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.     

Endovascular management versus surgery for proximal subclavian artery lesions

Current management of subclavian artery (SA) lesions is controversial. Subclavian-to-carotid artery transposition (SCT) may be challenging but exhibits unparalleled long-term results. Stent-supported percutaneous transluminal angioplasty (sPTA) is technically easier but not always feasible. Long-term results and comparisons have not been published. We compared both methods performed by vascular surgeons. Data were collected prospectively with retrospective analysis at a tertiary-care center. sPTA was performed through a retrograde transbrachial access using self-expanding nitinol stents. Open surgery was SCT only. Society for Vascular Surgery/International Society of Cardiovascular Surgery reporting standards were applied. Seventy-four patients underwent treatment from January 1995 to August 2007 (median age 62.6 years, 40 female; left-sided pathology 60 [81.1%]; risk factors: hypertension 45 [60.8%], dyslipidemia 47 [63.5%], diabetes 21 [28.4%], smoking 43 [58.1%], SA occlusion 50 [67.6%]). Forty patients (54.1%) underwent primary sPTA (62.5% occlusions) and 34 SCT (73.5% occlusions). The two groups were comparable with regard to risk factors. In 12 patients occlusions could not be recanalized (30%), and in two stents failed within 1 month (both for stenosis). All but one underwent subsequent uneventful SCT. All SCTs were successful. No risk factor could be identified for treatment failure except sPTA (p = 0.002, Fisher's exact test). Median follow-up was 50.1 months with sPTA and 52.6 months with SCT. No procedure failed during follow-up in either group. sPTA can be performed successfully by surgeons. Primary sPTA failed in 48% of occlusions (30% of all sPTAs). Prediction of failure is not possible. According to our experience, we recommend primary sPTA for SA stenosis and surgery for SA occlusions.     

Reattachment of subgingivally fractured central incisor with an open apex

Abstract –  A case report of a 6-year-old girl with a fractured maxillary left central incisor with an open apex is presented. The procedure used to repair the fracture included flap surgery with an intrasulcular incision and endodontic treatment. The patient was called for 3 months regular follow-up to check the root formation. At the end of 32 months just before the root was obturated by guttaperka, she fractured the same tooth. Flap surgery was repeated and the tooth was restored. The root canal was obturated with a root filling paste and guttaperka as the apex was closed. Examination 10 months after treatment revealed good periodontal health, aesthetics and normal function.     

Abdominal insufflation-deflation injury in small intestine in rabbits.

OBJECTIVE: To investigate the effect of increased intra-abdominal pressure followed by abdominal deflation on small intestine with or without previous intestinal ischaemia. DESIGN: Randomised experimental study. SETTING: University hospital, Turkey. ANIMALS: 78 male New Zealand white rabbits. INTERVENTIONS: Experiment 1: 30 rabbits (10 in each group) were subjected to intra-abdominal pressure of 0 mmHg (controls), 15 mmHg or 25 mmHg for 60 minutes. Experiment 2: 48 rabbits were divided into four groups (n = 12 in each). The first comprised sham-operated controls. In the other 3, the superior mesenteric artery was occluded for 60 minutes. Reperfusion was started and maintained under intra-abdominal pressure of 0 mmHg, 15 mmHg, or 25 mmHg for one hour. Intestinal specimens were obtained five and 60 minutes after abdominal deflation in the pressure groups and at identical times in the other groups in both experiments. MAIN OUTCOME MEASURES: Intestinal malondialdehyde concentration, wet:dry intestinal weight ratio, and mucosal injury score under light microscopy. RESULTS: In experiment I the malondialdehyde concentration, wet:dry weight ratio, and mucosal injury scores were higher in the 25 mmHg group than in the other groups in both specimens. There was a significant increase in malondialdehyde concentration in the 15 mmHg group in only the 5-minute specimen. In experiment 2, except for the wet:dry weight ratio in the 5-minute specimen in the 15 mmHg group, there were significant increases in malondialdehyde concentration, wet:dry weight ratio, and mucosal injury score in all groups except controls in both specimens. Malondialdehyde concentration and wet:dry weight ratio were higher in the 25 mmHg group than in the 0 mmHg group in the 60-minute specimen, and higher than the 15 mmHg group in both specimens. Wet:dry weight ratio was less in the 15 mmHg group than the 0 mmHg group in both specimens. Mucosal injury score was higher in the 25 mmHg group than the other groups in both specimens. CONCLUSION: Increased intra-abdominal pressure for 60 minutes followed by abdominal deflation led to an ischaemia-reperfusion-like injury in normal small intestine in rabbits, and added to reperfusion injury in the ischaemic small intestine at an intra-abdominal pressure of 25 mmHg.     

