Microsomal triglyceride transfer protein gene expression and ApoB secretion are inhibited by bitter melon in HepG2 cells

Momordica charantia or bitter melon is traditionally used as an antidiabetic agent in Asia, Africa, and South America. Recent studies indicate that bitter melon can also lower plasma lipids and VLDL in diabetic animal models as well as animals fed a high-fat diet, suggesting an effect on lipoprotein metabolism. The aim of this study was to delineate the cellular and molecular mechanisms involved in the lipid-lowering properties of bitter melon and regulation of apolipoprotein B (apoB). Human hepatoma cells, HepG2, treated with bitter melon juice (BMJ) for 24 h reduced apoB secretion with and without the addition of lipids (P < 0.05). However, BMJ did not increase apoB secretion in cells treated with N-acetyl-leucyl-leucyl-norleucinal, indicating a lack of effect on the proteasomal degradation pathway. BMJ reduced the secretion of new triglycerides (P < 0.05) and decreased microsomal triglyceride transfer protein (MTP) mRNA expression, suggesting that lipid bioavailability and lipidation of lipoprotein assembly are likely involved in decreased apoB secretion. Interestingly, BMJ increased the nuclear translocation of the mature form of sterol regulatory element-binding protein-1c (SREBP-1c, P < 0.05), involved in MTP secretion. Our data suggest that BMJ is a potent inhibitor of apoB secretion and TG synthesis and secretion that may be involved in the plasma lipid- and VLDL-lowering effects observed in animal studies.     

Measurement of cardiac output with first-pass determination during rubidium-82 PET myocardial perfusion imaging

In addition to providing useful clinical information, cardiac output determined during rubidium-82 positron emission tomography (PET) myocardial perfusion studies can be used in the measurement of absolute regional myocardial blood flow using Sapirstein's method. This investigation was conducted to compare cardiac output values obtained by post-processing data acquired in a list mode PET myocardial perfusion study with those obtained using a technetium-99m-labeled red blood cell method on the same patients. Results from 14 patients showed that cardiac output can be accurately measured simultaneously in a⁸²Rb PET myocardial study, allowing determination of multiple perfusion and functional parameters of the heart, thus improving the cost-effectiveness of the⁸²Rb PET study.     

Synthesis of 1-methyl-5-(pyrazol-3- and -5-yl- and 1, 2, 4-triazol-3- and 5-yl)-1, 2, 3, 6-tetrahydropyridine derivatives and their evaluation as muscarinic receptor ligands

A series of 1-methyl-5-(pyrazol-3- and -5-yl- and 1, 2, 4-triazol-3- and 5-yl)-1, 2, 3, 6-tetrahydropyridine derivatives structurally related to arecoline were synthesized and evaluated on M(1), M(2), and M(3) muscarinic receptors using [(3)H] pirenzepine and [(3)H] NMS as ligands. The binding affinity depended on the position and size of the substituents. The most interesting compounds were further evaluated in functional studies on isolated organs and in vivo for cholinergic side effects. Compounds 5 l and 6 i good M(1) and M(3) antagonistic properties in vitro and were devoid of cholinergic side effects in vivo.     

Synthesis of some new 2,5-disubstituted 1,3,4-thiadiazoles containing isomeric pyridyl as potent antimicrobial agents

Several new 2,5-disubstituted derivatives of 1,3,4-thiadiazoles containing isomeric pyridyl were obtained from cyclization of corresponding thiosemicarbazides under acidic conditions. The newly synthesized compounds were characterized using different methods of spectroscopy such as IR, 1H-NMR, 13C-NMR, MS and elemental analysis. The minimal inhibitory concentration (MIC) results of screening of some of the synthesized compounds were also reported. Most of the synthesized compounds have been found to be active against both Gram-positive and Gram-negative bacteria at less than 3.6 mg/ml. The compound (10b) is most active against all seventeen used gram-positive and gram-negative bacteria.     

Fructose, insulin resistance, and metabolic dyslipidemia

Obesity and type 2 diabetes are occurring at epidemic rates in the United States and many parts of the world. The "obesity epidemic" appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in the amount of dietary fructose consumption from high intake of sucrose and high fructose corn syrup, a common sweetener used in the food industry. A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG) synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism. These metabolic disturbances appear to underlie the induction of insulin resistance commonly observed with high fructose feeding in both humans and animal models. Fructose-induced insulin resistant states are commonly characterized by a profound metabolic dyslipidemia, which appears to result from hepatic and intestinal overproduction of atherogenic lipoprotein particles. Thus, emerging evidence from recent epidemiological and biochemical studies clearly suggests that the high dietary intake of fructose has rapidly become an important causative factor in the development of the metabolic syndrome. There is an urgent need for increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb the supplementation of packaged foods with high fructose additives. The present review will discuss the trends in fructose consumption, the metabolic consequences of increased fructose intake, and the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia.     

