Polymorphic metabolizing genes and susceptibility to atherosclerosis among cigarette smokers

Atherosclerosis (AR) is the leading cause of morbidity and mortality in the US and cigarette smoking is a major contributing factor to the disease. Like cigarette smoking in lung cancer, genetic susceptibility may be an important factor in determining who is more likely to develop AR. However, the current emphasis has been on susceptibility based on altered cardiovascular homeostasis. In this investigation, we studied 120 AR patients and 90 matched controls to elucidate the association between polymorphisms in some metabolizing genes (GSTM1, GSTT1, CYP2E1, mEH, PON1, and MPO) and susceptibility to AR. We found that the GSTT1 null allele and the fast allele of mEH(*) (exon 4) are associated with risk for AR. Furthermore, the combined genotypes GSTM1 null/ CYP2E1(*)5B, GSTM1 null/mEH YY, and GSTT1 null/mEH YY are significantly associated with susceptibility to AR (OR = 15.42, 95% CI = 1.33-77.93, P = 0.021; OR = 3.48, 95% CI = 1.63-8.04, P = 0.0008; OR = 3.4; 95% CI = 0.99-17.38, P = 0.05; respectively). We have also conducted cytogenetic analysis to elucidate if induction of chromosome aberrations (CAs) is a biomarker of AR susceptibility. We found that among cigarette smokers (AR patients and smoker controls), individuals having the GSTM1 null allele had a significantly higher frequency of CAs compared to those with the normal allele (P < 0.05). This association was not found among nonsmokers. In addition, individuals who had inherited the CYP2E1(*)5B allele exhibited a significantly higher CA frequency (8.0 +/- 0.82) compared to those with the CYP2E1 wild-type genotype (4.31 +/- 0.35). Since the analysis of genetic susceptibility factors is still in its infancy, our study may stimulate additional investigations to understand the roles of genetic susceptibility and cigarette smoking in AR.     

香烟烟雾提取物致小鼠生殖细胞的遗传学损伤

目的：研究香烟烟雾提取物对小鼠生殖细胞染色体和精子的影响,方法：给雄性小鼠腹腔注射不同剂量的香烟烟雾提取物,观察其精原细胞染色体畸变及精子畸形的情况,结果：精原细胞染色体畸变率及精子畸形率均增高,精子畸形率增高的程度大于精原细胞染色体畸变率。结论：香烟烟雾提取物可致雄性小鼠生殖细胞染色体畸变和精子畸形。     

被动吸烟对金黄地鼠致畸作用的研究

目的　采用被动吸烟方法研究香烟烟雾对金黄地鼠胚胎的致畸作用。②方法　应用被动吸烟笼具将不同妊娠时间的金黄地鼠分组进行被动吸烟 ,而后计数每组的胚胎植入数、活胎、吸收胎、死胎、畸胎及畸形数 ,并进行统计学处理。③结果　孕 1～ 6d ,7d ,9d以及 10～ 14d吸收胎加死胎的百分数比对照组略有增加 ,畸胎和畸形数无增加。而孕 8d吸收胎加死胎百分数、畸胎率均比对照组有显著增加 (χ2 =17.2 ,5 1.4,P <0 .0 0 1)。④结论　吸烟对胚胎有致畸作用。     

Children's Health and the Environment—The First Herbert L. Needleman Award Lecture

Children today are exposed extensively to toxins in the environment. Prominent among these are exposures to over 70,000 synthetic chemicals, all newly developed in the past 50 years and largely untested for their hazards to children's health. Children are uniquely vulnerable to toxins, and with increasing incidence they are developing chronic, disabling, life-threatening diseases known or suspected to be of environmental origin–asthma, endocrine disruption, cancer, and the diseases caused by tobacco. Pediatricians need to consider toxic etiologies in the differential diagnosis of childhood illness.     

烟溶液与温石棉对细胞增殖活性的影响

目的　探讨香烟烟雾溶液与温石棉单独及联合作用对细胞增殖活性的影响。方法　将人胚肺（ Ｈ Ｅ Ｌ） 成纤维细胞用不同浓度的烟溶液和温石棉单独及联合作用一定时间后,应用［３ Ｈ］ Ｔｄ Ｒ参入法测定了细胞的增殖能力。结果　低剂量的烟溶液与温石棉单独作用时均可促进细胞的增殖,但较高剂量的烟溶液和温石棉则可抑制细胞的增殖;当二者联合作用时,低剂量的烟溶液与温石棉可协同增加细胞的增殖,而较高剂量的烟溶液与温石棉则只表现为相加作用。结论　烟溶液与温石棉单独及联合作用均可影响 Ｈ Ｅ Ｌ细胞的增殖活性,但其促增殖和抑制增殖能力则随剂量不同而不同。     

Preliminary study of electrocautery smoke particles produced in vitro and during laparoscopic procedures

