Respiratory viral infection in lower airways of asymptomatic children

Aim: The aim of this study was to determine if asthmatic children have viruses more commonly detected in lower airways during asymptomatic periods than normal children. Methods: Fifty‐five asymptomatic children attending elective surgical procedures (14 with stable asthma, 41 normal controls) underwent non‐bronchoscopic bronchoalveolar lavage. Differential cell count and PCR for 13 common viruses were performed. Results: Nineteen (35%) children were positive for at least one virus, with adenovirus being most common. No differences in the proportion of viruses detected were seen between asthmatic and normal ‘control’ children. Viruses other than adenovirus were associated with higher neutrophil counts, suggesting that they caused an inflammatory response in both asthmatics and controls (median BAL neutrophil count, 6.9% for virus detected vs. 1.5% for virus not detected, p = 0.03). Conclusions: Over one‐third of asymptomatic children have a detectable virus (most commonly adenovirus) in the lower airway; however, this was not more common in asthmatics. Viruses other than adenovirus were associated with elevated neutrophils suggesting that viral infection can be present during relatively asymptomatic periods in asthmatic children.     

选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

Functional analysis of CaIPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans

In the present study we describe the isolation and functional analysis of a sphingolipid biosynthetic gene, IPT1, of Candida albicans. The functional consequence of the disruption of both alleles of IPT1 was confirmed by mass analysis of its sphingolipid composition. The disruption of both alleles or a single allele of IPT1 did not lead to any change in growth phenotype or total sphingolipid, ergosterol, or phospholipid content of the mutant cells. The loss of mannosyl diinositol diphosphoceramide [M(IP)(2)C] in the ipt1 disruptant, however, resulted in increased sensitivity to drugs like 4-nitroquinoline oxide, terbinafine, o-phenanthroline, fluconazole, itraconazole, and ketoconazole. The increase in drug susceptibilities of ipt1 cells was linked to an altered sphingolipid composition, which appeared to be due to the impaired functionality of Cdr1p, a major drug efflux pump of C. albicans that belongs to the ATP binding cassette superfamily. Our confocal and Western blotting results demonstrated that surface localization of green fluorescent protein-tagged Cdr1p was affected in ipt1 disruptant cells. Poor surface localization of Cdr1p resulted in an impaired ability to efflux fluconazole and rhodamine 6G. The effect of mannosyl inositol phosphoceramide accumulation in the ipt1 mutant and the absence of M(IP)(2)C from the ipt1 mutant on the efflux of drug substrates was very selective. The efflux of methotrexate, a specific substrate of CaMdr1p, another major efflux pump of major facilitator superfamily, remained unaffected in ipt1 mutant cells. Interestingly, changes in sphingolipid composition affected the ability of mutant cells to form proper hyphae in various media. Taken together, our results demonstrate that an altered composition of sphingolipid, which is among the major constituents of membrane rafts, affects the drug susceptibilities and morphogenesis of C. albicans.     

A RANDOMISED,DOUBLE-BLIND,PARALLEL-GROUP COMPARISON OF VENLAFAXINE AND DOTHIEPIN IN GERIATRIC PATIENTS WITH MAJOR DEPRESSION

This randomised, double-blind study conducted at nine sites in the UK and the Netherlands compared the safety and antidepressant efficacy of venlafaxine and dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression were randomly assigned to receive either venlafaxine or dothiepin for up to 43 days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg per day for the first 15 days, and thereafter could range from 50 to 150 mg per day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p 0.05) from baseline to the end of the study in both groups. A response to therapy was observed in 60% of patients in the venlafaxine group and 53% of patients in the dothiepin group on the MADRS, and in 60% of patients in both groups on the HAM-D. Suicidal ideation scores on the MADRS were significantly (p=0.042) lower in the venlafaxine group at week 6. Treatment-emergent study events were the primary reason for withdrawal in only 7% of venlafaxine-treated patients and 8% of dothiepin-treated patients. The results confirm the efficacy and tolerability of venlafaxine for treating major depression in the elderly.