Biochemical assessments of retinol, alpha-tocopherol, pyridoxal--5-phosphate oxidative stress index and total antioxidant status in adolescent professional basketball players and sedentary controls

Physical training is known to increase the antioxidant defence system and reduce exercise-induced oxidative stress. However, intense physical aerobic and anaerobic training with competition, such as those imposed on young professional basketball players can induce an increase of oxidative stress, which can be implicated with overtraining. The aim of this study was to test the effect of training and competition load on oxidative stress, antioxidant status, and vitamin levels in basketball players. Oxidative Stres Index (OSI 1), Total Peroxide (TPx) antioxidant (vitamin E, A and The total antioxidant status (TAC 1)), biochemical lipid parameters, as well as training results were measured. Results showed that all plasma vitamin levels were significantly higher in basketball players (vitamin A: 1.61 +/- 0.05 mmol/l, vitamin E: 26.45 +/- 0.72 mmol/l, vitamin B6: 10.58 +/- 0.7 mgr/l) than sedentary controls (vitamin A: 1.22 +/- 0.04 mmol /l, vitamin E: 19.24 +/- 0.73 mmol/l, vitamin B6: 6.0 +/- 0.35 mgr/l) (p < 0.01). In addition TAC 1 was 2.06 +/- 0.02 and 1.89 +/- 0.01 mmol Trolox eq/L in basketball players and controls, respectively (p < 0.01). Conversely OSI was 0.89 +/- 0.09 arbitrary unit and 0.88 +/- 0.071 arbitrary unit in basketball players and controls, respectively (p > 0.05). However, total plasma peroxide level (TPx) of basketball players and controls was not statistically different (18.55 +/- 2.07 and 17.18 +/- 1.61 micromol H2O2/L, respectively; p > 0.05). We conclude that physical exercise increase antioxidant levels and cause balance of the homeostasis. Training can not have positive or negative effects on oxidative stress depending on training load. The results suggested that oxidative stress and antioxidant measurement are significant in the biological follow-up of young basketball players.     

The Missense Alteration A5T of the Thyroid Peroxidase Gene is Pathogenic and Associated with Mild Congenital Hypothyroidism

Congenital hypothyroidism (CH) occurs with a prevalence of approximately 1:4000 live births. Defects of thyroid hormone synthesis account for 15-20% of these cases. Thyroid peroxidase (TPO) gene is the most common cause for dyshormonogenesis. So far, more than 60 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. We present an 8-day-old male with mild CH who was identified to have a G to A transition in the fifth codon of the TPO gene (c.13G>A; p.Ala5Thr). The unaffected family members were heterozygous carriers of the mutation, whereas 400 healthy individuals of the same ethnic background did not have the mutation. Mutation analysis of 11 known causative CH genes and 4 of our own strong candidate genes with next-generation sequencing revealed no mutations in the patient nor in any other family members. The results of in silico functional analyses indicated partial loss-of-function (LOF) in the resulting enzyme molecule due to mutation. The patient’s clinical finding s were consistent with the effect of this partial LOF of the mutation. In conclusion, we strongly believe that A5T alteration in the TPO gene is actually pathogenic and suggest that it should be classified as a mutation.     

Effects of Carvacrol on Survival,Mesenteric Blood Flow,Aortic Function and Multiple Organ Injury in a Murine Model of Polymicrobial Sepsis

Carvacrol (CRV) has strong cytoprotective, antioxidant, and anti-inflammatory properties. We aimed to demonstrate the possible protective effects of CRV on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wistar rats were allocated into the following four groups: Sham, CLP, Sham + CRV, and CLP + CRV. The animals were orally administered with CRV (80 mg/kg/day) or vehicle (corn oil; 1 mL/kg/day) for 7 days. At the eighth day, Sham or CLP procedure was applied. Twenty hours after the operations, MBF and contractile responses of isolated aortic preparations to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological assessments. Additionally, survival rates were recorded throughout 96 h. CRV administration improved the mesenteric perfusion, contractile function of aorta, and survival after CLP. CRV substantially prevented the elevations in the levels of LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) but could not prevent the elevations of AST and ALT after CLP. The decreased liver, kidney, and spleen glutathione levels and increased liver, kidney, lung, and spleen malondialdehyde levels induced by CLP were substantially restored by CRV. Also, histopathological protective effects of CRV on multiple organ damage due to CLP were observed. CRV possesses strong ameliorative effects on sepsis due to its protective effects on mesenteric perfusion and aortic function and its antioxidative and anti-inflammatory effects.