BDNF and GDNF serum levels in alcohol-dependent patients during withdrawal

Preclinical study results suggest that brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) modulate addictive behaviour. Therefore we investigated alterations in BDNF (81 male patients) and GDNF serum levels (52 male patients) in alcohol-dependent patients during alcohol withdrawal (day 1, 7 and 14) in comparison to healthy controls (41 male controls).     

Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi rats

Ethnopharmacological relevance

The use of an aqueous extract of coriander (Coriandrum sativum L.; Apiaceae, Umbelliferae) seeds (CS-extract) in Moroccan traditional treatment of diabetes remains to be experimentally validated.

Aim of the study

The study aim was to investigate potential hypoglycemic (and hypolipidemic) activity of CS-extract after a single oral dose and after daily dosing for 30 days (sub-chronic study) in normal and obese-hyperglycemic-hyperlipidemic (OHH) Meriones shawi rats.

Materials and methods

After a single oral dose of CS-extract (20 mg/kg; predetermined as optimum), plasma glucose, insulin, total cholesterol (TC), and triglycerides (TG) were measured in normal and OHH rats (hypercaloric diet and forced limited physical activity); glibenclamide (GLB; 2.5 mg/kg) was used as reference. In the sub-chronic study, the effect of CS-extract and GLB (at the above doses) on body weight (BW), plasma glucose, insulin, TC, LDL-cholesterol, HDL-cholesterol, TG, urea and creatinine was determined in normal and OHH rats; insulin resistance (IR as HOMA-IR), atherosclerotic and cardioprotective indices were calculated.

Results

A single dose of CS-extract or GLB suppressed hyperglycemia in OHH rats, and normo-glycemia was achieved at 6-h post-dose; there was no effect on lipids, TG or insulin, but IR decreased significantly. The hypoglycemic effect was lower in normal rats. In the sub-chronic study in OHH rats, the test substances (CS-extract > GLB) reduced plasma glucose (normoglycemia on Day 21), insulin and IR, TC, LDL-cholesterol, and TG. Atherosclerotic index decreased while cardioprotective indices increased only by CS-extract, with no effect on BW, urea or creatinine.

Conclusion

Sub-chronic administration of CS-extract in OHH Meriones shawi rats normalized glycemia and decreased the elevated levels of insulin, IR, TC, LDL-cholesterol and TG. Since, the CS-extract decreased several components of the metabolic syndrome and decreased atherosclerotic and increased cardioprotective indices, CS-extract may have cardiovascular protective effect. The present study validates the traditional use of coriander in diabetes.     

Few favorable associations between fruit and vegetable intake and biomarkers for chronic disease risk in American adults

Using 24-hour dietary recall data from the National Health and Nutrition Examination Survey 1999 to 2006, the possible link between fruit and vegetable intake and chronic disease risk was assessed. C-reactive protein (CRP), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), total cholesterol, and glycosylated hemoglobin were selected as biomarkers for chronic disease risk. It is hypothesized that individuals who consume more fruits and vegetables will have reduced chronic disease risk because of the healthful benefits of these foods. The objective of this study was to examine the relationship between fruit and vegetable consumption on selected biomarkers for chronic disease risk. Although some associations were significant for FPG, HDL-C, and low-density lipoprotein cholesterol in some of the models, no trend was present. After adjusting for demographic factors, socioeconomic factors, lifestyle factors, body mass index, total energy intake, and the presence of at least 1 of our 5 predetermined comorbidities, no associations of reduced or increased risk were observed in any quartiles of combined fruit and vegetable intake. Fruit and vegetable intakes were weakly associated with an increased HDL-C level and decreased FPG, glycosylated hemoglobin, and C-reactive protein levels in some of the models; however, no association was observed in the final model. Because selected biomarkers of future disease risk remained in reference ranges at both high and low intake and no significance was observed in the final model, no protective association was observed between fruit and vegetable intake and biomarkers for chronic disease risk. However, fruit and vegetable consumption is recommended as part of an overall healthy diet and to displace other energy-dense foods for weight maintenance, which can lead to a decrease in future disease risk.     

