Adipokine Visfatin's Role in Pathogenesis of Diabesity and Related Metabolic Derangements.

Visfatin is one of the prominent adipokines secreted by adipose tissue. The level of visfatin increases significantly in persons with obesity owing to increased body mass index (BMI). During obesity, the adipocytes, which populate adipose tissue, undergo hypertrophy and hyperplasia and secrete a number of adipocytokines including visfatin. Visfatin, which also acts as an enzyme nicotinamide phosphoribosyl transferase, is one of the prominent adipokines that influence metabolic homeostasis in the body. Visfatin exists in two forms, extracellular and intracellular, and enacts a multitude of actions. The direct and indirect evidence gathered from in-vitro, in-vivo and clinical studies indicate that visfatin modulates obesity and metabolic syndrome-related pathophysiological activities including enhanced inflammation, angiogenesis, synthesis of NAD mononucleotide, and upregulation of antiapoptotic proteins in a number of cell types. It has been implicated in a number of obesity-related alterations and metabolic derangement such as diabetes, cardiovascular complications and some forms of cancers. In this review, the novel hypothesis about the role of visfatin in diabesity has been proposed which implies recent advances in studies about the pathophysiological roles of visfatin during obesity and chronic high glucose in the circulation. Visfatin at high concentration attracts immune cells and produces chronic inflammation in adipocytes. Additionally, it induces insulin resistance in many tissues and causes pancreatic beta cells dysfunction at later stages. Further, its potential as an important target to develop molecular medicine in diabesity and related metabolic syndrome has been highlighted.

Cysteinyl Leukotrienes (CysLTs): Role in Obesity-Induced Asthma.

Epidemiological studies associate obesity with onset of asthma, especially in obese children, suggesting obesity as the risk factor for asthma. Obesity-induced chronic inflammation has been implicated in the lung inflammation, yet specific mediators and mechanisms are lacking. Obesity is associated with increased expression of 5-lipoxygenase (5-LO) pathway and increased Leukotrienes (LTs) production has been observed in obese asthma patients. However, the precise mechanism that predisposes lungs inflammation in obese is not clearly understood. This article discusses the production and regulation of LTs in obese individuals and presents probable mechanisms regarding the role of LTs in lung inflammation that may lead to obesity-induced asthma. Leukotrienes are well known mediators of asthma but their role in obesity-induced asthma is not clearly understood and thus needs further research. Since efficient antagonists and inhibitors of 5-LO pathways are known, understanding of molecular mechanism of LTs, especially Cysteinyl-LTs, in obesity-induced asthma could lead to optimal treatment regimens for the prevention and treatment of asthma in obese individuals.

Cell-death assessment by fluorescent and nonfluorescent cytosolic and nuclear staining techniques.

Apoptosis, a genetically programmed cellular event leads to biochemical and morphological changes in cells. Alterations in DNA caused by several factors affect nucleus and ultimately the entire cell leading to compromised function of the organ and organism. DNA, a master regulator of the cellular events, is an important biomolecule with regards to cell growth, cell death, cell migration and cell differentiation. It is therefore imperative to develop the staining techniques that may lead to visualize the changes in nucleus where DNA is housed, to comprehend the cellular pathophysiology. Over the years a number of nuclear staining techniques such as propidium iodide, Hoechst-33342, 4', 6-diamidino-2-phenylindole (DAPI), Acridine orange-Ethidium bromide staining, among others have been developed to assess the changes in DNA. Some nonnuclear staining techniques such as Annexin-V staining, which although does not stain DNA, but helps to identify the events that result from DNA alteration and leads to initiation of apoptotic cell death. In this review, we have briefly discussed some of the most commonly used fluorescent and nonfluorescent staining techniques that identify apoptotic changes in cell, DNA and the nucleus. These techniques help in differentiating several cellular and nuclear phenotypes that result from DNA damage and have been identified as specific to necrosis or early and late apoptosis as well as scores of other nuclear deformities occurring inside the cells.

Current prospective of aldose reductase inhibition in the therapy of allergic airway inflammation in asthma.

The prevalence of asthma and costs of its care have been continuously increasing, but novel therapeutic options to treat this inflammatory disease have not been brought to the US market. Current therapies such as inhaled steroids, long-acting beta-agonist bronchodilators, antihistamines and immunomodulators may control the symptoms of allergic asthma but fail to modify the underlying disease. Excessive use of steroids and other immunosuppresents alter the patient's quality of life, produce undesirable toxicities, and increase the risk of other pathologies such as diabetes. Hence novel therapeutic options to manage asthma are desirable. In the present review, we have discussed the role of the polyol pathway enzyme aldose reductase (AR) in the amplification of allergic airway inflammation. Recent studies have indicated that AR inhibition prevents the NF-κB-dependent generation of pro-inflammatory cytokines and chemokines in mouse models of allergic airway inflammation indicating the potential use of AR inhibition as a novel tool to control allergic responses. Since orally available AR inhibitors have already undergone phase III clinical trials for diabetic neuropathy and appear to have a manageable side effects profile, they could be readily developed as potential new drugs for the treatment of asthma and related complications.

Emerging role of antioxidants in the protection of uveitis complications.

Current understanding of the role of oxidative stress in ocular inflammatory diseases indicates that antioxidant therapy may be important to optimize the treatment. Recently investigated antioxidant therapies for ocular inflammatory diseases include various vitamins, plant products and reactive oxygen species scavengers. Oxidative stress plays a causative role in both non-infectious and infectious uveitis complications, and novel strategies to diminish tissue damage and dysfunction with antioxidant therapy may ameliorate visual complications. Preclinical studies with experimental animals and cultured cells demonstrate significant anti-inflammatory effects of a number of promising antioxidant agents. Many of these antioxidants are under clinical trial for various inflammatory diseases other than uveitis such as cardiovascular, rheumatoid arthritis and cancer. Well planned interventional clinical studies in the field of ocular inflammation will be necessary to sufficiently investigate the potential medical benefits of antioxidant therapies for uveitis. This review summarizes the recent investigations of novel antioxidant agents for ocular inflammation, with selected studies focused on uveitis.

Understanding the role of aldose reductase in ocular inflammation.

Aldose reductase, although identified initially as a glucose-reducing enzyme via polyol pathway, is believed to be an important component of antioxidant defense system as well as a key mediator of oxidative stress-induced molecular signaling. The dual role played by AR has made it a very important enzyme for the regulation of not only the cellular redox state by detoxifying the reactive lipid-aldehydes generated by lipid peroxidation which is crucial in the cellular homeostasis, but also in the regulation of molecular signaling cascade that may regulate oxidative stress-induced cytotoxic events. Search for the new molecular targets to restrain the oxidative stress-induced inflammation has resulted in the identification of AR as an unanticipated mediator of oxidative stress-induced signaling. Although, in last one decade or so AR has been implicated in various inflammation-related diseases conditions ranging from diabetes, sepsis, cancer, cardiovascular and ocular inflammation, however, a critical evaluation of the clinical efficacy of AR inhibitors awaits a better understanding of the role of AR in regulating inflammation, especially in ocular inflammation.