Pioglitazone: A review of analytical methods

Pioglitazone is an oral anti-hyperglycemic agent. It is used for the treatment of diabetes mellitus type 2. It selectively stimulates nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma). It was the tenth-best-selling drug in the U.S. in 2008. This article examines published analytical methods reported so far in the literature for the determination of pioglitazone in biological samples and pharmaceutical formulations. They include various techniques like electrochemical methods, spectrophotometry, capillary electrophoresis, high-performance liquid chromatography, liquid chromatography–electrospray ionization-tandem mass spectrometry and high-performance thin layer chromatography.     

NCOA5, a molecular link between type 2 diabetes and liver cancer

It is reported that nuclear receptor co-activator 5 (NCOA5) is a possible susceptibility gene to both type 2 diabetes (T2D) and hepatocellular carcinoma (HCC). The link between these two diseases is an important area of study with the growing prevalence of T2D. Thus, discovery of a genetic link may have great impact on the field. The group used NCOA5^+/– mice to observe the effects of the gene’s haploinsufficiency on the symptoms of T2D and HCC and claimed NCOA5’s regulation of IL-6 in the pathogenesis of the diseases.     

11β-Hydroxysteroid dehydrogenase type 1 inhibitors as therapeutic agents

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an essential role in regulating the access of glucocorticoids to nuclear receptors. Chronically elevated levels of glucocorticoids cause obesity, diabetes, cardiovascular disease (the metabolic syndrome) and impairments in memory. Dysregulation of 11β-HSD1 has been implicated in all of these disease states. Studies with transgenic mice have demonstrated that overexpression of 11β-HSD1 in adipose tissue produces the metabolic syndrome, while knockout of the enzyme produces mice with a cardioprotective phenotype that resist cognitive decline with ageing. Studies with selective 11β-HSD1 inhibitors have demonstrated that it is possible to lower plasma glucose and triglyceride levels as well as food intake and the rate of body weight gain. Consequently, 11β-HSD1 is an important target for the treatment of the metabolic syndrome and cognitive impairment, with many companies pursuing the development of inhibitors. This patent review focuses on the large number of patents published since 2005.     

腺性膀胱炎IL-6、IL-17和TGF-β的表达及意义

目的:探讨白细胞介素(IL)-6、IL-17和转化生长因子(TGF)-β在腺性膀胱炎(CG)组织中的表达及其在CG发病及进展中的作用。方法:将15例正常膀胱黏膜定为对照(A)组,43例未复发CG定为治愈(B)组,13例复发和癌变的CG定为进展(C)组;检测3组IL-6、IL-17和TGF-β的表达情况,并分析这些因子与CG发病及进展的相关性。结果:A组、B组及C组IL-6、IL-17和TGF-β的阳性表达率差异均有统计学意义(P0.01)。3种因子与CG发病(rs分别为0.431、0.545、0.354,P0.05)和进展(rs分别为0.426、0.333、0.288,P0.05)呈正相关;IL-17分别与IL-6、TGF-β呈正相关(rs分别为0.997、0.961,P0.05)。结论:IL-6、IL-17和TGF-β可能在CG的发病及进展中起重要作用。     

Consensus guidelines for glycemic monitoring in type 1/type 2 & GDM

Stringent monitoring of blood glucose in diabetes plays an important role as the treatment of the disease itself. Blood glucose monitoring (BGM) strategies such as measurement of Hb1Ac, Self-Monitoring of Blood Glucose (SMBG) and Continuous Glucose Monitoring (CGM) plays a vital role in achieving the important goal of preventing long term complications of diabetes. Although the use of BGM is recommended by various international guidelines in T1DM and T2DM, there is no consensus on the utility of BGM in India. So, there is a need to develop a guidance for uniform monitoring mechanism among the care givers taking into account the variations and challenges that are unique to Indian population. A committee was established that comprised of physicians, researchers and other healthcare professionals having expertise in diabetes treatment to oversee the formulation of guidelines on different monitoring and treatment aspects of diabetes. Extensive literature searches were conducted to identify and analyze the evidence available on BGM. An initial draft of BGM guidelines was presented to core members who discussed the subject matter and presented their opinion. This was then taken to wider expert audience to invite their comments that were incorporated in the initial draft. The first compilation was presented at a conference attended by nearly 200 experts. Again, their opinion was sought and the next version was prepared which was sent to core committee members for the final inputs. The Indian consensus guideline on BGM using Hb1Ac, SMBG and CGM as the primary tools was then finalized.     

An Update on the Clinical Development of Proprotein Convertase Subtilisin Kexin 9 Inhibitors,Novel Therapeutic Agents for Lowering Low‐Density Lipoprotein Cholesterol

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in the degradation of low‐density lipoprotein C (LDL‐C) receptors, and PCSK9 inhibitors have recently emerged as a potential treatment option to reduce LDL‐C. Our paper reviewed the current available Phase II clinical trials of PCSK9 inhibitors for the treatment of dyslipidemia. A second objective of this review was to evaluate the potential clinical role of PCSK9 inhibitors in the management of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9 inhibitors in patients with dyslipidemia were included. The monoclonal antibodies REGN727/SAR236553 and AMG145 have the most published clinical data. Seven phase II trials were retrieved that evaluated the efficacy and safety of REGN727/SAR236553 or AMG145 in patients with either hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). These two agents significantly decreased LDL‐C levels either as monotherapy or in combination with other lipid‐lowering agents. REGN727/SAR236553 and AMG145 have been well tolerated. The ongoing phase III trials of these two agents are summarized. REGN727/SAR236553 and AMG145 have demonstrated the potential to further decrease LDL‐C levels when added to conventional lipid‐lowering therapy. Morbidity and mortality data are required to define their roles in clinical practice.