Glutaredoxin proteins from E. coli isoforms were compared in terms of energy frustration.

Glutaredoxin (GRXs) protein plays a vital role inside the cell, including redox control of transcription to the cell's antioxidant defense, apoptosis, and cellular differentiation regulation. In this study, we have investigated the energy landscape and characterized the pattern of local frustration in different forms and states of the GRX protein ofE. coli.Analysis was done on the conformational alterations, significant changes in the frustration pattern, and different GRXs such as GRX-II, GRX-III, GRX-II-GSH, and GRX-III-GSH complex. We have found the practice of frustration, and structure was quite similar in the same isoform having different states of protein; however, a significant difference was observed between different isoforms. Moreover, oxidation of GRX-I introduced an extra α-helix increasing the destabilizing interactions within the protein. The study of frustrated contacts on oxidized and reduced GRX and with bound and unbound Glutathione indicates its potential application in activating and regulating the behavior of GRXs.

The inhibitory and anticancer properties of Annona squamosa L. seed extracts.

Although Annona squamosa Linn. (Annonaceae) has been used in traditional medicine and is known to have several pharmacological properties, its impact on EGFR kinase has not been fully investigated. An assay (biochemical) was used to govern the potential of different A. squamosa seed extracts to scavenge free radicals in petroleum ether, acetone, ethanol, and methanol. We also tested A. squamosa leaf extracts for their ability to inhibit the growth of HEK 293, MCF7, and HepG2 cell lines. The PSE, ASE, ESE, and MSE all contained anti-cancer substances like anethole, cyclopentane, 1,1,3-trimethyl, and phosphonate oxide tributyl, according to phytochemical analysis. ESE extracts from A. squamosa seeds have been selected based on free radical generation probabilities, cytotoxicity studies, and phytochemical analysis. Subsequent insilico studies have been conducted, and the results have shown that interactions between compounds present in ESE extracts and the EGFR kinase are what give these compounds their inhibitory effects. Preliminary phytochemical and pharmacological activities were studied and reported. A. squamosa ESE extracts inhibited the growth of MCF7 cells, and a pharmacokinetic study showed that the compounds anethole, cyclopentane, 1,1,3-trimethyl, and phosphonium oxide tributyl had few undesirable side effects. These substances can be used to both prevent and treat cancer diseases.

Biophysical and immunological characterization of 2-dRib modified HSA and its implications in diabetes mellitus.

Glycoxidation of protein may lead to develop diabetes. In the present study, different concentrations of 2-deoxy d-ribose (2-dRib) were used to modify human serum albumin (HSA). Nitro Blue Tetrazolium (NBT) assay results showed that yield of the fructosamine content was directly proportional to the concentration of 2-dRib. UV and fluorescence spectroscopy results showed an increment in hyperchromicity and decrease in fluorescence intensity of 2-dRib modified HSA as compared to native HSA. Further secondary structural changes were confirmed by UV-circular dichroism (UV-CD) and Fourier transform infrared spectroscopy (FT-IR). To evaluate the immunogenicity of 2-dRib modified HSA, rabbits were immunized with native and 2-dRib modified HSA. Modified HSA sera showed high antibodies titre as compared to native HSA. Moreover, the binding affinity of native and modified HSA with diabetic patient's sera has been evaluated by direct binding ELISA. It was found that diabetic patient's sera showed high binding affinity with the modified HSA as compared to native HSA. On the basis of above findings, it can be concluded that 2-dRib is a potential glycating agent that can cause alteration in HSA structure and make HSA more immunogenic that might play a role in onset and progression of diabetes mellitus and its complications.

Prevalence and assessment of role of SEN virus in acute and chronic hepatitis in India.

BACKGROUND AND AIM: SEN virus (SENV), is a recently discovered single-stranded DNA virus of Annelloviridae family and is believed may play a role in non A-E hepatitis. We conducted this study to identify the prevalence and clinical association of SENV with acute and chronic hepatitis. METHODS: 135 liver disease patients were studied. Extent of liver damage was assessed using the Model for End Stage Liver Disease (MELD) score. A-E viruses and HIV were detected by enzyme immunoassay. Nested PCR was performed for detection of SENV and its genotypes D and H. RESULTS: 34 cases (25.18%) were positive for SEN virus DNA, a statistically significant finding (p < 0.01) of which 22 (64%) had acute viral hepatitis, 4 (11.76%) had chronic viral hepatitis, 3 (8.82%) fulminant hepatic failure and 5 (14.70%) cirrhosis. Mean AST was 47.85 IU/L, ALT 51.2 IU/L and INR 1.73, mean MELD score was 18.38 (11 to 24). 17.64% had severely deranged MELD score. SENV-D genotype was detected in 13 (38%) and SENV-H in 19 (58%) cases. SENV-H occurred in both acute (53%) and chronic hepatitis (47%). SENV-D was strongly associated with acute hepatitis (85%). Cirrhotic and FHF cases were SENV-H positive. 12 (44.11%) were co-infected with HBV, 5 (14.7%) with TTV, 4(11.76%) with HEV, 2 (5.88%) with HCV and 5 (14.4%) with HIV. CONCLUSION: Significant prevalence of SENV in hepatitis patients was observed. On the basis of clinical findings and abnormal liver function tests, we conclude that SENV appears to be not only hepatotropic but also capable of liver damage. Higher prevalence of SENV-H in cirrhotics may point to its possible role in the development of cirrhosis.

Emergence of hepatitis B virus genotype f in aligarh region of north India.

