Boldine: a potential new antiproliferative drug against glioma cell lines

Malignant gliomas are the most common and devastating primary tumors of the central nervous system. Currently no efficient treatment is available. This study evaluated the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on glioma proliferation and cell death. Boldine decreased the cell number of U138-MG, U87-MG and C6 glioma lines at concentrations of 80, 250 and 500 μM. We observed that cell death caused by boldine was cell-type specific and dose-dependent. Exposure to boldine for 24 h did not activate key mediators of apoptosis. However, it induced alterations in the cell cycle suggesting a G₂/M arrest in U138-MG cells. Boldine had no toxic effect on non-tumor cells when used at the same concentrations as those used on tumor cells. Based on these results, we speculate that boldine may be a promising compound for evaluation as an anti-cancer agent.     

Time Poor: Rushing Decreases the Accuracy and Reliability of Blood Pressure Measurement Technique in Pregnancy

Background: In pregnancy, absolute blood pressure (BP) limits define preeclampsia. Therefore, BP in pregnancy should be measured accurately and in accordance with accepted guidelines. Accuracy of BP readings determined by rate of cuff deflation was analyzed. This study also investigated the compliance of clinical staff at Royal Prince Alfred Hospital, Australia, to guidelines for BP measurement. Methods: The study was an observational trial of 98 normotensive antenatal or recently postnatal patients. Two BP readings were taken, each with fast (>5 mm Hg/sec) and slow (≤2 mm Hg/sec) descent of mercury and compared by Bland-Altman analysis. Also, BP techniques used by junior doctors, specialist obstetricians, and midwives were compared using a 9-point scale. Findings: Australian national guidelines recommend slow descent of mercury. Fast descent underestimated the systolic BP by 9 mm Hg (95% confidence interval [CI], ?23 to +5 mm Hg) (p < 0.001). Fast descent measured the diastolic BP within 2 mm Hg (95% CI, ?10 to +14 mm Hg) (not different, p = 0.151). Accuracy of fast cuff deflation was 28% for systolic BP and 50% for diastolic BP for <5 mm Hg, and respectively, 64% and 68% for <10 mm Hg, 84% and 80% for <15 mm Hg and 91% and 87% for <20 mm Hg. Compliance with guidelines was greatest for specialists and midwives (p = 0.001) and their most commonly missed feature (76% to100%) was slow cuff deflation. Interpretation: Rapid cuff deflation underestimates the systolic BP compared to accepted guidelines (≤2 mm Hg/sec). Medical and midwifery staff may not follow accepted guidelines for BP measurement, particularly with regard to rate of cuff deflation. Potential misdiagnosis and under-treatment of patients with hypertension may compromise pregnancy outcomes.     

Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor α antagonists

Objective

To describe a group of patients who were treated with tumor necrosis factor α (TNFα) antagonists and who developed coccidioidomycosis, and to test the hypothesis that patients with inflammatory arthritis receiving TNFα antagonist therapy are at higher risk for developing symptomatic coccidioidomycosis.

Methods

Cases of coccidioidomycosis were identified and reviewed from among patients receiving TNFα antagonist therapy from May 1998 through February 2003 in 5 practices within the areas endemic for coccidioidomycosis (Arizona, California, and Nevada). In addition, the relative risk of developing symptomatic coccidioidomycosis was calculated in patients with inflammatory arthritis who were receiving treatment with infliximab, in comparison with patients with inflammatory arthritis who were not receiving infliximab, from January 2000 to February 2003 in a single medical center.

Results

Thirteen cases of documented coccidioidomycosis were associated with TNFα antagonist therapy. Twelve cases were associated with the use of infliximab and 1 case with etanercept. Among the cohort of patients from a single medical center, 7 of the 247 patients receiving infliximab and 4 of the 738 patients receiving other therapies developed symptomatic coccidioidomycosis (relative risk 5.23, 95% confidence interval 1.54–17.71; P < 0.01).

Conclusion

Patients with inflammatory arthritis who are undergoing treatment with infliximab appear to be at higher risk for developing symptomatic coccidioidomycosis as compared with those not receiving infliximab.

