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PubMed1998

A diet supplement for captive wild ruminants.

Nutritional husbandry of captive wild ruminants often requires feeding these animals a supplemental diet to enhance their health, reproductive performance, and productivity. Although supplemental diets for wild ruminants are commercially available, few have been evaluated in controlled intake and digestion trials. Voluntary intake, digestive efficiency, nitrogen retention, and gross energy utilization of pronghorn (Antilocapra americana), mule deer (Odocoileus hemionus), mountain sheep (Ovis canadensis), mountain goats (Oreamnos americanus), and wapiti (Cervus elaphus) consuming a high-energy, high-protein pelleted supplement were compared. Voluntary intake of dry matter, energy, and nitrogen were similar (P > 0.34) between mountain goats and mountain sheep and consistently lower (P < 0.03) for these species than for pronghorn, mule deer, and wapiti. Differences in digestive efficiency among species were inversely related to dry matter intake rates. Apparent digestibility of dry matter, organic matter, and neutral-detergent fiber was 10-20% higher for mountain goats and mountain sheep than for the other species (P < 0.04). Although these findings suggest a superior digestive efficiency for mountain goats and mountain sheep, species comparisons are inconclusive because of the confounding effects of season and ambient temperature on voluntary intake and digestion. Under the conditions of this experiment, the diet tested was safe, nutritious, and highly palatable. Protein and energy concentrations appear to be sufficient to meet or exceed known nutritional requirements of captive wild ruminants.

Animal Feed↗
PubMed2001

Quinacrine non-surgical female sterilization in Bangladesh.

This study was undertaken to evaluate the efficacy, safety, and acceptability of transcervical applications of quinacrine along with other adjuvants, such as ampicillin and ibuprofen, for sterilization. The cohort consisted of 750 normal women who requested sterilization and volunteered for this method at the family planning clinic of a tertiary hospital and community clinics in Chittagong, Bangladesh. Several different protocols were followed from October 1989 to April 1999. Each woman received one or two insertions of 180 mg or 252 mg quinacrine with or without adjuvants including 55.5 mg ibuprofen or 125 mg ampicillin. Supplementary contraception was given in the form of combined oral contraceptive pills, barrier methods, or injection of depot medroxyprogesterone acetate for 3 months. Details of each protocol are described in the text. The gross pregnancy failure rate for insertion of 180 mg in 590 women was 3.9% compared to 1.9% for the 160 who received 252 mg. There were no serious complications, and side effects were transient. We conclude that quinacrine non-surgical sterilization is a safe, acceptably effective method when two insertions of 252 mg quinacrine with medroxyprogesterone injection as a supplement is used.

Adult↗
PubMed2005

Contrasting children and women's health and the determinants of health in a small-sized city.

Contrasts that exist in urban infrastructure and accessibility of public health and social services between suburban and urban districts of mega-cities have been well defined. There has been less research in small-sized cities (population under 500,000). This cross-sectional study was done on 1,728 ever-married reproductive-aged women living in Manisa, Turkey, in the year 2000. The probability proportion to size cluster sampling approach was used in the sample selection. Data were collected for women and 7,016 inhabitants of the interviewed households. The data were collected from the women by face to face interviews. Suburban areas (illegally occupied public land called "Gecekondu" dwellings) in Manisa differ from other urban regions (legal settlements of the city) on socioeconomic factors including household occupancy, adult literacy, social class, rates of religious marriages, unemployment, health insurance coverage, migration, cultural segregation, and social status of women. Some traditional practices were also highly prevalent in gecekondu families, where poverty is more common. Although gross fertility rate (GFR), total fertility rate (TFR), and percent decrease of the TFR were higher for gecekondu women than urban women, total wanted fertility rate (TWFR) was lower. In urban neighborhoods, prevalence of contraceptive use was higher, and the infant and child mortality rates were lower; however, when rates were adjusted for mother's age, education and number of births, the differences turned out to be nonsignificant. Women living in urban areas receive better antenatal care, child immunization services, and professional health delivery assistance and services in a health facility; these services are very scarce in gecekondu districts. Health status of gecekondu populations can be improved by social and economic support and by making health services more available and accessible, especially maternity and child health services.

