Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies in diabetes type 1 patients.

Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and superoxide (O2(-)), has been implicated in the etiology of numerous disease processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via indirect radical-mediated mechanism. It can inflict both oxidative and nitrosative damages on DNA bases, generating abasic sites, resulting in the single strand breaks.

Role of early glycation Amadori products of lysine-rich proteins in the production of autoantibodies in diabetes type 2 patients.

In diabetes, protein glycation mostly occurs at intrachain lysine residues resulting in the formation of early stage Amadori products which are finally converted to advance glycation end products (AGEs). Several studies have reported autoantibodies against AGEs in diabetes but not much data are found in respect of Amadori products. In this study, poly-L-lysine (PLL) was glycated with 50 mM glucose and the resultant Amadori products were estimated by fructosamine or nitroblue tetrazolium assay.

Nonalcoholic fatty liver disease and cholesterol gallstones: which comes first?

Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are both highly prevalent in the general population and are associated with obesity, insulin resistance, dyslipidemia, and high dietary cholesterol intake. Insulin resistance is a key feature of both NAFLD and GD. Hepatic insulin resistance provides a crucial link between the metabolic syndrome, NAFLD, and increased cholesterol gallstone susceptibility.

A convergent synthesis of alkyne-azide cycloaddition derivatives of 4-α,β-2-propyne podophyllotoxin depicting potent cytotoxic activity.

A facile synthetic approach to construct the O-propargyl derivatives of 4α and 4β-(1,2,3-triazol-4-yl)-podophyllotoxin (9a-k & 10a-k) and 4'-Demethyl-4'-4β-(1,2,3-triazol-4-yl)-epipodophyllotoxin (12a-d) were synthesized by means of click chemistry. The chemical structures were confirmed by (1)H, (13)C, 2D NMR and HRMS spectral analysis and their cytotoxicities were measured against diverse human cancer cell lines viz. PC-3, PANC-1, COLO-205 and A-549 by MTT assay.

Genotoxicity and immunogenicity of crotonaldehyde modified human DNA.

DNA damage plays an important role in mutagenesis, carcinogenesis, aging and several other pathophysiological conditions. Crotonaldehyde is a four carbon unsaturated bifunctional aldehyde produced both exogenously and endogenously. It reacts with deoxyguanosine in DNA to form adducts.

insilico Characterization and Homology Modeling of Arabitol Dehydrogenase (ArDH) from Candida albican.

Background: Arabitol dehydrogenase (ArDH) is involved in the production of different sugar alcohols like arabitol, sorbitol, mannitol, erythritol and xylitol by using five carbon sugars as substrate. Arabinose, d-ribose, d-ribulose, xylose and d-xylulose are known substrate of this enzyme. ArDH is mainly produced by osmophilic fungi for the conversion of ribulose to arabitol under stress conditions.

Glycoxidative damage to human DNA: Neo-antigenic epitopes on DNA molecule could be a possible reason for autoimmune response in type 1 diabetes.

Advanced glycation end-products (AGEs) are known to be mutagenic, diabetogenic and vascular disease risk factors. Methylglyoxal (MG) is a dicarbonyl species that reacts with biological macromolecule (proteins, DNA and lipids) to give AGEs. Nonenzymatic glycation of MG with lysine (Lys) in the presence of copper (Cu(2+)) is reported to generate reactive oxygen species (ROS) capable of causing DNA damage.

Peroxynitrite modified DNA may be an antigenic trigger for antibodies in various cancers of gynecologic origin.

This study aimed towards probing the role of peroxynitrite damaged human DNA (ONOO(-)-DNA) in the induction of circulating antibodies in certain cancers of gynecologic origin. We have compared the binding specificity of DNA isolated from the lymphocytes of cancer patients with that of the experimentally modified DNA. Also, the induced anti-ONOO(-)-DNA antibodies have been used to probe oxidative damage in the DNA isolated from cancer patients.

Peroxynitrite induced structural changes result in the generation of neo-epitopes on human serum albumin.

Human serum albumin (HSA), the most abundant plasma protein, is quite vulnerable to oxidizing and nitrating agents. In this study, peroxynitrite induced nitration and oxidation of HSA was assessed by various physicochemical techniques. Cross-linking of HSA was evident on polyacrylamide gel electrophoresis.

Multi-resource peer assisted learning in postgraduate setting: a pilot study.

Objective: To evaluate the satisfaction of participants and the effectiveness of an enhanced and relatively formal type of peer assisted learning (PAL) in postgraduate (PG) setting.

Study Design: An observational study.

Place And Duration Of Study: Layton Rehmat Ullah Benevolent Trust, Eye Hospital, Sargodha between 2008 and 2009.

Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

Background: The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions.

