Longitudinal study of workers in an aluminum smelter

We conducted a 6-y follow-up study that included workers in an aluminum smelter in British Columbia. Of the original cohort, 951 workers left the industry and 985 workers participated in both studies. Comparison of those who left and those who remained showed that those who left were (1) older, (2) had a slightly higher prevalence of respiratory symptoms, and (3) had lower lung function; this was especially true for workers who were 50 + y of age at the time the initial study was conducted. Analyses were conducted only on 586 male workers who did not change their job location or smoking habits between the initial and the follow-up study. Potroom workers in the "high-exposure" group had a significant reduction in the prevalence of cough, but experienced an increase in the prevalence of wheeze. There was no significant difference in the annual decline in forced expiratory volume in 1 sec and forced vital capacity between the potroom workers and controls. In general, older workers and smokers had a greater decline in lung function compared to younger workers and nonsmokers. Leukocyte count done during the initial study was found to be an independent predictor of longitudinal decline in lung function. The lack of exposure effect on longitudinal decline in lung function could be due to "healthy worker" effect and improvement in the working condition of the smelter.     

Pulmonary function as a predictor of coronary heart disease

The role of pulmonary function as an independent predictor of coronary heart disease was examined in 1965-1983 in a cohort of Japanese-American men. As part of the Honolulu Heart Program, the authors measured pulmonary function in 5,924 men aged 45-68 years who were free of coronary heart disease at baseline examination and followed them for 15-18 years for the development of nonfatal myocardial infarction and fatal coronary heart disease. Per cent predicted forced expiratory volume in one second (%PFEV1) was significantly inversely related to coronary heart disease incidence in the total cohort after adjusting for age (p less than 0.0001) and then for all known coronary heart disease risk factors (p = 0.0004). However, when examined by smoking status, %PFEV1 was a predictor of coronary heart disease only among past and current smokers, and not for men who had never smoked cigarettes (p = 0.36). The association between pulmonary function and coronary heart disease can be explained by cigarette smoking, which leads to both lung impairment and coronary heart disease incidence.     

Clinical and microbiologic studies of genital ulcers in Kenyan women

The etiology of genital ulcers in women in tropical regions is poorly understood. Eighty-nine women, presenting to a sexually transmitted disease clinic in Nairobi (Kenya) with a primary complaint of genital ulcers, were evaluated prospectively in a clinical and laboratory study. A final etiologic diagnosis was possible for 60 (67%) of the women. Culture for Haemophilus ducreyi was positive for 43 women, eight had secondary syphilis with ulcerated condyloma latum, three had primary syphilis, one had both chancroid and syphilis, two had moniliasis, two had herpetic ulceration, and one had a traumatic ulcer. The clinical characteristics that best distinguished chancroid from secondary syphilis were ulcer excavation and a rough ulcer base. No etiologic diagnosis was established for 29 patients. However, the clinical and epidemiologic features of these patients suggested that they were similar if not identical to the patients with H. ducreyi culture-positive chancroid. Further studies are necessary to determine the etiology of ulcers in females in whom no pathogen was identified.     

Protein intake for skeletal muscle hypertrophy with resistance training in seniors

Variability in protein consumption may influence muscle mass changes induced by resistance exercise training (RET). We sought to administer a post-exercise protein supplement and determine if daily protein intake variability affected variability in muscle mass gains. Men (N=22) and women (N=30) ranging in age from 60 to 69 y participated in a 12-wk RET program. At each RET session, participants consumed a post-exercise drink (0.4 g/kg lean mass protein). RET resulted in significant increases in lean mass (1.1 +/- 1.5 kg), similar between sexes (P > 0.05). Variability in mean daily protein intake was not associated with change in lean mass (r < 0.10, P > 0.05). The group with the highest protein intake (1.35 g x kg(-1) x d(-1), n=8) had similar (P > 0.05) changes in lean mass as the group with the lowest daily protein intake (0.72 g x kg(-1) x d(-1), n=9). These data suggest that variability in total daily protein intake does not affect variability in lean mass gains with RET in the context of post-exercise protein supplementation.     

