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Interobserver and interequipment variability of echo-Doppler examination of the portal vein: effect of a cooperative training program.

The aim of this study was to assess the interobserver, interequipment, and time-dependent variabilities of echo-Doppler measurements of portal blood flow velocity (PBV), portal vein diameters (PVDs) and their derived parameters, portal blood flow (PBF), and congestion index (CI) in cirrhotic patients. The influence of a cooperative training program of the operators on the reproductibility of the results was also investigated. The echo-Doppler parameters were independently measured in 15 patients by four skilled operators, using four echo-Doppler machines (Acuson, ATL, Hitachi-Esaote, Toshiba. Eight of the 15 patients were restudied after 15 days by the same operators using only one machine. Significantly different values of PBV, PBF, and CI were obtained. PBV variance was equipment-related (32%) and operator-related in a smaller portion (5%). No systematic effect related to the time of investigation was found. After training to define a precise protocol, new measurements were performed by four operators on 8 different patients. No significant differences were found among the operators for any of the parameters and the 95% confidence limits (CL) and coefficients of variation (CV) of PBV showed a marked decrease (CL from +/- 26.4% to +/- 15.6%). These results indicate that (1) a significant systematic variability exists between Doppler measurements with different equipment; (2) there is no significant time-dependent systematic variability of Doppler measurements; and (3) a cooperative training program reduces the interobserver variability for direct measurements, such as PBV.

Analysis of Variance↗

Computational studies on conditions of the emergence of autopoietic protocells.

It has been pointed out that the acquisition of self-maintaining protocells was one of the most important evolutionary steps in the earliest stage of life. However, there remains little evidence to show what the components of the protocells were and how they were acquired. A theoretical study to investigate the possible process of the emergence of protocells is therefore required. In this paper, we present a computational model that demonstrates the emergence and evolution of self-maintaining and self-reproducing structures to analyze conditions under which precellular autocatalytic molecules could evolve into self-reproducing protocells. We focused on the supply rates of molecular resources as environmental parameters and explored the pathways of evolution from molecular replication to cellular reproduction under various conditions. The results showed that the spontaneous organization of protocells from a random initial state takes place in a parameter region where the metabolism becomes difficult because of an insufficient supply of resources, but once cell structures are organized, they can survive in a wider range of environments. We investigated the evolution in temporally or spatially changing environments and found that the protocells can take over the precellular metabolic system after the transition. These results suggest a possible scenario for the evolution from precellular to cellular reproduction.

Biological Evolution↗

[Parameters of cellular immunity in maternal and umbilical cord blood in relation to air pollution. Preliminary results of a pregnancy outcomes study].

BACKGROUND: The study is a part of the project Pregnancy Outcome (Teplice Program) examining effects of polluted environment on the quality of reproduction in Teplice (high polluted) and Prachatice (control) districts. Selected parameters of cell mediated and humoral immunity in maternal and umbilical samples after delivery were assayed. METHODS AND RESULTS: Lymphocytes in 768 samples of maternal venous blood and 739 samples of umbilical blood collected in May 1994-October 1997 were phenotyped using flow cytometry. Medical and personal questionnaires were used to obtain data on clinical risk factors during pregnancy, health and life style of mothers, the course and prolongation of labour and newborn's status. The percentages of T and NK lymphocytes in both umbilical and maternal blood were associated with a number of variables, including the course of labour. After adjustment for the other predictors, the percentage of NK lymphocytes was found significantly higher in Teplice than in Prachatice samples--in both maternal and umbilical blood. CONCLUSIONS: A part of the observed difference between distribution of NK and T lymphocytes can be attributed to living in the polluted district. To see effects of polluted environment, the association of seasonal difference in levels of major pollutants with seasonal changes in lymphocyte phenotype will be analyzed.

Air Pollution↗

Changes in cellular energy budget as a measure of whole effluent toxicity in zebrafish (Danio rerio).

