Haseeb A. Khan

Association between glycaemic control and serum lipids profile in type 2 diabetic patients: HbA1c predicts dyslipidaemia.

Impaired lipid metabolism resulting from uncontrolled hyperglycaemia has been implicated in cardiovascular complications in diabetes patients. The aim of this study was to examine the impact of glycaemic control on the lipid profile of diabetic patients. We also determined the ability of glycated haemoglobin (HbA1c) as an indirect marker of dyslipidaemia. A total of 1011 type 2 diabetic patients (males, 574; females, 437; mean age, 59.76 years) were included in this study. Venous blood samples were collected from all the subjects after at least 8 h fasting. The sera were analysed for HbA1c, fasting blood glucose (FBG), total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL). The levels of HbA1c, FBG and LDL did not differ significantly between males and females. Female patients showed significantly higher serum cholesterol and HDL but significantly lower TG levels as compared to males. There was a highly significant correlation between HbA1c and FBG. Both HbA1c and FBG exhibited direct correlations with cholesterol, TG and LDL and inverse correlation with HDL; the magnitude of significance for all these lipid parameters being greater with HbA1c than FBG. There was a linear relationship between HbA1c and dyslipidaemia. The levels of serum cholesterol and TG were significantly higher and of HDL significantly lower in patients with worse glycaemic control as compared to patients with good glycaemic control. The findings of this study clearly indicate that HbA1c is not only a useful biomarker of long-term glycaemic control but also a good predictor of lipid profile. Thus, monitoring of glycaemic control using HbA1c could have additional benefits of identifying diabetic patients who are at a greater risk of cardiovascular complications.

Bioapplication of graphene oxide derivatives: drug/gene delivery, imaging, polymeric modification, toxicology, therapeutics and challenges

Due to the wide range and various applications of graphene in multidisciplinary fields, such as electronics, solar cells, biomedicine, bioengineering, drug delivery, gene delivery and semiconductors, graphene and its derivatives have attracted most significant interest of diverse group of scientists in the last decades. Besides numerous applications in electrical and mechanical fields, their non-invasive biomedical imaging properties allow their wide-spread biological applications. Optical imaging probes play a pivotal role in early cancer detection, image based surgery, disease diagnosis and cellular imaging. Graphene has been widely studied in drug delivery systems due to its unique features and comparatively less/non-toxic properties in biological systems, thus promoting graphene quantum dots as potential organic optical imaging agents to substitute toxic cadmium or tellurium quantum dots. Many groups have also focused on different polymeric modification strategies to enhance the biocompatibility as well as the applications of graphene. In this review, we have summarized recent advances in graphene-based applications, and focused on the relation between chemical structure and polymeric modification with bio-safety issues. The lack of adequate biosafety studies and understanding of the interaction between graphene derivatives and biomolecules has hindered their progress in biomedical and biological applications. To proceed with biological applications of graphene derivatives, such as the development of graphene-based therapeutics and drug delivery systems, the research community must understand how graphene derivatives interact with cell lines and how they accumulate into cells. We also need to learn the fate of graphene derivatives in vivo once it invasively enters into a biological system.

A Brief Review of Molecular Techniques to Assess Plant Diversity

Massive loss of valuable plant species in the past centuries and its adverse impact on environmental and socioeconomic values has triggered the conservation of plant resources. Appropriate identification and characterization of plant materials is essential for the successful conservation of plant resources and to ensure their sustainable use. Molecular tools developed in the past few years provide easy, less laborious means for assigning known and unknown plant taxa. These techniques answer many new evolutionary and taxonomic questions, which were not previously possible with only phenotypic methods. Molecular techniques such as DNA barcoding, random amplified polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP), microsatellites and single nucleotide polymorphisms (SNP) have recently been used for plant diversity studies. Each technique has its own advantages and limitations. These techniques differ in their resolving power to detect genetic differences, type of data they generate and their applicability to particular taxonomic levels. This review presents a basic description of different molecular techniques that can be utilized for DNA fingerprinting and molecular diversity analysis of plant species.

Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP models of Parkinsonism in rodents

Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in the development of experimental parkinsonism. In this investigation an attempt was made to determine a possible protective effect of quinacrine (QNC), a PLA2 inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30 mg/kg, i.p.) daily for 5 days. QNC was injected i.p. in the doses of 0, 10, 30 and 60 mg/kg daily 30 min before MPTP in four different groups. Two other groups of mice received either vehicle (control) or a high dose of QNC (60 mg/kg). Two hours after the last injection of MPTP, striata were collected for the analysis of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and glutathione (GSH). For the 6-OHDA study, male Wistar rats were infused with 6-OHDA (60 microg) in the right striatum under chloral hydrate anesthesia. The rats in different groups were treated with 0, 5, 15 and 30 mg/kg QNC (i.p.) for 4 days, while first injection was given 30 min before 6-OHDA. On day 5, rats were sacrificed and striata were stored at -80 degrees C. Administration of MPTP or 6-OHDA significantly reduced striatal DA, which was significantly attenuated by QNC. Concomitant treatment with QNC also protected animals against MPTP or 6-OHDA-induced depletion of striatal GSH. Our findings clearly suggest the role of PLA2 in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further studies are warranted to explore the therapeutic potential of PLA2 inhibitors for the treatment of Parkinsons disease.

Environmental toxins and Parkinson's disease: putative roles of impaired electron transport chain and oxidative stress.

Despite recent advancements in the biomedical fields, the etiology and pathogenesis of Parkinsons disease (PD) is still poorly understood, though the crucial roles of oxidative stress and impaired mitochondrial respiration have been suggested in the development of PD. The oxidative modification of the proteins of mitochondrial electron transport chain alters their normal function leading to the state of energy crisis in neurons. Exposure of environmental chemicals such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone in mouse produces the symptoms akin to PD and therefore these neurotoxins are commonly used in experimental studies on PD. Another environmental toxin, paraquat (a commonly used herbicide) has also been implicated with the onset of PD. The neurotoxicity of these chemicals is accompanied by the blockade of electron flow from NADH dehydrogenase to coenzyme Q. The agents with the ability to improve mitochondrial respiration and ATP production have been shown to exert beneficial effects in PD patients as well as in the animal models of PD. This review summarizes the current research implicating the impairment of mitochondrial respiratory chain and the role of environmental toxins in the pathogenesis of PD.Despite recent advancements in the biomedical fields, the etiology and pathogenesis of Parkinson’s disease (PD) is still poorly understood, though the crucial roles of oxidative stress and impaired mitochondrial respiration have been suggested in the development of PD. The oxidative modification of the proteins of mitochondrial electron transport chain alters their normal function leading to the state of energy crisis in neurons. Exposure of environmental chemicals such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone in mouse produces the symptoms akin to PD and therefore these neurotoxins are commonly used in experimental studies on PD. Another environmental toxin, paraquat (a commonly used herbicide) has also been implicated with the onset of PD. The neurotoxicity of these chemicals is accompanied by the blockade of electron flow from NADH dehydrogenase to coenzyme Q. The agents with the ability to improve mitochondrial respiration and ATP production have been shown to exert benefici...

Benzene's toxicity: a consolidated short review of human and animal studies.

A large population of humans is exposed to benzene from various occupational and environmental sources. Benzene is an established human and animal carcinogen. Exposure to benzene has been associated with leukaemia in humans and several types of malignancies in animals. The exact mechanism of benzene-induced toxicity is poorly understood. It is believed that benzene exerts its adverse effects by metabolic activation to toxic metabolites. Certain benzene metabolites are genotoxic and mutagenic. This consolidated short-review is composed of human and animal studies to summarize the adverse effects of benzene with special reference to molecular mechanisms involved in benzene-induced toxicity.Human & Experimental Toxicology (2007) 26,677—685Benzene is commonly used as a starting material for the synthesis of several other chemicals of industrial and medicinal importance. It is used as an excellent solvent in various industries including dyes, varnish, lacquer, leather and so on. Benzene is also a component of cigarette smoke and gasoline. Huge numbers of population from entire globe are exposed to benzene either occupationally or due to environmental contamination. Benzene has been confirmed to be a human and animal carcinogen. Chronic exposure to low dose of benzene is associated with aplastic anaemia and leukaemia. Acute effects of benzene exposure include irritation of mucous membranes, restlessness, convulsions, excitement, depression and even death due to respiratory failure. The major toxic effect of benzene is its haematopoietic toxicity. This concise review is aimed to compile various aspects of benzene toxicity in humans and experimental animals by incorporating the relevant studies beginning from the decades old historical contributions to current insights on benzene toxicity.

Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats

Nicotinic acetylcholine receptors (nAChRs) are regarded as potential therapeutic targets to control various neurodegenerative diseases. Owing to the relevance of cholinergic neurotransmission in the pathogenesis of Huntingtons disease (HD) this investigation was aimed to study the effect of nicotine, a nAChR agonist, on 3-nitropropionic acid (3-NP)-induced neurodegeneration in female Wistar rats. Systemic administration of 3-NP in rats serves as an important model of HD. The animals received subcutaneous injections of nicotine (0, 0.25, 0.50 and 1.00 mg/kg) daily for 7 days. 3-NP (25 mg/kg, i.p.) was administered daily 30 min after nicotine for the same duration. One additional group of rats served as control (vehicle only). On day 8, the animals were observed for neurobehavioral performance (motor activity, inclined plane test, grip strength test, paw test and beam balance). Immediately after behavioral studies, the animals were transcardially perfused with neutral buffered formalin (10%) and brains were fixed for histological studies. Lesions in the striatal dopaminergic neurons were assessed by immunohistochemical method using tyrosine hydroxylase (TH) immunostaining. Treatment of rats with nicotine significantly and dose-dependently attenuated 3-NP-induced behavioral deficits. Administration of 3-NP alone caused significant depletion of striatal dopamine (DA) and glutathione (GSH), which was significantly and dose-dependently attenuated by nicotine. Preservation of striatal dopaminergic neurons by nicotine was also confirmed by immunohistochemical studies. These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.

Neurodegeneration and Neuroprotection in Diabetic Retinopathy

Diabetic retinopathy is widely considered to be a neurovascular disease. This is in contrast to its previous identity as solely a vascular disease. Early in the disease progression of diabetes, the major cells in the neuronal component of the retina consist of retinal ganglion cells and glial cells, both of which have been found to be compromised. A number of retinal function tests also indicated a functional deficit in diabetic retina, which further supports dysfunction of neuronal cells. As an endocrinological disorder, diabetes alters metabolism both systemically and locally in several body organs, including the retina. A growing body of evidences indicates increased levels of excitotoxic metabolites, including glutamate, branched chain amino acids and homocysteine in cases of diabetic retinopathy. Also present, early in the disease, are decreased levels of folic acid and vitamin-B12, which are potential metabolites capable of damaging neurons. These altered levels of metabolites are found to activate several metabolic pathways, leading to increases in oxidative stress and decreases in the level of neurotrophic factors. As a consequence, they may damage retinal neurons in diabetic patients. In this review, we have discussed those potential excitotoxic metabolites and their implications in neuronal damage. Possible therapeutic targets to protect neurons are also discussed. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. By protecting retinal neurons early in diabetic retinopathy cases, damage of retinal vessels can be protected, thereby helping to ameliorate the progression of diabetic retinopathy, a leading cause of blindness worldwide.

Gastric antisecretory and antiulcer effects of simvastatin in rats.

Background and Aim:  Recently, statins have appeared to have additional benefits beyond their lipid lowering effects, which has led to the interest in the use of this class of drugs outside the realm of cardiovascular disease. Simvastatin (SIM) is a commonly prescribed statin with anti‐inflammatory and antioxidant properties. Excessive generation of oxygen‐derived free radicals (ODFR) and proinflammatory mediators has been implicated in the pathogenesis of gastric ulcers. This investigation aimed to study the effect of SIM on experimentally induced gastric acid secretion and ulcer formation.

Bioluminometric assay of ATP in mouse brain: Determinant factors for enhanced test sensitivity

Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific method for the analysis of adenosine-5-triphosphate (ATP) in biological samples. Earlier attempts to modify the FLB test for enhanced sensitivity have been typically based onin vitro cell systems. This study reports an optimized FLB procedure for the analysis of ATP in small tissue samples. The results showed that the sensitivity of the FLB test can be enhanced several fold by using ultraturax homogenizer, perchloric acid extraction, neutralization of acid extract and its optimal dilution, before performing the assay reaction.