Adolescent↗
PubMed1993

Hypovirulence-associated traits induced by a mycovirus of Cryphonectria parasitica are mimicked by targeted inactivation of a host gene.

Expression of the Vir2 gene of Cryphonectria parasitica is down-regulated in strains of the fungus containing a double-stranded RNA genetic element that reduces fungal virulence (W. A. Powell and N. K. Van Alfen, Mol. Cell. Biol. 7:3688-3693, 1987). We have sequenced the Vir2 gene and characterized its structure; the mRNA contains a short open reading frame whose product has structural similarities to several fungal pheromones. A null mutant was constructed by homologous recombination to determine the function of the Vir2 gene and whether its disruption resulted in any of the altered phenotypes exhibited by many hypovirulent strains, such as reductions in virulence, pigmentation, and sporulation. The Vir2 null mutant (18dm) exhibited a wild-type phenotype with respect to gross colony morphology, growth rate, pigmentation, asexual spore viability, and virulence in apple fruit and chestnut trees. However, numbers of asexual fruiting bodies (pycnidia) and conidia were reduced significantly in comparison with the wild-type strain EP155/2. In sexual crosses of 18dm with a wild-type strain of the opposite mating type, perithecia (sexual fruiting bodies) developed but were barren. Deletion of the Vir2 gene results in a phenotype that mimics that of many double-stranded-RNA-containing hypovirulent strains; i.e., the null mutant exhibits significant reductions in asexual sporulation and pycinidum production as well as impaired sexual crossing ability. To our knowledge, this is the first report of the partial reproduction of a virus-induced phenotype by deletion of a virus-perturbed host gene.

Amino Acid Sequence↗
PubMed2004

Comparison of an auto-stereoscopic display and polarized stereoscopic projection for macroscopic pathology.

We investigated stereoscopic imaging for gross examination in telepathology. A conventional macroscopic station was equipped with two cameras mounted 6.5 cm apart and images were produced of 30 different routine pathology specimens. Still images were displayed on a three-dimensional auto-stereoscopic display with a lenticular plate (which did not require the viewer to wear special glasses) and as a three-dimensional projection that required the viewer to wear glasses with polarized lenses. Nine observers (pathologists, laboratory technicians and engineers) viewed the three-dimensional images first on the auto-stereoscopic display and then with polarized projection. The observers scored the images for spatial reproduction, surface structure, proportions, colour and sharpness (10 indices in total, each rated on a five-point Likert scale of 1-5, with lower scores indicating better quality). Results were compared with those from five observers who had previously viewed the corresponding two-dimensional images on a conventional (two-dimensional) display. The mean scores across each of the 10 indices were 2.9 (two-dimensional display), 2.1 (auto-stereoscopic display) and 1.6 (polarized projection). All observers stated that the polarized projection had superior image quality with regard to resolution, colour and surface structures. The results obtained in the present study with still images have encouraged us to integrate stereoscopy into a dynamic telepathology system.

Automation↗
PubMed1998

Developmental toxicity evaluation of a scrubbing solution used in petroleum refineries.

The developmental toxicity potential of a scrubbing solution used extensively in petroleum refineries to remove CO2 from hydrogen gas streams was evaluated via inhalation. Pregnant female CD (Sprague-Dawley) rats were exposed to aerosols of a "used" scrubbing solution at 0.05, 0.1, 0.2, or 0.3 mg/l for 6 h/d on d 6-19 of pregnancy. Control animals were exposed to filtered air under the same exposure conditions. Dams were sacrificed on d 20 of pregnancy and a laparohysterectomy was performed. The mass median aerodynamic diameter of the aerosol revealed that all particles ranged from 1.6 to 2.8 microm, with geometric standard deviations between 2.0 and 2.3 microm. The overall pregnancy rate was high (>95%) and equivalent across all groups. All pregnant dams had live litters, and 22-24 litters were examined in each group. Treatment-related clinical signs consisted of rales, observed at all exposure levels, and gasping noted only at the 0.3 mg/l exposure level. The occurrence of rales was presumably a localized effect on the respiratory tract and likely due to the irritating properties of the scrubbing solution. Maternal toxicity was exhibited in the 0.3 mg/l group, including reduced body weight, weight gain, and food consumption and one possible treatment-related death on gestation d 17. At scheduled necropsy, there were no treatment-related gross pathological observations and no statistically significant reproductive and developmental effects. The incidences of fetuses with skeletal variations involving the sternum were clustered in two litters at the highest exposure level with atypically low term fetal body weights. Under the conditions of this investigation, potassium carbonate scrubbing solution is not a selective developmental toxicant.

