Potential beneficial effect of naringenin on lipid peroxidation and antioxidant status in rats with ethanol‐induced hepatotoxicity

Objectives The aim was to study the effect of naringenin, a biologically active compound, on tissue antioxidant status and lipid peroxidation in ethanol‐induced hepatotoxicity in rats. Methods Rats were divided into four groups: Groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg daily for 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) daily for the last 30 days of the experiment. Key findings The results showed significantly elevated levels of serum aspartate and alanine transaminases, γ‐glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content, and significantly lowered activities/levels of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase, reduced glutathione and vitamins C and E in ethanol‐treated rats compared with control rats. Administration of naringenin to rats with ethanol‐induced liver injury significantly decreased the levels of serum aspartate and alanine transaminases, γ‐glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content and significantly elevated the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione‐S‐transferase, and the levels of reduced glutathione and vitamins C and E in the tissues compared with unsupplemented ethanol‐treated rats. Histological changes observed in the liver correlated with the biochemical findings. Conclusions Taken together these findings suggest that naringenin has a therapeutic potential in the abatement of ethanol‐induced hepatotoxicity.     

Unrecognized GERD Symptoms Are Associated with Excessive Daytime Sleepiness in Patients Undergoing Sleep Studies

Sleep disturbances are commonly reported by patients who suffer from gastroesophageal reflux disease (GERD) but it is uncertain if GERD plays a role in patients with sleep disorders of undetermined origin. The prevalence of GERD in patients with sleep disorders of unknown etiology is uncertain; the aim of this study was to determine this prevalence. Three hundred eighty-five consecutive patients reporting to an outpatient clinic for evaluation of sleep disorders were assessed for their sleepiness in relation to reflux symptom intensity. Reflux symptoms that met the survey criteria for a diagnosis of GERD were present in 45 of the 385 subjects (12.8%). These subjects did not have a diagnosis of GERD and were not being treated. Multiple regression analysis showed that excessive sleepiness was associated with intensity of GERD symptoms. Patients with GERD had significantly higher Epworth sleep scores than patients without GERD (12.8 vs. 10.6; p=0.007), indicating more daytime sleepiness. We conclude that unrecognized and untreated GERD are present in many patients presenting with sleep disorders. Patients with GERD had significantly greater sleepiness. Further studies of the impact of GERD treatment in this population are necessary.     

Aspirin is a substrate for paraoxonase-like activity: implications in atherosclerosis

Paraoxonase 1 (PON 1) is an enzyme that is promiscuous in its ability to hydrolyze various types of substrates. It hydrolyzes aryl esters, phosphate esters, lactones, and reduces lipid peroxides to hydroxides. Aspirin is an aryl ester with a short plasma half life. We hypothesized that aspirin would be effectively hydrolyzed by PON 1 and many of its anti-atherogenic effects, at least in part, could be accounted for by its antioxidant product, salicylic acid. In this study, we determined the ability of human plasma and PON 1-rich HDL to hydrolyze acetyl ester of salicylic acid (aspirin). The ability of aspirin to compete for the hydrolysis of paraoxon and p-nitrophenylacetate was determined. In addition, nitrated aspirin was synthesized and tested directly for hydrolysis. Aspirin competed for the hydrolysis of paraoxon and p-nitrophenylacetate by HDL in a dose-dependent manner. Human plasma and HDL were also able to hydrolyze nitroaspirin and aspirin and release nitrosalicylic acid and salicylic acid, respectively. These findings suggest that salicylic acid might be generated in the plasma from aspirin. The ability of long-term treatment with aspirin to retard atherosclerosis might be dependent on the generation of free salicylic acid, a scavenger of free radicals.     

Circulating succinate is elevated in rodent models of hypertension and metabolic disease

BACKGROUND: Recent evidence suggests that succinate, long known as an intermediate in the citric acid cycle, may also have a role as a signaling molecule through GPR91 and that activation of this receptor results in blood pressure (BP) elevation via the renin-angiotensin system. We sought to test the hypothesis that GPR91 contributes to BP elevation in hypertension. In addition we investigated whether elevated succinate in diabetes could contribute to the increased rate of gluconeogenesis in that condition. METHODS: Circulating succinate concentration was measured using liquid chromatography tandem mass spectrometry in rodent models of hypertension and metabolic disease as well as in human hypertensives and type 2 diabetics in comparison to control subjects. RESULTS: Elevated succinate was detected in spontaneously hypertensive rats (SHR), ob/ob mice, db/db mice, and fa/fa rats in comparison to their non-diseased controls. The changes in concentration are consistent with activation of GPR91. In contrast, neither human hypertensives nor diabetic patients had elevated succinate in comparison to controls. CONCLUSIONS: These findings are consistent with a role of GPR91 signaling in rodent hypertension and diabetes models but not in the analogous human diseases.     

