Exposure of Children to Environmental Tobacco Smoke (ETS) and Its Association with Respiratory Ailments

Objectives. To assess the impact of domestic passive smoking (cigarettes or narghile) on the development of respiratory ailments among children ages 10-15 years. Methods. Students were recruited from five private schools in Beirut, and information on demographic, in-home smoking, and students' respiratory tract illnesses (cough, wheezing, runny nose, or nasal congestion) were collected from each participant. Results. Of 625 students surveyed, 438 (70.1%) had at least one individual smoking at home. Compared with the nonexposed group, the odds ratio of having respiratory illness for children exposed to narghile or cigarette smoke were 2.3 (95% Confidence Iinterval [CI] 1.1-5.1) and 3.2 (95% CI 1.9-5.4), respectively. Conclusions. In addition to the well-established effect of smoking, domestic passive smoking of the misconceived “innocuous” habitual smoking device, narghile, is associated with significant respiratory health ailments.     

离子色谱法同时测定葡萄糖酸钙及其杂质(Cl-,SO42-)的含量

本文采用Waters ILC-1离子液相色谱仪,IC-PAK A50×4.6mm色谱柱,pH6.61×10^-3mol/L邻苯二甲酸溶液为流动相,430型电导检测器检测,由外标法和外标单点校正法同时测定了葡萄糖酸钙及其杂质(Cl^-,SO₄^2-)的含量。方法简便、快速,测定结果与中国药典法一致。外标法和外标单点校正法测定Cl^-,SO₄^2-的平均回收率为100.8%和100.2%,相关系数分别为0.9951(n=8)和0.9961(n=8)。     

基于受体结构的药物分子设计系统:维甲类分子与其结合蛋白之间相互作用的研究

大分子解剖程序,配体分子契合适配和DOCK程序,以及计算化学的其它程序等,已集成为基于受体结构和分子间相互作用的进行分子设计的软件系统,定名为BIOS(Biomolecularinteractionsandorientationsimulator)。BIOS软件可在普通的微机上运行。使用BIOS分别剥离了细胞浆维甲结合蛋白(CRBP)和副睾维甲酸结合蛋白(E-RABP)两种蛋白的配体结合腔,剥离是围绕配体以同样的分子距离进行的。从而得到了芳香性残基分布相似的两个结合腔,其结合位点的几何排布却有相当差别。揭示出的结合腔已用于一系列的维甲类化合物的DOCK研究。E-RABP的结合腔可做为设计新维甲类分子的模板。     

Administration of dexamethasone induces proteinuria of glomerular origin in mice

The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observed that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration. One fourth of mice also intermittently presented with slight hematuria beginning on day 12. Renal lesions in the dexamethasone-treated mice, which were killed on day 23, were characterized by mild mesangial expansion, segmental or global hyalinosis/sclerosis in deep cortical glomeruli, and focal tubular changes. No glomerular inflammatory cell infiltration or proliferative lesion was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mesangial matrix, dilated mesangial channels filled with slightly electron-dense material or mesangial lysis-like appearance showing intracytoplasmic microcysts filled with electron-lucent material, and evidence to support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of IgG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the dexamethasone-treated mice. Charge analysis showed no impairment in anionic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuated by treatment with a low molecular weight heparin, although it was not reduced by an angiotensin-converting enzyme inhibitor. Data from these experiments suggest that a large dose of glucocorticoids is potentially nephrotoxic. Alteration of a size-dependent permeability may predominantly contribute to the dexamethasone-induced proteinuria. However, the effect of glomerular hyperfiltration may be only partially involved in the pathogenesis of this dexamethasone-induced glomerulopathy in mice.     

Esophageal pH exposure and epithelial cell differentiation

It is proposed that epithelial changes induced by gastroesophageal reflux disease are related to the pH environment of the esophageal lumen. We hypothesized that the various types of esophageal epithelium are associated with specific pH environments that induce their formation. The aim of this study was to compare the luminal pH environment to the histology of the distal esophageal epithelium in patients with gastroesophageal reflux disease. A total of 197 symptomatic patients with increased esophageal acid exposure on 24-hour pH monitoring were grouped according to the histology based on biopsies from the distal esophagus: 17 with squamous epithelium, 126 with cardiac epithelium (CE), and 54 with Barrett's epithelium (BE). All were free of Helicobacter pylori infection and monitored off acid suppression therapy. Acid exposure was expressed as the percent of time the luminal pH was at intervals of 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, and 6–7 over a 24-hour period. Patients with BE spent significantly more time at pH intervals 2–3, 3–4, and 4–5 than those with CE. This pattern switched at pH interval 5–6, where patients with cardiac mucosa spent more time than those with BE. Patients with squamous and CE had similar pH exposure at all intervals. Patients with BE have significantly longer exposure time at the pH interval of 2 to 5 compared to those with cardiac and squamous epithelium. This suggests that the exposure of stem cells to a luminal pH between 2 and 5 may trigger the differentiation of CE into intestinalized CE.     

