Safety and efficacy of an indigenous human recombinant interferon alpha 2b (Shanferon) in patients with chronic hepatitis B.

Interferon treatment is the established option for the treatment of patients with chronic hepatitis B without decompensated liver disease. However, such treatment is expensive. We report here our data of a multi-center, open-label trial of the use of an indigenously produced interferon in the treatment of chronic HBeAg-positive chronic hepatitis B. Adult patients with chronic HBeAg-positive hepatitis B with elevated serum transaminase activity and positive serum HBV DNA test were treated with 5 MU/day of an indigenously produced interferon (Shanferon; Shantha Biotechnics, Hyderabad, India) for 4 months, and were then followed up for 6 months. Of the 39 patients enrolled, 36 completed the treatment and 33 completed the post-treatment follow-up. Of the 33 patients who completed the study, end-of-treatment biochemical and virological responses were observed in 10 (30%) and 5 (15%) respectively. Sustained biochemical and virological responses were observed in 15 (45%) and 7 (21%), patients respectively. Adverse effects led to the discontinuation of treatment in only one patient. Our data suggest that safety and efficacy of the indigenously produced interferon were similar to those previously reported results with interferon from other sources.     

The effect of typicality on online category verification of inanimate category exemplars in aphasia

Background: A previous study (Kiran & Thompson, 2003a Kiran, S. and Thompson, C. K. 2003a. Effect of typicality on online category verification of animate category exemplars in aphasia.. Brain and Language, 85(3): 441–450.  [Google Scholar]) investigated the effect of typicality on online category verification of animate categories in patients with fluent or nonfluent aphasia and their normal controls. Results revealed a robust effect of typicality: typical examples were faster and more accurate than atypical examples of animate categories. Patients with fluent aphasia did not demonstrate the expected effects of typicality.

Aims: The aim of the present study was to extend this work to examine the effect of typicality on inanimate categories such as furniture, clothing, and weapons.

Methods & Procedures: Normal young, older, and aphasic individuals participated in an online category verification task where primes were superordinate category labels whereas targets were either typical or atypical examples of inanimate categories (e.g., clothing, furniture, weapons) or nonmembers belonging to animate categories. Aphasic participants were divided into two groups, semantic impairment group (SI) and no semantic impairment group (NSI), based on their performance on offline standardised semantic processing tests. The reaction time to judge whether the target belonged to the preceding category label was measured.

Outcomes & Results: Results indicated that all four groups were significantly faster and more accurate on typical examples compared to atypical examples. Further, differences emerged in the processing of categories, wherein responses to clothing were more accurate than responses to furniture or weapons. In the SI group, representation of typical examples and atypical examples were impaired, as evidenced by poor accuracy rates.

Conclusions: The present experiment demonstrated the typicality effect in normal individuals and in individuals with aphasia. Further, differences emerged in the processing of categories, where responses to clothing were more accurate than responses to furniture or weapons.     

Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis

Acute kidney injury may increase the risk for chronic kidney disease and end-stage renal disease. In an attempt to summarize the literature and provide more compelling evidence, we conducted a systematic review comparing the risk for CKD, ESRD, and death in patients with and without AKI. From electronic databases, web search engines, and bibliographies, 13 cohort studies were selected, evaluating long-term renal outcomes and non-renal outcomes in patients with AKI. The pooled incidence of CKD and ESRD were 25.8 per 100 person-years and 8.6 per 100 person-years, respectively. Patients with AKI had higher risks for developing CKD (pooled adjusted hazard ratio 8.8, 95% CI 3.1-25.5), ESRD (pooled adjusted HR 3.1, 95% CI 1.9-5.0), and mortality (pooled adjusted HR 2.0, 95% CI 1.3-3.1) compared with patients without AKI. The relationship between AKI and CKD or ESRD was graded on the basis of the severity of AKI, and the effect size was dampened by decreased baseline glomerular filtration rate. Data were limited, but AKI was also independently associated with the risk for cardiovascular disease and congestive heart failure, but not with hospitalization for stroke or all-cause hospitalizations. Meta-regression did not identify any study-level factors that were associated with the risk for CKD or ESRD. Our review identifies AKI as an independent risk factor for CKD, ESRD, death, and other important non-renal outcomes.     

