Tyrosine-derived novel antimicrobial hydantoin polymers: synthesis and evaluation of anti-bacterial activities

A new approach for the design and synthesis of cyclic N-halamine polymers having anti-bacterial activity based on a vinyl derivative of tyrosine-derived hydantoin is reported. The synthesis of N-halamine polymers generally involves the chemical modification of 5,5′-disubstituted hydantoin to introduce polymerizable vinyl moieties thereby restricting the halogen capture only on the amide nitrogen. Here we show the possibility of synthesizing vinyl monomers of N-halamine from α-amino acids wherein both the amide and imide nitrogens are available for halogen capture. Thus, a hydantoin monomer was synthesized from L-tyrosine and copolymerized with methyl methacrylate and 2-(hydroxyethyl)methacrylate, to obtain random co-polymers. The monomer and its co-polymers were characterized using NMR, IR, HRMS, GPC, DSC, EDAX and TGA analysis. Films of the co-polymers cast from 10% acetone solutions were exposed to sodium hypochlorite solution to activate the hydantoin moieties. The oxidative chlorine content of the films ranged from 0.6 to 0.9%. The activated films were exposed to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria using standard protocols. Polymers having chlorine content as little as 0.6% exhibited 6 log reduction in the bacterial growth within 30 min of exposure. The method allows the halogenation of both amide and imide nitrogens and could be applied to the preparation of a number of vinyl hydantoins from many amino acids.     

Impact of Tropospheric Ozone on Crop Plants

Tropospheric ozone (O₃) is the most important regional atmospheric pollutant causing risk to food production across the globe due to its phytotoxicity and prevalence over agricultural areas. Peak O₃ concentrations have declined in Europe and North America due to reductions in precursors during the last decades, however, emissions of O₃ precursors have increased in Asia. The current critical level of ozone is determined by the threshold for yield loss which is based on the seasonal sum of the external concentration above 40?ppb. In the present article, the impact of tropospheric O₃ on crop photosynthesis, defense mechanism, growth, reproductive processes and yield of crop plants have been documented. O₃ upon its entry into the leaf intercellular spaces rapidly forms reactive oxygen species and reacts with components of the leaf apoplast to initiate a complex set of responses that constitute variable countermeasures by antioxidative enzymes. Ozone affects photosynthetic process by influencing photosynthetic pigments, chlorophyll fluorescence kinetics and electron transport as well as carbon fixation in terms of decreased Rubisco activity and quantity. Translocation and allocation pattern of photosynthate also get influenced under O₃, which affect reproductive processes and yield of crops. Plant species and cultivars exhibit a range of sensitivity to O₃, which is identifiable in terms of biochemical, physiological, molecular and yield responses. Hence, understanding of cultivar sensitivity in context to O₃ would be helpful in development of potential O₃ biomarkers and O₃ tolerant variables.     

Intrahepatic biliary duct branching patterns,cystic duct anomalies,and pancreas divisum in a tertiary referral center: A magnetic resonance cholangiopancreaticographic study

Background

Knowledge about anatomic variations in intrahepatic biliary ducts (IHBD) is relevant for performing biliary drainage and for avoiding bile duct injury during cholecystectomy and liver resections. Low insertion of cystic duct (LICD) is a common anatomic variant. Pancreas divisum is the commonest congenital anomaly of pancreas; it has been causally linked with recurrent acute pancreatitis (RAP).

Methods

Magnetic resonance cholangiopancreaticography (MRCP) images of 500 consecutive patients were reviewed for anatomic variants of IHBD, cystic duct, and pancreatic duct.

Results

Anatomy of IHBD could be evaluated in 458 MRCP’s, of these 301 (65.72 %) had ‘typical’ anatomy. The variant in 157 persons included ‘triple confluence’ in 56 (12.23 %), ‘right posterior segmental duct (RPSD) draining to left hepatic duct (LHD)’ in 64 (14 %), ‘RPSD to common hepatic duct (CHD)’ in 20 (4.4 %), ‘RPSD to cystic duct’ in 2 (0.4 %), ‘accessory duct to CHD’ in 3 (0.7 %), ‘accessory duct to right hepatic duct (RHD)’ in 1 (0.2 %), ‘segment 2 and 3 separately to CHD’ in 1 (0.2 %), and complex variants in 10 (2.2 %). Cystic duct could be evaluated in 338 patients; of these, 15 (4.4 %) had LICD. Patients with RAP had pancreas divisum more often than those without any pancreatic disease, (?/?,10 % and ?/?, 0.8 %; p?=?0.004).

Conclusions

Nearly one third of MRCPs showed atypical IHBD pattern with RPSD draining to LHD being the commonest. LICD was the most common cystic duct variant. Pancreas divisum was more frequent in patients with RAP than in persons without pancreatic disease.