Increased contractile response to 5-hydroxytryptamine1-receptor stimulation in pulmonary arteries from chronic hypoxic rats: role of pharmacological synergy

1. 5-Hydroxytryptamine (5-HT)(1)-receptor-induced contraction is enhanced, or uncovered, by elevated vascular tone in many arteries including pulmonary arteries. In hypoxia-induced pulmonary hypertension, the endogenous tone of pulmonary arteries is elevated and this may contribute to increased 5-HT(1)-receptor-induced contraction. Here we investigate the influence of vascular tone induced by endothelin-1 (ET-1), neuropeptide Y (NPY), KCl, 4-aminopyridine (inactivator of K(v) channels, 4-AP) or the calcium ionophore A23187 on contractile responses to the 5-HT(1)-receptor agonist 5-carboxamidotryptamine (5-CT) in small muscular pulmonary arteries from control rats and rats exposed to chronic hypoxia. The influence of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) was also studied. These conditions were chosen to mimic those that influence pulmonary vascular tone in hypoxia-induced pulmonary hypertension. 2. In control rat small pulmonary arteries, only high concentrations of 5-CT (>1 microM) induced vasoconstriction. Tone induced by NPY, 4-AP and A23187 had no effect on responses to 5-CT whilst responses to 5-CT were increased by ET-1- and KCl-induced tone. In the presence of L-NAME these responses to 5-CT were enhanced further. 3. Responses to 5-CT were enhanced 3 - 4 fold in small pulmonary arteries from hypoxia-exposed, pulmonary hypertensive rats and neither L-NAME nor increasing tone with NPY, 4-AP, A23187, ET-1 or KCl had any further effect on responses to 5-CT. 4. The results suggest that inhibition of nitric oxide synthase combined with KCl- or ET-1-induced vascular tone potentiates responses to 5-HT(1)-receptor-induced contraction in pulmonary arteries in a synergistic fashion and this mimics the effects of chronic hypoxic exposure.     

Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension

Background and purpose:

Voltage-gated potassium (K_v) channels contribute to resting membrane potential in pulmonary artery smooth muscle cells and are down regulated in patients with pulmonary arterial hypertension (PAH) and a contribution from K_v7 channels has been recently proposed. We investigated the effect of the K_v7 channel activator, flupirtine, on PAH in two independent mouse models: PAH induced by hypoxia and spontaneous PAH in mice over-expressing the 5-HT transporter (SERT⁺ mice).

Experimental approach:

Right ventricular pressure was assessed in vivo in mice chronically treated with flupirtine (30 mg·kg⁻¹·day⁻¹). In separate in vitro experiments, pulmonary arteries from untreated mice were mounted in a wire myograph. Relaxations to acute administration of flupirtine and contractions to K_v channel blocking drugs, including the K_v7 channel blocker linopirdine, were measured.

Key results:

In wild-type (WT) mice, hypoxia increased right ventricular pressure, pulmonary vascular remodelling and right ventricular hypertrophy. These effects were attenuated by flupirtine, which also attenuated these indices of PAH in SERT⁺ mice. In the in vitro experiments, flupirtine induced a potent relaxant response in arteries from untreated WT and SERT⁺ mice. The relaxation was fully reversed by linopirdine, which potently contracted mouse pulmonary arteries while other K_v channel blockers did not.

Conclusions and implications:

Flupirtine significantly attenuated development of chronic hypoxia-induced PAH in mice and reversed established PAH in SERT⁺ mice, apparently via K_v7 channel activation. These results provide the first direct evidence that drugs activating K_v7 channels may be of benefit in the treatment of PAH with different aetiologies.     

