Involvement of adipokines in rimonabant‐mediated insulin sensitivity in ob/ob mice

Objectives It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin‐sensitising effects of the CB1 antagonist rimonabant is not clear. Methods ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test. The expression of different adipokines in white adipose tissue was analysed by quantitative real‐time PCR. Key findings Rimonabant (30 mg/kg) significantly inhibited body weight and fat pad weight gain (P < 0.05) and improved glucose tolerance. Gene expression analysis indicated that tumour necrosis factor‐α, visfatin and retinol binding protein‐4 were downregulated in the adipose tissue of ob/ob mice treated with rimonabant compared with controls, whereas adiponectin was significantly upregulated. Conclusions Rimonabant‐mediated alteration of adipokines in white adipose tissues may play a role in improving insulin sensitivity in obese animals.     

Effects of rapid and slow potassium repolarization currents and calcium dynamics on hysteresis in restitution of action potential duration

We used a mathematical model to investigate effects of repolarizing currents I_kr and I_ks, calcium (Ca) current I_CaL, and Ca dynamics in network sarcoplasmic reticulum and junctional sarcoplasmic reticulum (JSR) on hysteresis in restitution of action potential duration. Enhanced I_kr increased slope of restitution, hysteresis loop thickness, and delay between peaks of diastolic intervals and action potential duration. Increase in I_ks decreased loop thickness and peak delay. Decrease in I_CaL had effects similar to increasing I_kr, except slope of restitution decreased markedly. Uptake of Ca into the network sarcoplasmic reticulum had less effect on hysteresis than transfer of Ca into JSR. Faster transfer of Ca into JSR markedly decreased loop thickness and peak delay. Our results provide insight into mechanisms responsible for this newly identified property of restitution. Such information will be valuable in studies where modification of hysteresis is used to investigate its role in arrhythmogenesis.     

Antibodies to periodontal organisms are associated with decreased kidney function. The Dental Atherosclerosis Risk In Communities study

BACKGROUND/AIMS: Increasing evidence suggests that clinical signs of periodontal disease are independently associated with renal impairment. However, no studies have examined the possible linkage of kidney disease with serum antibody to oral pathogens. METHODS: The periodontal disease status was assessed in an older community-dwelling population (Dental Atherosclerosis Risk in Communities) to include: clinical measurements; oral biofilm microbial composition by DNA checkerboard, and serum antibody immunoglobulin-gamma (IgG) titers to specific bacteria by immunocheckerboard. Baseline characteristics were used to compute estimated glomerular filtration rate defining eGFR <60 ml/min/1.73 m(2) as impaired renal function in 103 of 5,032 subjects. Levels of serum IgG to specific oral bacteria were categorized by quartiles (comparing upper vs. lower three) as high titer and GFR <60 as the dependent variable in logistic regression models, adjusting for multiple comparisons (Hotelling T(2)) and traditional risk factors including age, race, smoking, diabetes, hypertension, body mass, waist-to-hip ratio, serum triglycerides, HDL, and LDL cholesterol. RESULTS: High levels of serum IgG to selected periodontal pathogens including Porphyromonas gingivalis, Treponema denticola and Aggregobacter actinomycetemcomitans were associated with an increased odds for GFR <60 ml/min/1.73 m(2), adjusted odds ratio ranging from 1.6 to 1.8 and p < 0.05. CONCLUSIONS: Elevated IgG to periodontal pathogens is significantly associated with impaired kidney function, independent of traditional risk factors. Prospective studies are necessary to confirm these findings.     

A ten-year retrospective review: does pyloric exclusion improve clinical outcome after penetrating duodenal and combined pancreaticoduodenal injuries?

