Leptin Increasing Sympathetic Nerve Outflow in Obesity: A Cure for Obesity or a Potential Contributor to Metabolic Syndrome?

Leptin increasing sympathetic nerve outflow in obesity: A cure for obesity or a potential contributor to metabolic syndrome?

Adipocyte. 2012 Jul 1; 1(3): 177-181
Simonds SE, Cowley MA, Enriori PJ

Obesity is a global problem and effective drug therapy treatment is still unavailable. Obesity develops due to an imbalance between energy intake and energy expenditure (EE). Understanding what happens to EE in obesity may be the key to developing new treatments for obesity. If EE in obesity can be elevated, it could be a potential therapeutic target. We recently discovered that in baseline conditions obese mice have increased EE, in terms of thermogenesis. However, this increase in EE is not great enough to offset the elevated calorie intake that leads to the development of obesity. In obesity, the adipose derived hormone leptin is significantly elevated. This elevated leptin concentration appears to cause an increase in thermogenesis through increased sympathetic nerve activity (SNA) to brown adipose tissue deposits. The brain region of the dorsomedial hypothalamus (DMH) appears to be a key region that leptin activates in obesity to cause this increased thermogenesis. One unsettling finding is that the sympathetic nervous system (SNS) in obesity is elevated via leptin and it seems unlikely that SNA would be selectivity increased to only brown adipose tissue. Previously, it has been observed that leptin can increase SNA to numerous organs including the kidney. Furthermore, in obesity, SNA is increased in numerous organs. This leads to the critical question: is the leptin-mediated elevation of SNA and thermogenesis also chronically activating the kidney and contributing to the development of hypertension in obesity? HubMed – drug

Quantitative dynamics of adipose cells.

Adipocyte. 2012 Apr 1; 1(2): 80-88
Jo J, Shreif Z, Periwal V

Adipose cells are unique in the dynamism of their sizes, a requisite for their main function of storing and releasing lipid. Lipid metabolism is crucial for energy homeostasis. However, the regulation of lipid storage capacity in conditions of energy excess and scarcity is still not clear. It is not technically feasible to monitor every process affecting storage capacity such as recruitment, growth/shrinkage and death of individual adipose cells in real time for a sufficiently long period. However, recent computational approaches have allowed an examination of the detailed dynamics of adipose cells using statistical information in the form of precise measurements of adipose cell-size probability distributions. One interesting finding is that the growth/shrinkage of adipose cells (> 50 ?m diameter) under positive/negative energy balance is proportional to the surface area of cells, limiting efficient lipid absorption/release from larger adipose cells. In addition to the physical characteristics of adipose cells, quantitative modeling integrates dynamics of adipose cells, providing the mechanism of cell turnover under normal and drug-treated conditions. Thus, further use of mathematical modeling applied to experimental measurements of adipose cell-size probability distributions in conjunction with physiological measurements of metabolic state may help unravel the intricate network of interactions underlying metabolic syndromes in obesity. HubMed – drug

Assessing the Quality of Randomized Controlled Urological Trials Conducted by Korean Medical Institutions.

Korean J Urol. 2013 May; 54(5): 289-296
Chung JH, Lee SW

To assess the quality of randomized controlled urological trials conducted by Korean medical institutions.Quality assessment was conducted by using the Jadad scale; in addition, the van Tulder scale and the Cochrane Collaboration risk of bias tool were used as individual indices. All assessments were performed by two reviewers. If the outcomes differed, the two reviewers and a third reviewer adjusted the discrepancy in the results through discussion. Starting from 1986, a quality analysis of randomized controlled trials (RCTs) was conducted in 1-year and 5-year units. The quality assessment was conducted by subject, type of intervention, presence of double blinding, presence of funding, and review by an Institutional Review Board (IRB).Whereas the number of RCTs published has gradually increased, there was no significant difference in the quality of the RCTs according to publication year. Drug studies, double-blind studies, studies with funding, and studies reviewed by IRBs had higher quality scores and a higher percentage of high-quality RCTs than did other studies. Thirty-six RCTs were published in journals included in the Science Citation Index and 20 RCTs were published in journals included in the Science Citation Index Expanded. The largest number of RCTs (32.32%) were published by the Korean Journal of Urology.A quantitative increase was observed in RCTs over time, but no qualitative improvement in the RCTs was observed. It seems necessary to put effort into the quality improvement of RCTs at the design stage. HubMed – drug

Antiviral Lectins from Red and Blue-Green Algae Show Potent In Vitro and In Vivo Activity against Hepatitis C Virus.

PLoS One. 2013; 8(5): e64449
Takebe Y, Saucedo CJ, Lund G, Uenishi R, Hase S, Tsuchiura T, Kneteman N, Ramessar K, Tyrrell DL, Shirakura M, Wakita T, McMahon JB, O’Keefe BR

Hepatitis C virus (HCV) infection is a significant public health problem with over 170,000,000 chronic carriers and infection rates increasing worldwide. Chronic HCV infection is one of the leading causes of hepatocellular carcinoma which was estimated to result in ?10,000 deaths in the United States in the year 2011. Current treatment options for HCV infection are limited to PEG-ylated interferon alpha (IFN-?), the nucleoside ribavirin and the recently approved HCV protease inhibitors telaprevir and boceprevir. Although showing significantly improved efficacy over the previous therapies, treatment with protease inhibitors has been shown to result in the rapid emergence of drug-resistant virus. Here we report the activity of two proteins, originally isolated from natural product extracts, which demonstrate low or sub-nanomolar in vitro activity against both genotype I and genotype II HCV. These proteins inhibit viral infectivity, binding to the HCV envelope glycoproteins E1 and E2 and block viral entry into human hepatocytes. In addition, we demonstrate that the most potent of these agents, the protein griffithsin, is readily bioavailable after subcutaneous injection and shows significant in vivo efficacy in reducing HCV viral titers in a mouse model system with engrafted human hepatocytes. These results indicate that HCV viral entry inhibitors can be an effective component of anti-HCV therapy and that these proteins should be studied further for their therapeutic potential. HubMed – drug