Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice.

Excessive body fat and the related dysmetabolic diseases affect both developed and developing countries. The aim of this study was to investigate the beneficial role of a bacterial culture supernatant (hereafter: BS) of Lactobacillus and Bifidobacterium and their potential mechanisms of action on white-fat browning and lipolysis. For selection of four candidates among 55 Lactic acid producing bacteria (LAB) from human infant faeces, we evaluated by Oil Red O staining and Ucp1 mRNA quantitation in 3T3-L1 preadipocytes. The expression of browning and lipolysis markers was examined along with in vitro assays. The possible mechanism was revealed by molecular and biological experiments including inhibitor and small interfering RNA (siRNA) assays. In a mouse model, physiological, histological, and biochemical parameters and expression of some thermogenesis-related genes were compared among six experimental groups fed a high-fat diet and one normal-diet control group. The results allow us to speculate that BS treatment promotes browning and lipolysis both in vitro and in vivo. Moreover, the BS may activate thermogenic programs via a mechanism involving PKA-CREB signaling in 3T3-L1 cells. According to our data, we can propose that two LAB strains, Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508, may be good candidates for a dietary supplement against obesity and metabolic diseases; however, further research is required for the development as dietary supplements or drugs.

Onset time of hyperkalaemia after angiotensin receptor blocker initiation: when should we start serum potassium monitoring?

WHAT IS KNOWN AND OBJECTIVE: Angiotensin receptor blockers (ARBs) frequently induce hyperkalaemia in high-risk patients. Early detection of hyperkalaemia can reduce the subsequent harmful effects. This study was performed to examine the onset time of hyperkalaemia after ARB therapy. METHODS: We carried out a retrospective analysis to determine the onset time of hyperkalaemia (serum potassium >5·5 mm) among hospitalized patients newly starting ARB therapy between 2004 and 2012, in a tertiary teaching hospital. Predefined possible risk factors and concomitant medications were evaluated. RESULTS AND DISCUSSION: During the 97-month study period, a total of 4267 hospitalized patients started ARBs as new drugs and 225 patients showed hyperkalaemia. A significantly increased risk of hyperkalaemia was detected among patients with a high baseline potassium [odds ratio (OR) 6·0] and those who took non-potassium-sparing diuretics (OR 2·2) or potassium supplements (OR 1·6). A high glomerular filtration rate (GFR) was associated with a lower risk of hyperkalaemia (OR 0·992). Fifty-two percentage of hyperkalaemic events occurred within the first week after initiation of ARB therapy. The highest frequency of hyperkalaemia occurred on the first day after initiation of ARBs. Hyperkalaemia occurred earlier in patients with a high baseline serum potassium level, reduced GFR, diabetes and in those without heart failure. WHAT IS NEW AND CONCLUSION: Hyperkalaemia occurs most frequently at the beginning of ARB therapy in hospitalized patients. Monitoring of serum potassium and estimated GFR after initiation of ARBs should be started within a few days or not later than 1 week, especially in patients with risk factors.

Asarone inhibits adipogenesis and stimulates lipolysis in 3T3-L1 adipocytes.

Asarone is a molecule found in certain plants such as Acorus calamus, the root of which is used in traditional medicine to treat diabetes. We determined the molecular mechanism underlying the anti-diabetic activity of asarone. Treatment of asarone significantly inhibited the differentiation of 3T3-L1 preadipocytes through suppression of expression of the transcription factors, CCAAT/enhancer binding protein-alpha and peroxisome proliferator activated receptor-gamma, which activate adipogenesis. Intracellular triglyceride levels were reduced by asarone in a dose-dependent manner and asarone treatment stimulated the phosphorylation of hormone-sensitive lipase. Together, the present findings indicate that asarone inhibits adipogenesis by down-regulation of PPARgamma and C/EBPalpha and reduces lipid accumulation by stimulation of lipolysis through an increase in hormone-sensitive lipase activity.

Controllable dimension of ZnO nanowalls on GaN/c-Al2O3 substrate by vapor phase epitaxy method.

Vertically well-aligned ZnO nanowalls were successfully synthesized at 950-1050 degrees C. Ar gas was introduced into the furnace at a flow rate of 2000-2500 sccm. An Au thin film with a thickness of 3 nm was used as a catalyst. The ZnO nanowalls were successfully grown on the substrate and most of them had nearly the same thickness and were oriented perpendicular to the substrate. The morphology and chemical composition of the ZnO nanowalls were examined as a function of the growth conditions examined. It was found that the grown ZnO nanowalls have a single-crystalline hexagonal structure and preferred c-axis growth orientation based on the X-ray diffraction and high-resolution transmission electron microscope measurements. The room temperature photoluminescence showed a strong free-exciton emission band with negligible deep level emission, indicating the high optical property of our ZnO nanowall samples.

Effect of dietary supplementation with conjugated linoleic acid, with oleic, linoleic, or linolenic acid, on egg quality characteristics and fat accumulation in the egg yolk.