Pantethine, a derivative of vitamin B5 used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation

Safety and efficacy of a biologically active derivative of vitamin B₅ (pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that pantethine would lower TC and low-density lipoprotein in low-CVD-risk North American subjects in a similar manner as reported in high-CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, pantethine demonstrated significant (P < .005) and sustained reductions (from baseline to week 16) in TC (6 mg/dL, 0.16 mmol/L, 3%), LDL-C (4 mg/dL, 0.10 mmol/L, 4%), and apolipoprotein B (4 mg/dL, 0.04 g/L, 5%). Our data suggest that pantethine supplementation for 16 weeks (600 mg/d for weeks 1-8 then 900 mg/d for weeks 9-16) is safe and significantly lowers TC and LDL-C over and above the effect of TLC diet alone. Although the absolute magnitude of these effects was small in these low- to moderate-risk North Americans (4-6 mg/dL), the results are noteworthy as prior studies have shown that, for each 1 mg/dL (0.026 mmol/L) reduction in LDL-C, there is a concomitant 1% reduction in overall future CVD risk.     

脂肝康药效学研究

目的：观察脂肝康对动物实验性脂肪肝的治疗作用。方法：采用乙硫氨酸、高脂饲料复制动物脂肪肝模型,iv高分子右旋糖苷复制大鼠“血瘀”模型,观察脂肝康的作用。结果：脂肝康能明显降低实验性脂肪肝动物肝脏、血液中的总胆固醇（TC）、三酰甘油（TG）的量;明显抑制“血瘀”大鼠全血粘度的升高。结论：脂肝康对脂肪肝大鼠有明显的治疗作用。     

游离脂肪酸对βTC6细胞葡萄糖刺激胰岛素分泌的影响及吡格列酮的干预作用

目的：观察游离脂肪酸（FFA）对体外培养的βTC6细胞胰岛素分泌功能的影响及盐酸吡格列酮作用的干预。方法：体外培养βTC6细胞,0.5mmol/LFFA分别干预1h、48h,放射免疫法检测胰岛素。不同浓度的吡格列酮（0.1、1.0、10.0μmol/L）与FFA共同干预βTC6细胞48h,放射免疫法检测胰岛素浓度。结果：FFA干预1h后,βTC6细胞的葡萄糖刺激的胰岛素分泌（GSIS）增加（P〈0.05）,FFA干预48h后,βTC6细胞的GSIS较干预前下降（P〈0.05）。FFA与吡格列酮共同干预时,随着吡格列酮浓度的升高,GSIS呈上升的趋势,1.0μmol/L和10.0μmol/吡格列酮与FFA共同干预组GSIS较FFA干预48h增加（P〈0.05）。结论：FFA对B细胞具有短期刺激作用及脂毒性作用,吡格列酮可以部分改善脂毒性作用。     

Validation of connectivity-based thalamic segmentation with direct electrophysiologic recordings from human sensory thalamus

Connectivity-based segmentation has been used to identify functional gray matter subregions that are not discernable on conventional magnetic resonance imaging. However, the accuracy and reliability of this technique has only been validated using indirect means. In order to provide direct electrophysiologic validation of connectivity-based thalamic segmentations within human subjects, we assess the correlation of atlas-based thalamic anatomy, connectivity-based thalamic maps, and somatosensory evoked thalamic potentials in two adults with medication-refractory epilepsy who were undergoing intracranial EEG monitoring with intrathalamic depth and subdural cortical strip electrodes. MRI with atlas-derived localization was used to delineate the anatomic boundaries of the ventral posterolateral (VPL) nucleus of the thalamus. Somatosensory evoked potentials with intrathalamic electrodes physiologically identified a discrete region of phase reversal in the ventrolateral thalamus. Finally, DTI was obtained so that probabilistic tractography and connectivity-based segmentation could be performed to correlate the region of thalamus linked to sensory areas of the cortex, namely the postcentral gyrus. We independently utilized these three different methods in a blinded fashion to localize the “sensory” thalamus, demonstrating a high-degree of reproducible correlation between electrophysiologic and connectivity-based maps of the thalamus. This study provides direct electrophysiologic validation of probabilistic tractography-based thalamic segmentation. Importantly, this study provides an electrophysiological basis for using connectivity-based segmentation to further study subcortical anatomy and physiology while also providing the clinical basis for targeting deep brain nuclei with therapeutic stimulation. Finally, these direct recordings from human thalamus confirm early inferences of a sensory thalamic component of the N18 waveform in somatosensory evoked potentials.     

