Onset of mucosal, dermal, and general symptoms in relation to biomarkers and exposures in the dwelling: a cohort study from 1992 to 2002.

UNLABELLED: We examined the associations between biomarkers of allergy and inflammation, indoor environment in dwellings, and incidence and remission of symptoms included in the sick building syndrome (SBS) and changes in the home environment of 452 adults who were followed from 1992 to 2002 within the Uppsala part of the European Community Respiratory Health Survey (ECRHS). The 10-year incidence (onset) of general, mucosal, and dermal symptoms was 8.5%, 12.7%, and 6.8%, respectively. Dampness or indoor molds at baseline was a predictor of incidence of general (relative risk [RR] = 1.98), mucosal (RR = 2.28), and dermal symptoms (RR = 1.91). Women had higher incidence of general (RR = 1.74) and mucosal symptoms (RR = 1.71). Indoor painting increased the incidence of general symptoms (RR = 1.62). Bronchial responsiveness (BR), eosinophil counts in blood, total IgE and eosinophilic cationic protein (ECP) in serum at baseline were predictors of incidence of SBS. At follow-up, BR, total IgE, and C-reactive protein (CRP ) were associated with increased incidence of SBS. Moreover, subjects with doctor-diagnosed asthma at baseline had a higher incidence of general (RR = 1.65) and mucosal symptoms (RR = 1.97). In conclusion, female gender, dampness or indoor molds, indoor painting, and biomarkers of allergy and inflammation were associated with a higher incidence of SBS symptoms, in particular mucosal symptoms. PRACTICAL IMPLICATIONS: The focus in Sweden on indoor environment issues over the last few decades has resulted in improvements in dwellings, and reduced tobacco smoking, which could be beneficial for public health. Reducing dampness and molds in the dwelling place is another important way of reducing occurrence of SBS symptoms in the general adult population. The association between the incidence of SBS symptoms and clinical biomarkers of allergy and inflammation suggests a common etiology between inflammatory diseases, including asthma, rhinitis, and SBS. Lastly, good agreement between self-reported and clinically diagnosed atopy indicates that questionnaire data on atopy can be used in epidemiological studies.

Sick building syndrome in relation to domestic exposure in Sweden--a cohort study from 1991 to 2001.

BACKGROUND: Most studies on sick building syndrome (SBS) are cross-sectional and have dealt with symptoms among office workers. There are very few longitudinal cohort studies and few studies on SBS in relation to domestic exposures. The aim of this study was to investigate changes in SBS symptoms during the follow-up period and also to investigate changes in different types of indoor exposures at home and relate them to SBS symptoms in a population sample of adults from Sweden. We also wanted to investigate if there was any seasonal or regional variation in associations between exposure and SBS. METHODS: A random sample of 1,000 people of the general population in Sweden (1991) was sent a self administered questionnaire. A follow-up questionnaire was sent in 2001. RESULTS: An increased risk for onset of any skin symptoms (risk ratio (RR) 2.32, 1.37-3.93), mucosal symptoms (RR 3.17, 1.69-5.95) or general symptoms (RR 2.18, 1.29-3.70) was found for those who had dampness or moulds in the dwelling during follow-up. In addition people living in damp dwellings had a lower remission of general symptoms and skin symptoms. CONCLUSIONS: Dampness in the dwelling is a risk factor for new onset of SBS symptoms. Focus on indoor environment improvements in dwellings can be beneficial both for the inhabitants and the general population. Reducing dampness in buildings is an important factor for reducing SBS symptoms in the general population.

Indoor environment in dwellings, asthma, allergies, and sick building syndrome in the Swedish population: a longitudinal cohort study from 1989 to 1997.

OBJECTIVES: To investigate changes of sick building syndrome (SBS) and different types of indoor exposures at home over an 8-year follow-up period (1989-1997), and onset of SBS symptoms in relation to size of residence town and education level. METHODS: A random sample (0.1%) of the population in a 3-county region in Sweden, initially aged 20-65 years (n = 466). In total, 348 (75%) answered the postal follow-up questionnaire. RESULTS: Water leakage during the last year had decreased from 11.2 to 4.8% visible indoor mould had decreased from 4.7 to 1.6%, and any sign of building dampness decreased from 16.1 to 9.5%. The prevalence of current smoking had decreased from 30 to 19%. Smokers at baseline reported more onset of SBS symptoms than non-smokers. Furthermore, remission from mucosal symptoms was less likely in subjects that were tobacco smoker. Subjects with any indoor painting during follow-up period reported more onset of SBS symptoms, and those with intermediate education level had more onset of skin symptoms. CONCLUSION: Smoking and indoor painting could be predictors of new onset of SBS symptoms. Focus on indoor environment in Sweden the last decades may have resulted in environmental improvements in the dwellings, which can be beneficial both for the inhabitants and for the future public health.

Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles.

BACKGROUND: To adequately perform peritonectomy, the use of an electrocautery device at a high voltage is recommended. The aim of this study was to analyse the amount of airborne and ultrafine particles (UFP) generated during peritonectomy and to compare this with standard colon and rectal cancer surgery (CRC). METHOD: UFP was measured approximately 2-3 cm from the breathing area of the surgeon (personal sampling) and 3 m from where the electrocautery smoke was generated (stationary sampling) from 14 consecutive peritonectomy procedures and 11 standard CRC resections. The sampling was by P-Trak UFP counter that has the capacity to detect particle size ranging from 0.02 to 1 microm. RESULTS: The cumulative level of UFP of personal sampling in the peritonectomy group was higher (9.3 x 10(6) particle/ml/h (pt/ml/h)) than in the control group (4.8 x 10(5) pt/ml/h). A higher cumulative level of UFP in stationary sampling was observed in the PC group (2.6 x 10(6) pt/ml/h) than in the control group (3.9 x 10(4)pt/ml/h). CONCLUSION: Peritonectomy procedure with high voltage electrocautery generates elevated levels of UFP than standard CRC surgery does. The level of UFP produced by a peritonectomy is comparable to cigarette smoking. More efficient smoke evacuator systems are needed in order to reduce the levels of UFP generated during electrocautery surgery.

Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues.

The further development of allosteric HIV-1 RT inhibitors in the urea analogue series of PETT (phenylethylthiazolylthiourea) derivatives is described here. The series includes derivatives with an ethyl linker (1-5) and racemic (6-16) and enantiomeric (17-20) cis-cyclopropane compounds. The antiviral activity was determined both at the RT level and in cell culture on both wild-type and mutant forms of HIV-1. Most compounds have anti-HIV-1 activity on the wt in the nanomolar range. Resistant HIV-1 was selected in vitro for some of the compounds, and the time for resistant HIV-1 to develop was longer for urea-PETT compounds than it was for reference compounds. Preliminary pharmacokinetics in rats showed that compound 18 is orally bioavailable and penetrates well into the brain. The three-dimensional structure of complexes between HIV-1 RT and two enantiomeric compounds (17 and 18) have been determined. The structures show similar binding in the NNI binding pocket. The propionylphenyl moieties of both inhibitors show perfect stacking to tyrosine residues 181 and 188. The cyclopropyl moiety of the (+)-enantiomer 18 exhibits optimal packing distances for the interactions with leucine residue 100 and valine residue 179.

Metabolic profiles of endogenous and ethynyl steroids in plasma and urine from women during administration of oral contraceptives.

Conjugated ethynyl and endogenous steroids in plasma and urine from two women taking an oral contraceptive (Conlumin) containing 1 mg norethindrone and 50 micrograms mestranol have been analyzed by methods based on anion and ligand exchange chromatography and gas chromatography-mass spectrometry. Conjugated norethindrone and its reduced metabolites with 3 alpha,5 alpha, 3 alpha,5 beta, 3 beta,5 beta and 3 beta,5 alpha configurations were identified in the fluids. The quantitatively major metabolites in plasma were a disulphate of the 3 alpha,5 alpha isomer and a monosulphate of the 3 alpha,5 beta isomer. The renal clearance of the former compound was low. The major urinary metabolite of norethindrone was the 3 alpha,5 beta isomer conjugated with glucuronic or sulphuric acid. Disulphates constituted only a small portion of urinary ethynyl steroids. Metabolic profiles of endogenous neutral steroids in plasma and urine during the contraceptive cycle were compared with profiles during a physiological menstrual cycle. The concentrations of steroids in plasma during contraception were similar to those during the follicular and mid phases of the menstrual cycle, whereas levels of progesterone metabolites were higher in the luteal phase. The urinary excretion of steroids was 15-30% lower during the contraceptive cycle, due to a decrease in excretion of C21O5 steroids, 11-oxygenated androgens and etiocholanolone. The increase of urinary progesterone metabolites seen during the luteal phase was not observed during contraception, but the excretion of 5 beta-pregnane-3 alpha,20 alpha-diol glucuronide was higher than during the follicular and mid phases of the menstrual cycle.