Too much of a good thing: random practice scheduling and self-control of feedback lead to unique but not additive learning benefits.

We examined the impact of self-controlled knowledge of results on the acquisition, retention, and transfer of anticipation timing skill as a function of random and blocked practice schedules. Forty-eight undergraduate students were divided into experimental groups that practiced under varying combinations of random or blocked as well as self-controlled or yoked practice conditions. Anticipation timing performance (5, 13, and 21 mph) was recorded during acquisition and during a short term no-feedback retention test.

Preferential recognition of epitopes on AGE-IgG by the autoantibodies in rheumatoid arthritis patients.

Incubation of proteins with glucose lead to their non-enzymatic glycation ultimately resulting in the formation of advanced glycation end products (AGEs) in vivo. AGEs alter unique three dimensional structures of various plasma proteins such as IgG. The role of oxidative stress in the pathogenesis of rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease, is well established.

Modulation of LPS induced inflammatory response by Lawsonyl monocyclic terpene from the marine derived Streptomyces sp.

In continuing research for compounds with immunosuppressive activity, Lawsonone (1), a novel Lawsonyl derivative isolated from marine-derived bacteria Streptomyces sp. was evaluated for its potent immunosuppressive activity on immune system. The effect of Lawsonone (1) was elucidated on the immune cells (splenocytes and macrophages) collected from BALB/c mice.

Physicochemical and immunological studies on 4-hydroxynonenal modified HSA: implications of protein damage by lipid peroxidation products in the etiopathogenesis of SLE.

4-Hydroxynonenal (HNE) is the most abundant and toxic aldehyde generated by the oxidation of plasma membrane polyunsaturated fatty acids. Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is primarily characterized by increased levels of autoantibodies, predominantly against ds-DNA. However, the initial antigenic stimulus for the disease etiopathogenesis has remained elusive.

Serum inhibin B as a diagnostic marker of male infertility.

Background: Infertility affects about 15% of all couples in the world. Approximately 40% of all infertility cases could be attributed entirely to male factors. Serum inhibin B has emerged as a sensitive marker of male fertility.

Role of serum-ascites albumin gradient in differential diagnosis of ascites.

Background: The classification of ascites as 'exudative' and 'transudative' based on ascitic fluid total protein (AFTP) has been challenged in many clinical conditions like cardiac ascites, patients on prolonged diuretic therapy and malignant ascites because it had poor diagnostic efficacy. These drawbacks have led to the development of another approach to classify ascites, which is based on Serum-Ascites Albumin Gradient (SAAG) to differentiate ascitic fluid into two categories: SAAG > or = 11 g/L in ascites due to portal hypertension and SAAG < 11 g/L in ascites unrelated to portal hypertension. Objective of this study was to compare the diagnostic efficacy of serum/ascites fluid albumin gradient and ascitic fluid total protein in patients having ascites.

Immunological studies on glycated human IgG.

Aims: To study the immunogenicity of advanced glycation end product (AGE) modified IgG (AGE-IgG) in experimental animals.

Main Methods: Human IgG was subjected to in vitro glycation with glucose and the formation of N(ε)-(carboxymethyl)lysine (CML) was evaluated by high performance liquid chromatography (HPLC). The immunogenicity of native and AGE-IgG was investigated by raising polyclonal antibodies against them in rabbits.

Human DNA damage by the synergistic action of 4-aminobiphenyl and nitric oxide: an immunochemical study.

4-Aminobiphenyl (4-ABP), an aromatic amine is a major environmental carcinogen found mainly in cigarette smoke. It has been vastly implicated in mutagenesis and cancer development. In this study, commercially available human placental DNA was exposed to 4-ABP (1.

Acquired immunogenicity of human DNA damaged by N-hydroxy-N-acetyl-4-aminobiphenyl.

4-Aminobiphenyl, a known carcinogen, has many environmental sources like cigarette smoke, industrial waste, and so forth. It can be metabolized to form a potent mutagen, N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP) that undergoes further processing to form electrophilic nitrenium ions which interact with DNA-forming covalent adducts, thereby exerting genotoxic effects. While the mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been performed to assess the immunogenicity of N-OH-AABP-modified DNA.

Hydroxyl radical modification of collagen type II increases its arthritogenicity and immunogenicity.

Background: The oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo-antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA.

Methodology/principal Findings: Hydroxyl radicals were generated by the Fenton reaction.

Physicochemical studies on glycation-induced structural changes in human IgG.

Glycation of biomolecules leads to the formation of advanced glycation end products (AGEs). Glycation of immunoglobulin G (IgG) has been implicated in autoimmune diseases such as rheumatoid arthritis (RA). In this study, human IgG was glycated with physiological concentration of glucose.