moreover, in the results of the test using aurothioglucose-induced obese mice, the extract showed a significant antihyperliposis effect. A. formosanus grown in the wild and propagated by tissue culture contain ten compounds, including a major known component, (3R)-3-(beta-D-glucopyranosyloxy)butanolide (kinsenoside; 1), and two new components, (3R)-3-(beta-D-glucopyranosyloxy)-4-hydroxybutanoic acid (2) and 2-[(beta-D-glucopyranosyloxy)methyl]-5-hydroxymethylfuran (3), along with the known compounds, isopropyl-beta-D-glucopyranoside (4), (R)-3,4-dihydroxybutanoic acid gamma-lactone (5), 4-(beta-D-glucopyranosyloxy) benzyl alcohol (6), (6R,9S)-9-(beta-D-glucopyranosyloxy)megastigma-4,7-dien-3-one (7), and (3R)-3-(beta-D-glucopyranosyloxy)-4-hydroxybutanolide (8). Since a higher concentration of kinsenoside (1) was detected in the crude drugs A. formosanus and A. koshunensis by high-performance liquid chromatography (HPLC) analysis, we proved a simple purification system for kinsenoside (1), giving 180 mg of kinsenoside (1) from 1 g of dried samples for further pharmacological experiments. In an anti-hyperliposis assay using high-fat-diet rats, 1 significantly reduced the weights of the body and the liver, and also decreased the triglyceride level in the liver compared to those of control rats. On the other hand, the epimer of 1, (3S)-3-(beta-D-glucopyranosyloxy)butanolide, goodyeroside A (9), which was isolated from the Goodyera species, had no effect for anti-hyperliposis. In aurothioglucose-induced obese mice, 1 suppressed the body and liver weight increase, significantly ameliorated the triglyceride level in the liver, and also reduced the deposition of uterine fat pads. The anti-hepatoxic activities of 9 and goodyerosides B (10) were studied on injury induced by CCl(4) in primary cultured rat hepatocytes by measuring the levels of LDH, GOT, and GPT. In the CCl(4)-treated control group, there were marked increases in LDH, GOT, and GPT activities compared with the normal group. In contrast, these levels were suppressed in 9- and 10-treated groups. Goodyerin (11), a new typical flavone glycoside, exhibited a significant and dose-dependent sedative and anticonvulsant effect.

Nadanaka S, Kitagawa H. · Department of Biochemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan. · J Biochem. · Pubmed #18367479 No free full text.

Abstract: Proteoglycans carrying heparan sulphate (HS) chains are ubiquitously expressed at cell surfaces and in extra-cellular matrices, and HS chains interact with numerous proteins, including growth factors, morphogens and extra-cellular-matrix proteins. These interactions form the basis of HS-related biological phenomena. Thus, the biosynthesis of HS regulates key events in embryonic development and homeostasis, and deranged HS biosynthesis could cause diseases. EXT1 and EXT2 genes encoding the polymerase responsible for HS biosynthesis are known as causative genes of hereditary multiple exostoses, a dominantly inherited genetic disorder characterized by the formation of multiple cartilaginous tumours. In this review, we will summarize HS biosynthesis in several model animals, the effects on cellular functions by alteration of HS biosynthesis, and HS-associated diseases. This review suggests that HS biosynthetic enzymes would be potential candidates for drug targets in various diseases.

Sadiq Butt M, Tahir-Nadeem M, Khan MK, Shabir R, Butt MS. · Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan. · Eur J Nutr. · Pubmed #18301937 No free full text.

Abstract: This review is intended to focus on the composition of oat and its therapeutic potential in the pharmacology that supports its use to cure various maladies. Oat (Avena sativa) is distinct among the cereals due to its multifunctional characteristics and nutritional profile. Recent advancement in food and nutrition has revealed the importance of its various components. It is a good source of dietary fiber especially beta-glucan, minerals and other nutrients. Oat and oat by products have been proven to be helpful in the treatment of diabetes and cardiovascular disorders. Oat bran in particular, is good source of B complex vitamins, protein, fat, minerals besides heart healthy soluble fiber beta-glucan. The beta-glucan has outstanding functional properties and is of immense importance in human nutrition. Different physiological effects of beta-glucan are related to its viscosity, attenuation of postprandial plasma glucose and insulin responses, high transport of bile acids towards lower parts of the intestinal tract and high excretion of bile acids thereby lowering of serum cholesterol levels. Moreover, it is helpful against coeliac disease. The incorporation of oat grains and oat bran in the food products improves not only the nutrition but also a therapy against various maladies.

Ikeda I. · Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Scicence, Tohoku University, Sendai, Japan. · Asia Pac J Clin Nutr. · Pubmed #18296354 No free full text.

Abstract: Tea catechins reduce serum cholesterol concentrations and suppress postprandial hypertriacylglycerolemia in experimental animals and humans. These effects are mainly ascribed to the gallate esters of catechins, (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG). During pasteurization of tea drinks, tea catechins are epimerized to so-called heat-treated tea catechins such as (-)-catechin gallate (CG) and (-)-gallocatechin gallate (GCG). We showed that both tea catechins and heat-treated tea catechins with the galloyl moiety lowered intestinal absorption of cholesterol by inhibiting micellar solubility of cholesterol. Since they inhibited pancreatic lipase in vitro and slowed down lymphatic absorption of triacylglycerols, it is suggested that delayed intestinal absorption of triacylglycerols after the feeding of catechin preparations causes suppression of postprandial hypertriacylglycerolemia. It has been reported that tea catechins and heat-treated tea catechins with the galloyl moiety suppress deposition of visceral fat in experimental animals and humans. Some studies suggest that the stimulation of hepatic beta-oxidation might be a cause for reduced deposition of visceral fat. However, our study did not show any acceleration of beta-oxidation in rat livers. Although there are some controversial observations, results obtained suggest a possibility that tea catechins and heat-treated tea catechins with the galloyl moiety improve lipid metabolism and contribute to the prevention of the metabolic syndrome.