Organisms exposed to suboptimal conditions face an a priori cost of combating stress in terms of metabolic resources. The energy available for maintenance, growth, and reproduction, based on the biochemical analysis of the energy budget rather than on the direct measurement of those endpoints, may therefore provide a sensitive measure of stress in an organism. The aim of this study was to validate changes in energy budget as an ecologically relevant sublethal parameter by comparing these responses with physiological, growth, and reproductive endpoints. A toxicity test with zebrafish (Danio rerio) was conducted where fish were exposed to a control and 50, 75, and 100% effluent for 28 d under flow-through conditions. Effects of effluent exposure were measured as changes in glycogen, lipid, and protein budgets. Furthermore, the observed effects were linked to different processes like growth, condition, respiration, and reproduction within the same populations. Our results indicate that changes in lipid budgets in exposed fish were the most sensitive endpoint. Excellent relations were found between cellular energy budgets, relative condition factor, and respiration (r2 = 0.795, p < 0.001; and r2 = 0.735, p < 0.001, respectively), but relations were poorer for reproductive output (r2 = 0.410, p < 0.034). As a whole, especially changes in lipid energy budgets provide a sensitive and fast indicator of altered condition in zebrafish under the given exposure regime and allow linking cellular effects to other endpoints within the same exposed populations.

Animals↗

Results and evaluations of 48 continuous breeding reproduction studies conducted in mice.

Results of 48 continuous breeding reproduction (RACB) studies are summarized and control data from these studies are used to determine the statistical sensitivity of each endpoint from different parts of these studies. Results of testing individual chemicals compared well with results of multigeneration studies reported in the literature. Continuous breeding studies were able to discriminate reproductive toxicants from nontoxicants, and provided valuable structure-activity information. When mice in continuous cohabitation produce multiple litters, the statistical sensitivity of fertility endpoints is quite high and is comparable to that associated with other sensitive indicators of reproductive function, such as testis weight and sperm parameter measures. The principal advantages of the RACB protocol in comparison to multigeneration studies are: (1) the increased sensitivity and statistical power, (2) the ability to monitor progression of toxicity and to detect subfertility, (3) use of a battery of endpoints including sperm measures, (4) the ability to determine the affected sex(es), and (5) slightly reduced testing time.

Animals↗

Two-generation reproduction studies in Rats fed di-isodecyl phthalate.

Di-isodecyl phthalate (DIDP) is a commercial plasticizer with low toxicity in many animal studies. The effects of dietary DIDP administration on fertility and developmental parameters were assessed in Sprague-Dawley rats utilizing two generation reproductive toxicity studies generally consistent with current regulatory guidelines. Dietary levels ranged from 0.02 to 0.8% (or approximately 15 to 600 mg/kg/day). In the reproductive studies, there were no effects on fertility, but there were decreases in adult body weight along with corresponding increases in liver and kidney weights and histopathologic changes indicative of peroxisomal proliferation. There were no effects on live birth index, but reduced offspring survival was observed at postnatal days 1 to 4. This reduced survival was more pronounced in the F2 generation in which statistical significance was achieved at levels of 0.2% DIDP and greater. There were also transient decreases in offspring body weights prior to weaning, corresponding to rapid offspring growth, and high levels of food consumption. There were no notable alterations in developmental landmarks. Overall, these studies provided experimentally defined No-Observed-Adverse-Effect Levels (NOAELs) of 0.06% (approximately 50 mg/kg/day) for F2 offspring survival and 0.8% (approximately 600 mg/kg/day) for fertility, other measures of reproductive function, and developmental landmarks. Statistical evaluation of the data from both studies identified 108 mg/kg/day with a 95% lower bound value of 86 mg/kg/day as a theoretical NOAEL for reduced F2 offspring survival.

Animals↗

ESS analysis of mechanistic models for territoriality: the value of scent marks in spatial resource partitioning.

In this paper elements of game theory are used to analyse a spatially explicit home range model for interacting wolf packs. The model consists of a system of nonlinear partial differential equations whose parameters reflect the movement behavior of individuals within each pack and whose solutions describe the patterns of space-use by each pack. By modifying the behavioral parameters, packs adjust their patterns of movement so as to maximize their reproductive output. This involves a tradeoff between maximizing prey intake and minimizing conflict with neighbors. Evolutionarily stable choices of the behavioral parameters yields territories that are immune to invasion by groups with alternate behaviors.

Animals↗

Megabase deletions of gene deserts result in viable mice.

The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts can be well tolerated by an organism. We deleted two large non-coding intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regard to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further detailed analysis of the expression of multiple genes bracketing the deletions revealed only minor expression differences in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (more than 100 base pairs, 70% identity). Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially 'disposable DNA' in the genomes of mammals.

Animals↗

Endocrine alterations and signaling changes associated with declining ovarian function and advanced biological aging in follicle-stimulating hormone receptor haploinsufficient mice.