     

Anti-inflammatory activity in the aqueous crude extract of the leaves of Nidularium procerum: A bromeliaceae from the Brazilian coastal rain forest

Nidularium procerum LINDMAN, a common bromeliaceae from the Brazilian flora, remains poorly studied regarding its chemical and pharmacological properties. We have recently published that N. procerum has potent analgesic and anti-inflammatory activities. In the present work, we have investigated potential mechanisms involved in the anti-inflammatory effects of N. procerum aqueous extract on lipopolysaccharide (LPS)-, platelet activating factor (PAF)- or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced pleurisy models of inflammation. We found that the aqueous extract of N. procerum leaves (leaf aqueous extract; LAE) inhibits the neutrophil migration, production of inflammatory cytokines interleukin-1 and -6 (IL-1 and IL-6) and the generation of prostaglandin E2 (PGE2) in LPS-induced pleural inflammation in mice. Such inhibitory effect of N. procerum on PGE2 generation was tightly correlated to the inhibition of formation of new cytoplasmic lipid bodies within recruited leukocytes. N. procerum also blocked the in vivo neutrophil influx induced by injection of PAF or fMLP into the mouse pleural cavity and directly inhibited PAF-induced neutrophil chemotaxis in vitro. The data obtained in this study indicate that N. procerum LAE exerts its anti-inflammatory effects by interfering with the capacity of the host to respond to injury at different levels. Among the different functions affected by N. procerum LAE, lipid body formation, PGE2 and cytokine production and neutrophil chemotaxis are readily evidenced in relevant surrogate models. The N. procerum bioactive profile makes it an attractive candidate for future development as a drug or phytomedicine.     

Mannose-binding lectin genotypes and pre-eclampsia: a case-control study

Both immunological and placental factors are involved in the pathogenesis of pre-eclampsia. The complement factor mannose-binding lectin (MBL) is associated with adverse pregnancy outcomes and has been suggested to play a role in abnormal placentation. We investigated whether MBL genotypes are associated with the systemic maternal syndrome pre-eclampsia. MBL2 gene polymorphisms were determined in a case-control study including 157 women with pre-eclampsia (case subjects) and 157 women with uncomplicated pregnancies (control subjects). Considering MBL polymorphisms, case and control subjects were categorized in groups of high (A), intermediate (B), and low (C) MBL production. No association was found between MBL genotypes and pre-eclampsia; adjusted odds ratios and 95% confidence intervals (95% CI) for group B were 0.97 (95% CI = 0.46-2.07) and for group C were 1.44 (95% CI = 0.52-3.94). A trend was found between MBL genotype groups B and C and severe pre-eclampsia or eclampsia. MBL genotypes were not found to be associated with pre-eclampsia; however low-MBL production genotypes might be considered as disease modifier. This suggests that MBL may play a role in modulating placental inflammation by facilitating clearance of apoptotic cells and cell debris.     

Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units

OBJECTIVE: Although the development of ventilator-associated pneumonia (VAP) is assumed to increase costs of intensive care unit stay, it is unknown whether prevention of VAP by means of oropharyngeal decontamination is cost-effective. Because of wide ranges of individual patient costs, crude cost comparisons did not show significant cost reductions. DESIGN: Based on actual cost data of 181 individual patients included in a former randomized clinical trial, cost-effectiveness of prevention of VAP was determined using a decision model and univariate sensitivity analyses, and bootstrapping was used to assess the impact of variability in the various outcomes. DATA SOURCE: Published data on prevention of VAP by oropharyngeal decontamination, which resulted in a relative risk for VAP of 0.45, with a baseline rate of VAP of 29% among control patients. The mean costs of the intervention were 351 dollars per patient (32 dollars per patient per day). All other costs were derived from the hospital administrative database for all individual patients. RESULTS OF BASE-CASE ANALYSIS: Prevention of VAP led to mean total costs of 16,119 dollars and 18,268 dollars for patients without preventive measures administered. Thus, costs were saved and instances of VAP were prevented. Similar results were observed in terms of overall survival. RESULTS OF SENSITIVITY ANALYSIS: Prevention of VAP remains cost-saving if the relative risk for VAP because of intervention is <0.923, the costs of the intervention are less than 2,500 dollars, and the prevalence of VAP without intervention is >4%. Bootstrapping confirmed that, with about 80% certainty, oropharyngeal decontamination results in prevention of VAP and simultaneously saves costs. In terms of a survival benefit, the results are less evident; the results indicate that with only about 60% certainty can we confirm that oropharyngeal decontamination would result in a survival benefit and simultaneously save costs. CONCLUSIONS: This study provides strong evidence that prevention of VAP by means of oropharyngeal decontamination is cost-effective.     

Prediction of obstructive sleep apnea: comparative performance of three screening instruments on the apnea-hypopnea index and the oxygen desaturation index

Sleep and Breathing - To evaluate the performance of the NoSAS&nbsp;(neck, obesity, snoring, age, sex) score, the STOP-Bang&nbsp;(snoring, tiredness, observed apneas, blood pressure, body...