Accidents, Occupational↗
PubMed2005

Potential ecotoxic effects of polychlorinated biphenyls on Xenopus laevis.

We examined potential ecotoxic effects of polychlorinated biphenyl (PCB)3, PCB5, Aroclor 1254, and Aroclor 1242 on Xenopus laevis. Tadpoles were exposed to PCBs from stage 46/47 (system of Nieuwkoop and Faber) to the completion of metamorphosis. We demonstrated, to our knowledge for the first time, forelimb malformations caused by PCBs (malformation rate, > 70%). The malformed forelimbs were fixed in the adduction-backward rotation position and could not move. Therefore, malformed male frogs were destined to have no offspring, because they could not grasp the females with their forelimbs to mate. Alcian blue-alizarin red double-staining indicated that the forelimb malformation resulted from the shoulder abnormality. Compared with the normal shoulder joint, the proximal humerus with the humerus inter-rotated 90 degrees in the abnormal shoulder joint. Moreover, testes from more than a third of male frogs with exposed to PCBs exhibited feminization to different degrees at gross morphology and histology, with fewer or abnormal spermatogonia and oocytes. Gonadal abnormalities would lead directly to reproductive dysfunction and population decline. These results suggest that PCBs have potentially ecotoxic effects on amphibian populations. We infer that PCBs could play roles in amphibian malformations and population declines, at least at sites that are polluted heavily with PCBs.

Animals↗
PubMed2004

Organochlorine pesticides and thiamine in eggs of largemouth bass and American alligators and their relationship with early life-stage mortality.

Thiamine deficiency has been linked to early mortality syndrome in salmonids in the Great Lakes. This study was conducted to compare thiamine concentrations in American alligators (Alligator mississippiensis) and Florida largemouth bass (Micropterus salmoides floridanus) eggs from sites with high embryo mortality and high exposure to organochlorine pesticides (OCPs) (Lakes Apopka and Griffin, and Emeralda Marsh, Florida, USA) to those from sites that have historically exhibited low embryo mortality and low OCPs (Lakes Woodruff and Orange, Florida). During June-July 2000, 20 alligator clutches were collected from these sites, artificially incubated, and monitored for embryo mortality. Thiamine and OCPs were measured in one egg/clutch. During February 2002, 10 adult female bass were collected from Emeralda Marsh and Lake Woodruff and mature ovaries analyzed for thiamine and OCP concentrations. Although ovaries from the Emeralda Marsh bass contained almost 1,000-fold more OCPs compared with the reference site, Lake Woodruff, there were no differences in thiamine concentrations between sites (11,710 vs. 11,857 pmol/g). In contrast, alligator eggs from the reference site had five times the amount of thiamine compared with the contaminated sites (3,123 vs. 617 pmol/g). Similarly, clutches with >55% hatch rates had significantly higher concentrations of thiamine compared with clutches with <54% hatch rates (1,119 vs. 201 pmol/g). These results suggest that thiamine deficiency might be playing an important role in alligator embryo survival but not in reproductive failure and recruitment of largemouth bass. The cause(s) of this thiamine deficiency are unknown but might be related to differences in the nutritional value of prey items across the sites studied and/or to the presence of high concentration of contaminants in eggs.

Alligators and Crocodiles↗
PubMed1978

Polybrominated biphenyl (PBB) in the growing pig diet.