Reproductive aging in female mammals is characterized by a progressive decline in fertility due to loss of follicles and reduced ovarian steroidogenesis. In this study we examined some of the endocrine and signaling parameters that might contribute to a decrease in ovulation and reproductive performance of mice with haploinsufficiency of the FSH receptor (FSH-R). For this purpose we compared ovarian changes and hormone levels in FSH-R heterozygous (+/-) and wild-type mice of different ages (3, 7, and 12 mo). Hormone-induced ovulations in immature and 3-mo-old +/- mice were consistently lower. The number of corpora lutea (CL) were lower at 3 and 7 mo, and none were present in 1-yr-old +/- females. The plasma steroid and gonadotropin levels exhibited changes associated with typical ovarian aging. Plasma FSH and LH levels were higher in 7-mo-old +/- mice, but FSH levels continued to rise in both genotypes by 1 yr. Serum estradiol and progesterone were lower in +/- mice at all ages, and testosterone was several-fold higher in 7-mo-old and 1-yr-old +/- mice. Inhibin alpha (Western blot) appeared to be lower in +/- ovaries at all ages. FSH-R (FSH* binding) declined steadily from 3 mo and reaching the lowest point at 1 yr. LH receptor (LH* binding) was high in the 1-yr-old ovary, and expression was localized in the stroma and interstitial cells. Our findings demonstrate that haploinsufficiency of the FSH-R gene could cause premature exhaustion of the gonadal reserves previously noted in these mice. This is accompanied by age-related changes in the hypothalamic-pituitary axis. As these features in our FSH-R +/- mice resemble reproductive failure occurring in middle-age women, further studies in this model might provide useful insights into the mechanisms underlying ovarian aging.

Aging↗

Semen parameters and conception rates after intraperitoneal insemination.

OBJECTIVE: To analyze the reproductive outcome in infertile couples which underwent intraperitoneal insemination (IPI). METHODS: We analyzed a series of 216 couples who underwent IPI. Indications for treatment were unexplained infertility in 51 couples and male factor in 165. The 51 couples with unexplained infertility underwent a total of 71 cycles (20 couples underwent a second IPI cycle). The 165 couples with male factor underwent 243 cycles (165 first cycles and 78 second cycles). RESULTS: Out of the 314 cycles performed, a total of 41 clinical pregnancies were observed, with a corresponding conception rate of 13.1%. The values of conception rates for unexplained and male factor infertility were 21.1 (based on 15 pregnancies) and 10.7% (based on 26 pregnancies), respectively. Out of the 41 pregnant women, 26 gave birth to a child, thus the overall livebirth rate was 8.3% (12.7 and 7.0%, respectively, for unexplained infertility and male factor diagnostic subgroups). Considering the couples with unexplained infertility, the conception rates were 9.0, 30.8 and 20.0% for strata of < 5, 5-10 and > or = 10 millions of inseminated spermatozoa. The corresponding values were 6.8, 12.5 and 18.5%, respectively, in couples with male factor infertility (chi(2)1 trend p < 0.05). CONCLUSION: In conclusion, this series provides quantitative estimates of pregnancy rates after IPI in Italian couples with unexplained infertility or male infertility and suggested that the number of motile sperm inseminated is a determinant of pregnancy with this technique.

Female↗

Genetic evidence reveals density-dependent mediated success of alternative mating behaviours in the European bitterling (Rhodeus sericeus).

The reproductive success of alternative mating behaviours may vary within and among populations in relation to environmental factors and demographic parameters. We used behavioural and genetic data to investigate how male density affects reproductive success of territoriality and sneaking in the European bitterling (Rhodeus sericeus, Cyprinidae), a freshwater fish that spawns on the gills of living freshwater mussels. Keeping the number of spawning sites constant, we manipulated male densities in laboratory and mesocosm experiments. We showed that sneaked fertilizations were common in R. sericeus, and that they increased significantly with male density. Territorial mating was almost 17 times more successful than sneaking at the lowest male density treatment, and still 2-3 times more successful at intermediate densities. However, both behaviours conferred the same fitness pay-off at the highest male density. While the success of territorial males declined with male density, the success of individual sneaking males remained constant across densities. Notably, the capacity of territorial males to outcompete sneakers by preoviposition sperm loading was the best predictor of male reproductive success, rather than aggression, body size or postoviposition ejaculation.

