VEGF protects brain against focal ischemia without increasing blood--brain permeability when administered intracerebroventricularly.

Delayed administration of vascular endothelial growth factor (VEGF) promotes functional recovery after focal cerebral ischemia. However, early intravenous injection of VEGF increases blood-brain barrier (BBB) leakage, hemorrhagic transformation and infarct volume whereas its application to cortical surface is neuroprotective. We have investigated whether or not early intracerebroventricular administration of VEGF could replicate the neuroprotective effect observed with topical application and the mechanism of action of this protection. Mice were subjected to 90 mins middle cerebral artery (MCA) occlusion and 24 h of reperfusion. Vascular endothelial growth factor (8 ng, intracerebroventricular) was administered 1 or 3 h after reperfusion. Compared with the vehicle-treated (intracerebroventricular) group, VEGF decreased the infarct volume along with BBB leakage in both treatment groups. Neurologic disability scores improved in parallel to the changes in infarct volume. Independently of the decrease in infarct size, VEGF also reduced the number of TUNEL-positive apoptotic neurons. Phospo-Akt levels were significantly higher in ischemic hemispheres of the VEGF-treated mice. Contrary to intracerebroventricular route, intravenous administration of VEGF (15 microg/kg) enhanced the infarct volume as previously reported for the rat. In conclusion, single intracerebroventricular injection of VEGF protects brain against ischemia without adversely affecting BBB permeability, and has a relatively long therapeutic time window. This early neuroprotective action, observed well before recovery-promoting actions such as angiogenesis, possibly involves activation of the PI-3-Akt pathway.     

The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis

Despite constant contact with the large population of commensal bacteria, the colonic mucosa is normally hyporesponsive to these potentially proinflammatory signals. Here we report that the single immunoglobulin IL-1 receptor-related molecule (SIGIRR), a negative regulator for Toll-IL-1R signaling, plays a critical role in gut homeostasis, intestinal inflammation, and colitis-associated tumorigenesis by maintaining the microbial tolerance of the colonic epithelium. SIGIRR-deficient (Sigirr(-/-)) colonic epithelial cells displayed commensal bacteria-dependent homeostatic defects, as shown by constitutive upregulation of inflammatory genes, increased inflammatory responses to dextran sulfate sodium (DSS) challenge, and increased Azoxymethane (AOM)+DSS-induced colitis-associated tumorigenesis. Gut epithelium-specific expression of the SIGIRR transgene in the SIGIRR-deficient background reduced the cell survival of the SIGIRR-deficient colon epithelium, abrogated the hypersensitivity of the Sigirr(-/-) mice to DSS-induced colitis, and reduced AOM+DSS-induced tumorigenesis. Taken together, our results indicate that epithelium-derived SIGIRR is critical in controlling the homeostasis and innate immune responses of the colon to enteric microflora.     

The Search for High‐Impact Diagnostic and Management Tools for Low‐ and Middle‐Income Countries: A Self‐Powered Low‐Cost Blood Pressure Measurement Device Powered by a Solid‐State Vibration Energy Harvester

The World Health Organization has established recommendations for blood pressure measurement devices for use in low‐resource venues, setting the “triple A” expectations of Accuracy, Affordability, and Availability. Because of issues related to training and assessment of proficiency, the pendulum has swung away from manual blood pressure devices and auscultatory techniques towards automatic oscillometric devices. As a result of power challenges in the developing world, there has also been a push towards semiautomatic devices that are not dependent on external power sources or batteries. Beyond solar solutions, disruptive technology related to solid‐state vibrational energy harvesting may be the next iterative solution to attain the ultimate goal of a self‐powered low‐cost validated device that is simple to use and reliable.     

Management of skin,mucosa and joint involvement of Behçet’s syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet’s syndrome

Objectives

The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet’s syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS.

Induced sputum evaluation in microwave popcorn production workers

OBJECTIVE: Severe airways obstruction and bronchiolitis obliterans have been reported in microwave popcorn production workers and attributed to inhalation of flavoring agents. We investigated whether exposure to flavoring agents is associated with airways inflammation in popcorn production workers. METHODS: Fifty-nine workers with high exposures and 22 patients with low exposures to flavoring vapors completed a questionnaire, spirometry, and sputum induction. Sputum cell counts were categorized as "high" if greater than (and "low" if less than or equal to) the median cell counts of a healthy external control group (n = 24). We compared high- and low-exposure groups as well as all workers with control subjects. RESULTS: Neutrophil concentrations in nonsmoking workers were significantly higher than those of the healthy nonsmoking control group (p < 0.05). The smoking-adjusted odds ratio for high neutrophil count (> 1.63 x 10(5)/mL) was 3.8 (95% confidence interval, 1.3 to 11.5) in the high-exposure group compared with the low-exposure group. Sputum interleukin-8 and eosinophil cationic protein levels were higher in high-exposure workers than in low-exposure workers (p < 0.05). For the worker group, mean values of FEV1 percentage of predicted and FEV1/FVC percentage of predicted were > 95%. There were no relationships between sputum characteristics and the presence of airways obstruction. CONCLUSIONS: High exposure to popcorn flavoring agents is associated with neutrophilic airway inflammation in popcorn production workers. These data provide further evidence that popcorn production workers face a significant occupational hazard through exposure to flavoring agents.     

Intravenous dexmedetomidine for treatment of intraoperative penile erection

Background  

Intraoperative penile erections following the initiation of either regional or general anaesthesia is rare; however, when it occurs in patients undergoing urologic procedures it may delay, or even cancel the planned surgery. The aetiology is unclear. Various treatments proposed for producing detumescence are not always effective. Use of intracavernous alpha-adrenergic agonists is an efficient and rapid but short-lasting treatment. Furthermore, repeated intracavernous injections of vasoactive drugs may be harmful. Dexmedetomidine is a potent, selective α₂-adrenoreceptor agonist. In our study, we evaluated the effect of dexmedetomidine on intraoperative penile erection.     

Exhaled nitric oxide measurement in workers in a microwave popcorn production plant

Airways obstruction in microwave-popcorn workers has been attributed to inhalation of flavoring agents. Two former workers at a microwave-popcorn plant were found by lung biopsy to have bronchiolitis obliterans. The study's aim was to determine whether exhaled nitric oxide (FENO) levels were associated with exposure levels, respiratory symptoms, or airways obstruction. A questionnaire, spirometry, and FENO measurements were completed by 135 workers. The FENO levels of workers with high flavoring exposures (n = 107) were compared with those of workers with low exposures (n = 28) and healthy external controls (n = 31). FENO levels were significantly lower in the high-exposure group (p < 0.05). There is no indication that FENO is useful as a marker of lung injury in a flavoring-exposed worker population with a substantial lung disease burden, but the finding of low FENO in the high-exposure group should not be dismissed.