Oligomeric proanthocyanidins protect myocardium by mitigating left ventricular remodeling in isoproterenol‐induced postmyocardial infarction

Extracellular matrix (ECM) remodeling is a major pathophysiological process during post‐myocardial infarction (MI). The activation, differentiation, and proliferation of cardiac fibroblasts to myofibroblasts regulate the expression of ECM proteins. The signaling by bone morphogenetic protein (BMP‐4), an extracellular ligand of the TGF‐β family, has recently been identified as an essential pathway in regulating cardiovascular dysfunctions including myocardial fibrosis. Oligomeric proanthocyanidins (OPC) are well known for their cardioprotective activity. The primary aim of the study was to investigate BMP‐4‐mediated ECM turnover in cardiac fibrosis during isoproterenol‐induced post‐MI and its downregulation by OPC. Myocardial injury was evaluated by assaying serum markers LDH and CK. Oxidative stress and the enzymatic and nonenzymatic antioxidant levels were assessed to support the cardioprotective nature of OPC. The total collagen level was analyzed by measuring hydroxyproline levels. The ISO‐induced group showed a significant decrease in the levels of antioxidants due to severe oxidative stress and increased expression of BMP‐4 which reflects the increased expression of MMP 2 and 9 with a concomitant increase and deposition of fibrillary collagens type I and III responsible for the fibrotic scar formation as evidenced in the histological analysis.BMP‐4 activation, thus, is strongly associated with cardiac fibrosis which was downregulated upon OPC supplementation. This study provides an evidence supporting the antifibrotic effect of OPC via regulation of BMP‐4‐mediated ECM turnover and also substantiates the remarkable antioxidant efficacy of OPC against isoproterenol induced severe oxidative stress and subsequent post‐MI cardiac fibrosis.     

Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: a single center's experience

BACKGROUND: Chronic renal failure leads to amenorrhea, and successful pregnancy is rare. The aim of the present report is to examine the outcome of pregnancies under tacrolimus after kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx). METHOD: All pregnancies under tacrolimus after KTx or SPKTx from 1993 to April 2002 were retrospectively examined. Renal function and the mother's survival were followed until December 2002. RESULTS: Thirteen mothers after KTx delivered 19 babies, and 2 mothers after SPKTx delivered 3 babies. All mothers survived the pregnancy and retained allograft function. One mother had a stillborn baby from an unrecognized amniotic fluid leak and a small ischemic placenta. The mean gestational period was 34.4 +/- 5.1 weeks. Mean birth weight was 2373 +/- 1001 g. Birth-weight percentile to gestational period was 40 +/- 28. None of the mothers experienced rejection during the pregnancy. Three pregnancies in mothers with KTx experienced toxemia of pregnancy, and one mother with SPKTx developed pre-eclampsia during both pregnancies. Five mothers (6 deliveries, 27.3%) required caesarian section. During the follow-up period, one mother died from a cerebrovascular accident. Another five mothers returned to dialysis 55.6 +/- 32.4 months after the last delivery and 99.4+28.5 months after the last KTx. Both SPKTx mothers have maintained normal renal and pancreatic allograft function 42 and 62 months postdelivery. CONCLUSION: All mothers survived the pregnancy. One baby was stillborn. Forty-one percent of babies were either preterm or premature, and 27% of babies were delivered by caesarean section. Toxemia of pregnancy or pre-eclampsia was observed in 23% of pregnancies postKTx and SPKTx. None of the mothers experienced rejection during their pregnancy.     

Synthesis of 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives as potential antimicrobial agents

In the present study, a series of 1-ethyl/benzyl-6-fluoro-7-(substituted piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid were synthesized and characterized by IR, 1H-NMR, mass spectral and elemental analysis. The in vitro antibacterial and antifungal activities of the compounds were evaluated by paper disc diffusion method. The minimum inhibitory concentrations (MIC) of the compounds were also determined by agar streak dilution method. The in vivo antibacterial activity of the compounds against Escherichia coli was also evaluated by mouse protection test. All the compounds exhibited significant antibacterial and weak antifungal activities. The in vivo antibacterial activity (ED50) against E. coli was 50-160 mg kg(-1) in the order of 7<9<8<10. 1-ethyl-6-fluoro-7-(2,5-dioxo-piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid (7) was found to exhibit the most potent in vitro antimicrobial activity with MIC of 4.1, 3.1, 3.1, 2.4, 1, 1, 25 and >100 microg mL(-1) against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, E. coli, Klebsiella pneumoniae, Candida albicans and Aspergillus niger.     

Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center's experience update at 13 years

BACKGROUND: Chronic liver disease often leads to amenorrhea in women of childbearing age. There are several reports of successful pregnancy after liver transplantation (LTx) with cyclosporine A immunosuppression. Tacrolimus has been increasingly used in solid-organ transplantation, and the effect of the drug on pregnancy is still of interest to clinicians. This study updates our single-center experience. METHODS: All pregnancies after LTx with tacrolimus immunosuppression were followed prospectively. Patients' clinical courses during pregnancy and labor along with gestational period and birth weight were catalogued. Changes in liver function, renal function, and immunosuppression also were recorded. The birth weight percentile was calculated on the basis of the gestational period using a standard chart. RESULTS: Thirty-seven mothers delivered 49 babies. Three mothers delivered three times, and six mothers delivered two times. Thirty-six mothers (97%) survived the pregnancy, and 36 allografts (97%) survived. The one death and graft loss was in a patient who demonstrated infra-aortic arterial graft, which clotted by the gravid uterus during labor. The patient developed a gangrenous liver and died before she could undergo retransplantation. The mean gestational period was 36.4+/-3.2 weeks, excluding two premature deliveries at 23 and 24 weeks gestation. Twenty-two babies (46.9%) were delivered by cesarean section, and the other babies were delivered vaginally. In addition to the two premature babies, one baby, who was born to a mother with Alagille syndrome, died from congenital birth defects. The rest of the newborns survived. The mean birth weight was 2,797+/-775 g, with 38 babies (78%) weighing more than 2,000 g. The mean birth weight percentile to gestational period was 54+/-23. Four babies (8.5%) had a birth weight percentile of less than 25, and 28 babies (59.6%) had a birth weight percentile greater than 50. Twelve patients demonstrated an increase in hepatic enzymes without jaundice during the pregnancy. All of them responded to augmentation of immunosuppression. CONCLUSION: The present report reconfirms the safety of tacrolimus during pregnancy after LTx. Preterm delivery and low birth weight seem to be a persistent problem in all solid-organ transplantation under any form of immunosuppression. However, toxemia of pregnancy and new onset of hypertension seem to be have a low occurrence with the use of tacrolimus.     