Animals↗

[Fertility of women after surgical intervention on organs of reproduction].

The research included 114 female patients treated at the Clinic of Obstetrics and Gynaecology in the years 1986-1991. Information was based on a questionnaire, with 40 (35%) answers. Basic parameters of fertility were evaluated in women, who underwent surgical intervention on reproductive organs and they were discussed in connection with other conditioning. It was ascertained that the decision concerning infertility treatment is taken up by young patients, up to 25 years of age, during the first 5 years of marriage. Duration of the treatment in the majority of patients lasts longer than 5 years. Routine surgical interventions in the area of reproductive organs do not increase significantly the possibility of conception. Whereas in this group we deal more often with ectopic pregnancy.

Adult↗

Endogenous gonadal, LH and molt rhythms in tropical stonechats: effect of pair bond on period, amplitude, and pattern of circannual cycles.

To investigate the effects of reproduction and associated stimuli on the circannual cycles of African stonechats Saxicola torquata axillaris birds were held for 29 months in aviaries under a constant equatorial (12.25 h) photoperiod, either singly (10 females and 10 males) or in 10 male/female pairs. The birds of all 3 groups went through circannual cycles in gonadal size, plasma LH and molt, but groups differed with regard to actual reproductive performance. During the second cycle, only one of the singly-held females laid eggs and incubated. In contrast, in the paired females egg-laying and incubation occurred in all but one bird. About 50% of the clutches from paired females contained fertilized eggs confirming the expectation of behavioral differences between the paired and unpaired birds. However, despite differences in reproductive performance there were no differences in either circannual period or duration of reproductive phases. Moreover, there was no correlation between number of broods produced per season and circannual parameters of the paired females. Therefore, the temporal course and, particularly, the period during which reproduction is possible is rigidly determined by an endogenous program that is not influenced by reproductive performance. A rigid program of this kind may be advantageous in the tropics because it prevents prolongation of the breeding season in years with favourable conditions which in turn could jeopardize optimal timing of breeding in the following year and thus reduce lifetime reproductive success.

Africa↗

Modeling the concentration-response function of the herbicide dinoseb on Daphnia magna (survival time, reproduction) and Pseudokirchneriella subcapitata (growth rate).

Models describing dose-response relationships are becoming increasingly popular in ecotoxicology. They allow simple and thorough evaluations of toxicity test results, including inter- and extrapolations to concentrations or exposure times other than those tested. Simple parametric regression models are of particular interest because their parameters may be attributed mechanistic meanings and they can be applied without sophisticated mathematical and computational support. We recently proposed a four-parameter logistic regression model to fit the survival data of Daphnia magna under dinoseb stress. The model parameters are the maximum survival time, the minimum time required for an individual to die, effect concentration, EC(50), and a curve shape parameter. This model has now been applied to compare the lethality and reproduction toxicity of D. magna and the growth inhibition of Pseudokirchneriella subcapitata under dinoseb stress. It can be fitted adequately to all the measured data and the parameters can be attributed biological meanings in any of the three endpoints. A comparison of the modeled concentration-response functions of all three endpoints for dinoseb toxicity shows that the range of ECs with respect to both D. magna and algae is steep (a decrease of between 0.1 and 0.6 mg/L). The survival and reproduction of D. magna exhibit similar characteristic concentration-response functions and toxicities. The statistical no-effect concentration (SNEC) is 0.14 (survival) and 0.11 (reproduction)mg/L, respectively. On the other hand, algae seem to be less sensitive to dinoseb than D. magna (SNEC: 0.48 mg/L). However, further investigations of individual algae may lead to a more suitable comparison. We speculate that the four parameters of the model function can be related to specific properties of chemicals and organisms. Characterization of these properties would allow simple and appropriate estimation of the toxic effects of these chemicals.

2,4-Dinitrophenol↗

Lifestyle factors fail to explain the variation in plasma leptin concentrations in women.