OBJECTIVES: We sought to determine whether the performance of pyloric exclusion during repair of penetrating advanced duodenal injuries prevents postoperative duodenal fistulas and improves clinical outcome. METHODS: A retrospective chart review of patients from 1995 to 2004 with penetrating duodenal injuries >or=grade II and all combined pancreaticoduodenal injuries was performed. Patients managed either without or with pyloric exclusion were compared on the basis of age, sex, mechanism, injury grade, Injury Severity Score (ISS), hemodynamic stability, the presence of vascular injury or associated injuries, postoperative complications, length of hospital stay, and mortality. RESULTS: Fifteen of 29 patients were managed without pyloric exclusion and 14 with exclusion. Both groups were similar with respect to age, sex, mechanism, injury grade, ISS, hemodynamic stability, the presence of vascular injury, associated abdominal injuries, and mortality rates. A trend toward a higher overall complication rate (71% vs. 33%), pancreatic fistula rate (40% vs. 0%), and length of hospital stay (24.3 days vs. 13.5 days) was evident in the pyloric exclusion group. No duodenal fistula was detected in either patient group. CONCLUSION: In our study population, the performance of pyloric exclusion for penetrating advanced duodenal injury and combined pancreatic and duodenal injuries did not improve clinical outcome. The trend toward a greater overall complication rate, pancreatic fistula rate, and increased length of hospital stay in the pyloric exclusion group suggests that simple repair without pyloric exclusion is both adequate and safe for most penetrating duodenal injuries.     

Immediate postoperative complications of combined penetrating rectal and bladder injuries

BACKGROUND: Combined penetrating trauma involving the rectum and bladder has been associated with increased postoperative morbidity. Specific complications resulting from these injuries include colovesical fistula, urinoma, and abscess formation. METHODS: A retrospective review of Temple University Hospital trauma database was performed. Patients were categorized by having an isolated rectal (n = 29), isolated bladder (n = 16), or combined injury (n = 24). Records were reviewed for sex, age, site of injury, location of rectal and bladder injuries, operative intervention, fistula formation, urinoma formation, abscess formation, time to urinary catheter removal, length of intensive care unit stay, and length of hospital stay. RESULTS: Patient sex and age did not differ significantly between groups, nor was there a significant difference in location of rectal injury between groups. Presacral drainage was utilized in all patients with extraperitoneal injuries. Fecal diversion was performed in all patients, except two with intraperitoneal rectal injuries. Omental flap interposition between rectal and bladder injuries was utilized in one patient. No significant difference was noted in immediate postoperative complications between groups including fistula, urinoma, and abscess formation. However, all cases of colovesical fistula (n = 2) and urinoma (n = 2) formation were noted in those patients with rectal and posterior bladder injuries. CONCLUSIONS: Combined rectal and bladder injuries were not associated with an increase in immediate postoperative complications compared with isolated rectal and bladder injuries. However, postoperative fistula and urinoma formation occurred only in patients with a combined rectal and posterior bladder injury. Consequently, these patients may benefit from omental flap interposition between injuries to decrease fistula and urinoma formation.     

The spectrum of somatic and germline NF1 mutations in NF1 patients with spinal neurofibromas

Neurofibromatosis type 1 (NF1) is a common inherited complex multi-system disorder associated with the growth of various benign and malignant tumors. About 40% of NF1 patients develop spinal tumors, of whom some have familial spinal neurofibromatosis (FSNF), a variant form of NF1 in which patients present with multiple bilateral spinal tumors but have few other clinical features of the disease. We have studied 22 spinal neurofibromas derived from 14 unrelated NF1 patients. Seven of these patients satisfied the diagnostic criteria of NF1 while the remaining seven had only few features of NF1. The latter group defined as FSNF harbored significantly higher number of missense or missense and splice-site germline mutations compared to the group with classical NF1. This is the first study to describe NF1 somatic mutations in spinal neurofibromas. Loss-of-heterozygosity (LOH) was identified in 8/22 of the spinal tumors, 75% of LOH observed was found to result from mitotic recombination, suggesting that this may represent a frequent mutational mechanisms in these benign tumors. No evidence for LOH of the TP53 gene was found in these tumors.     

Drowned in information yet starved for knowledge; evidence-based dentistry, what's in it for me?

A graduate of the ADA Evidence-based Dentistry Champions Conference explains what he has learned about the techniques of EBD literature and literature searches. EBD is the area of overlap among the literature, clinical experience, and patient characteristics. This paper focuses on evidence from the literature. Sources of summarized evidence are mentioned that can be accessed via the Internet, especially those that summarize evidence of the greatest research rigor that have been summarized systematically.