PML-RARα融合基因监测急性早幼粒细胞白血病微小残留病

 目的　观察PML-RARα融合基因在监测急性早幼粒细胞白血病（APL）微小残留病（MRD）中的临床意义。方法　诱导缓解及巩固维持治疗期间,采用筑巢式反转录-聚合酶链反应（RT-PCR）技术检测患者骨髓细胞中PML-RARα融合基因的动态变化、PML-RARα融合基因。结果　长期随访的18例完全缓解（CR）患者,2例出现分子学复发。其中1例发生于CR1后4个月,诱导缓解治疗后获得CR2,CR2后2个月再次出现分子学与血液学的复发,诱导治疗1个疗程获得CR3;1例发生于CR1后74个月,诱导缓解治疗后获得CR2,随访结束时生存期已达106个月。结论　在CR期定期监测PML-RARα融合基因,可早期发现分子学复发,及时干预治疗可避免血液学复发。     

黄连素对肺腺癌A549细胞增殖、迁移与黏附的影响

背景与目的：研究表明,黄连素在清热解毒、抗菌消炎的同时,还具有诱导肿瘤细胞凋亡的作用,但最近的研究认为黄连素还能抑制肿瘤细胞的转移和扩散。为了进一步探讨黄连素对肿瘤细胞转移的作用及机制,本研究对黄连素作用后的肺腺癌A549细胞的增殖、迁移及黏附能力进行了检测。方法：应用MTT法检测不同浓度黄连素作用后细胞增殖情况;通过划痕试验和黏附试验测定黄连素作用前后细胞迁移和黏附能力;半定量RT-PCR法检测MMP2、MMP9的mRNA表达;明胶酶谱法测定MMP2、MMP9的活性。结果：黄连素能显著抑制A549增殖,并呈现一定的量效和时效关系（P〈0.05）;细胞的迁移率和黏附率明显降低,并且呈现剂量依赖性（P〈0.05）;经黄连素作用后的A549细胞,MMP2和MMP9的mRNA的表达明显降低,MMP2和MMP9降解明胶的能力下降,尤以100μg/mL的作用最为明显（P〈0.05）。结论：黄连素能够抑制A549细胞的迁移和黏附能力,其机制可能与下调MMP2和MMP9的mRNA表达,从而降低其活性有关。     

重组人血管内皮抑制素联合电子线照射对肺腺癌A549移植瘤的实验研究

背景与目的:有研究表明放疗能够上调和强化肿瘤血管的生成过程,导致放疗耐受;重组入血管内皮抑制素(recombinant human endostatin,rh-endostatin)可抑制肿瘤血管生成,改善由放疗引起的耐受性.本研究旨在探讨rh-endostatin与顺铂(cisplatin,DDP)分别联合电子线照射对肺腺癌A549移植瘤的抑制作用.方法:建立A549肺腺癌移植瘤模型,待瘤径达1.0 cm时,将实验鼠随机分成4组(每组6只):对照组、照射组、照射+DDP组和照射+rh-endostatin组.定期测量肿瘤最长径和最大垂直径,第16天时处死裸鼠,取出肿瘤组织,检测肿瘤细胞凋亡率,RT-PCR检测bFGF mRNA表达水平,免疫组织化学法检测VEGF表达水平.结果:对照组、照射组、照射+DDP组和照射+rh-endostatin组肿瘤的生长速率分别为(162±6)%、(131±8)%、(104±7)%和(108±11)%(P<0.05);照射+rh-endostatin组与照射组相比以及照射+DDP组与照射组相比,差异均具有统计学意义(P<0.01);照射+rh-endostatin组与照射+DDP组相比,差异无统计学意义(P>0.05).肿瘤细胞凋亡率,对照组、照射组、照射+DDP组和照射+rh-endostatin组分别为(12.2±1.1)%、(16.5±0.8)%、(24.4±1.5)%和(20.5±1.9)%,各组间差异具有统计学意义(P<0.05).照射组bFGF mRNA和VEGF表达水平高于对照组,照射+rh-endostatin组bFGF mRNA和VEGF表达水平明显低于对照组、照射组、照射+DDP组(P<0.05).结论:rh-endostatin明显提高了照射对A549n肺腺癌移植瘤的抑制情况;rh-endostatin联合照射肺腺痛A549移植瘤可取得与DDP联合放疗相似的结果.