Khan Ismail

Bio: Khan Ismail is an academic researcher from University of Peshawar. The author has contributed to research in topics: DNA damage & Superoxide dismutase. The author has an hindex of 1, co-authored 1 publications receiving 734 citations.

Diabetes mellitus and oxidative stress—A concise review

Abstract: Human body is continuously exposed to different types of agents that results in the production of reactive species called as free radicals (ROS/RNS) which by the transfer of their free unpaired electron causes the oxidation of cellular machinery. In order to encounter the deleterious effects of such species, body has got endogenous antioxidant systems or it obtains exogenous antioxidants from diet that neutralizes such species and keeps the homeostasis of body. Any imbalance between the RS and antioxidants leads to produce a condition known as “oxidative stress” that results in the development of pathological condition among which one is diabetes. Most of the studies reveal the inference of oxidative stress in diabetes pathogenesis by the alteration in enzymatic systems, lipid peroxidation, impaired Glutathione metabolism and decreased Vitamin C levels. Lipids, proteins, DNA damage, Glutathione, catalane and superoxide dismutase are various biomarkers of oxidative stress in diabetes mellitus. Oxidative stress induced complications of diabetes may include stroke, neuropathy, retinopathy and nephropathy. The basic aim of this review was to summarize the basics of oxidative stress in diabetes mellitus.

When the Pancreas

Abstract: 1757 Identification of Ocular Sebaceous Neoplasia with Evaluation for Mismatch Repair Proteins L Schoenfield, J Anthony, R Djohan, I Lalak, M Levine, P Ng, J Perry, A Singh, T Plesec. Cleveland Clinic, Cleveland, OH. Background: Recognizing sebaceous carcinoma is important because of its risk for metastasis and tumor death. Histopathology alone is often difficult because fresh tissue for oil red-O stain is not always available. Several immunohistochemical stains (IHC) have been evaluated but often the diagnosis is elusive. Furthermore, the diagnosis of a sebaceous adenoma or carcinoma raises the possibility of Lynch syndrome, a cancer predisposition syndrome. Mismatch repair protein(MMR) abnormalities are a feature of Lynch syndrome, and they can be detected with IHC for the MLH1, MSH2, PMS2, and MSH6 proteins. Design: 14 sebaceous carcinomas and 3 adenomas from the eyelid (17 specimens) from 14 patients were evaluated for oil red-O when possible as well as IHC for AR, EMA, BER-EP4, CAM5.2 for diagnosis. MMR for MLH1, MSH2, PMS2, and MSH6 by IHC were evaluated as a possible screening panel for Lynch syndrome. Two patients already had other tissue tested by PCR for microsatellite instability (MSI) for Lynch syndrome. Results: Oil red-O was done on 6 of 17 specimens and positive in 5 of the 6 (83%). AR was positive in 2 of 3 adenomas (67%) and 5 of 14 carcinomas (36%). EMA was positive in 2 of 3 adenomas (67%) and 11 of 14 carcinomas (79%). BER-EP4 was negative in all 3 adenomas and positive in 7 of 14 carcinomas (50%). CAM5.2 was positive in 1 of 3 adenomas (33%) and 8 of 14 carcinomas (57%). All 17 specimens(100%) showed positive nuclear staining for MLH1 and PMS2, indicative of normal protein expression. In 14 of 17 specimens from 12 patients, MSH2 and MSH6 were also normal. 3 specimens from 2 patients that had rare positive cells for MSH2 and MSH6. Both patients had previous colonic tumors tested for MSI and were found to be MSI-H, indicative of possible Lynch syndrome. Conclusions: Diagnosing sebaceous carcinoma is important prognostically but sometimes challenging with routine histopathology. In our experience androgen receptor (AR) was found to be confirmatory in only 36% of cases and not dependent on the size of the tumor available. The other IHC stains were of marginal benefit and not specific. While none of the cases showed complete loss of expression of a MMR protein, there were 2 patients in with only rare positive cells who had known MSI-H tumors in the colon, suggestive of Lynch syndrome. Additional studies of these eyelid tumors may elucidate the possible role of using them for screening for Lynch syndrome.

Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus: How Are They Interlinked?

Abstract: Oxidative stress has been considered as a major hallmark for the pathogenesis and development of type 2 diabetes mellitus (T2DM), but still it is debatable whether it is a mere aggregation of inflammatory-induced responses or clinical entity that underlies with various pathophysiological factors. In this regard, the latest studies have shown the increasing trends for the involvement of reactive oxygen species (ROS) and oxidative stress in the pathogenesis and development of T2DM. ROS are highly reactive species and almost all cellular components are chemically changed due to the influence of ROS that ultimately results in the production of lipid peroxidation. Lipid peroxidation is a major causative factor for the development of oxidative stress that leads to overt T2DM and its associated micro- and macro-vascular complications. In this article, we have briefly described the role of various causative factors, transcriptional and metabolic pathways which are responsible to increase the production of oxidative stress, a most pivotal factor for the pathogenesis and development of T2DM. Therefore, we conclude that measurement of oxidative stress biomarkers may be one of the optional tool for the diagnosis and prediction of T2DM. Moreover, the key findings described in this article also provides a new conceptual framework for forthcoming investigations on the role of oxidative stress in pathogenesis of T2DM and drug discovery. J. Cell. Biochem. 118: 3577-3585, 2017. © 2017 Wiley Periodicals, Inc.

Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship.

Abstract: The incidence and prevalence of metabolic and musculoskeletal diseases are increasing. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, inflammation, advanced glycation end-product accumulation and increased oxidative stress. These characteristics can negatively affect various aspects of muscle health, including muscle mass, strength, quality and function through impairments in protein metabolism, vascular and mitochondrial dysfunction, and cell death. Sarcopenia is a term used to describe the age-related loss in skeletal muscle mass and function and has been implicated as both a cause and consequence of T2DM. Sarcopenia may contribute to the development and progression of T2DM through altered glucose disposal due to low muscle mass, and also increased localized inflammation, which can arise through inter- and intramuscular adipose tissue accumulation. Lifestyle modifications are important for improving and maintaining mobility and metabolic health in individuals with T2DM and sarcopenia. However, evidence for the most effective and feasible exercise and dietary interventions in this population is lacking. In this review, we discuss the current literature highlighting the bidirectional relationship between T2DM and sarcopenia, highlight current research gaps and treatments, and provide recommendations for future research.

Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/ RNS generation

Abstract: Reactive oxidative species (ROS) toxicity remains an undisputed cause and link between Alzheimer’s disease (AD) and Type-2 Diabetes Mellitus (T2DM). Patients with both AD and T2DM have damaged, oxidized DNA, RNA, protein and lipid products that can be used as possible disease progression markers. Although the oxidative stress has been anticipated as a main cause in promoting both AD and T2DM, multiple pathways could be involved in ROS production. The focus of this review is to summarize the mechanisms involved in ROS production and their possible association with AD and T2DM pathogenesis and progression. We have also highlighted the role of current treatments that can be linked with reduced oxidative stress and damage in AD and T2DM.