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Previous research has suggested an unexpected negative association between smoking and susceptibility to COVID-19. This study, drawing on population-based data from three Nordic countries-Sweden, Norway, and Finland-aims to investigate this association further, capitalizing on diversity introduced by different containment measures. The objective of this research was to examine the association between cigarette smoking and snus (smokeless tobacco) use and the risk of confirmed COVID-19 infection. A pooled analysis integrating original data from 547,685 participants across three countries. We used a multiple imputation approach based on conditional probabilities to impute the systematically missing covariates. The associations between tobacco use and COVID-19 infection were assessed, controlling for potential confounding factors. Current cigarette smokers had a lower risk of a confirmed COVID-19 case, whereas there was an increased risk among snus users. Our sensitivity analysis confirmed that the associations between tobacco use and COVID-19 infection risk are robust, remaining consistent regardless of whether covariate imputation was applied. Findings support a negative association between smoking and SARS-CoV-2 infection, but not the hypothesis that nicotine may be protective against the risk of contracting SARS-CoV-2 infection., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: The association between maternal smoking in pregnancy and offspring intellectual disability (ID) is less well understood than that of smoking and fetal growth restriction. As fetal growth and cognitive development may share similar confounding structures, comparison of the two associations may improve understanding of the causal nature of the association with ID. Furthermore, comparisons of smoking with smokeless tobacco use may aid identification of mechanisms of action., Methods: This was a cohort study of all Swedish births between 1999 and 2012 (n = 1 070 013), with prospectively recorded data. We assessed the association between maternal smoking during pregnancy and offspring outcomes ID and born small for gestational age (SGA). Analyses were repeated for snus use in pregnancy. Using a sibling design, we estimated within-family effects that control for shared sibling characteristics., Results: Those exposed to maternal smoking in pregnancy had increased odds of ID [odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.16-1.33] and SGA (OR = 2.19, 95% CI: 2.11-2.27) after confounder adjustment. Within-family effects were found for SGA (OR = 1.44, 95% CI: 1.27-1.63) but not ID (OR = 0.92, 95% CI: 0.74-1.14). For snus use, the results for ID were similar to smoking. We found increased odds of offspring SGA among mothers who used snus in pregnancy in sensitivity analyses but not in primary analyses., Conclusions: Our findings are consistent with a causal effect of maternal smoking in pregnancy on risk of offspring born SGA but not on risk of ID. We found no evidence for a causal effect of snus use in pregnancy on ID and inconclusive evidence for SGA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: There is an emerging evidence that the migration and the ethnic minority status are associated with the risks of autism spectrum disorder (ASD) and intellectual disability (ID). This systematic review aimed to investigate whether associations are specific to ASD or ID; whether and which migration-related or ethnically determined factors are associated with the risk of ASD and ID; and what mechanisms may explain these risks., Methods: A systematic literature search was conducted using Embase, Medline and PsycINFO for studies reporting on the risks of ASD and/or ID among migrants, descendants of migrants and/or ethnic minorities. Risks of any ASD, ASD + ID, ASD - ID and any ID were reviewed in relation to migration and ethnic minority status, with consideration to the study quality. In addition, possible underlying mechanisms suggested in the included studies were summarized., Results: Thirty-five studies were included. The summarized evidence indicated an increased risk of ASD + ID and a decreased risk of ASD - ID in migrants, descendants of migrants and ethnic minorities. These associations appeared more pronounced among children of migrant mothers, with origin in low-income countries, and among descendants of migrants. Data on ID were scarce. Suggested mechanisms explaining the increased risks of ASD + ID included environmental factors acting in utero and genetic factors (including consanguinity), while ascertainment bias was proposed to account for the lowered risks of diagnosed ASD - ID., Conclusion: Migration-related factors acting in utero and/or associated with origin in low-income countries may be important in the ASD + ID aetiology, although further confirmative studies are needed., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project., Methods: We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978-2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use., Results: Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20-1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15-1.41) and other cause mortality (aHR 1.37, 95% CI 1.24-1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00-1.26). These mortality risks increased with duration of snus use, but not with weekly amount., Conclusions: Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium., Methods: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries., Results: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH., Conclusions: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Smoking and use of Swedish smokeless tobacco (snus) are associated with increased risk of type 2 diabetes (T2D). Our aim was to estimate the unique and shared genetic components of these traits and to what extent the association is explained by shared genetic factors., Methods: We used twins of the Swedish Twin Registry who responded to a questionnaire between 1998 and 2006 (n = 40 247) and were followed until 2015 in the National Prescription and Patient Registries. We estimated hazard ratios (HRs) and odds ratios (ORs) for the association between smoking/snus use and T2D (n = 2130) and used structural equation models to estimate genetic and environmental variance components and genetic correlations., Results: Current smokers [HR 1.69, 95% confidence interval (CI), 1.49-1.92] and snus users (HR 1.19, 95% CI 1.01-1.41) had an increased risk of T2D. In within-pair analyses of monozygotic twins, corresponding ORs were 1.36, 95% CI 0.75-2.46 (smoking) and 1.54, 95% CI 0.80-2.99 (snus). Heritability was 43% (95% CI 36-51) for ever smoking, 58% (95% CI 44- 70) for ever snus use and 66% (95% CI 59-72) for T2D. The genetic correlation with T2D was 18% (95% CI 1-35) for smoking and -6% (95% CI -24 to 4) for snus use, indicating that only a small fraction of the genetic