Hepatitis C virus (HCV) RNA level in plasma and kidney tissue in HCV antibody‐positive donors: Quantitative comparison

Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real‐time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody‐positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8 IU/50 nL kidney). In three NAT‐negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT‐positive donors, HCV RNA was positive in plasma (range: 5807‐19 134 177 IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5 million IU/μL. HCV RNA correlated between right and left kidneys (P = 0.75) and between kidney and plasma (r = 0.86). When normalized by volume, HCV RNA median (range) was 49 (0‐957) IU/50 nL plasma and 1.0 (0‐103) IU/50 nL kidney, significantly lower in kidney (P = 0.005) than in plasma (14‐fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post‐transplant management in extended utilization of HCV antibody‐positive donors.     

Oriental cholangiohepatitis masquerading as cholangiocarcinoma: A rare presentation that surgeons need to know

INTRODUCTIONThe detection of an abnormal hepatic mass with ductal dilatation is highly concerning for malignancy. However, if such patients happen to be immigrants from endemic parts of Asia or South America, further investigations are necessary to rule out oriental cholangiohepatitis, a rare recurrent disease of the hepatobiliary system that can masquerade as cholangiocarcinoma.PRESENTATION OF CASEWe report a case of a patient of South Asian origin who presented to us with acute cholangitis and moderately dilated left hepatic ducts. The findings were highly suspicious for advanced hepatic malignancy; however the laboratory and pathological investigations remained normal. We suspected an unlikely etiology and proceeded with conservative hepatic resection. The histology revealed cholangiohepatitis without any evidence of malignancy.DISCUSSIONCholangiohepatitis is a complex hepatobiliary disease that commonly manifests as recurrent cholangitis or overt biliary sepsis and can rarely present as an abnormal hepatic mass. It results from the development of intrahepatic or extrahepatic strictures that causes stone formation and biliary dilation in the absence of gallbladder disease. Although it is endemic in many parts of the world, it is rare in the western world, and therefore it can present as a significant diagnostic enigma.CONCLUSIONCholangiohepatitis is a rare clinical entity that requires a multi-disciplinary team approach. Surgery plays a dominant role in the management of such patients and therefore surgeons need to be aware of this disease.     

Primary fallopian tube carcinoma

Primary fallopian tube cancer constitutes 1% of gynecologic malignancies. Early clinical manifestation and prompt investigations lead to diagnosis in the early stage of disease accounting for a better survival compared with ovarian cancer. Principles of management generally follow that of epithelial ovarian cancer. This article reviews the current understanding of this rare cancer. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the clinical features of a patient with fallopian tube carcinoma, to list the prognostic factors associated with fallopian tube cancer, and to outline the treatment options for a patient with fallopian tube cancer.     

Glycoprotein changes in non-insulin dependent diabetic rats: effect of N-benzoyl-D-phenylalanine and metformin

The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin on neonatal streptozotocin (nSTZ) induced diabetes has been studied on plasma and tissue glycoproteins. In some pathological conditions, such as cancer, rheumatoid arthritis and diabetes, there is an abnormal glycosylation of acute phase serum proteins. As most serum proteins are produced in the liver, we have examined glycoprotein metabolism in diabetic condition. To induce non-insulin-dependent diabetes mellitus (NIDDM) a single dose of streptozotocin (100 mg/kg body weight) was injected into two day old rats. After 10-12 weeks, rats weighing above 150 g were selected for NIDDM model. In these rat, blood glucose and plasma glycoproteins were significantly increased whereas plasma insulin was significantly decreased. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in tissues. Oral administration of NBDP and metformin to diabetic rats decreased blood glucose and plasma glycoproteins. Plasma insulin and tissue sialic acid were increased whereas tissue concentrations of hexose, hexosamine and fucose were near normal. Our study suggests that NBDP and metformin possess a significant beneficial effect on glycoproteins in addition to their antidiabetic effect.     

The interaction of sonochemically synthesized gold nanoparticles with serum albumins

Spherical gold nanoparticles of approximately 16 nm were synthesized using a sonochemical reduction method and characterized using UV–vis spectroscopy, atomic force microscopy (AFM) and transmission electron microscopy (TEM). The binding of these gold nanoparticles with bovine serum albumin (BSA) and human serum albumin (HSA) was investigated using UV–vis absorption and fluorescence spectroscopic techniques. A strong quenching of the fluorescence from serum albumins was observed due to the formation of a ground state complex with gold nanoparticles (static quenching). The fluorescence quenching constants, number of binding sites and binding constants were determined using Stern–Volmer and Benesi–Hildebrand plots. Using Forster Resonance Energy Transfer (FRET) theory, the distance between the donor (serum albumins) and acceptor (gold nanoparticles) was obtained, which showed that HSA has more affinity towards sonochemically synthesized gold nanoparticles compared to gold nanoparticles synthesized using other methods.