The characterization of sulphated metabolites of norethindrone in human milk after oral administration of contraceptive steroids.

The excretion of ethynyl steroids in milk from a lactating woman taking a daily dose of an oral contraceptive (Conlumin) containing 1 mg of norethindrone and 50 micrograms of mestranol has been studied. Milk was diluted with aq. triethylamine sulphate and steroids were extracted on a Sep-Pak C18 cartridge at 60-64 degrees C. Groups of unconjugated steroids, glucuronides, mono- and disulphates were separated on triethylaminohydroxypropyl Sephadex LH-20. Following hydrolysis and further purification, steroids possessing an ethynyl-substituent were isolated by chromatography on sulphohydroxypropyl Sephadex LH-20 in silver form. Gas chromatographic-mass spectrometric analysis of the O-methyloxime-trimethylsilyl ether derivatives of these steroids, showed the presence of norethindrone and mestranol in the free fraction and of tetrahydro metabolites of norethindrone with 3 alpha,5 alpha, 3 alpha,5 beta and 3 beta,5 alpha configurations in the mono- and disulphate fractions. The disulphate of the 3 alpha,5 alpha isomer was the most abundant ethynyl steroid in milk after 13 days of administration. The site of conjugation of the monosulphates was established by acetylation prior to solvolysis and analysis by gas chromatography-mass spectrometry. This showed that the 3 alpha,5 alpha isomer was conjugated mainly in the 17 beta-position while the 3 alpha,5 beta isomer was conjugated at C-3.

Identification and quantitation of free and conjugated steroids in milk from lactating women.

A method for analysis of metabolic profiles of free and conjugated steroids in milk has been developed. Milk is diluted with aqueous triethylamine sulphate and liquid-solid extraction is achieved on a Sep-Pak C18 cartridge at 60-64 degrees C. Steroids are purified by chromatography on small columns of Lipidex 5000 and sulphohydroxypropyl Sephadex LH-20 [H+] prior to separation into neutral and phenolic compounds, glucuronide, mono- and disulphate conjugate groups on the lipophilic strong anion exchanger triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20). Conjugated steroids are released by enzymatic or solvolytic procedures and separated into a neutral and a phenolic fraction on TEAP-LH-20. The O-methyloxime and trimethylsilyl ether derivatives of the steroids are analyzed by capillary column gas chromatography-mass spectrometry. Fifty steroids were identified in milk collected from women a few days after delivery. Quantitatively about 80% were present as sulphates, 15% as glucuronides and only 5% were unconjugated steroids. The steroid pattern was similar to that in late pregnancy plasma with pregnanolone, pregnanediol and pregnanetriol isomers and dehydroepiandrosterone being predominant. About 10% of the steroid content consisted of estrogens. The total concentration of steroids 2 days after delivery was 20-116 ng/ml, i.e. about 1-5% of the concentration was about 10 ng/ml 1 month after delivery. In one milk sample, collected 2 days after delivery, the steroid concentration (3.6 micrograms/ml) was similar to that in plasma.

Group separation and gas chromatography--mass spectrometry of conjugated steroids in plasma.

A method is described for analysis of metabolic profiles of conjugated steroids in plasma. Steroids are extracted by Amberlite XAD-2 or Sep-Pak C18 cartridges at 60 64 C in the presence of triethylamine sulphate and separated into unconjugated neutral and phenolic compounds, glucuronide, monosulphate and disulphate conjugate groups by chromatography on the lipophilic strong anion exchanger triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20). The conjugate moiety is hydrolyzed by brief enzymatic or solvolytic procedures and released steroids are separated into a neutral and a phenolic fraction on TEAP-LH-20. The O-methyloxime and trimethylsilyl ether derivatives of the steroids are analyzed by glass capillary column gas liquid chromatography and gas chromatography mass spectrometry. Examples of the application of the method to analysis of conjugated steroids in plasma from pregnant women are given.

Analysis of isomeric ethynylestradiol glucuronides in urine.

A method for separation and analysis of conjugates of ethynylestradiol in urine is described. Steroid conjugates are separated on a lipophilic strong anion exchanger (triethylaminohydroxypropyl Sephadex LH-230), and phenolic steroids released by enzyme hydrolysis or solvolysis ar isolated by chromatography on the same ion exchanger. Steroids carrying an ethynyl group are isolated by chromatography on SP-Sephadex (Ag+). Ethynylestradiol is analyzed by gas chromatography-mass spectrometry of the trimethylsilyl ether, using [9,11,11,12,12-(2)H5] ethynylestradiol and internal standard.