Interaction of angiotensin-converting enzyme and apolipoprotein E gene polymorphisms in ischemic stroke involving large-vessel disease

A relationship between apolipoprotein E (Apo E) genotype and angiotensin-converting enzyme (ACE) insertion-deletion (Ins-Del) mutation and stroke was suggested. We investigated the association of Apo E4 and ACE Ins/Del genotypes with stroke risk and changes in serum lipids in 228 consecutive Tunisian stroke patients, and 323 age-and gender-matched controls. Comparable frequencies of ACE Ins/Del alleles were seen between patients and controls. The prevalence of Apo ε3 allele and Apo E3/E3 were lower (P < 0.001), while the frequency of Apo ε4 allele and ε4-containing genotypes (E3/E4 and E4/E4) were elevated (P < 0.001) among patients. Higher proportion of Apo E4-carrying + ACE Del/Del positive cases were seen in young (<50 years) patients (P = 0.012), and was associated with large vessel stroke (P = 0.035). Mean serum cholesterol, LDL, HDL, and triglycerides were comparable between E4-containing and no E4-containing and ACE Del/Del-positive patients. Apo E4 and ACE Del/Del genotype combination substantially increase stroke risk, supporting the notion that interactions of multiple gene variants influence stroke pathogenesis.     

Manipulation of liver regeneration with macrophages to influence the hepatic progenitor cell niche

Insufficient regeneration of the adult liver is believed to cause failure to recover from severe liver disease. An undifferentiated cell population with stem-cell-like qualities known as hepatic progenitor cells (HPCs) is hypothesised to have a central role in regeneration of the adult liver during massive or chronic liver disease. Stem cells in other organ systems are believed to reside in a specialised microenvironment or niche that supports their maintenance and function. The existence of a hepatic stem cell niche might provide a means of therapeutically manipulating endogenous HPCs in vivo as a regenerative therapy.To investigate the physiological potential of HPCs to regenerate the mammalian liver, we have established a novel model of hepatocellular injury and HPC activation using genetic manipulation of hepatocytes. After hepatocyte senescence and death in this model (AhCre Mdm2^flox), HPCs expand and bring about the complete regeneration of the liver parenchyma.We demonstrate that a stereotypical niche, consisting partly of macrophages, exists in both animal models and correlating human disease. Using cell tracking, we show active recruitment of extrahepatic macrophages into this niche during injury. In health, intravenous injection of macrophages results in macrophage engraftment to the liver niche, with subsequent HPC activation and changes to liver structure and function.Within the niche, macrophages use paracrine signalling to control both HPC proliferation and cell fate via TWEAK (tumour-necrosis-factor-like weak inducer of apoptosis) and the Wnt signalling pathway, respectively. After hepatocellular injury, macrophages ingest hepatocyte debris, and release Wnt which promotes HPC differentiation into hepatocytes. TWEAK is vital for HPC proliferation in the AhCre Mdm2^flox model of regeneration. Here, the absence of TWEAK signalling results in liver failure and mortality.This work has demonstrated for the first time the ability of a solid organ to fully regenerate in the adult mammal from progenitor cells, and additionally highlights mechanisms by which this process can be modulated by either small molecule or cell therapy.FundingUniversity of Edinburgh.     

HLA class II haplotypes distinctly associated with vaso-occlusion in children with sickle cell disease

We investigated the association of HLA class II alleles and haplotypes with sickle cell anemia vaso-occlusive crisis (VOC). DRB1*100101 was positively associated, while DRB1*140101, DRB1*150101, and DQB1*060101 were negatively associated, with VOC. Both susceptible (DRB1*100101-DQB1*050101) and protective (DRB1*110101-DQB1*030101 and DRB1*150101-DQB1*060101) haplotypes were identified, indicating that HLA class II haplotypes influence VOC risk.     

Modulation of type 1 diabetes susceptibility by tumor necrosis factor alpha -308 G/A and lymphotoxin alpha +249 A/G haplotypes and lack of linkage disequilibrium with predisposing DQB1-DRB1 haplotypes in Bahraini patients

Tumor necrosis factor alpha (TNF-α) −308 G/A and lymphotoxin alpha (LTα) +249 A/G single-nucleotide polymorphisms were investigated in 228 type 1 diabetes mellitus (T1DM) patients and 240 controls. Only LTα +249G allele and +249G/+249G genotype frequencies were higher among patients, and no linkage disequilibrium was found between TNF-α/LTα alleles and susceptible/protective DRB1-DQB1 haplotypes. TNF-α/LTα T1DM-susceptible (−308G/+249G) and protective (−308G/+249A) haplotypes were identified.