Association of interleukin-28B rs12979860 and rs8099917 polymorphisms with sustained viral response in hepatitis C virus genotype 1 and 3 infected patients from the Indian subcontinent.

BACKGROUND: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) have been shown to impact treatment responses in hepatitis C virus (HCV) infected patients. The association of these polymorphisms with sustained viral response (SVR) has been studied in HCV genotype 3 infected patients in India, but not in genotype 1. OBJECTIVES: This study aimed to determine the association of IL28B gene polymorphisms and other host and viral factors with treatment response in patients with HCV genotype 1 and 3 infection. MATERIALS AND METHODS: DNA from 42 HCV-infected patients on antiviral therapy was analysed for the IL28B polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Bidirectional sequencing was performed on a subset of samples for verification of PCR-RFLP results. Information on age, weight, height, diabetic status, pre-treatment viral load and alanine aminotransferase (ALT) levels was obtained from clinical records. The IL28B genotypes and the other factors were analysed for their association with SVR. RESULTS: The frequency distribution of rs12979860 CC/CT/TT genotypes was found to be 66.7%, 26.2% and 7.1%, respectively. For rs8099917 genotype, the TT/GT/GG distribution was 73.8%, 21.4% and 4.8%, respectively. SVR was seen in 61.9% of cases (55.6% in genotype 1 and 62.5% in genotype 3). CC genotype at rs12979860 and TT genotype at rs8099917 were significantly higher in responders (P = 0.013 and 0.042, respectively). Lower baseline ALT and rapid viral response were also found to be associated with SVR. On logistic regression analysis, CC genotype at rs12979860 emerged as the most powerful predictor of treatment response. CONCLUSION: IL28B polymorphisms are strong predictors of SVR in patients from the Indian subcontinent infected with HCV genotype 3 and genotype 1.

Pathological changes in hippocampal neuronal circuits underlie age-associated neurodegeneration and memory loss: positive clue toward SAD.

Among vertebrates hippocampus forms the major component of the brain in consolidating information from short-term memory to long-term memory. Aging is considered as the major risk factor for memory impairment in sporadic Alzheimer's disease (SAD) like pathology. Present study thus aims at investigating whether age-specific degeneration of neuronal-circuits in hippocampal formation (neural-layout of Subiculum-hippocampus proper-dentate gyrus (DG)-entorhinal cortex (EC)) results in cognitive impairment. Furthermore, the neuroprotective effect of Resveratrol (RSV) was attempted to study in the formation of hippocampal neuronal-circuits. Radial-Arm-Maze was conducted to evaluate hippocampal-dependent spatial and learning memory in control and experimental rats. Nissl staining of frontal cortex (FC), subiculum, hippocampal-proper (CA1→CA2→CA3→CA4), DG, amygdala, cerebellum, thalamus, hypothalamus, layers of temporal and parietal lobe of the neocortex were examined for pathological changes in young and aged wistar rats, with and without RSV. Hippocampal trisynaptic circuit (EC layerII→DG→CA3→CA1) forming new memory and monosynaptic circuit (EC→CA1) that strengthen old memories were found disturbed in aged rats. Loss of Granular neuron observed in DG and polymorphic cells of CA4 can lead to decreased mossy fibers disturbing neural-transmission (CA4→CA3) in perforant pathway. Further, intensity of nissl granules (stratum lacunosum moleculare (SLM)-SR-SO) of CA3 pyramidal neurons was decreased, disturbing the communication in schaffer collaterals (CA3-CA1) during aging. We also noticed disarranged neuronal cell layer in Subiculum (presubiculum (PrS)-parasubiculum (PaS)), interfering output from hippocampus to prefrontal cortex (PFC), EC, hypothalamus, and amygdala that may result in interruption of thought processes. We conclude from our observations that poor memory performance of aged rats as evidenced through radial arm maze (RAM) analysis was due to the defect in neuronal-circuits of hippocampus (DG-CA4-CA1-Sub) that were significantly damaged leading to memory impairment. Interestingly, RSV was observed to culminate pathological events in the hippocampal neuronal circuit during aging, proving them as potent therapeutic drug against age-associated neurodegeneration and memory loss.

Removal of nickel(II) from aqueous solution using Citrus Limettioides peel and seed carbon.

The agricultural wastes like Citrus Limettioides peel and seed to be suitable precursor for the preparation of carbon [Citrus Limettioides peel carbon (CLPC) and seed carbon (CLSC)] has been explored in the present work, utilizing sulfuric acid as the activating agent. Adsorption studies were performed by varying contact time, solution pH, adsorbent dose and temperature. The equilibrium time for Ni(II) ions was determined as 4h and optimal pH was 4-7. Surface morphology and functionality of the CLPC and CLSC were characterized by SEM, EDX and FT-IR. The experimental data were analysed using the Freundlich, Langmuir, Temkin, Redlich-Peterson, Sips and Dubinin-Radushkevich adsorption isotherm equations using nonlinear regression analysis. Equilibrium data were found to fit well in the Langmuir isotherm, which confirmed the monolayer coverage of Ni(II) ions. The Langmuir monolayer adsorption capacity of CLPC and CLSC was found to be 38.46 and 35.54 mg/g. The thermodynamic parameters indicated that the adsorption process was spontaneous and exothermic in nature. The kinetic data followed pseudo-second order model with film diffusion process. The adsorbents were tested with Ni(II) plating wastewater in connection with the reuse and selectivity of the adsorbents.