influence is shared., Conclusions: We could confirm that consumers of snus and cigarettes are at increased risk of T2D. Both snus use and smoking have strong genetic components, which appears to be attributable primarily to genes that are distinct from those promoting T2D., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Cigarette smoking is associated with a lower risk of Parkinson's disease. It is unclear what constituent of tobacco smoke may lower the risk. Use of Swedish moist smokeless tobacco (snus) can serve as a model to disentangle what constituent of tobacco smoke may lower the risk. The aim of this study was to determine whether snus use was associated with a lower risk of Parkinson's disease., Methods: Individual participant data were collected from seven prospective cohort studies, including 348 601 men. We used survival analysis with multivariable Cox regression to estimate study-specific relative risk of Parkinson's disease due to snus use, and random-effects models to pool estimates in a meta-analysis. The primary analyses were restricted to never-smokers to eliminate the potential confounding effect of tobacco smoking., Results: During a mean follow-up time of 16.1 years, 1199 incident Parkinson's disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson's disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson's disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83)., Conclusions: Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Clinical anecdote suggests that rates of eating disorders (ED) vary between schools. Given their high prevalence and mortality, understanding risk factors is important. We hypothesised that rates of ED would vary between schools, and that school proportion of female students and proportion of parents with post-high school education would be associated with ED, after accounting for individual characteristics., Method: Multilevel analysis of register-based, record-linkage data on 55 059 females born in Stockholm County, Sweden, from 1983, finishing high school in 2002-10. Outcome was clinical diagnosis of an ED, or attendance at a specialist ED clinic, aged 16-20 years., Results: The 5-year cumulative incidence of ED diagnosis aged 16-20 years was 2.4%. Accounting for individual risk factors, with each 10% increase in the proportion of girls at a school, the odds ratio for ED was 1.07 (1.01 to 1.13), P = 0.018. With each 10% increase in the proportion of children with at least one parent with post-high school education, the odds ratio for ED was 1.14 (1.09 to 1.19), P < 0.0001. Predicted probability of an average girl developing an ED was 1.3% at a school with 25% girls where 25% of parents have post-high school education, and 3.3% at a school with 75% girls where 75% of parents have post-high school education., Conclusions: Rates of ED vary between schools; this is not explained by individual characteristics. Girls at schools with high proportions of female students, and students with highly educated parents, have higher odds of ED regardless of individual risk factors., (© The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: Recent studies question whether the risk for psychotic disorder associated with prenatal exposure to infection are due to infections per se, or to shared susceptibility of both infections and psychiatric disorders. Moreover, the potential link between prenatal infection and serious infections during childhood, another alleged risk factor for psychotic disorder, remains unknown. The aim of this study was to investigate the role of maternal infections during pregnancy in context of parental psychiatric disorders and subsequent childhood infections., Method: All children born in Sweden 1978-1997 were linked to the National Patient Register. Hazard ratios of nonaffective psychosis were estimated in relation to maternal infection during pregnancy and odds ratios of childhood infection were calculated in relation to maternal infection during pregnancy. Relative excess risk due to interaction (RERI) estimated biological synergism between parental psychiatric disorder and maternal infection during pregnancy, and between maternal infection during pregnancy and childhood infection., Results: Maternal infection during pregnancy was not statistically significantly associated with offspring psychosis (adjusted hazard ratio: 1.06, 95% CI 0.88-1.27). However, maternal infection during pregnancy and maternal psychiatric disorders acted synergistically in offspring psychosis development (RERI 1.33, 95% CI 0.27-2.38). Maternal infection during pregnancy increased the risk of offspring childhood infections (OR 1.50, 95% CI 1.45-1.54). These 2 factors also interacted in psychosis development (RERI 0.63, 95% CI 0.12-1.14)., Conclusions: Among mothers with a history of psychiatric disease, infection during pregnancy increases the risk of psychosis in offspring. Maternal infections during pregnancy appear to contribute to the risk of childhood infections, which together render the child more vulnerable to psychosis development., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Prenatal environmental factors such as maternal adiposity may influence the risk of offspring autism spectrum disorders (ASD), though current evidence is inconsistent. The objective of this study was to assess the relationship of parental BMI and gestational weight gain (GWG) with risk of offspring ASD in a population-based cohort study using family-based study designs., Methods: The cohort was based in Stockholm County, Sweden, including 333,057 individuals born 1984-2007, of whom 6420 were diagnosed with an ASD. We evaluated maternal body mass index (BMI) at first antenatal visit, GWG and paternal BMI at the time of conscription into the Swedish military as exposures using general estimating equation (GEE) models with logit link., Results: At the population level, maternal overweight/obesity was associated with increased risk of offspring ASD [odds ratio (OR)25 ≤ BMI < 30 1.31, 95% confidence interval = 1.21-1.41; ORBMI ≥ 30 1.94, 1.72-2.17], as was paternal underweight (ORBMI < 18.5, 1.19, 1.06-1.33) and obesity (ORBMI ≥ 30 1.47, 1.12-1.92) in mutually adjusted models. However, in matched sibling analyses, the relationship between elevated maternal BMI and ASD risk was not apparent. GWG had a U-shaped association with offspring ASD at the population level (ORinsufficient 1.22, 1.07-1.40; ORexcessive 1.23, 1.08-1.40). Matched sibling analyses were suggestive of elevated risk with excessive GWG (ORinsufficient 1.12, 0.68-1.84; ORexcessive 1.48, 0.93-2.38)., Conclusions: Whereas population-level results suggested that maternal BMI was associated with ASD, sibling analyses and paternal BMI analyses indicate that maternal BMI may also be a proxy marker for other familial risk factors. Evidence is stronger for a direct link between GWG and ASD risk., (© The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.)