     

Minimally invasive mitral valve surgery

BACKGROUND: To reduce surgical trauma and the drawbacks associated with sternotomy, we performed robotically controlled, video-assisted mitral valve surgery, using either the port-access or the transthoracic clamp technique. METHODS AND RESULTS: Between September 1997 and September 2000, 221 patients (78 males, 143 females) underwent mitral valve surgery through a small right minithoracotomy using the port-access endovascular cardiopulmonary bypass system. Mitral valve exposure was facilitated with an endoscope attached to a voice-controlled robotic arm (AESOP 3000) allowing stabilization and voice-activated camera positioning. Twenty-six patients underwent mitral valve repair and 195 had valve replacement. In 197 patients, mitral valve surgery was the primary operation, while 24 were redo cases. Skin-to-skin mean operating time was 3.5 +/- 1.2 hours and aortic cross-clamp time was 58 +/- 16 min, mean intensive care unit stay was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. There was no re-exploration for bleeding. There was no late death or re-operation on mean follow-up of 16.4 +/- 12.2 months. Patients showed improvement in their NYHA functional class from 2.6 +/- 0.5 to 1.4 +/- 0.8 postoperatively. Outcomes were compared with those of our previous 220 patients who underwent mitral valve surgery with the median sternotomy approach. CONCLUSIONS: The use of video and robotic assistance in port-access mitral valve surgery not only minimizes the length of the incision, but also gives full visualization of the entire mitral valve apparatus. This approach provides comparable results with the sternotomy approach, as well as marked advantages of reduced intensive care unit stay. ,ower blood transfusion requirement, better cosmesis and earlier hospital discharge.     

Addition of Plasmapheresis Decreases the Incidence of Acute Antibody-Mediated Rejection in Sensitized Patients with Strong Donor-Specific Antibodies

Background and objectives: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies.Design, setting, participants, & measurements: Thirty-five complement-dependent cytotoxicity T cell cross-match–negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match–positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor-specific antibodiesResults: Whereas no group 1 patients had acute rejection, 66% of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular rejection). The protocol was then changed to the addition of peritransplantation plasmapheresis to patients with strong donor-specific antibodies (group 3). This change resulted in a dramatic decrease in the acute rejection rate to 7%. During a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow-up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%) lost some of donor-specific antibodies and/or decreased the strength of existing donor-specific antibodies.Conclusions: These results indicated that in patients with strong donor-specific antibodies, the addition of plasmapheresis to high-dosage intravenous Ig decreases the incidence of acute rejection. The majority of the patients, whether they received intravenous Ig alone or with plasmapheresis, lost their donor-specific antibodies during follow-up.Donor-specific anti-HLA antibodies (DSA) in patients who are sensitized through pregnancy, previous blood transfusions, or organ transplantation is an important obstacle in kidney transplantation. Sensitized patients wait longer on the deceased-donor transplantation list, may not receive a transplant, and may have greater morbidity and mortality. Some sensitized patients may have living donor candidates, but transplantation cannot be performed because of cross-match positivity. Recent desensitization protocols using the combination of plasmapheresis (PP) or immunoadsorption to remove DSA and/or intravenous Ig (IVIG) and rituximab to downregulate antibody-mediated immune responses have made kidney transplantation feasible by abrogating complement-dependent cytotoxicity (CDC) T cell cross-match positivity. In previous studies, two protocols were examined: High-dosage IVIG (2.0 g/kg) (1–3) and PP with low-dosage IVIG (100 mg/kg after each PP session) (4–8); however, acute antibody-mediated rejection (AMR) continued to be an important barrier and was still observed in at least 30 to 40% of the recipients included in these desensitization protocols, even when rituximab was added to the protocol.Whereas CDC T cell cross-match positivity is an absolute contraindication to kidney transplantation, the clinical significance of CDC B cell or flow cytometry (FC) T and/or B cell cross-match positivity are less clear. Most studies have demonstrated that CDC T cell cross-match–negative but CDC B or FC T/B cell cross-match–positive patients with DSA are at higher risk for developing acute cellular, antibody-mediated, and chronic rejection and graft loss (9,10). The role of desensitization protocols for these patients has not been studied in a large cohort. We previously reported our initial experience using low-dosage IVIG (300 mg/kg) and Thymoglobulin induction treatment in 15 patients (11,12). Because of early AMR in three patients, the IVIG dosage was increased to a total of 2.0 mg/kg in subsequent patients. Now, we present our experience in CDC T cell–negative but CDC B cell or FC T and/or B cell cross-match–positive kidney transplant recipients with DSA, who were stratified according to mean fluorescence indices of Luminex flow beads. The results showed that patients with strong DSA were at much higher risk for developing acute AMR early after transplantation, and the addition of peritransplantation PP to high-dosage IVIG and Thymoglobulin treatment significantly decreased the incidence of AMR. The majority of the patients, whether they received IVIG alone or with PP, lost DSA during follow-up.     

Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II

INTRODUCTION: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Baseline predictors of temporal BMD changes (DeltaBMD) in AN, including 1) gastrointestinal peptides regulating food intake and appetite that have been related to bone metabolism and 2) bone turnover markers, have not been well characterized. We hypothesized that baseline levels of nutritionally regulated hormones and of bone turnover markers would predict DeltaBMD overall. METHODS: In a prospective observational study, lumbar and whole-body BMD was measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls. Baseline body mass index, lean mass, nutritionally regulated hormones [IGF-I, cortisol, ghrelin, leptin, and peptide YY (PYY)], bone formation, and resorption markers were examined to determine nutritional and hormonal predictors of bone density changes. RESULTS: In a regression model, baseline ghrelin and PYY predicted changes in spine bone measures; and baseline ghrelin, cortisol, and PYY predicted changes in whole-body bone measures independent of baseline nutritional status. CONCLUSIONS: Neuroendocrine gastrointestinal-derived peptides regulating food intake are independent predictors of changes in bone mass in AN.