Introduction. HBV genotypes and subtypes are useful clinical and epidemiological markers. In this study prevalent HBV genotypes were assessed in relation to serological profile and clinical status. Material & Methods. 107 cases of HBV were genotyped. Detailed clinical history was elicited from them. HBsAg, HBeAg, anti-HBs, anti-HBe, and anti-HBc-IgM were assessed. HBV genotyping was performed using Kirschberg's type specific primers (TSP-PCR), heminested PCR, and Naito's monoplex PCR. Nucleotide sequencing was performed. Results. A total of 97 (91%) were genotyped following the methods of Kirschberg et al./Naito et al. Genotype D was by far the most prevalent genotype 91 (85.04%) in this region. A surprising finding was the detection of genotype F in 5 (4.67%) of our patients. Genotype A strangely was observed only in one case. In 85.7% genotype D was associated with moderate to severe liver disease, 43.9% HBeAg, and 18.7% anti-HBc-IgM positivity. Majority of genotype F (80%) was seen in mild to moderate liver disease. It was strongly associated with HBeAg 60% and 20% anti-HBc-IgM positivity. Conclusion. Emergence of genotype F in India merits further study regarding its clinical implications and treatment modalities. Knowledge about HBV genotypes can direct a clinician towards more informed management of HBV patients.

Prevalence of leptospira in acute hepatitis syndrome and assessment of IL-8 and TNF-alpha level in leptospiral hepatitis.

To study the prevalence of leptospira in acute hepatitis syndrome and to assess interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha levels in the pathogenesis of hepatitis due to leptospiral infection. Two hundred and forty-seven consecutive cases with symptoms of acute hepatitis and 30 healthy controls were enrolled in the study and detailed clinical history was elicited from them. Enzyme-linked immunosorbent assays (ELISAs) for HAV, HBV, HCV and HEV were performed to rule out common viral aetiology of hepatitis. IgM antibodies to leptospira were detected by ELISA. IL-8 and TNF-alpha levels were estimated in leptospira-positive cases and healthy controls by ELISA. Out of 247 cases of acute hepatitis, 46 (18.62%) were observed to be positive for IgM antibodies for leptospira. The mean age of these patients was 31.99 ± 0.28 years (25 males and 21 females; M/F ratio: 1.19:1). The mean ALT, AST and ASP were raised in the majority of patients. IL-8 was found to be elevated (130.81 pg/ml) in a large majority of cases 41/46, 89.1% (P < 0.001). Patients with more severe symptoms were associated with higher levels of IL-8. One mortality was observed due to leptospira. Unpredictably, TNF-alpha level was largely suppressed (45.63 pg/ml) in most of the leptospira-positive patients in comparison with healthy controls. Leptospira-induced hepatitis should be actively looked for in patients negative for A-E viral hepatitis. IL-8 appears to play an important role in the pathogenesis of leptospiral hepatitis. High TNF-alpha should alert clinicians for aggressive in hospital management of patients.

Clinical manifestations and role of proton pump inhibitors in the management of laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) refers to the backflow of stomach contents into the throat that is into the hypopharynx. LPR is different from classical Gastroesophageal reflux disease (GERD) in many ways. Proton pump inhibitors have become the treatment of choice even though conflicting results exists in their response. Treatment requires acid suppression to be as complete as possible and treatment failure is not uncommon. In this article we present here our prospective study of 50 patients diagnosed as a case of LPR on the basis of reflux finding score and reflux symptom index. We tried to evaluate the role of PPI in LPR management by observing the effect of PPI on reflux finding score (RFS) and reflux symptom index (RFI) during the follow up period of 16 weeks.

A clinico-epidemiological study of pyogenic meningitis in children.

PIP: The study was conducted among the inpatients of the pediatric ward of J.N. Medical College Hospital, Aligarh Muslim University in India, from January 1989 to December 1991, to determine the etiological factors and the prevalence of pyogenic meningitis. Personal and family histories were recorded. Of 8168 patients admitted to the pediatric ward during the study period; 226 (2.73%) had pyogenic meningitis. 48.23% were under 3 years old, 17.73% were 9-14 years old. A male predominance (male to female ratio = 1.89 : 1) was observed. 67.94% of patients with pyogenic meningitis were urban dwellers, 71.05% lived in overcrowded conditions, and 82.75% belonged to large families. Seasonal variation of pyogenic meningitis was also noted with the peak (58.25%) in winter months. Mothers of 57.96% patients with pyogenic meningitis were illiterate. Proportional mortality was 3.7%. Maximum cerebrospinal fever rate (CFR) was noted in children under 3 years old (41.79% in males and 45.23% in females), belonging to large families (38.09%), those with illiterate mothers (49.01%), and those residing in rural areas (48.82%). CFR was highest (52.82%) among the patients who had to travel more than 10 km to reach the hospital and who were hospitalized 6-9 days after the onset of symptoms (52.45%). Since younger people are at risk of developing meningitis, health care services should also integrate facilities for early diagnosis and treatment of pyogenic meningitis, with an ambulance available at the primary health center level.^ieng

Role of dietary fibre on platelet adhesiveness.

Fifty five adult patients of diabetes mellitus and fourteen normal healthy subjects matched for age and sex were studied to see the effect of dietary fibre on platelet adhesiveness. In patients of diabetes mellitus the platelet adhesiveness 2 1/2 hrs. after a load of glucose was significantly higher (p = less than 0.001) as compared to normal individuals under the same conditions. After a glucose load with fibre the platelet adhesiveness in patients with diabetes mellitus fell significantly (p = less than 0.001). Although there was a fall in platelet adhesiveness in normal subjects also, it was statistically not significant. Supplements of fibre in the diet of diabetic patients may prevent or delay the vascular complications.