A growing body of literature suggests that exposure to infections, particularly maternal infections, during pregnancy confers risk for later development of psychotic disorder. Though brain development proceeds throughout childhood and adolescence, the influence of infections during these ages on subsequent psychosis risk is insufficiently examined. The aim of this study was to investigate the potential association between infections during childhood and nonaffective psychoses in a large population-based birth cohort with follow up long enough to include peak incidence of nonaffective psychosis. We included all individuals born in Sweden between 1973 and 1985, (N = 1172879), with follow up on first time inpatient care with nonaffective psychosis from age 14 years until 2006, (N = 4638). Following adjustment for differences in sex, socioeconomic status, family history of psychosis, and hospital admissions involving noninfectious, nonpsychiatric care, we observed a small but statistically significant association between hospital admissions for infections, in general, throughout childhood (0-13 years) and a later diagnosis of nonaffective psychosis, hazard ratio (HR) = 1.10 (95% CI 1.03-1.18), and this association seemed to be driven by bacterial infection, HR = 1.23 (95% CI 1.08-1.40). Bacterial infections and central nervous system infections during preadolescence (10-13 years) conferred the strongest risk, HR 1.57 (95% CI 1.21-2.05) and HR 1.96 (95% CI 1.05-3.62), respectively. Although preadolescence appeared to be a vulnerable age period, and bacterial infection the most severe in relation to psychosis development, the present findings can also indicate an increased susceptibility to hospital admission for infections among children who will later develop nonaffective psychosis due to social or familial/genetic factors., (© The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nicotine from maternal smoking during pregnancy can cross the placental barrier, possibly resulting in fetal brain sensitization, as indicated by studies in which prenatal exposure to maternal smoking was associated with an increased risk of tobacco use among adolescent offspring. We investigated whether this association persists beyond adolescence by studying cigarette smoking and the use of snus (Swedish oral moist snuff) among 983 young adults from a prospective cohort study conducted in Stockholm, Sweden, between 2006 and 2010. Self-reported questionnaire data were linked with data from national population-based registers from 1983 onward. Maternal smoking during pregnancy was consistently associated with snus use in offspring (e.g., for lifetime daily snus use, adjusted odds ratio = 2.04, 95% confidence interval: 1.32, 3.16; for use of >3 cans of snus per week vs. less, odds ratio = 3.85, 95% confidence interval: 1.57, 10.15). No association was apparent with offspring's smoking, age at onset of tobacco use, or changes in use between 2006 and 2010. These findings indicate that prenatal exposure to maternal smoking is associated with regular and heavy nicotine intake from smokeless tobacco rather than from smoking. This should be further explored in epidemiologic studies that simultaneously address the roles of genetics and social environments., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID)., Methods: The sample consisted of 417 303 Swedish children born 1984-2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD., Results: Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63-1.89] at ages 40-45. For fathers, compared with the median age of 32 years, the OR for ages 55-59 was 1.39 (1.29-1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40-45 (≥97.2th percentile) had an estimated 18.63 (95% CI: 17.25-20.01) ASD cases per 1000 births, whereas fathers aged 55-59 (≥99.7th percentile) had 16.35 (95% CI: 15.11-17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers ≤35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID., Conclusions: We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age.