Role of salivary vascular endothelial growth factor (VEGF) in palatal mucosal wound healing

The mucosa of alimentary tract heals more rapidly than cutaneous wounds. The underlying mechanisms of this enhanced healing have not been completely elucidated. Constant exposure to salivary growth factors has been shown to play a critical role in mucosal homeostasis and tissue repair. Angiogenesis also has an essential role in successful wound repair. One of the main angiogenic growth factors, vascular endothelial growth factor (VEGF), has a pleiotropic role in tissue repair via neovascularization, reepithelialization, and regulation of extracellular matrix. We have previously reported a critical role for salivary VEGF in bowel adaptation after small bowel resection. We hypothesize that salivary VEGF is an essential stimulus for oral mucosal tissue repair, and use the murine palatal wound model to test our hypothesis. In a loss‐of‐function experiment, we removed the primary source of VEGF production through selective submandibular gland (SMG) sialoadenectomy in a murine model and observed the effects on wound closure and neovascularization. We then performed a selective loss‐of‐function experiment using the protein VEGF‐Trap to inhibit salivary VEGF. In a gain‐of‐function experiment, we supplemented oral VEGF following SMG sialoadenectomy. After SMG sialoadenectomy, there was significant reduction in salivary VEGF level, wound closure, and vessel density. Lower levels of salivary VEGF were correlated with impaired neovascularization and reepithelialization. The selective blockade of VEGF using VEGF‐Trap resulted in a similar impairment in wound healing and neovascularization. The sole supplementation of oral VEGF after SMG sialoadenectomy rescued the impaired wound healing phenotype and restored neovascularization to normal levels. These data show a novel role for salivary‐VEGF in mucosal wound healing, and provide a basis for the development of novel therapeutics aimed at augmenting wound repair of the oral mucosa, as well as wounds at other sites in the alimentary tract.     

Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer

Prostate cancer is the most commonly diagnosed cancer disease in men in the Unites States and its management remains a challenge in everyday oncology practice. Thus, advanced therapeutic strategies are required to treat prostate cancer patients. Curcumin (CUR) is a promising anticancer agent for various cancer types. The objective of this study was to evaluate therapeutic potential of novel poly(lactic-co-glycolic acid)- CUR nanoparticles (PLGA-CUR NPs) for prostate cancer treatment. Our results indicate that PLGA-CUR NPs efficiently internalize in prostate cancer cells and release biologically active CUR in cytosolic compartment of cells for effective therapeutic activity. Cell proliferation (MTS), clonogenic, and Western blot analyses reveal that PLGA-CUR NPs can effectively inhibit proliferation and colony formation ability of prostate cancer cells than free CUR. PLGA-CUR NPs showed superior tumor regression compared to CUR in xenograft mice. Further investigations reveal that PLGA-CUR NPs inhibit nuclear β-catenin and AR expression in cells and in tumor xenograft tissues. It also suppresses STAT3 and AKT phosphorylation and leads to apoptosis via inhibition of key anti-apoptotic proteins, Mcl-1, Bcl-xL and caused induction of PARP cleavage. Additionally, significant downregulation of oncogenic miR21 and up-regulation of miR-205 was observed with PLGA-CUR NPs treatment as determined by RT-PCR and in situ hybridization analyses. A superior anti-cancer potential was attained with PSMA antibody conjugated PLGA-CUR NPs in prostate cancer cells and a significant tumor targeting of ¹³¹I labeled PSMA antibody was achieved with PLGA-CUR NPs in prostate cancer xenograft mice model. In conclusion, PLGA-CUR NPs can significantly accumulate and exhibit superior anticancer activity in prostate cancer.     

Fat-soluble nutraceuticals and their composition in heat-processed wheat germ and wheat bran

Nutraceuticals availability in heat-processed foods is considered to be the index for healthy food. This study has made an attempt to optimize the temperature to retain nutraceuticals in wheat bran (WB) and wheat germ (WG). Heated WG (130?°C &; 140?°C) and WB (140?°C &; 150?°C) were analyzed for sensory profiles. Extracted oils were subjected to physicochemical parameter as well as its nutraceuticals. Increased oil yield, color values and reduced free fatty acids were found with varied temperatures. Fat-soluble compounds total tocols, steryl ferulates and carotenoids found in WG (0.316, 0.058 and 0.011%) and WB (0.228, 0.595 and 0.015%) and maximum reductions started in WG (0.183%, 0.034% and 0.004%) at 130?°C. The free radical-scavenging activities of control samples showed high EC₅₀ values than processed samples; however, no differences were observed between two temperatures. Study may clearly spell out that the reduced nutraceuticals observed after subjecting food raw materials to optimum temperature eventually lead to its quality.     

Congenital diaphragmatic hernia repair in patients on extracorporeal membrane oxygenation: How early can we repair?

Background

The benefits to early repair (< 72?h postcannulation) of infants with congenital diaphragmatic hernia (CDH) on extracorporeal membrane oxygenation (ECMO) are increasingly recognized. Yet it is not known if even earlier repair (< 24?h) results in comparable or improved patient outcomes. The goal of this study was to compare “super-early” (< 24?h) to early repair (24-72?h) of CDH patients on ECMO.