Twelve pigs which averaged 13.7 kg were randomly allotted from litters to a corn-soybean meal grower diet containing 0, 20, or 200 ppm of polybrominated biphenyls (PPB). During a 16-week growth trial, average daily gain (kg), average daily feed (kg) and feed/gain for pigs on diets containing 0, 20, or 200 ppm of PBB, respectively, were 0.82, 2.45, 2.99; 0.67, 1.88, 2.79; 0.45, 1.23, 2.70. Mean daily gain differences between all lots were highly significant (p < 0.01). Blood from each pig was withdrawn biweekly through the first 8 weeks of the trial and at 4 week intervals thereafter. Hemoglobin and hematocrit differed significantly only at the 6 weeks bleeding, being reduced in pigs receiving 200 ppm of PBB. Erythrocyte reduced glutathione concentration and glutathione peroxidase activity were not significantly influenced by level of dietary PBB. Serum lactic dehydrogenase activity was significantly higher in control pigs than in either PBB supplemented lots at 16 weeks. There was no significant influence of PBB upon serum glutamic oxaloacetic transaminase, serum alkaline phosphatase or serum creatine phosphokinase. Based on these enzyme assays, PBB produced no evidence of significant necrosis of liver, myocardium, or skeletal muscle. There was no consistent effect of dietary PBB upon total serum protein concentration or electrophoretic profile. Pigs on either level of PBB did not have overt clinical signs of toxicity during the 16-week test period with the exception of a dermatosis on the ventral surface of two of the pigs receiving 200 ppm of PBB. There was a marked increase in liver weight of pigs receiving either level of dietary PBB. Heart, kidney, and adrenals of pigs receiving either level of dietary PBB were heavier as a percent of body weight than that of control pigs. Fat retention of PBB and urinary and fecal PBB excretion were significantly affected by dietary PBB level. Grossly, the glandular portion of the stomach appeared somewhat hyperplastic in pigs on 200 ppm of PBB. Two pigs which had received 200 ppm of PBB were placed on the control diet and over the next 14 weeks normal growth rate occurred. One of these pigs was killed and organ weights were normal. The other pig, a gilt, came into estrus. She was bred and conceived. At the end of gestation, four pigs were born. Three survived and grew normally; the one death at birth examined at gross necropsy did not reveal changes in organ size or other tissue alterations.

Animal Feed↗
PubMed1987

Effectiveness of IUDs: a review.

Large, multicenter, randomized trials of IUDs conducted between 1970 and 1986 encompass more than 50,000 woman-years of experience in the two-year interval following device insertion. Taken singly and collectively, these trials demonstrate that IUD failure rates are strongly affected by the age of participants, notably by the proportion of women under age 25 admitted to the studies. Individual trials and overall comparisons indicate further that: 1. Non-medicated devices such as the Mahua steel ring and Lippes loop D have pregnancy rates above 2 per 100 woman-years. 2. The first approved copper IUDs, the Copper 7 and the TCu 200, do not markedly differ in pregnancy rates from standard plastic devices with rates significantly above 2 per 100 woman-years. 3. Five more recent, widely used copper IUDs have had failure rates significantly below 2 per 100 woman-years in multicenter trials. The point estimate of the failure rate was less than 1 pregnancy per 100 woman-years for three of these IUDs. One copper-bearing device had a failure rate significantly below 1 per 100 woman-years. 4. Devices releasing either 25 mcg/day of progesterone or 2 mcg/day of levonorgestrel have had significantly higher failure rates than the more effective copper-releasing IUDs; however, devices releasing 20 mcg/day of levonorgestrel appear at least as effective as the most effective copper IUDs. Long-term IUD failure rates derived from straight assignment as well as randomized trials indicate 4-year gross cumulative failure rates do not exceed 10 per 100 for any of the standard copper devices or the Lippes loop D. Point estimates of the four-year gross cumulative pregnancy rates have been below 5 per 100 users in studies of the TCu 220C, the Nova T, the TCu 380A, and the MLCu 375.

Adolescent↗
PubMed1979

A comparison of gross and microsurgical techniques for repair of cornual occlusion in infertility: a retrospective study, 1968-1978.

A 10-year experience is recounted moving from traditional gross implantation methods to microsurgical anastomosis in the repair of cornual occlusion in infertility. Two gross surgical implantation techniques, one involving reaming out the intramural portion of the uterine tube and the other dissecting it out via a transfundal incision, are compared with microsurgical uterotubal anastomosis. The author reports a 4.7 times improvement in the term pregnancy rate after turning to microsurgery and describes his method for anastomosing the transected ampulla or isthmus to the intramural portion of the tube.

Fallopian Tubes↗
PubMed1993

Toxicology and Carcinogenesis Studies of 5,5-Diphenylhydantoin (CAS No. 57-41-0) (Phenytoin) in F344/N Rats and B6C3F1 Mice (Feed Studies).