The effects of conjugated linoleic acid (CLA) with other fatty acids on the fatty acid composition of egg yolk and on egg quality characteristics were studied in 5 groups: 1) CLA 0% (control), 2) CLA 2%, 3) CLA 2%+oleic acid (OA) 2% (CLA+OA), 4) CLA 2%+linoleic acid (LA) 2% (CLA+LA), and 5) CLA 2%+alpha-linolenic acid (LNA) 2% (CLA+LNA). Some parameters of egg quality such as shell thickness, shell strength, yolk color, yolk index, egg diameter, and Haugh units were aggravated when CLA was fed alone, but the quality was improved when CLA was combined with some other fatty acids. The egg production rate, which was decreased by feeding CLA alone, was improved by co-supplementation with LA or OA. An increase in CLA content was observed in all the dietary groups fed CLA for 2 wk. Feeding hens with CLA+LNA led to a linear increase in CLA content in the egg yolk after the fourth week of the feeding trial. Egg yolks from hens given CLA had considerably higher amounts of saturated fatty acids and lower amounts of monounsaturated fatty acids than egg yolks from the control group. The pattern of change in CLA concentration during the feeding trial was similar to the level of C18:0, which was inversely correlated with the level of C18:1. The unsaturated fatty acid co-supplementation strategy applied in this study offers insight into the mechanism of CLA accumulation in the egg yolk without apparent adverse effects on egg quality and egg production.

Effect of bioflavonoids extracted from the bark of Pinus maritima on proinflammatory cytokine interleukin-1 production in lipopolysaccharide-stimulated RAW 264.7.

Currently, bioflavonoids have been known to have strong antioxidant capacities, and a variety of efforts have been made to identify the utilities of bioflavonoids in treating various diseases based on their antioxidant capacities. The effects of bioflavonoids extracted from the bark of Pinus maritima Pycnogenol (PYC) on free radical formation, activation of redox sensitive transcription factors, as well as interleukin-1 beta (IL-1 beta) production were investigated in murine macrophage cell lines. PYC exerted strong scavenging activities against reactive oxygen species generated either by H(2)O(2) or PMA in RAW 264.7 and IC-21 cells, respectively. In situ ELISA, immunoblot analysis, and competitive RT-PCR demonstrated that PYC pretreatment of LPS-stimulated RAW 264.7 cells dose-dependently reduced both the production of IL-1 beta and its mRNA levels. Furthermore, in the same cells, PYC blocked the activation of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1), two major transcription factors centrally involved in IL-1 beta gene expression. When RAW 264.7 cells were stimulated with LPS, the inhibitor protein I kappa B largely disappeared from cytosolic fractions. However, pretreatment of the cells with PYC abolished the LPS-induced I kappa B degradation. These results suggest that PYC can inhibit the expression of the proinflammatory cytokine IL-1 by regulating redox-sensitive transcription factors. This study may support the possibility that bioflavonoids including PYC can be used as antiinflammatory and immunosuppressive drugs based on their radical scavenging activities.

Allium sativum potentiates suicide gene therapy for murine transitional cell carcinoma.

This study evaluated the synergistic effect of Allium sativum (AS) with suicide gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS liquid extract was injected at the site of tumor transplantation on Day 1 for three weeks (Experiment I) and into the established tumors weekly for five weeks (Experiment II) in combination with or without gene therapy using a replication-defective adenoviral vector containing a herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV) promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20 mg/kg/day i.p.). AS demonstrated a statistically significant reduction in incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene therapy significantly inhibited the tumor growth compared with the controls, which was evidenced by apoptosis on histomorphological and immunohistochemical studies. These results suggest that AS had a definite antitumor effect in inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment combined with suicide gene therapy had significant additive antitumor effects on TCC and may provide a novel and effective treatment modality for TCC of the bladder.

Do dialysis patients need extra folate supplementation?

To assess folate status and to evaluate the need for conventional folate supplementation in patients on dialysis, we measured serum folate, vitamin B12, and red cell folate concentrations by radioimmunoassay. Thirty-four continuous ambulatory peritoneal dialysis (CAPD) patients and 60 hemodialysis (HD) patients who had not been supplemented with folate were enrolled. Serum folate levels (5.8 +/- 3.6 ng/mL vs 2.0 +/- 1.1 ng/mL, p < 0.001) and vitamin B12 levels (831.4 +/- 416.9 pg/mL vs 513.9 +/- 213.3 pg/mL, p < 0.001) were significantly higher in CAPD patients than HD patients. The red cell folate levels (849.7 +/- 489.4 ng/mL vs 491.0 +/- 253.2 ng/mL, p < 0.001) were also significantly higher in CAPD patients. The incidences of folate deficiency in CAPD and HD patients were overestimated using the cut-off value for serum folate concentration (3.0% vs 71.7%, respectively), but the incidence of true folate deficiency was lower using the cut-off value for red cell folate level (0.0% vs 10.0%, respectively). In conclusion, the true incidence of folate deficiency in stable CAPD and HD patients is surprisingly low, even in patients who may not be taking folate supplements. The need for conventional folate supplementation in patients with end-stage renal disease on dialysis must therefore be re-evaluated. Before the decision is made to use folate supplementation, measurement of red cell folate is essential to assess of folate reserves of the patients on dialysis.