Background: The objective of this preliminary study was to describe the particles contained in cautery smoke produced during five laparoscopic procedures and verify the collection method during three laboratory experiments on ex vivo animal tissue. Methods: A cascade impactor collected the smoke according to particle size, and particle weights were calculated on an electronic microbalance. Electron microscopic analysis and energy dispersive X-ray evaluation were used to determine particle morphology and elemental composition. Results: The particles, distributed according to size on the seven rotating trays of the impactor, had diameters ranging from 0.05 to >25 m, with most being 0.1–1 m. In vitro experiments yielded more particles, especially larger (>5 m) ones, than the surgical procedures, because the cauterized specimens could be placed much closer to the cascade impactor in the laboratory environment, eliminating most obstacles to particle recovery. In the laparoscopic surgery patients, larger particles, because of their physical properties, were more likely to remain trapped in the abdomen or to drop off in the collection apparatus. Uniformly, two populations of particles were demonstrated—either large, irregular fragments (2–25 m) rich in carbon and oxygen, suggesting structural cellular components, or small homogeneous spheres (0.1–0.5 m) composed of sodium, magnesium, calcium, and potassium salts. Conclusions: This study demonstrates the presence of breathable areosols and cell-size fragments in the cautery smoke produced during laparoscopic procedures. Their exact chemical composition and potential adverse effects for patients and personnel are not known.     

Programmes for tobacco and alcohol users in Australian work-places

This article presents findings from a survey of programmes available for tobacco and alcohol users working in 455 of Australia's top 600 companies. Companies were twice as likely to have programmes for smokers (43%) as for problem drinkers (24%) and these programmes were more apparent in large companies. The majority of programmes for smoking were delivered within a health promotion context which included other life-style issues, such as nutrition, exercise, weight management and stress management. Although Employee Assistance Programs (EAPs) were the most commonly available type of work-place programme for excessive drinkers and other drug users, followed by Alcoholics Anonymous and local hospital clinics, only 6% had an EAP for alcohol. Only 21% of programmes for smokers and 12% for excessive alcohol users were evaluated. Around one-quarter of companies knew the costs of smoking programmes, and 9% reported costs of conducting programmes for excessive alcohol consumers.     

Acute changes in forearm haemodynamics produced by cigarette smoking in healthy normotensive non-smokers are not influenced by propranolol or pindolol

Summary The aim of the present study was to examine the effect of cigarette smoking in healthy non-smokers on blood pressure and forearm haemodynamics after acute oral administration of non-selective -adrenoceptor blockers with and without intrinsic sympathomimetic activity, viz. pindolol 15 mg and propranolol 80 mg. A preliminary study was done to compare cigarette smoking and sham smoking to evaluate the time-course of the haemodynamic effects of cigarette smoking. The second experiment was then carried out in the same six volunteers, according to a double-blind randomized placebo-controlled crossover design, to evaluate the possible effect of pre-treatment with -adrenoceptor blockers on blood pressure, heart rate and forearm haemodynamics (forearm blood flow, brachial artery diameter and brachio-radial pulse-wave velocity) measured at baseline, during smoking and every five minutes up to 1 h afterwards.No major difference from placebo in blood pressure or forearm haemodynamics was found and pre-treatment with beta-blockers did not prevent the acute vascular effects of cigarette smoking.     

Characteristics of tetrahydrocannabinol (THC)-produced discrimination in rats

Rats were trained in a T-shaped maze to discriminate the effects produced by i.p. injections of tetrahydrocannabinol (THC) and the no-drug state (state-dependency, StD). Several doses of both ⁸-THC (range: 0.75–5.0 mg/kg) and ⁹-THC (range: 0.75–10.0 mg/kg) were used in order to compare the number of sessions required by the animals until reaching criterion performance. An additional group of rats had to discriminate pentobarbital sodium (20.0 mg/kg) from the no-drug state.Results: THC discrimination was proportional to dose i.e., animals that had to differentiate high doses of THC from no drug acquired the T-maize task faster than animals trained with the lower doses of THC. Acquisition data further suggest that ⁸-THC is somewhat less potent than the ⁹-isomer. ⁹-THC (10.0 mg/kg) produces strong StD, as defined by Overton (1971), since both this group and the barbiturate group reached the criterion within the first 10 training sessions. Time and dose testings suggest that stimulus properties of drugs vary in a quantitative way and that the calculated ED₅₀ values are mainly determined by the training dose used. It was found that the higher the training dose used the higher was the corresponding ED₅₀ value. Hashish smoke can maintain drug responding among THC-trained rats. A lowered content of brain catecholamines and/or serotonin, induced by AMPT (150 mg/kg) and PCPA (310–350 mg/kg), did not lessen ⁹-THC (2.5 mg/kg) discrimination.Portions of the results were presented at the Fourth Scandinavian Meeting on Physiology and Behavior, Oslo May 22–24, 1975.