The Stockholm Public Health Cohort was set up within the Stockholm County Council public health surveys to inform on determinants and consequences of significant contributors to the current burden of disease. Participants are 89 268 randomly selected individuals from the adult population of Stockholm County. Baseline surveys took place in 2002, 2006 and 2010 via self-administered questionnaires. So far, participants recruited in 2002 were re-surveyed twice, in 2007 and 2010, and those enrolled in 2006 were re-surveyed once, in 2010. Self-reported data are regularly supplemented by information from national and regional health data and administrative registers, for study participants and their relatives (including their offspring). Available data are extensive and include a wide array of health, lifestyle, perinatal, demographic, socio-economic and familial factors. The cohort is an international resource for epidemiological research, and the data available to the research community for specific studies obtained approval from the Stockholm Public Health Cohort Steering Committee and the Stockholm Regional Ethical Review Board.

Background: Unopposed estrogen replacement therapy (i.e., estrogen without progestins) increases the risk of endometrial cancer. In this study, we examined the endometrial cancer risk associated with combined estrogen-progestin regimens currently in use, since the safety profiles of these regimens have not been clearly defined., Methods: We conducted a nationwide population-based, case-control study in Sweden of postmenopausal women aged 50-74 years. We collected information on use of hormone replacement from 709 case patients with incident endometrial cancer and from 3368 control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) as estimates of relative risks. All individual comparisons were made with women who never used the respective hormone replacement regimens., Results: Treatment with estrogens alone was associated with a marked duration- and dose-dependent increase in the relative risk of endometrial cancer. Five or more years of treatment had an OR of 6.2 for estradiol (95% confidence interval [CI] = 3.1-12.6) and of 6.6 for conjugated estrogens (95% CI = 3.6-12.0). Following combined estrogen-progestin use, the association was considerably weaker than that for estrogen alone; the OR was 1.6 (95% CI = 1.1-2.4) after 5 or more years of use. This increase in risk was confined to women with cyclic use of progestins, i.e., fewer than 16 days per cycle (most commonly 10 days per cycle [OR = 2.9; 95% CI = 1.8-4.6 for 5 or more years of use]), whereas continuous progestin use along with estrogens was associated with a reduced risk (OR = 0.2; 95% CI = 0.1-0.8 for 5 or more years of use)., Conclusion: The risk of developing endometrial cancer is increased after long-term use of estrogens without progestins and with cyclically added progestins. Continuously added progestins may be needed to minimize the endometrial cancer risk associated with estrogen replacement therapy.