Manna P, Sinha M, Sil PC. · Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata 700009, West Bengal, India. · Arch Toxicol. · Pubmed #18197399 No free full text.

Abstract: Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO2 was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO2 at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO2 intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property.

Kawano S, Kumagai S. · Department of Clinical Laboratory, Kobe University Hospital. · Nippon Rinsho. · Pubmed #18161157 No free full text.

This publication has no abstract.

Shamir R, Feig JE, Fisher EA. · Institute of Gastroenterology, Nutrition and Liver Diseases. Schneider Children's Medical Center of Israel, Israel. · Pediatr Endocrinol Rev. · Pubmed #18084159 No free full text.

Abstract: Hypercholesterolemia is associated with increased risk of premature cardiovascular disease in adults, while early atherosclerotic lesions (reversible fatty streaks and non reversible fibrous plaques) are also associated with cardiovascular risk factors including low density lipoprotein-cholesterol (LDL-C). Although LDL-C is a risk factor that should be addressed in high risk children such as those with familial hypercholesterolemia, it is unclear, at present, whether there is a certain plasma LDL-C level that would call for an intervention regardless of the etiology of elevated LDL-C. Therefore, at present, screening the entire population to identify subjects with hypercholesterolemia is not justified. The aims of this review are to familiarize the reader with inherited diseases that are associated with elevated LDL-C and discuss the management of children with elevated LDL-C.

Fukumoto Y, Shimokawa H. · Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #18074533 No free full text.

This publication has no abstract.

Yanai H, Tomono Y, Ito K, Furutani N, Yoshida H, Tada N. · Department of Internal Medicine, The Jikei University School of Medicine, Chiba, Japan. · Nutr J. · Pubmed #18072966 links to  free full text

Abstract: Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. The elevated fasting and postprandial triglyceride-rich lipoprotein levels is the central lipid abnormality observed in the metabolic syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective for fasting and postprandial hyperlipidemia and preventing excess adiposity by increasing postprandial energy expenditure. We will here discuss the mechanisms of DAG-mediated improvements in hyperlipidemia and in postprandial energy expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat. Further, the therapeutic application of DAG for the metabolic syndrome will be considered.

Harada E, Yasue H, Mizuno Y, Ito T, Sakaino N, Yasue S, Masuzaki H. · Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, 6-8-1 Yanamuro, Kumamoto City, Japan. · Am J Med Sci. · Pubmed #18030188 No free full text.

Abstract: The metabolic disorders associated with chronic hypoxemia in adult patients with tetralogy of Fallot (TOF) have not been fully appreciated. We report a 53-year-old male patient with TOF who presented with fasting hypoglycemia, hypertriglyceridemia, increased blood levels of free fatty acids, adiponectin, B-type natriuretic peptide, and uric acid. The cluster of these metabolic derangements has not been previously reported, and the possible role of chronic hypoxia in the production of these disturbances is discussed with a review of pertinent literatures.

Ito T. · Division of Cardiovascular Disease, Tokyo Teishin Hospital. · Nippon Rinsho. · Pubmed #17953022 No free full text.

This publication has no abstract.

Fusazaki T. · Department of Internal Medicine II, Iwate Medical University School of Medicine and Memorial Heart Center. · Nippon Rinsho. · Pubmed #17948700 No free full text.

This publication has no abstract.

Cerasi E, Ktorza A. · Service d'Endocrinologie et Métabolisme, Département de Médecine Interne, Centre Médical Hadassa, Université Hébraïque de Jérusalem, 91120 Jérusalem, Israël. · Med Sci (Paris). · Pubmed #17937902 No free full text.

Abstract: The most common form of diabetes, type 2 diabetes (T2D) is a major Public Health issue which is receiving a great deal of attention both in industrial and public research, in order to develop new and more effective drugs. The hyperglycaemia of T2D is the result of two interdependent defects : decreased biological efficacy of insulin in target tissues (insulin resistance), and a decreased capacity for beta cells to secrete insulin in response to glucose. Furthermore, hyperglycaemia evolves with time and even with rigorous treatment there is a progressive deterioration of glucose homeostasis. Seventy five percent of DT2 patients are obese and show a perturbed lipid profile. beta-cell plasticity is a unique property of these cells to adapt their number and volume (beta-cell mass) and their function to the increased secretory demand linked to insulin resistance. This is well documented in physiological (pregnancy) as well in pathophysiological conditions (obesity, acromegaly). Although the lack of reliable techniques makes it very difficult to document it in humans, this property is likely altered in DT2, mainly as a consequence of the prolonged exposure of islet cells to high plasma levels of glucose and free fatty acids (gluco-lipotoxicity). The mechanisms by which hyperglycaemia and hyperlipidemia exert their deleterious effects on the beta-cell include the generation of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and Advanced Glycosylation End Products (AGE). Altogether the prevailing clinical and experimental data urge us to consider that the pathophysiology of DT2 lies, at least in part, the inability of beta-cells to adapt their functional mass to the prevailing insulin demand. This re-evaluation of the pathophysiology of DT2 stimulates the research of new therapeutic approaches aimed at maintaining and/or restoring the functional beta-cell mass by targeting the mechanisms responsible for its decrease.