5,5-Diphenylhydantoin and its sodium salt are primarily used in the treatment of grand mal and psychomotor seizures, often in combination with other anticonvulsants, including phenobarbital. 5,5-Diphenylhydantoin is a suspected human carcinogen and was one of three compounds selected by the NTP to investigate the potential value of perinatal exposures in assessing chemical carcinogenicity. Chronic toxicity and carcinogenicity studies of 5,5-diphenylhydantoin were conducted in male and female F344/N rats and B6C3F1 mice. The studies were designed to determine the following: a) the effects of 5,5-diphenylhydantoin in the diet given to rats and mice during the adult (F1) period only (a typical carcinogenicity study), b) the toxic and carcinogenic effects of 5,5-diphenylhydantoin in rats and mice receiving perinatal (F0) exposure only (dietary exposure of dams prior to breeding and throughout gestation and lactation), and c) the effects of combined perinatal and adult exposure to 5,5-diphenylhydantoin. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse Iymphoma cells, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse bone marrow cells. STUDIES IN F344/N RATS: A 13-week toxicity study was conducted to select the exposure levels for adults in the 2-year study. The exposure levels for the 13-week study ranged from 300 to 4,800 ppm 5,5-diphenylhydantoin in the diet. The final mean body weights of males and females exposed to 2,400 or 4,800 ppm were significantly decreased. All groups showed a net weight gain over the study period, although the mean body weight gain of females in the 4,800 ppm group was only one-half that of the controls. Feed consumption also decreased with increasing exposure level. No chemical-related gross lesions were present in the tissues of exposed rats. Microscopically, centrilobular hypertrophy of hepatocytes was observed in the liver of rats in the 4,800 ppm groups. Based on these results, 2,400 ppm was selected as the highest exposure for the adult-only portion of the 2-year carcinogenicity study. A gestational study was performed to select the exposure levels for the perinatal portion of the 2-year study. The exposure levels ranged from 80 to 2,400 ppm 5,5-diphenylhydantoin in the diet of the dams. The 2,400 ppm exposure level was found to have reproductive and embryotoxic effects, as none of the sperm-positive females delivered litters. In the 800 ppm group, a greater number of pups died between postnatal day 1 and day 28 than in the control group. No gross external malformations were observed among fetuses or pups surviving to term in any exposure group, and no gross or histopathologic lesions were observed in the animals exposed to 800 ppm for 4 weeks following weaning. Based on these results, 630 ppm was selected as the highest exposure level for the perinatal portion of the 2-year carcinogenicity study. The eight F0:F1 exposure combinations selected for the 2-year study are listed in the table (contained in full report - page 6). In the 2-year study, male and female rats in the 630:2,400 ppm groups evaluated at 9 months had increased relative liver weights. Hematologic evaluations indicated mild but consistent chemical-related increases in erythrocyte and platelet counts in male and female rats. Mild decreases in triglyceride concentrations and alanine aminotransferase enzyme activity were seen generally in the high-exposure groups. In the 2-year study, the survival of exposed rats was similar to that of the controls. However, body weights of exposed rats were lower than those of the controls, and body weights were 11% to 35~ lower in rats receiving adult exposure of 2,400 ppm 5,5-diphenylhydantoin. Feed consumption was similar for exposed and control groups. Hepatocellular neoplasms, primarily adenomas, occurred with a positive trend in male rats fed 5,5-diphenylhydantoin only as adults (0:0 ppm, 0/50; 0:800 ppm, 2/50; 0:2,400 ppm, 4/50). There were no increased neoplasm incidences at other sites in exposed males or at any site in exposed females.emales. Perinatal-only or combined perinatal and adult exposure to 5,5-diphenylhydantoin did not enhance the overall incidences of liver neoplasms in male or female rats. However, the finding of 5/49 hepatocellular adenomas in the 630:2,400 male rat group was consistent with the marginally elevated liver neoplasm rate observed in the 0:2,400 group. Decreased incidences of a number of different neoplasms in exposed groups were most likely related to the lower body weights. STUDIES IN B6C3F1 MICE: A 13-week toxicity study was conducted to select the exposure levels for adults in the 2-year study. The exposure levels for the 13-week study ranged from 75 to 1,200 ppm 5,5-diphenylhydantoin in the diet. With the exception of one male, all mice exposed to 1,200 ppm died before the end of the study. No other chemical-related deaths occurred. All groups of mice except the 1,200 ppm groups gained weight over the 13-week period; however, an exposure related decrease in body weight gain was seen in males and females. Feed consumption by exposed and control groups was generally similar. Chemical related histomorphologic lesions were present in the liver of exposed mice, particularly 600 ppm males, and consisted of centrilobular hypertrophy of hepatocytes. Females appeared to be less sensitive than males to the effects of 5,5-diphenylhydantoin on growth and on histomorphologic liver lesions. Based on these results, 300 ppm (males) and 600 ppm (females) were selected as the highest exposure levels for the adult-only portion of the 2-year carcinogenicity study. A gestational study was performed to select the exposure levels for the perinatal portion of the 2-year study. The exposure levels for males and females ranged from 20 to 600 ppm 5,5-diphenylhydantoin in the diet. In general, reproductive performance and maternal care were poor in all groups, including the controls, thus restricting the sample size and sensitivity of this evaluation. There were no litters in the 600 ppm group, and maternal weight gain was depressed. There were no gross external malformations among pups surviving to term, and no gross or histopathologic lesions were observed in any mice exposed for 4 weeks following weaning. Based on these results, 210 ppm was selected as the highest exposure level for the perinatal portion of the 2-year carcinogenicity study. The F0:F1 exposure combinations selected for the 2-year study are listed in the following table (contained in full report - page 7). For mice evaluated at 9 months, males and females receiving the highest F0:F1 exposure levels had increased relative liver weights. In the 2-year study, the survival of exposed animals was similar to that of the controls; however, body weights were lower for exposed groups, and decreased body weights were most severe in adult females receiving 600 ppm 5,5-diphenylhydantoin. Feed consumption was similar for exposed and control groups. The incidences of hepatocellular neoplasms were increased in female mice receiving adult-only exposure (0:0 ppm, 5/48; 0:200 ppm, 14/49; 0:600 ppm, 30/50) or combined perinatal and adult exposure (210:200 ppm, 16/50; 210:600 ppm, 34/50). A marginally increased incidence of liver neoplasms (12/49) occurred in females in the perinatal-only (210:0) exposure group. There were no chemical-related increased incidences of liver neoplasms in males receiving adult-only or perinatal-only exposure. However, males receiving the high-exposure combined perinatal and adult exposure regimen (210:300 ppm) had an increased incidence of liver neoplasms (41/50) compared to the 0:0 (29/50), 0:300 (26/49), and 210:0 (33/50) groups. As a result, there was a significant enhancement (interaction) associated with combined perinatal and adult exposure. Such enhancement of neoplasia did not occur in female mice. Decreased incidences of malignant neoplasms in exposed groups were most likely related to the lower body weights. GENETIC TOXICOLOGY: In general, tests for genotoxic activity of 5,5-diphenylhydantoin were negative. All in vitro testing was performed in the presence and the absence of exogenous metabolic activation (S9). 5,5-Diphenylhydantoin did not induce mutations in Salmonella typhimurium, in L5178Y mouse Iymphoma cells, or in germ cells of male Drosophila melanogaster, nor did it induce chromosomal aberrations in cultured Chinese hamster ovary cells. A small but statistically significant increase was obtained in the cultured Chinese hamster ovary cell test for induction of sister chromatid exchanges in the presence of S9; without S9, no increase in sister chromatid exchanges was observed. In vivo, 5,5-diphenylhydantoin did not induce micronuclei polychromatic erythrocytes or chromosomal aberrations in bone marrow cells of male mice; equivocal results were obtained in an in vivo test for induction of sister chromatid exchanges in mouse bone marrow cells. CONCLUSIONS: Adult-Only Exposure: Under the conditions of these 2-year, adult-only, dietary exposure studies, there was equivocal evidence of carcinogenic activity of 5,5-diphenylhydantoin in male F344/N rats based on marginally increased incidences of hepatocellular neoplasms. There was no evidence of carcinogenic activity of 5,5-diphenylhydantoin in female F344/N rats given 240, 800, or 2,400 ppm. There was no evidence of carcinogenic activity of 5,5-diphenylhydantoin in male B6C3F1 mice given 30,100, or 300 ppm. There was clear evidence of carcinogenic activity of 5,5-diphenylhydantoin in female B6C3F1 mice based on increased incidences of hepatocellular neoplasms. Perinatal-Only Exposure: Perinatal exposure alone (through dietary administration of 210 ppm 5,5-diphenylhydantoin during the perinatal period) caused a marginal increase in the incidences of hepatocellular neoplasms in female B6C3F1 mice evaluated 2 years after cessation of exposure. In male and female F344/N rats, exposure to 630 ppm during the perinatal period did not influence the incidences of hepatocellular or other neoplasms. Similarly, exposure of male B6C3F1 mice to dietary levels of 210 ppm 5,5-diphenylhydantoin during the perinatal period did not affect neoplasm incidences. No teratologic effects were observed. Combined Perinatal and Adult Exposure: Combined perinatal and adult dietary exposure to 5,5-diphenylhydantoin confirmed the findings of the increased incidences of hepatocellular neoplasms for adult-only exposures in male F344/N rats and female B6C3F1 mice, although combined exposure did not enhance these neoplastic effects. However, in male B6C3F1 mice, combined perinatal and adult exposure resulted in increased incidences of hepatocellular neoplasms (hepatocellular carcinomas and multiple adenomas) that were not seen when dietary exposure was limited to the adult exposure period only. Synonyms: Diphenylhydantoin; 5,5-diphenyl-2,4-imidazolidinedione Trade names: Difhydan; Dihycon; Di-Hydan; Di-Lan; Dilabid; Dilantin; Ekko; Hydantol; Lehydan; Zentropil