Skin biopsies of 31 non-atopic patients, 20 with mycosis fungoides, six with psoriasis and five with contact dermatitis, and of five non-atopic healthy controls were compared for the presence of cell-bound IgE and vacant IgE binding sites. IgE+ cells were demonstrated in the cutaneous infiltrate of nine (45%) patients with mycosis fungoides, two (33%) with psoriasis and one (20%) with contact dermatitis. Following pre-incubation of skin sections with IgE myeloma protein to saturate vacant IgE-binding sites, 14 out of 16 patients (88%) with stage I mycosis fungoides, five (83%) patients with psoriasis and one (20%) with contact dermatitis showed an increase in the number of IgE+ cells. While cell-bound IgE was positively related to serum IgE levels the expression of IgE-binding sites was not. All IgE+ cells were HLA-DR+ dendritic cells identified as either macrophages (CD68+, CD14+) or Langerhans cells (CD1+). Skin biopsies of non-atopic healthy controls or clinically uninvolved skin in mycosis fungoides had neither any IgE+ cells nor any vacant binding sites. Inhibition studies with IgG1, IgG4 and IgE myeloma proteins as well as with several enzymatic fragments of IgE demonstrated that IgE interacted with Fc epsilon-receptors through isotype-specific structures on the Fc epsilon-fragment. Four anti-CD23 monoclonal antibodies, however, were unable to stain vacant Fc epsilon-receptors nor could they block IgE-binding. We hypothesize that locally-secreted lymphokines, like IL-4 or interferon-gamma, induce Fc epsilon-receptors on dendritic cells in the cutaneous infiltrate and that these receptors become occupied in parallel with elevated serum IgE levels.

The adenylate cyclase activator forskolin was used to study the role of cAMP for oocyte meiosis and follicular steroid secretion. Follicular and cumulus cAMP production was stimulated dose-dependently by forskolin, as was the follicular secretion of progesterone, testosterone and estradiol. Forskolin induced meiosis in follicle-enclosed oocytes with a maximal effect at 1 microM, with lower and higher concentrations being less effective. The spontaneous resumption of meiosis in isolated cumulus-enclosed oocytes was dose-dependently retarded by forskolin. Meiosis of cumulus-free oocytes was also retarded but only slightly. These data support the earlier hypothesis that a limited increase in follicular cAMP levels triggers meiosis, whereas sustained levels of cAMP in the oocyte itself prevent meiosis.

The effect of an agonistic gonadotropin releasing hormone (GnRH)-analog (D-Ala6, des-Gly10-NH2-GnRH-ethylamide, GnRHa) on granulosa cell steroidogenesis in the presence or absence of follicle-stimulating hormone (FSH) or luteinizing hormone (LH) was studied. Granulosa cells, isolated from preovulatory follicles of pregnant mare's serum gonadotropin (PMSG)-treated immature rats or from the less mature follicles of untreated immature rats, were cultured for a period of 72 h with daily changes of medium, and progesterone and its metabolite, 20 alpha-dihydro-progesterone (20 alpha-OHP), were assayed in the medium. In granulosa cells from preovulatory follicles, LH and FSH caused a much greater stimulation of steroidogenesis than did GnRHa. There appeared to be no interaction between GnRHa and FSH during the first 10 h, but at 24 h and later the presence of GnRHa clearly inhibited the steroidogenic response to LH and FSH. Steroidogenesis in granulosa cells from immature rats was considerably lower and the effects of GnRHa and FSH alone less pronounced. In these cells, FSH-stimulated progesterone secretion was inhibited by GnRHa only at 72 h. In contrast, 20 alpha-OHP secretion in the same cultures was potentiated by the combined presence of FSH and GnRHa. In conclusion, it seems as though the effects of GnRHa on granulosa cell steroidogenesis varies with exposure time, the initial response being stimulatory and the later inhibitory. Furthermore, the response is also to some extent determined by the maturational stage of the granulosa cells.