Stromal myofibroblasts in oral squamous cell carcinoma and potentially malignant disorders.

INTRODUCTION: Concurrent with the progression of a non- diseased epithelium to the pre-cancerous epithelium to carcinoma, the stroma also undergoes modifications. Myofibroblasts are important stromal cells that play a crucial role in carcinogenesis. The current study investigated the presence of myofibroblasts in healthy oral mucosa, potentially malignant disorders (PMDs) and squamous cell carcinoma (SCC). MATERIALS AND METHODS: The study material consisted of a total of 106 samples categorized into three groups, namely, Group I - Oral SCC (OSCC) (n = 42), Group II - PMDs (n = 32) and Group III - Oral healthy mucosa (n = 32) subjected to immunohistochemical analysis using alpha Smooth Muscle Actin. RESULTS: Among the 42 cases of OSCC, the staining index was negative in 23 cases (54.7%), low in 9 cases(21.4%) and moderate in 10 cases (23.8%). The stroma of cases of verrucous carcinoma, cases of Hyperkeratosis with epithelial dysplasia, 77.5% of the cases of oral Submucous Fibrosis (OSMF) and healthy oral mucosa were devoid of myofibroblasts resulting in a grade of "0" in all cases.Two of the cases of OSMF (12.5%) showed low staining index for myofibroblast. There was a significant difference in the myofibroblasts expression between the Groups (Kruskal-Wallis test P<0.001). CONCLUSION: The findings of the current study justify "myofibroblast" as one among the key stromal element in tumor progression. Future studies involving a larger sample size along with follow up of patients with PMDs are essential to identify the exact stage in which they emerge in the stroma of these lesions.

The role of single nucleotide polymorphisms of the ERCC1 and MMS19 genes in predicting platinum-sensitivity, progression-free and overall survival in advanced epithelial ovarian cancer.

OBJECTIVE: This study aims to assess the role of polymorphisms in DNA repair genes, excision repair cross-complementation group 1 (ERCC1) and methyl-methanesulfonate sensitivity 19 (MMS19), in tumor response to platinum-based chemotherapy and survival in advanced epithelial ovarian cancer (EOC). METHODS: Single nucleotide polymorphism (SNP) analysis was performed on the paraffin-embedded tumor tissue of women with advanced EOC, treated with platinum-based chemotherapy at the University of Oklahoma Health Sciences Center. Polymorphisms from two ERCC1 (codon-118 and C8092A) and three MMS19 (rs2211243, rs2236575 and rs872106) gene loci were evaluated by real time PCR Allelic Discrimination Assay. RESULTS: Genotyping was performed in 107 patients, 45 platinum-sensitive and 62 platinum-resistant. ERCC1, codon-118 and C8092A genotyping was evaluable in 98 and 106 patients respectively and in all 107 patients for MMS19 polymorphisms. No differences were observed in genotype between platinum-sensitive and platinum-resistant patients. Polymorphisms in the ERCC1, codon-118 and MMS19 genes did not correlate with overall survival (OS), although a trend toward improved progression free survival (PFS) was observed in patients expressing the minor (GG) alleles of the rs872106 MMS19 gene. Women homozygous for the ERCC1-C8092A minor (AA) alleles had a significant increase in PFS compared to AC and CC patients and both AA and AC genotypes conferred improved survival over the major (CC) genotype. CONCLUSIONS: Polymorphisms in ERCC1, codon-118 and MMS19 genes are not associated with clinical response to platinum or survival. The ERCC1-C8092A genotypes containing an "A" allele were associated with significant improvement in PFS and OS strengthening the value of this specific genotype in survival.

BACE1 in Alzheimer's disease.

Targeting BACE1 (ß-site APP cleaving enzyme 1 or ß-secretase) is the focus of Alzheimer's disease (AD) research because this aspartyl protease is involved in the abnormal production of ß amyloid plaques (Aß), the hallmark of its pathophysiology. Evidence suggests that there is a strong connection between AD and BACE1. As such, strategies to inhibit Aß formation in the brain should prove beneficial for AD treatment. Aß, the product of the large type1 trans-membrane protein amyloid precursor protein (APP), is produced in a two-step proteolytic process initiated by BACE1 (ß-secretase) and followed by γ-secretase. Due to its apparent rate limiting function, BACE1 appears to be a prime target to prevent Aß generation in AD. Following its discovery, the BACE1 has been cloned, its structure solved, novel physiologic substrates discovered and numerous inhibitors developed. This review focuses on elucidating the role of BACE1 to facilitate drug development in the treatment of AD.