Did natural selection for increased cognitive ability in humans lead to an elevated risk of cancer?

Despite the overall genetic similarity that exists between humans and chimpanzees, the species are phenotypically distinct. Among the most notable distinctions are differences in brain size and cognitive abilities. Previous studies have shown that significant differences in gene expression exist between the human and chimpanzee brain. Integration of currently available gene expression data with known metabolic and signaling pathways indicates that the expression of genes involved in the programmed cell death of brain neurons is significantly different between humans and chimpanzees and predictive of a reduced level of neuron apoptosis in the human brain. This pattern of expression is generally maintained in other human organs suggesting that apoptosis is reduced in humans relative to chimpanzees. We propose that a decreased rate of programmed neuron death may have been a consequence of selection for increased cognitive ability in humans. Since reduced apoptotic function is associated with an increased risk of cancer and related diseases, we hypothesize that selection for increased cognitive ability in humans coincidently resulted in an increased risk of cancer and other diseases associated with reduced apoptotic function.     

Fine needle aspiration cytology in a case of fibrous dysplasia of jaw

Fibro‐osseous lesions of the jaw comprise of a spectrum of diseases which include osseous dysplasia, fibrous dysplasia, and ossifying fibroma. The differentiation amongst these individual pathological lesions is difficult and a combined clinico‐radiological and histological correlation is essential for exact categorization. Fine needle aspiration cytology (FNAC) is frequently carried out to distinguish between benign and malignant lesions of the jaw as is a quick and reliable modality of investigation which guides in further management. We report, a case of a jaw swelling in a young male, diagnosed as fibrous dysplasia on FNAC. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

The application of next-generation sequencing technologies to drug discovery and development

Next-generation sequencing (NGS) technologies represent a paradigm shift in sequencing capability. The technology has already been extensively applied to biological research, resulting in significant and remarkable insights into the molecular biology of cells. In this review, we focus on current and potential applications of the technology as applied to the drug discovery and development process. Early applications have focused on the oncology and infectious disease therapeutic areas, with emerging use in biopharmaceutical development and vaccine production in evidence. Although this technology has great potential, significant challenges remain, particularly around the storage, transfer and analysis of the substantial data sets generated.     

Evaluation of three commercially available Japanese encephalitis virus IgM enzyme-linked immunosorbent assays

We evaluated performance of three commercial Japanese encephalitis virus (JEV) IgM antibody capture enzyme-linked immunosorbent assay (MAC ELISA) kits with a panel of serological specimens collected during a surveillance project of acute encephalitis syndrome in India and acute meningitis and encephalitis syndrome in Bangladesh. The serum and cerebral spinal fluid specimens had been referred to the Centers for Disease Control and Prevention (CDC) for confirmatory testing. The CDC results and specimen classifications were considered the reference standard. All three commercial kits had high specificity (95-99.5%), but low sensitivities, ranging from 17-57%, with both serum and cerebrospinal fluid samples. Specific factors contributing to low sensitivity compared with the CDC ELISA could not be determined through further analysis of the limits and dilution end points of IgM detection.     

Epalrestat, an aldose reductase inhibitor, in diabetic neuropathy: An Indian perspective

Background:

A number of diabetic patients with diabetic neuropathy, in India, were treated with epalrestat, an aldose reductase inhibitor. In this study, more than 2000 patients with diabetic neuropathy, who were treated with epalrestat for 3-12 months, were analyzed to assess the efficacy and the adverse reactions of the drug.

Method:

We analyzed the subjective symptoms (spontaneous pain, numbness, coldness and hypoesthesia) and the nerve function tests (motor nerve conduction velocity, sensory nerve conduction velocity and vibration threshold).

Result:

The improvement rate of the subjective symptoms was 75% (slightly improved or better) and that of the nerve function tests 36%. Adverse drug reactions were encountered in 52 (2.5%) of the 2190 patients, none of which was severe.

Conclusion:

Although data are limited, it is strongly suggested that epalrestat is a highly effective and safe agent for the treatment of diabetic neuropathy.