Effects of a membrane-permeable radical scavenger, Tempol, on healing of colonic anastomoses in the cecal ligation and puncture model of polymicrobial sepsis in rats

BACKGROUND: Tempol (Sigma-Aldrich, Steinheim, Germany) is a stable piperidine nitroxide of low molecular weight that permeates biologic membranes and scavenges superoxide anions in vitro. In recent animal studies, the delaying effect of intraperitoneal sepsis on the healing of colonic anastomoses has been shown. In this study we aimed to investigate the effects of Tempol on the healing of colonic anastomoses in the presence of polymicrobial sepsis. METHODS: Anastomosis of the left colon was performed on the day after cecal ligation and puncture (CLP) in 30 rats that were divided into 3 groups: sham-operated control (laparotomy and cecal mobilization, group I, n = 10), CLP (group II, n = 10), Tempol-treated group (30 mg/kg intravenously before the construction of colonic anastomosis, group III, n = 10). On postoperative day 6, all animals were killed and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of anastomotic hydroxyproline (HP) contents, perianastomotic myeloperoxidase (MPO) activity, malondialdehyde (MDA), and glutathione (GSH) levels. RESULTS: There was a statistically significant increase in MPO activity and MDA levels in the CLP group (group II), along with a decrease in GSH levels, anastomotic HP contents, and bursting pressure values when compared with controls (group I). However, Tempol treatment led to a statistically significant increase in anastomotic bursting pressure values, tissue HP contents, and GSH levels, along with a decrease in MPO activity and MDA levels in group III (P < .05). CONCLUSIONS: This study showed that Tempol treatment significantly prevented the delaying effect of CLP-induced polymicrobial sepsis on anastomotic healing in the left colon. Further clinical studies are needed to clarify whether Tempol may be a useful therapeutic agent to increase the safety of the anastomosis during particular surgeries in which sepsis-induced organ injury occurs.     

Genetic,molecular and functional analyses of complement factor I deficiency

Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patients with no detectable serum FI and also close family members revealed homozygous or compound heterozygous mutations in several domains of FI. These mutations were introduced into recombinant FI and the resulting proteins were purified for functional studies, while transient transfection was used to analyze expression and secretion. The G170V mutation resulted in a protein that was not expressed, whereas the mutations Q232K, C237Y, S250L, I339M and H400L affected secretion. Furthermore, the C237Y and the S250L mutants did not degrade C4b and C3b as efficiently as the WT. The truncated Q336x mutant could be expressed, in vitro, but was not functional because it lacks the serine protease domain. Furthermore, this truncated FI was not detected in serum of the patient. Structural investigations using molecular modeling were performed to predict the potential impact the mutations have on FI structure. This is the first study that investigates, at the functional level, the consequences of molecular defects identified in patients with full FI deficiency.     

Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury

Acetylation/deactylation of histones is an important mechanism to regulate gene expression and chromatin remodeling. We have previously demonstrated that the HDAC inhibitor trichostatin A (TSA) protects cortical neurons from oxygen/glucose deprivation in vitro which is mediated--at least in part--via the up regulation of gelsolin expression. Here, we demonstrate that TSA treatment dose-dependently enhances histone acetylation in brains of wildtype mice as evidenced by immunoblots of total brain lysates and immunocytochemical staining. Along with increased histone acetylation dose-dependent up regulation of gelsolin protein was observed. Levels of filamentous actin were largely decreased by TSA pre-treatment in brain of wildtype but not gelsolin-deficient mice. When exposed to 1 h filamentous occlusion of the middle cerebral artery followed by reperfusion TSA pre-treated wildtype mice developed significantly smaller cerebral lesion volumes and tended to have improved neurological deficit scores compared to vehicle-treated mice. These protective effects could not be explained by apparent changes in physiological parameters. In contrast to wildtype mice, TSA pre-treatment did not protect gelsolin-deficient mice against MCAo/reperfusion suggesting that enhanced gelsolin expression is an important mechanism by which TSA protects against ischemic brain injury. Our results suggest that HDAC inhibitors such as TSA are a promising therapeutic strategy for reducing brain injury following cerebral ischemia.     

Incidence of hypothyroidism after radiotherapy for nasopharyngeal carcinoma

Objectives: The thyroid gland is frequently affected by radiotherapy applied for the treatment of head and neck tumors. Hypothyroidism is observed as a late side effect of radiotherapy, especially seen in the patients who have surgery in the treatment procedure. Methods: We evaluated the radiation-induced hypothyroidism for a selected type of head and neck cancer—nasopharyngeal cancer (NPC)—which does not include surgery involving the thyroid gland in the treatment. Results: We observed 12 patients (14%) who developed hypothyroidism, two of which were subclinical hypothyroidism. The patients with hypothyroidism were statistically significantly younger than the euthyroid patients, but there were no statistically significant differences among the two groups in disease stages, radiotherapy neck doses, and gender. Conclusions: We recommend life-long TSH screening after RT to the neck owing to the incidence of RT-induced hypothyroidism and the importance of early thyroid hormone replacement therapy in patients becoming hypothyroid for maintaining optimal quality of life.     

Minimal intervention dentistry for managing dental caries – a review

This publication describes the history of minimal intervention dentistry (MID) for managing dental caries and presents evidence for various carious lesion detection devices, for preventive measures, for restorative and non‐restorative therapies as well as for repairing rather than replacing defective restorations. It is a follow‐up to the FDI World Dental Federation publication on MID, of 2000. The dental profession currently is faced with an enormous task of how to manage the high burden of consequences of the caries process amongst the world population. If it is to manage carious lesion development and its progression, it should move away from the ‘surgical’ care approach and fully embrace the MID approach. The chance for MID to be successful is thought to be increased tremendously if dental caries is not considered an infectious but instead a behavioural disease with a bacterial component. Controlling the two main carious lesion development related behaviours, i.e. intake and frequency of fermentable sugars, to not more than five times daily and removing/disturbing dental plaque from all tooth surfaces using an effective fluoridated toothpaste twice daily, are the ingredients for reducing the burden of dental caries in many communities in the world. FDI's policy of reducing the need for restorative therapy by placing an even greater emphasis on caries prevention than is currently done, is therefore, worth pursuing.     

Simultaneous Determination of Cefixime,Cefdinir and Clavulanic Acid by High Performance Liquid Chromatography

Pharmaceutical Chemistry Journal - In this study, two cephalosporin groups of antibiotics (cefepime and cefixime) and their combinations with clavulanic acid, beta lactamase inhibitor, were...