Synthesis,antitubercular and anticancer activity of new Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives

Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on Mycobacterium tuberculosis H₃₇Rv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds (3j–l) have shown significant activity against Mycobacterium strain and the compound 3l has shown specific cytotoxic activity.     

In Vitro Analysis of Bacosine as Novel Therapeutic Agent for Murine Breast Cancer

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The anti-metastatic activity of bacosine (Bacopa monnieri plant) was studied using 4T1 murine breast cancer...     

Surgeons often underestimate the amount of blood loss in replacement surgeries

Objective：To assess the accuracy of the clinically estimated blood loss （EBL） when compared with the actual blood loss （ABL） in replacement surgeries.Methods：This prospective study was done in Sri Ramachandra Medical Centre from April 2011 to April 2013.Altogether 140 patients undergoing total hip replacement or total knee replacement were included with the inclusion criteria being patients with haemoglobin higher than 100 g/ml and coagulation profile within normal limits.Exclusion criteria were intake of antiplatelet drug or anti-coagulant,bleeding disorders,thrombotic episode,and haematological disorders.There were 65 men and 75 women.In this study,the consultants were free to use any clinical method to estimate the blood loss,including counting the blood-soaked mops and gauze pieces （estimating the volume of blood carded in all the mops and gauzes）,measuring blood lost to suction bottles and blood in and around the operative field.The ABL was calculated based on a modification of the Gross＇s formula using haematocrit values.Results：In 42 of the 140 cases,the EBL exceeded the ABL.These cases had a negative difference in blood loss （or DIFF-BL＜0） and were included in the overestimation group,which accounted for 30％ of the study population.Of the remaining 98 cases （70％）,the ABL exceeded the EBL.Therefore they were put into the underestimation group who had a positive difference in blood loss （DIFF-BL＞0）.We found that when the average blood loss was small,the accuracy of estimation was high.But when the average blood loss exceeded 500 ml,the accuracy rate decreased significantly.This suggested that clinical estimation is inaccurate with the increase of blood loss.Conclusion：This study has shown that using clinical estimation alone to guide blood transfusion is inadequate.In this study,70％ of patients had their blood loss underestimated,proving that surgeons often underestimate blood loss in replacement surgeries.     

Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis

We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.     

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.     

Acute Renal Failure after Cesarean Section

Urinary ascites is a rare diagnosis, commonly associated with bladder rupture. We present a case of intraperitoneal bladder injury following a Cesarean section with subsequent development of urinary ascites. Initial laboratory data with elevated serum creatinine and blood urea nitrogen (BUN) raised the suspicion for acute kidney injury due to the recent obstetrical procedure. This case highlights the importance of including intraperitoneal bladder injury with urinary ascites as a key differential in the workup of acute renal failure, particularly in the obstetric surgical setting. The rapid development of ascites with elevated serum BUN and creatinine should prompt work up for evaluating intraperitoneal bladder injury. Early diagnosis and treatment can yield gratifying results and avoid unnecessary workup of other causes of renal failure.     

印度传统医药临床试验的现状和监管

根据世界卫生组织的定义,传统医药包括多样的保健行为、方法、知识和信念,结合植物、动物和/或矿物性药物、精神疗法、手工技术和训练,以单独或合并的方式提供,以维持健康,治疗、诊断或预防疾病。传统药物在发展中国家仍得到广泛的发展,同时,补充和替代药物在发达国家也增长迅速。印度在传统医药管理的发展和执行上正面临着巨大挑战,这些挑战涉及到管理、安全性和功效的评估、质量控制和安全监管等。一旦违背了一贯的使用方法和信念,传统医药可能构成严重的健康威胁。除了直接的副作用和药物的相互作用,还有一个间接的威胁就是,没有被证明效…     

Synthesis and antitumour evaluation of 4-bromophenyl semicarbazones

4-Bromophenyl semicarbazone derivatives have been synthesized and their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analyses. The in vitro evaluation in the 3-cell line, one dose primary anticancer assay is described. The 4-bromo substituted p-nitrobenzylidene phenyl semicarbazone (5) showed significant activity against breast MCF7 cell line and was further evaluated for potential anticancer activity in an in vitro human disease-oriented tumour cell line screening panel that consisted of 59 human tumour cell lines arranged in nine subpanels, representing diverse histologies. Melanoma UACC-62 cell line was relatively more sensitive to compounds 5 (growth inhibitions: GI50 = 15.3 mumol/l).     

Radiation exposure impairs luteinizing hormone signal transduction and steroidogenesis in cultured human leydig cells.

Therapeutic, accidental, and experimental radiation exposures decreased serum testosterone in males, leading to various sexual problems. Since testicular Leydig cells are the predominant source of circulating testosterone, findings on the direct effects of radiation on Leydig cell steroidogenesis and the mechanism behind such effects would be of greater importance to the use of safer radiation doses in cancer therapy and to adopt preventive or therapeutic measures to alleviate postirradiation lesions, respectively. Therefore, this study was undertaken to explore the same using cultured human Leydig cells. Testicles removed from advanced prostatic carcinoma patients were used for isolation and purification of Leydig cells. Purified Leydig cells were cultured and then exposed to different doses (2, 4, 6, 8, and 10 Gy) of fractioned gamma radiation. Normal and irradiated cells were used for luteinizing hormone (LH) receptor quantification or total RNA isolation to study LH receptor mRNA expression or LH/cyclic AMP (cAMP) stimulation test. While LH-stimulated cells were used for cAMP assay, LH- and cAMP-stimulated cells were used for the estimation of steroidogenic enzymes, testosterone and estradiol production. Radiation exposure caused adverse effects on Leydig cell steroidogenesis in a dose-dependent manner. While lower doses (2 and 4 Gy) were ineffective, higher doses (6 Gy and above) drastically decreased LH receptor, basal and LH-stimulated cAMP generation, and basal, LH-, and cAMP-stimulated steroidogenesis. While 2 Gy of radiation exposure increased the LH receptor mRNA level, other doses did not induce any significant change. Therefore, it is concluded that higher doses of radiation impair Leydig cell steroidogenesis by affecting LH signal transduction at the level of both pre- and post-cAMP generation. Decreased level of LH receptors following higher doses of radiation exposure is not coupled with impaired expression of its mRNA.