The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia

We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague-Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 min of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.     

Application of Confocal Raman Microscopy for the Characterization of Topical Semisolid Formulations and their Penetration into Human Skin Ex Vivo

Pharmaceutical Research - The quality testing and approval procedure for most pharmaceutical products is a streamlined process with standardized procedures for the determination of critical quality...     

The ansacarbamitocins: polar ansamitocin derivatives

The ansacarbamitocins are a new family of maytansinoids that are unusually substituted with a glucose subunit and two carbamate functional groups and exhibit modest activity against some agricultural fungal disease organisms. Ansacarbamitocins A-F ( 1- 6) all consist of the same macrocyclic core as the ansamitocins, with variation occurring on the glucose unit, while ansacarbamitocins A1 and B1 ( 7, 8) additionally lack the epoxide group on C-4 and C-5.     

Corrosion of tungsten coils after peripheral vascular embolization therapy: influence on outcome and tungsten load.

The purpose of this study was to evaluate coil corrosion and the long-term outcome after peripheral vascular embolization therapy performed with tungsten coils. We studied 14 patients who received tungsten coils on an average of 26 months prior to follow-up. The protocol included plain radiography and contrast-enhanced magnetic resonance angiography to investigate corrosion of tungsten coils and recanalization of the embolized vessels. Whole blood, hair, and urine tungsten levels were assayed when available. Corrosion of tungsten coils was detected in 9 of 14 patients by plain radiography. No evidence of recanalization of the embolized vessel and no adverse clinical effects of tungsten resorption were detected. Blood levels of tungsten were elevated in 6 of 14 patients and urine levels of tungsten were elevated in all 12 patients tested. Tungsten coil corrosion and elevated tungsten levels in blood, hair, and urine were found in most patients, although no adverse clinical effects of tungsten resorption were detected. Since the overall effect of high tungsten blood levels remains unclear, its use as an implant should be avoided.     

Topical treatment of chronic low back pain with a capsicum plaster

The efficacy and tolerance of a capsicum plaster in non-specific low back pain was investigated in a double-blind, randomised, placebo-controlled multicentre parallel group study. A total of 320 patients were randomly assigned to two groups of n=160 subjects treated by the active or the placebo plaster. The main outcome measures used were a compound pain subscore of the Arhus low back rating scale (continuous variable), and a response criterion of a reduction in pain subscore=30% from baseline to final assessment (secondary, non-continuous variable). In addition, the partial pain scores, disability and mobility restriction subscores, the total score of the Arhus low back rating scale, the global evaluation of efficacy by investigator and patient, adverse events, a patient questionnaire on use of the plaster, and an evaluation of tolerance by investigator and patient were obtained. After 3 weeks treatment with capsicum and placebo plaster respectively, the compound pain subscore was reduced by 42% (capsicum) and 31% (placebo) from values on entry. Responder rate was 67% versus 49% (p=0.002). The investigators rated efficacy as "excellent" or "good" by 74% and 36%; the patient's efficacy rating "symptomfree" or "improved" reached 82% and 50%. Adverse local drug reactions were found in 12 patients (7.5%) on capsicum and 5 (3.1%) on placebo. No systemic side-effects were observed. The superiority of the treatment of chronic non-specific low back pain with capsicum plaster compared to placebo was clinically relevant and highly statistically significant. The capsicum plaster offers a genuine alternative in the treatment of non-specific low back pain.     

Periannular extension of infective endocarditis

OBJECTIVES: This prospective study was designed to assess the current clinical course, risk factors, microbiologic profile and echocardiographic findings of patients with left-sided endocarditis and perivalvular complications. BACKGROUND: Periannular complications worsen the prognosis of patients with endocarditis. The relation between these complications and the clinical and microbiologic data has not been clearly defined. METHODS: In this clinical cohort study, 211 patients with left-sided endocarditis, according to the Duke criteria, were prospectively recruited. All patients underwent conventional and transesophageal echocardiography. The mean follow-up interval was 151 days. RESULTS: Perivalvular complications were detected in 78 patients (37%). The incidence of periannular extension of infection in native and prosthetic valves was 29% and 55%, respectively. The presence of prosthesis (relative risk [RR] 1.88, 95% confidence interval [CI] 1.35 to 2.64) and previous endocarditis (RR 1.78, 95% CI 1.16 to 2.7) were the only pre-existing heart conditions associated with perivalvular complications. Aortic infection (RR 1.8, 95% CI 1.23 to 2.66) and the development of atrioventricular (AV) block (RR 2.55, 95% CI 1.91 to 3.41) were related with the existence of these complications. Coagulase-negative staphylococci were very common in patients with perivalvular complications (RR 1.77, 95% CI 1.21 to 2.59), and small vegetations were more frequent in these patients (RR l.45, 95% CI 0.95 to 2.22). An operation was more frequently performed in patients with perivalvular complications, but mortality was similar in patients with and without these complications. CONCLUSIONS: Aortic infection, prosthetic endocarditis, new AV block and coagulase-negative staphylococci were independent risk factors of periannular complications. The period between symptom onset and diagnosis, the incidence of pericardial effusion and persistent signs of infection were similar between patients with and without perivalvular complications. Patients with perivalvular complications did not demonstrate a difference in the presence or size of vegetations or the frequency of embolism. An operation was more frequently performed in these patients, but mortality was similar in both groups.     

Epithelial–Mesenchymal Transition in Chronic Rhinosinusitis: Differences Revealed Between Epithelial Cells from Nasal Polyps and Inferior Turbinates

The pathogenesis of chronic rhinosinusitis (CRS) remains unclear to date. The tissue remodeling in nasal polyps may be the result of inflammatory mediators and may involve epithelial–mesenchymal transition (EMT) and EMT-associated features such as cell motility in nasal epithelial cells (NECs). We determined whether NEC in nasal polyps of CRS already display features of EMT in vivo or respond with EMT to growth factor stimulation in vitro. Nasal polyp tissues expressed both epithelial and mesenchymal markers. Primary NEC from inferior turbinates and nasal polyps responded to the EMT-inducing agents transforming growth factor (TGF)-β1 and epidermal growth factor (EGF) with different expression patterns of EMT markers (E-cadherin, N-cadherin, Snail, Slug, Twist), however, only NEC from nasal polyps were susceptible to TGF-β1 and EGF-dependent cell migration. Our data suggest that a partial EMT is associated with the pathogenesis of nasal polyps in CRS patients. Furthermore, we show for the first time that epithelial cells from both nasal polyps and inferior turbinates were able to undergo an EMT-like process following exposure to TGF-β1 or EGF in vitro but that only NEC from nasal polyps responded with enhanced cell motility. Our data suggest that NEC from CRS patients have undergo partial EMT and that this process may be involved in the pathogenesis of CRS.