Intestinal assembly and secretion of highly dense/lipid-poor apolipoprotein B48-containing lipoprotein particles in the fasting state: evidence for induction by insulin resistance and exogenous fatty acids

Emerging evidence suggests that overproduction of intestinally derived apolipoprotein (apo) B48-containing lipoprotein particles may be an important contributor to both fasting and postprandial dyslipidemia in insulin-resistant states. Mechanisms regulating the assembly and secretion of apoB48-containing lipoproteins are not fully understood particularly in the diabetic/insulin-resistant intestine. In the present study, we have investigated the density profile of apoB48 lipoproteins assembled in primary hamster enterocytes. Both intracellular and secreted apoB48 particles were examined in intestinal enterocytes isolated from normal or insulin-resistant fructose-fed hamsters, as well as in enterocytes treated with exogenous oleic acid. Microsomal luminal contents and culture media were analyzed by discontinuous and sequential ultracentrifugation on sucrose and KBr gradients, respectively. ApoB48 was mostly secreted on VLDL-, LDL-, and denser HDL-sized particles in the fasting state. In pulse-chase labeling experiments, nascent apoB48-containing particles initially accumulated in the microsomal lumen as HDL-sized particles, with subsequent formation of apoB48-VLDL particles, with only a minute amount of chylomicrons observed. Treatment with 720 mu mol/L of oleic acid, increased microsomal apoB48 HDL synthesis, and induced a marked shift toward lighter more buoyant particles. A marked enhancement in assembly of apoB48-containing lipoproteins was also observed in the microsomal lumen of fructose-fed hamster enterocytes, suggesting facilitated assembly and secretion of dense intestinal lipoprotein particles in insulin-resistant states. Overall, these observations suggest that a major proportion of apoB48-containing lipoprotein particles is assembled and secreted as highly dense, HDL-sized particles. The production of these small, dense, and potentially atherogenic apoB48 particles can be stimulated by increased free fatty acid flux as well as in insulin-resistant diabetes.     

Non-COX-2 targets and cancer: expanding the molecular target repertoire of chemoprevention

Chemoprevention represents a highly promising approach for the control of cancer. That nonsteroidal anti-inflammatory drugs (NSAIDs) prevent colon and other cancers has led to novel approaches to cancer prevention. The known inhibitory effect of NSAIDs on the eicosanoid pathway prompted mechanistic and drug development work focusing on cyclooxygenase (COX), culminating in clinical trials of cyclooxygenase 2 (COX-2) inhibitors for cancer prevention or treatment. However, two COX-2 inhibitors have been withdrawn due to side effects. Here we review several pathways of the eicosanoid cascade that are relevant to cancer; summarize the evidence regarding the role of COX-2 as a target for cancer prevention; and discuss several of the molecular targets that may mediate the chemopreventive effect of NSAIDs. The clinically modest results obtained to date with COX-2 specific inhibitors used in cancer prevention; the multiple COX-2-independent targets of both NSAIDs and COX-2 inhibitors; and the limitations of some COX-2 inhibitors indicate that exploiting these (non-COX-2) molecular targets will likely yield effective new approaches for cancer chemoprevention.     

SCHWIND AMARIS准分子激光联合丝裂霉素C行LASEK术矫治远视的研究

目的：评估SCHWIND AMARIS准分子激光在LASEK术中矫治远视手术中的有效性,安全性和可预测性。

方法：回顾性研究LASEK术联合使用丝裂霉素C矫治远视患者33例66眼,平均年龄35.42±1.12岁(范围 18～56a)。每位患者予SCHWIND AMARIS准分子激光行LASEK术。术后对其可预测性、安全性、有效性及主观验光情况进行评估,并分析客观验光、裸眼视力、最佳矫正视力及不良反应。

结果：平均屈光度为3.2±1.6D(0～7D),术前及术后平均等效球镜分别为2.34±1.76D(-1.25～7D)及0.30±0.84D(-0.2～0.8D)(P=0.001)。术后6～12mo,平均远视为0.63±0.84D(-1.75～2.76D)。平均散光度为0.68±0.43D(0～2D),61眼(78.2%)和31眼(39.7%)散光度分别在±1D和±0.50D范围内。安全指数和有效性指数分别为1.08和1.6。

结论：应用SCHWIND AMARIS准分子激光联合丝裂霉素C行LASEK术矫治远视具有良好的视觉和屈光结果,而且无严重并发症。     

Gender and asthma-chronic obstructive pulmonary disease overlap syndrome

Objective: To assess relationships between obstructive lung diseases, respiratory symptoms, and comorbidities by gender. Methods: Data from 12?594 adult respondents to the 2012 South Carolina Behavioral Risk Factor Surveillance System telephone survey were used. Five categories of chronic obstructive airway disease (OAD) were defined: former asthma only, current asthma only, chronic obstructive pulmonary disease (COPD) only, asthma-COPD overlap syndrome (ACOS), and none. Associations of these categories with respiratory symptoms (frequent productive cough, shortness of breath, and impaired physical activities due to breathing problems), overall health, and comorbidities were assessed using multivariable logistic regression for men and women. Results: Overall, 16.2% of men and 18.7% of women reported a physician diagnosis of COPD and/or asthma. Former asthma only was higher among men than women (4.9% vs. 3.2%, t-test p = 0.008). Current asthma only was more prevalent among women than men (7.2% vs. 4.7%, p < 0.001), as was ACOS (4.0% vs. 2.2%, p < 0.001). Having COPD only did not differ between women (4.3%) and men (4.4%). Adults with ACOS were most likely to report the 3 respiratory symptoms. COPD only and ACOS were associated with higher likelihoods of poor health and most comorbidities for men and women. Current asthma only was also associated with these outcomes among women, but not among men. Conclusions: In this large population-based sample, women were more likely than men to report ACOS and current asthma, but not COPD alone. Gender differences were evident between the OAD groups in sociodemographic characteristics, respiratory symptoms, and comorbidities, as well as overall health.