Combined use of high-sensitivity C-reactive protein and apolipoprotein B/apolipoprotein A-1 ratio prior to elective coronary angiography and oral glucose tolerance tests

Objectives

The study aimed to investigate the predictive value of the combination of high-sensitivity C-reactive protein (hs-CRP) and apolipoprotein B (apoB)/apoA-1 ratio for the outcomes of coronary angiography (CAG), echocardiography and oral glucose tolerance tests (OGTTs).

Design and methods

Hs-CRP, apoB, apoA-1, and the profiles of CAG, echocardiography and OGTTs as well as traditional risk factors were measured in 1757 cardiology patients.

Results

Hs-CRP or apoB/apoA-1 ratio was significantly correlated with the presence and severity of angiographic profiles, the levels of left ventricular (LV) ejection fraction, LV mass and LV mass index, and the presence of abnormal glucose metabolism. The combination of hs-CRP and apoB/apoA-1 ratio had greater correlation with abnormal glucose metabolism than its individual components in patients with normal fasting glucose, and was an independent predictor for coronary artery disease.

Conclusions

The combination of hs-CRP and apoB/apoA-1 ratio may be a strong predictor for coronary artery disease and abnormal glucose metabolism.     

The H₁-H₂ domain of the α₁ isoform of Na+-K+-ATPase is involved in ouabain toxicity in rat ventricular myocytes

Metals and metalloid species are involved in homeostasis in energy systems such as glucose metabolism. Enlarged adipocytes are one of the most important causes of obesity-associated diseases. In this study, we studied the possibility that various metals, namely, CoCl₂, HgCl₂, NaAsO₂ and MnCl₂ pose risk to or have beneficial effects on white adipose tissue (WAT). Exposure to the four metals resulted in decreases in WAT weight and the size of enlarged adipocytes in mice fed a high-fat diet (HFD) without changes in liver weight, suggesting that the size and function of adipocytes are sensitive to metals. Repeated administration of CoCl₂ significantly increased serum leptin, adiponectin and high-density lipoprotein (HDL) cholesterol levels and normalized glucose level and adipose cell size in mice fed HFD. In contrast, HgCl₂ treatment significantly decreased serum leptin level with the down-regulation of leptin mRNA expression in WAT and a reduction in adipocyte size. Next, we tried to investigate possible factors that affect adipocyte size. Repeated exposure to HgCl₂ significantly decreased the expression levels of factors upon the regulation of energy such as the PPARα and PPARγ mRNA expression levels in adipocytes, whereas CoCl₂ had little effect on those genes expressions compared with that in the case of the mice fed HFD with a vehicle. In addition, repeated administration of CoCl₂ enhanced AMPK activation in a dose-dependent manner in the liver, skeletal muscle and WAT; HgCl₂ treatment also enhanced AMPK activation in the liver. Thus, both Co and Hg reduced WAT weight and the size of enlarged adipocytes, possibly mediated by AMKP activation in the mice fed HFD. However, inorganic cobalt may have a preventive role in obesity-related diseases through increased leptin, adiponectin and HDL-cholesterol levels, whereas inorganic mercury may accelerate the development of such diseases. These results may lead to the development of new approaches to establishing the role of metals in adipose tissue of obesity-related diseases.