Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation

Endothelial cell activation plays a critical role in regulating leukocyte recruitment during inflammation and infection. Based on recent studies showing that acetylcholine and other cholinergic mediators suppress the production of proinflammatory cytokines via the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) expressed by macrophages and our observations that human microvascular endothelial cells express the alpha7 nAChR, we examined the effect of cholinergic stimulation on endothelial cell activation in vitro and in vivo. Using the Shwartzman reaction, we observed that nicotine (2 mg/kg) and the novel cholinergic agent CAP55 (12 mg/kg) inhibit endothelial cell adhesion molecule expression. Using endothelial cell cultures, we observed the direct inhibitory effects of acetylcholine and cholinergic agents on tumor necrosis factor (TNF)-induced endothelial cell activation. Mecamylamine, an nAChR antagonist, reversed the inhibition of endothelial cell activation by both cholinergic agonists, confirming the antiinflammatory role of the nAChR cholinergic pathway. In vitro mechanistic studies revealed that nicotine blocked TNF-induced nuclear factor-kappaB nuclear entry in an inhibitor kappaB (IkappaB)alpha- and IkappaBepsilon-dependent manner. Finally, with the carrageenan air pouch model, both vagus nerve stimulation and cholinergic agonists significantly blocked leukocyte migration in vivo. These findings identify the endothelium, a key regulator of leukocyte trafficking during inflammation, as a target of anti-inflammatory cholinergic mediators.     

Effective Range of FSSW Parameters for High Load-Carrying Capacity of Dissimilar Steel A283M-C/Brass CuZn40 Joints

In the current study, a 2 mm thick low-carbon steel sheet (A283M—Grade C) was joined with a brass sheet (CuZn40) of 1 mm thickness using friction stir spot welding (FSSW). Different welding parameters including rotational speeds of 1000, 1250, and 1500 rpm, and dwell times of 5, 10, 20, and 30 s were applied to explore the effective range of parameters to have FSSW joints with high load-carrying capacity. The joint quality of the friction stir spot-welded (FSSWed) dissimilar materials was evaluated via visual examination, tensile lap shear test, hardness test, and macro- and microstructural investigation using SEM. Moreover, EDS analysis was applied to examine the mixing at the interfaces of the dissimilar materials. Heat input calculation for the FSSW of steel–brass was found to be linearly proportional with the number of revolutions per spot joint, with maximum heat input obtained of 11 kJ at the number of revolutions of 500. The temperature measurement during FSSW showed agreement with the heat input dependence on the number of revolution. However, at the same revolutions of 500, it was found that the higher rotation speed of 1500 rpm resulted in higher temperature of 583 °C compared to 535 °C at rotation speed of 1000 rpm. This implies the significant effect for the rotation speed in the increase of temperature. The macro investigations of the friction stir spot-welded joints transverse sections showed sound joints at the different investigated parameters with significant joint ligament between the steel and brass. FSSW of steel/brass joints with a number of revolutions ranging between 250 to 500 revolutions per spot at appropriate tool speed range (1000–1500 rpm) produces joints with high load-carrying capacity from 4 kN to 7.5 kN. The hardness showed an increase in the carbon steel (lower sheet) with maximum of 248 HV and an increase of brass hardness at mixed interface between brass and steel with significant reduction in the stir zone hardness. Microstructural investigation of the joint zone showed mechanical mixing between steel and brass with the steel extruded from the lower sheet into the upper brass sheet.     

Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues

BACKGROUND: Many members of the human kallikrein gene family are differentially expressed in cancer and a few have potential as diagnostic/prognostic markers. KLK14 is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues. Since KLK14 was found to be regulated by steroid hormones in prostate cancer cell lines, we hypothesized that it will be differentially expressed in prostate cancer tissues compared to their normal counterparts. METHODS: Matched prostate tissue samples from the cancerous and non-cancerous parts of the same prostates were obtained from 100 patients who underwent radical prostatectomy. Quantitative analysis of KLK14 expression levels were performed by real-time RT-PCR using SYBR Green I dye on the LightCycler trade mark system. Associations with clinico-pathological parameters were analyzed. RESULTS: KLK14 overexpression in the cancerous compared to non-cancerous tissue was found in 74% of patients (P < 0.001). Mean level of expression was 154 arbitrary units (Au) in cancerous tissues and 14.2 Au in the non-cancerous tissues. The ratio of the cancerous to non-cancerous KLK14 expression values was higher in patients with late stage (stage III) compared to stage II (P = 0.002), and in grade 3 compared to grade 1/2 tumors (P = 0.001). A statistically significant increase was also observed in patients with higher in Gleason score (>6) compared to Gleason score = 6 tumors (P = 0.027). No correlation was found between KLK14 tissue expression levels and serum prostate-specific antigen. CONCLUSIONS: KLK14 expression is significantly higher in cancerous compared to non-cancerous prostatic tissue. The up-regulation of the KLK14 gene in advanced and more aggressive tumors may indicate a possible role for the hK14 protein in tumor spread and opens the possibility of hK14 being a candidate new marker for prostate cancer diagnosis and prognosis.     