The 170 kDa glucose regulated stress protein is a large HSP70-, HSP110-like protein of the endoplasmic reticulum.

The existence of a family of unusually large and highly diverged hsp70-like proteins (the hsp110/SSE family) has recently been described. The 170 kDa glucose regulated stress protein (grp170) is a retained endoplasmic reticulum glycoprotein that may be involved in immunoglobulin folding and/or assembly. We describe here the cloning of the cDNA for grp170 and show that it, like hsp110, is a large and highly diverged hsp70-like polypeptide which shares specific features with hsp70 (the dnaK family) and the hsp110/SSE family, while also differing from both. Grp170 contains an ATP binding domain and binds ATP, it possesses a carboxyl terminal NDEL sequence, and its mRNA is anoxia inducible.

Morbidity and mortality in the martial arts: a warning.

Approximately 1.5 to 2 million Americans participate in the martial arts. Injury anecdotes are reported from 10 years of providing medical coverage at martial arts activities. Included are data from two national Tae Kwon Do tournaments, one adult and one junior level. Previously unreported injuries, including a video-recorded fatality, demonstrate the danger inherent in participation. Of particular concern is the potential for serious neurologic injury. Recommendations are made for reducing the severity and frequency of injuries.

Adrenal function in thalassemia major following long-term treatment with multiple transfusions and chelation therapy. Evidence for dissociation of cortisol and adrenal androgen secretion.

Eight patients with beta-thalassemia who were given long-term treatment with combined multiple transfusions and chelation therapy underwent adrenal testing. The six male and two female patients ranged in age from 7 to 19 years. Six of eight patients had delayed bone ages and height greater than 2.5 SDs below the mean. Of the six patients more than 13 years of age, two had clinical evidence of isolated adrenarche and only one had evidence of true puberty. Cortisol levels were similar in patients and controls at zero time (10.6 +/- 1.8 micrograms/dL [292 +/- 50 nmol/L] vs 10.8 +/- 1.4 micrograms/dL [298 +/- 39 nmol/L]) and at 60 minutes (26.6 +/- 2.5 micrograms/dL [734 +/- 69 nmol/L] vs 24.9 +/- 1.9 micrograms/dL [687 +/- 52 nmol/L]) after insulin hypoglycemia (all values are the mean +/- SE). During an eight-hour infusion of ACTH, cortisol responses in the patients with thalassemia were not significantly different from those of controls. Baseline levels of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were significantly lower in the subjects with thalassemia compared with controls of similar bone age and pubertal status. The prolonged ACTH infusion caused a significant increase in the DHEA level (79.2 +/- 14.7 ng/dL [2.74 +/- 0.51 nmol/L] vs 538.6 +/- 38.1 ng/dL [18.67 +/- 4.79 nmol/L]) and the DHEA-S level (37.5 +/- 10.8 micrograms/dL [1.02 +/- 0.29 mumol/L] vs 70.5 +/- 18.3 micrograms/dL [1.19 +/- 0.50 mumol/L]) in the patients. The patients' peak stimulated levels of DHEA-S were significantly lower than those of the controls, whereas peak levels of DHEA were similar in the patients and the controls. These results indicate that combined multiple transfusions and chelation therapy preserve the integrity of the ACTH-cortisol axis in patients with thalassemia. The reduced levels of adrenal androgens, short stature, and delayed puberty noted in our patients suggest, however, that alternative approaches to the therapy of thalassemia are needed.

Some effects of acupuncture at Jen Chung (Go-26) on cardiovascular dynamics in dogs.

The cardiovascular effects of two types of acupuncture, needling with twirling and moxibustion by electrocautery, at Jen Chung (Go-26) were studied in dogs with chronically implanted electromagnetic flowmeter probes, during 0.75% halothane anesthesia with a succinylcholine drip to allow controlled ventilation. Cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, acid-base and blood gases were measured over a two hour period. During and following moxibustion by electrocautery at Jen Chung (Go-26) there was a generally significant increase (5% level) in cardiac output and stroke volume and an initially significant increase in heart rate, mean arterial pressure and pulse pressure. There was a significant decrease in total peripheral resistance following moxibustion by electrocautery and an initially significant decrease in total peripheral resistance following moxibustion by electrocautery and an initially significant decrease in total peripheral resistance following needling with twirling. It was observed in this investigation that moxibustion by electrocautery at Jen Chung (Go-26) produced more significant changes in cardiovascular dynamics in dogs than needling with twirling.