Soluble CD14 at 2 yr of age: Gender-related effects of tobacco smoke exposure, recurrent infections and atopic diseases

The endotoxin receptor soluble CD14 (sCD14) has been implicated in the 'hygiene hypothesis' suggesting reduced allergic sensitization with bacterial stimulation. However, the relationship between early life sCD14 and allergic diseases is conflicting. We aimed to investigate whether possible risk factors for allergic diseases were associated with sCD14 levels at 2 yr of age. In the nested case-control study of the birth cohort studies 'Environment and Childhood Asthma study in Oslo' 411 children selected with recurrent bronchial obstruction (rBO) (n=241) and no bronchial obstruction (n=170) by 2 yr were investigated with skin prick test and structured parental interview at age 2 yr. Exposure to tobacco smoke, pets and infections was recorded semi-annually by questionnaires (0-2 yr). The sCD14 was analysed from frozen, stored serum by ELISA technique. Regression analyses were performed in all subjects with complete data (n=406, 180 girls), and in girls and in boys separately. Mean sCD14 (ng/ml) was significantly higher among girls 2035 (1973-2096) vs. 1947 (1890-2004) (boys). The sCD14 was significantly reduced among girls exposed to antenatal maternal smoking and with parental asthma, after adjusting for age, parental rhino-conjunctivitis, pet keeping and childhood infections. Recurrent otitis media (OM) increased and common colds significantly decreased sCD14 levels in girls. Boys with atopic dermatitis and rBO had reduced sCD14. Pet exposure was not significantly associated with sCD14. We report novel gender-related effects of sCD14 in early life and suggest that gender, tobacco smoke exposure, age and middle ear disease in particular should be accounted for when assessing the role of sCD14 in childhood allergic diseases.     

The effect of cigarette smoke on the bovine lens

Smoking has recently been identified from epidemiological studies as a possible cause of cataract but the mechanism involved is not known. Therefore, our laboratory has initiated studies aimed at elucidating these mechanisms. Whole bovine lenses were cultured to examine possible effects of cigarette smoke on amino acid uptake and protein synthesis. Cigarette smoke, filtered to remove nicotine and tar which would not reach the eye in vivo, was bubbled through culture medium. Bovine lenses were incubated in this medium in the presence of [¹⁴C]-leucine for four days. A significant decrease in uptake of [¹⁴C]-leucine and a decrease in protein synthesis were found with smoke treated lenses. This is the first demonstration of an effect of cigarette smoke on the lens. Further work is needed to determine how this metabolic upset is mediated and how it could lead to cataract.     

The child with recurrent respiratory infections: normal or not?

Respiratory infections (RI) are one of the major complaints in children and adolescents, and represent a demanding challenge for the pediatrician. It has been estimated that at least 6% of Italian children younger than 6 yr of age present recurrent respiratory infections (RRI). Children with RRI are not affected by severe alterations of the immune system. RRI represent essentially the consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still largely immature. Several social and environmental factors, such as day-care attendance, family size, air pollution, parental smoking, and home dampness, represent important risk factors for airway diseases and may contribute in various degrees to determine the incidence of RRI. The main problem for the pediatrician is to discriminate normal children with high RI frequency related to an augmented exposure to environmental risk factors from children affected by other underlying pathological conditions (immunological or not), predisposing to infectious diseases. When RRI diagnosis has been formulated, removal of environmental risk factors (i.e. precocious day-care attendance, smoking in the household) must first be suggested.     

Cigarette smoke toxicants alter growth and survival of cultured mammalian cells.

Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three types of cultured mammalian cells (human umbilical vein endothelial cells [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of the tested chemicals. After 48 h, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products and should be subjected to further toxicological testing.     

棉尘及吸烟对肺功能影响的观察

对８３名接触棉尘的健康者作肺功能测定，并与３９名不接触棉尘的健康者对照。其中男性均为吸烟者；女性均为不吸烟者。结果表明，ＭＭＥＦ、ＰＥＦＲ、Ｖ２５％～７５％均明显低于对照组（分别为Ｐ＜０．０１和Ｐ＜０．０５）．在男性吸烟组，ＶＣ，ＭＢＣ，ＦＥＶ１％也有明显下降（Ｐ＜０．０１），作者认为棉尘对人体的危害主要部位在小气道，吸烟者因损害严重可累及大气道。以往对棉尘反应的肺功能评估仅以ＦＥＶ１％为指标，不能反映早期的变化，有必要进一步完善。     

Safety assessment of high fructose corn syrup (HFCS) as an ingredient added to cigarette tobacco