The effect of full‐mouth tooth extraction on glycemic control among patients with type 2 diabetes requiring extraction of all remaining teeth: a randomized clinical trial

Khader YS, Al Habashneh R, Al Malalheh M, Bataineh A. The effect of full‐mouth tooth extraction on glycemic control among patients with type 2 diabetes requiring extraction of all remaining teeth: a randomized clinical trial. J Periodont Res 2010; 45: 741–747. © 2010 John Wiley & Sons A/S Background and Objective: Several studies have shown that periodontitis can complicate the severity of diabetes by worsening the degree of glycemic control. The purpose of this study was to determine the effect of full‐mouth tooth extraction on glycemic control among type 2 diabetic patients. Material and Methods: A total of 58 patients with type 2 diabetes mellitus and advanced periodontitis who were requiring extraction of all remaining teeth were randomized consecutively into treatment (full‐mouth tooth extraction) and control groups (no treatment). Eight patients were lost to follow‐up or reported use of antibiotics, leaving 50 patients to be included in the analysis. All patients had all their remaining teeth in a hopeless condition. Relevant data were collected, and glycosylated hemoglobin (HbA_1c) and fasting blood glucose levels were measured at baseline and at follow‐up times of 3 and 6 mo. Results: At baseline, the mean (SD) HbA_1c level was 8.6% (1.24) in the treatment group and 7.7% (0.87) in the control group. In the treatment group, the mean HbA_1c level decreased significantly from 8.6% at baseline to 7.4% after 3 mo of denture treatment, and continued to decrease to 7.3% after 6 mo. In the control group, the mean HbA_1c decreased from 7.7% at baseline to 7.5% after 3 mo, and remained almost the same after 6 mo. After adjusting for the baseline HbA_1c, the mean reduction in HbA_1c after 3 mo in the treatment group [1.23% (0.79)] was significantly higher than the mean reduction in the control group [0.28% (0.87)]. Conclusion: Full‐mouth tooth extraction resulted in an improvement in glycemic control among diabetic patients. Large‐scale multicentre clinical trials are needed to confirm the current evidence.     

Gastroesophageal reflux in mechanically ventilated pediatric patients and its relation to ventilator-associated pneumonia

Introduction  

The objective was to determine the frequency of gastroesophageal reflux (GER) in mechanically ventilated pediatric patients and its role as a risk factor for ventilator-associated pneumonia (VAP), which may be enhanced among those patients.     

Polyarthritis with chondronecrosis associated with osteonecrosis, panniculitis and pancreatitis

Arthritis associated with panniculitis complicating pancreatitis is well described in the literature, usually associated with osteonecrosis. Chondronecrosis has not been reported before in association with pancreatitis. We report a patient with chronic pancreatitis who presented with polyarthritis, panniculitis, osteonecrosis, but in addition had clear evidence of chondronecrosis. We suggest that direct extension of noxious materials from nearby subchondral osteonecrotic bone lesion could be the cause of the osteonecrosis and one of the pathological mechanisms leading to arthritis in patients with pancreatitis.     

Relationship between 25-hydroxyvitamin D and metabolic syndrome among Jordanian adults

Evidence of the association between 25-hydroxyvitamin D (25(OH)D) and metabolic syndrome (MeS) remains uncertain and incongruent. This study aimed to determine the association between 25(OH)D and MeS among Jordanian adults. A complex multistage sampling technique was used to select a national population-based household sample. The present report deals exclusively with adults aged > 18 years who had complete information on all components of MeS (n = 3,234). A structured questionnaire was used to collect all relevant information. Anthropometric, clinical, and laboratory measurements were obtained. MeS was defined according to the International Diabetes Federation (IDF) definition. Of the total, 42.0% had MeS and 31.7% had 25(OH)D < 30 ng/ml. In a stratified analysis, the prevalence of MeS did not differ significantly between subjects with low and normal 25(OH)D levels for men and women in all age groups. In the multivariate analysis, the odds of MeS were not significantly different between subjects with low and normal 25(OH)D levels (OR = 0.85, 95% CI: 0.70, 1.05, P-value = 0.133). The association between 25(OH)D and MeS remained non-significant when 25(OH)D was analyzed as a continuous variable (OR = 1.004, 95% CI; 1.000, 1.008, P = 0.057) and when analyzed based on quartiles. None of the individual components of MeS were significantly associated with 25(OH)D level. This study does not provide evidence to support the association between 25(OH)D level and MeS or its individual components. Prospective studies are necessary to better determine the roles of 25(OH)D levels in the etiology of MeS.     

Prevalence and risk indicators of gingivitis and periodontitis in a Multi-Centre study in North Jordan: a cross sectional study

Background  

There are limited data about the epidemiology and risk factors/indicators of gingivitis, aggressive periodontitis (AgP) and chronic periodontitis (CP) in Jordan. The aim of this study was to assess the prevalence and risk indicators of gingivitis, AgP and CP.     

Automutilation of the penis performed by the kitchen's knife

Automutilation of the penis performed by the kitchen's knife is described. Surgical techniques, the most important goals of therapy as well as psychiatric aspects of the automutilation are discussed.