To assess the relationship between circulating leptin concentrations, metabolic parameters, and lifestyle factors such as alcohol intake, physical activity level, smoking habits, and reproductive history, a cohort of 359 women was drawn from a population-based study conducted in Victoria, Australia. The parameters measured included body mass index (BMI); waist and hip circumference; blood pressure; and fasting glucose, insulin, triacylglycerol, cholesterol, and leptin concentrations. In addition, a self-administered questionnaire was used to assess reproductive history, physical activity level, alcohol intake, and smoking habits. Our results demonstrated that BMI, body weight, waist circumference, and hip circumference were all strongly correlated with circulating leptin concentrations in this population (r > 0.56, P < 0.001 in all cases). Waist/hip ratio, triacylglycerols, insulin, glucose, and cholesterol were also associated with leptin (P < 0.05), but there was no association between leptin and age, height, or blood pressure. When these associations were adjusted for BMI, age, glucose, and waist circumference were significantly associated with leptin. The lifestyle factors examined did not help to explain the observed variation in leptin concentrations between individuals when results were adjusted for degree of adiposity and age.

Adult↗

The seasonal pattern of dengue in endemic areas: mathematical models of mechanisms.

In dengue-endemic areas such as Thailand, there is clear seasonality in the number of reported cases of dengue virus disease. However, the roles of different entomological and biological variables in determining this pattern have not been ascertained. To investigate this, seasonally-varying parameters were introduced in a step-wise fashion into a mathematical model of the transmission dynamics of dengue viruses. The predicted prevalence of infection was then compared to observed seasonal patterns of disease. The strongest influences on the pattern of infection and its seasonal variation were duration of infectiousness of the host, vector mortality, and biting rate. However, seasonally-varying parameters such as the latent period of infection in the vector had to be incorporated into the model to generate the correct timing of peak infection prevalence. A few limiting variables usually control the prevalence of an infectious disease because small changes in their values can carry the infection beyond the threshold at which its basic reproductive number is one. It was changes in such parameters (vector biting and mortality rate) which caused seasonal prevalence, but the timing of peak prevalence was a result of time delays within the system.

Dengue↗

Male reproductive toxicity of sodium arsenite in mice.

The effect of chronic oral exposure to arsenic on male mouse testicular and accessory sex organ weights, sperm parameters and testicular marker enzymes was studied. In addition, the distribution of arsenic in reproductive organs was measured using atomic absorption spectrophotometry. Sodium arsenite administered to mice (Mus musculus) via drinking water at a dose of 53.39 micromol/L (4 ppm As) for 365 days caused a decrease in the absolute and relative testicular weight. However, epididymal and accessory sex organ weight was similar to control. The activities of marker testicular enzymes such as sorbitol dehydrogenase, acid phosphatase and 17beta-hydroxy-steroid dehydrogenase (17beta-HSD) were significantly decreased, but those of lactate dehydrogenase and gamma-glutamyl transpeptidase (gamma-GT) were significantly increased. A decrease in sperm count and sperm motility, along with an increase in abnormal sperm, was observed in arsenite-exposed mice. A significant accumulation of arsenic in testes, epididymis, seminal vesicle and prostate gland was observed in treated animals. Thus long term exposure (365 days) at the dose level of 53.39 micromol/L sodium arsenite (4 ppm As), to which human beings are likely to be exposed via drinking water, may cause testicular and spermatotoxic effect.

Administration, Oral↗

Effects of leucocytospermia on semen parameters and outcomes of intracytoplasmic sperm injection.

Leucocytes are present throughout the male reproductive tract but the clinical significance of leucocytic infiltration in the human ejaculate is controversial. The World Health Organization (WHO) defines leucocytospermia as the presence of peroxidase-positive leucocytes in concentrations of > or =1 x 10(6)/mL of semen. The goals of this study were to clarify the relationship between leucocytospermia and semen parameters including sperm concentration, progressive and total motility before and after semen preparation, and intracytoplasmic sperm injection (ICSI) outcomes, including fertilization, embryo development, embryo morphology, cleavage and pregnancy rates. We compared the semen parameters and ICSI outcome of 34 leucocytospermic and 36 non-leucocytospermic control couples who were undergoing ICSI because of male factor infertility including oligo and/or astheno and/or teratozoospermia. Semen parameters including progressive motility rate (1.5% vs. 3%) and sperm concentrations (12 vs. 29 million/mL) were significantly lower in the leucocytospermic group compared with the control group. Other semen parameters were not affected by the presence of leucocytes. ICSI outcome, including fertilization (82% vs. 87%) and embryo development rates (79% vs. 86%) were significantly lower in the leucocytospermic group compared with the control group although there were no statistical difference for embryo quality, embryo cleavage and pregnancy rates. These results indicate that some semen parameters and the outcome of ICSI were negatively affected by the presence of leucocytospermia.

Adult↗