Salivary ferritin as a predictive marker of iron deficiency anemia in children.

OBJECTIVES: The objective of the study was to determine the salivary Ferritin levels in children with iron deficiency anemia and its reliability as a predictive marker of the disease and whether these levels could give a new hypothetical insight on the oral epithelial changes seen in patients with iron deficiency anemia. STUDY DESIGN: The study comprised of 60 children of which the study group comprised of 30 individuals; aged 8-14 years with iron deficiency anemia. Venous blood was collected and hematological examination was performed to determine the hemoglobin and serum ferritin levels to confirm the diagnosis. Saliva was then collected from 30 children with iron deficiency anemia and an equal number of controls. The ferritin levels in saliva were then analyzed using solid phase ELISA. RESULT: The mean value of salivary ferritin in iron deficient cases was 153.24 +/- 46.58 microg/dl and the mean ferritin levels in control subject were 93.87 +/- 30.15 microg/dl. Thus the salivary ferritin was found to be significantly higher in iron deficient subjects compared to the controls. CONCLUSION: The result of our research affirms the fact that the expression of ferritin in saliva of iron deficiency anemia may be due to the enzymatic functions in the saliva and the endocytosis of ferritin which can possibly elevate the salivary ferritin. The diminished level of cytochrome oxidase, together with its relatively high Ferritin content, depicts the association of oral epithelial changes and ferritin occurring in iron deficiency anemia.

Age estimation in an Indian population using pulp/tooth volume ratio of mandibular canines obtained from cone beam computed tomography.

The present study assessed the suitability of pulp/tooth volume ratio of mandibular canines for age prediction in an Indian population. Volumetric reconstruction of scanned images of mandibular canines from 140 individuals (aged ten - 70 years), using computed tomography was used to measure pulp and tooth volumes. Age calculated using a formula reported earlier for a Belgian sample, resulted in errors > ten years in almost 86% of the study population. The regression equation obtained for the Indian population: Age = 57.18 + (- 413.41 x pulp/tooth volume ratio), was applied to an independent control group (n = 48), and this resulted in mean absolute errors of 8.54 years which was significantly (p < 0.05) lower than those derived with the Belgian formula. The pulp/tooth volume ratio is a useful indicator of age, although correlations may vary in different populations and hence, specific formulae should be applied for the estimates.

Venous thrombo-embolism in India.

INTRODUCTION: Venous thrombo-embolism (VTE) has traditionally been considered rare in Asia. Recent reports from Hong Kong and Singapore indicate an increasing incidence of VTE. OBJECTIVES: To determine the incidence of VTE among hospitalised patients and study the predisposing factors and hence to increase the awareness of the need for VTE prophylaxis. METHODS: This is a retrospective study carried out on all patients diagnosed with VTE between 1996 and 2005 at our hospital. In-patient records were used to collect data while out-patient records were used for follow-up outcomes. RESULTS: The incidence of VTE was 17.46 per 10,000 admissions. Malignancy (31%) was the most common predisposing factor, followed by postoperative status (30%). The incidence following surgery was five per 10,000 operations. General surgery patients had the highest incidence of deep vein thrombosis (DVT; 40.3%), while the incidence in orthopaedic patients was 20.1%. Low-molecular-weight heparin (LMWH) has been increasingly used therapeutically over the years. Pulmonary embolism was diagnosed in 14.9% of the study patients. Mortality in those with confirmed pulmonary embolism was 13.5%. CONCLUSION: VTE is no longer a rarity in India. General surgical operations are the most common causes of postoperative DVT. Pulmonary embolism continues to be 'suspected' more often than it is diagnosed.

Production of diamino propionic acid ammonia lyase by a new strain of Salmonella typhimurium PU011.

BACKGROUND: Seeds of the legume plant Lathyrus sativus, which is grown in arid and semi arid tropical regions, contain Diamino Propionic acid (DAP). DAP is a neurotoxin, which, when consumed, causes a disease called Lathyrism. Lathryrism may manifest as Neurolathyrism or Osteolathyrism, in which the nervous system, and bone formation respectively, are affected. DAP ammonia lyase is produced by a few microorganisms such as Salmonella typhi, Salmonella typhimurium and Pseudomonas, and is capable of detoxifying DAP. RESULTS: S. typhimurium PU011, a non-virulent bacterial strain isolated in our lab, was found to produce DAP ammonia lyase enzyme when grown in minimal medium containing DAP. There was a direct correlation between biomass yield and enzyme activity, until 16 h post inoculation in minimal medium containing DAP. Following ammonium sulphate precipitation and passing through Sephadex G100, CM-Sephadex and DEAE-Sephacel for crude enzyme extract preparation, about 68-fold enzyme purity was obtained. The purified enzyme gave maximum activity at pH 8.0 and was stable up to 45 degrees C. The Km value for the substrate was found to be 0.685 mM, calculated from a Line Weaver Burk plot. CONCLUSION: A new bacterial strain, S.typhimurium PU 011, which is capable of producing DAP ammonia lyase, was isolated.