Cataract and its risk factor among adults residing in South Bihar, India

Background: Cataract is considered as one of the most common causes of visual impairment and the leading cause of blindness in the world. Age related cataract occurs in people above 50 years of age and the its pathogenesis is multifactorial. Therefore, the present study was aimed to assess the prevalence and risk factors for cataract.Methods: Community based cross sectional study was conducted among adults residing at urban areas of South Bihar. The data was collected by interview method, using pre-tested semi-structured questionnaire which contains socio-demographic data, dietary habits, history of diabetes or hypertension, family history of cataract and long-term sun exposure.Results: Among 240 participants, 94 (39.2%) were male and 146 (60.8%) were female. Maximum participants were aged more than 70 years. The prevalence of cataract was 52.1%.Conclusions: The prevalence of cataract was quite high and was significantly associated with age, long term sun exposure and family history of cataract

183 A phase 1B/2A trial of tofacitinib, an oral janus kinase inhibitor, in systemic lupus erythematosus

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Biotechnology-based pharmaceutical products

Biotechnology-based pharmaceutical products as an essential portion of the marketed therapeutic agents are continuously evolving due to the increased number of approved products as well as products entering clinical trials. Biotechnology involves the use of a living organism or their products for human use including medical purposes. Production of therapeutic agents through biotechnology is a complex multistep process that requires careful considerations in various aspects. Therefore it is essential to understand the differences between biotechnology-based drugs and conventional drugs. Currently, different classes of therapeutic agents are produced via biotechnology, such as antibiotics, enzymes, vaccines, and monoclonal antibodies. In this chapter, the general production process of biotechnology-based pharmaceutical products is discussed along with their pharmacokinetic properties with particular emphasis on the common problems associated with these products. Finally, biotechnology-based therapeutic approaches such as gene therapy and pharmacogenomics are also briefly discussed

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Atovaquone Suppresses the Growth of Metastatic Triple-Negative Breast Tumors in Lungs and Brain by Inhibiting Integrin/FAK Signaling Axis

Triple-negative breast cancer (TNBC) is considered to be the most aggressive and malignant neoplasm and is highly metastatic in nature. In the current study, we investigated the anti-metastatic potential of atovaquone, a protozoal drug prescribed for Pneumocystis pneumonia. We showed that atovaquone induced apoptosis and reduced the survival of several aggressive metastatic TNBC cell lines including metastatic patient-derived cells by reducing the expression of integrin α6, integrin β4, FAK, Src, and Vimentin. In order to study the efficacy of atovaquone in suppressing metastasized breast tumor cells in brain and lungs, we performed three in vivo experiments. We demonstrated that oral administration of 50 mg/kg of atovaquone suppressed MDA-MB-231 breast tumor growth by 90% in lungs in an intravenous metastatic tumor model. Anti-metastatic effect of atovaquone was further determined by intracardiac injection of 4T1-luc breast tumor cells into the left ventricle of mouse heart. Our results showed that atovaquone treatment suppressed the growth of metastatic tumors in lungs, liver and brain by 70%, 50% and 30% respectively. In an intracranial model, the growth of HCC1806-luc brain tumors in atovaquone treated mice was about 55% less than that of control. Taken together, our results indicate the anti-metastatic effects of atovaquone in vitro and in vivo in various breast tumor metastasis models

Abstract 3176: Inhibition of HER2/β-catenin signaling by penfluridol overcomes resistance to paclitaxel in breast cancer

Abstract Paclitaxel is a first line treatment option for patients with metastatic breast cancer. However, inherited or acquired resistance is a limiting factor for therapy with paclitaxel. The mechanism of paclitaxel resistance remains obscured and hinders the development of therapeutic strategies. HER2 is an oncogene overexpressed in about 30% of breast cancer patients and plays role in drug resistance leading to poor prognosis. To identify more clinically relevant mechanism of paclitaxel resistance, we developed resistance to paclitaxel in MCF-7 and 4T1 breast cancer cell lines. The continuous exposure to paclitaxel for several months resulted in &amp;gt;1000 fold resistance in MCF-7 cells and &amp;gt;100 fold resistance in 4T1 cells. Western blot analysis showed enhanced expression of HER2, β-catenin and downstream molecules such as TCF/LEF, c-Myc, Cyclin D in these resistant cells. We have recently demonstrated that penfluridol, an anti-psychotic drug, suppresses the growth of triple negative metastatic breast cancer cells (Ranjan and Srivastava, Cancer Res 2016; 76(4): 877-890), giving us the rationale to evaluate whether penfluridol inhibits HER2 and β-catenin signaling. Our current results showed that penfluridol treatment not only suppressed HER2 but also inhibited β-catenin expression. We also observed down regulation of LEF-1/TCF, Cyclin D1 and c-Myc expression with penfluridol treatment in paclitaxel sensitive as well as resistant cells resulting in reduced survival of cells. Our results further showed that penfluridol treatment synergistically enhanced the growth suppressive effects of paclitaxel in MCF-7 and 4T1 paclitaxel resistant cells. Treatment of paclitaxel resistant 4T1 cells with 1.5μM of penfluridol in combination with 50nM of paclitaxel resulted in 65% of cell growth suppression whereas either treatment alone was not cytotoxic at all. We also observed an enhanced down regulation of proteins involved in paclitaxel resistance such as HER2, β-catenin, c-Myc and Cyclin D1 as well as increase in apoptotic markers such as Cl-PARP and Cl-Caspase3 when paclitaxel treatment was combined with penfluridol in resistant cells. Taken together, our results provided a novel insight into the mechanism of resistance to paclitaxel and also opened new avenues for application of penfluridol in cancer therapeutics. Further detailed mechanistic and in vivo studies are in progress. (Supported in part by RO1 grant CA129038, awarded by National Cancer Institute, NIH). Citation Format: Nehal Gupta, Parul Gupta, Sanjay Srivastava. Inhibition of HER2/β-catenin signaling by penfluridol overcomes resistance to paclitaxel in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3176. doi:10.1158/1538-7445.AM2017-3176</jats:p