PACIA, a homogeneous non-radioimmunoassay, has been adapted to the determination of serum alpha 1-fetoprotein. This technique is based on the agglutination of latex particles coated with antibodies to the antigen to be determined. The agglutination is measured by using an optical cell counter designed to count blood cells, to determine the reduction in the number of non-agglutinated particles. Interferences by serum constituents are avoided by coating the particles with the F(ab')2-fragments of th immunoglobulin G fraction of the antiserum. The system is automated, with a sampling rate of 50/h and an incubation time of 26 min. Concentrations used in preparing the standard curve ranged from 1 to 50 microgram/L; analytical recoveries were 93.5 to 98.4%; the correlation coefficient of PACIA with radioimmunoassay, calculated from results on 127 samples, was 0.98; maximum within- and between-assay CVs were 7.4% and 9.6%, respectively.

We describe a non-radioisotopic automated immunoassay for serum digoxin in the therapeutic range at 50 samples per hour by use of the particle-counting immunoassay technique and a special reagent, rheumatoid factor. Digoxin is determined by evaluating its inhibitory activity on the agglutination of digoxin-coated latex particles. The agglutinating system consists of the anti-digoxin IgG mixed with rheumatoid factor. This anti-IgG autoantibody reacts with IgG when they are aggregated or bound to a surface. Interference by serum proteins was prevented by pepsin digestion at 37 degrees C. Correlation with radioimmunoassay was r = 0.94 for 109 samples with concentrations between 0 and 5.7 micrograms/L. Analytical recovery overall averaged 102%. Within-assay precision (CV) ranged from 12.5% at 0.96 micrograms/L to 4.4% at 2.97 micrograms/L; between-assay precision varied from 8.4% at 0.75 micrograms/L to 5.8% at 2.92 micrograms/L.

A potent analogue of gonadotropin releasing hormone [D-Ala6- Des-Gly10-NH2]-GnRH ethylamide (GnRHa) caused oocyte maturation and ovulation when injected in the afternoon of proestrus in immature PMSG-treated female rats, hypophysectomized on the morning of proestrus. This action of GnRHa was accompanied by a marked increase in ovarian PGE levels. Furthermore, the pretreatment of the animals with a prostaglandin synthetase inhibitor (indomethacin) completely inhibited this PGE increase and ovulation. These data suggest a role for prostaglandins in GnRHa induced ovulation.

In the cumulus-oocyte complex (COC), as well as in the whole ovarian follicle, gonadotropins stimulate glycolysis, measured as lactate accumulation. In contrast to this, COC oxygen consumption is decreased by gonadotropins. One possible explanation for this inhibition is a competition for a limited supply of cofactors, common for both the glycolytic pathway and the respiratory chain. In the present study, addition of adenosine to COCs cultured with gonadotropins restored the oxygen consumption to basal levels. This effect was specific for metabolizable adenosine. Other nucleosides or non-metabolizable 2-chloro-adenosine had no effect. Adenosine also increased ATP and decreased lactate accumulation by the COC. The nucleoside transport inhibitor dipyridamol abolished the effects of adenosine on oxygen consumption and ATP accumulation. Taken together, these results support the hypothesis that a relative lack of adenosine-derived cofactors is probably involved in the decrease of oxygen consumption in vitro by gonadotropin-stimulated cumulus cells.

Oxygen consumption by human oocytes and blastocysts was analysed using a sensitive micro-spectrophotometric technique. Oocytes were obtained from women undergoing laparotomy for sterilization or hysterectomy, and blastocysts were obtained as spare embryos from the local in-vitro fertilization programme. There was no significant difference between oocyte oxygen consumption on the day of isolation and after 1 day of culture, 0.53 +/- 0.08 (n = 9) and 0.35 +/- 0.06 (n = 5) nl/h oocyte, respectively. Blastocyst oxygen consumption was measured after a culture period of 5-8 days after in-vitro fertilization. Mean oxygen consumption by healthy looking blastocysts was 0.34 +/- 0.03 (n = 15) nl/h blastocyst, and there was no change in oxygen consumption with culture time. This level of respiration was lower than expected, both when compared with the oocytes and when compared with levels reported for blastocysts of other species.