A tiered testing strategy has been developed to evaluate the potential for new ingredients, tobacco processes, and technological developments to alter the biological activity that results from burning tobacco. A series of studies was initially conducted with cigarettes containing 3% high fructose corn syrup (HFCS) as an alternate tobacco casing material to corn syrup/invert sugar, including determination of selected mainstream cigarette smoke (MS) constituent yields, Ames assay, sister chromatid exchange (SCE) assay in Chinese hamster ovary (CHO) cells, a 30-week dermal tumor-promotion evaluation of cigarette smoke condensate (CSC) in SENCAR mice, and a 13-week subchronic inhalation study of MS in Sprague-Dawley rats. A second series of studies was conducted with cigarettes containing 3%, 4% and 5% HFCS including MS chemistry, Ames assay, SCE assay in CHO cells, and a neutral red cytotoxicity assays. Collectively, mainstream smoke chemistry, genotoxicity, dermal tumor-promotion, and inhalation toxicity studies demonstrated no differences between cigarettes with 3% HFCS and cigarettes with 3% corn syrup/invert sugar. Also, mainstream smoke chemistry and genotoxicity of cigarettes with 4% and 5% HFCS were not different from cigarettes with 3% HFCS. In conclusion, the addition of up to 5% HFCS to cigarette does not alter the mainstream smoke chemistry or biological activity of mainstream smoke or mainstream smoke condensate as compared to cigarettes with 3% corn syrup/invert sugar with regard to the parameters investigated and presented.     

Progesterone and environmental tobacco smoke act synergistically to exacerbate the development of allergic asthma in a mouse model

BACKGROUND: Asthma affects males and females differently. Females have a higher incidence than males after the onset of puberty. This suggests a hormonal component to the development of the disease. Progesterone, a female hormone, has previously been shown to illicit a T-helper type 2 (TH2) immune response similar to that seen in allergic asthma. Previous studies performed by our laboratory have shown that exposure to environmental tobacco smoke (ETS) enhances the immune response to allergens. OBJECTIVE: To determine if the combination of exposure to ETS and progesterone would further exacerbate the immune response in a mouse model of allergic asthma. METHODS: Female mice were ovariectomized and then implanted with time-release progesterone pellets. Mice were housed in either filtered air (FA) or ETS chambers and half were exposed to aerosolized house dust mite allergen (HDMA). Bronchoalveolar lavage was performed for cell differentials; lung and spleen cells were harvested to compare IL-4 and IFN-gamma production by ELISPOT. RESULTS: Progesterone pellet implantation resulted in increased serum progesterone levels (28.3+/-8.43 vs. 13.5+/-7.22 ng/mL in placebo-treated mice, P<0.0001). Serum total IgE levels were significantly greater in progesterone vs. non-progesterone treated animals that were also exposed to HDMA. ETS exposure enhanced total IgE levels as well. Lung homogenate cells from HDMA/progesterone-treated animals stimulated with Concavalin A produced significantly more IL-4 compared with HDMA/placebo-treated animals (200+/-17.6 vs. 146+/-17.5 spots/well, P<0.01 in ETS exposed animals and 221+/-28.9 vs. 167+/-23.4 spots/well, P<0.01 in animals housed in FA). HDMA/ETS-treated animals had higher eosinophilia in lavage than all other groups. CONCLUSION: Increased serum progesterone levels exacerbate the allergic asthmatic phenotype in a mouse model. These effects are further exacerbated by the addition of environmental tobacco smoke. Progesterone provides a major contribution to the gender differences seen in the development and elicitation of the asthmatic response.     

Cotinine levels in follicular fluid and serum of IVF patients: effect on granulosa-luteal cell function in vitro

Cigarette smoking is accepted as a risk factor for pregnancybut its effect on fertility is uncertain. In this study we determinedthe concentration of cotinine, a nicotine metabolite, in follicularfluid and serum from women participating in an In-vitro fertilizationand embryo transfer (IVF-ET) programme. Cotinine was undetectableIn serum and follicular fluid of non-smokers but ranged from<5 to 371 ng/ml in follicular fluid and from 24 to 245 ng/mlin serum of smokers. Granulosa-luteal cells, obtained from IVFpatients and cultured for 4 days, secreted progesterone and,when an aromatizable androgen was added, oestradiol-17. Theaddition of cotinine or nicotine did not alter progesteroneor oestradlol-17 secretion. However, the presence of cotininein follicular fluid of women smokers provides evidence for accessof at least one component of cigarette smoke to the developinggamete and the cells of the follicle. Further work is requiredto determine whether fertllity is compromised by the presence,In follicular fluid, of contaminants derived from cigarettesmoke.