Journal Article↗
PubMed2002

Three-generation reproduction study of rats receiving acrylonitrile in drinking water.

Acrylonitrile, a high volume organic chemical, was tested for reproductive effects in a three generation drinking water study with two matings per generation. Sprague-Dawley rats were exposed to acrylonitrile in drinking water at 0, 100, or 500 ppm. This corresponds to 0, 11+/-5 and 37+/-10 mg/kg, respectively, for males and 0, 20+/-3 and 40+/-8 mg/kg per day for the females, respectively. Water consumption was reduced in F0 rats in the 100 and 500 ppm groups. At 500 ppm, acrylonitrile reduced body weight gain and food intake of the first generation parental rats (F0). These parameters were not investigated at subsequent generations. The pup survival (both viability and lactation indices) was reduced at the 500 ppm treatment level in both matings of all three generations. Fostering the 500 ppm pups onto untreated mothers following the second mating lessened mortality, suggesting a maternal effect consistent with decreased water consumption. There was no remarkable change in the reproductive capacity in any of matings in rats at the 100 ppm concentration. In contrast, in all three generations, the body weights of the pups of the 500 ppm treatment level were reduced on Day 21 at both matings. No adverse findings were observed in the tissues of a limited number of third generation weanlings (F3b) upon gross and microscopic evaluation. No effect on the sciatic nerve was evident among the adult female rats held for 20 weeks after weaning of the second litter. There was a dose-related effect of acrylonitrile on gross masses in female rats at each parental generation held 20 weeks after the weaning of the second litter. Histopathological evaluation of these dams showed an increase in astrocytomas and zymbal gland tumors.

Acrylonitrile↗
PubMed2003

Developmental outcome of levetiracetam, its major metabolite in humans, 2-pyrrolidinone N-butyric acid, and its enantiomer (R)-alpha-ethyl-oxo-pyrrolidine acetamide in a mouse model of teratogenicity.

PURPOSE: The purpose of this study was to test the teratogenic potential of the antiepileptic drug (AED) levetiracetam (LEV), its major metabolite in humans, 2-pyrrolidone-N-butyric acid (PBA), and enantiomer, (R)-alpha-ethyl-oxo-pyrrolidine acetamide (REV), in a well-established mouse model. METHODS: All compounds were administered by intraperitoneal injections once daily to SWV/Fnn mice on gestational days 8-1/2 to 12-1/2. LEV was administered at doses of 600, 1,200, and 2,000 mg/kg/day, piracetam (PIR) and PBA, at 600 and 1,200 mg/kg/day, and REV, at 600 mg/kg/day. On gestational day 18(1/2), fetuses were examined for gross external malformations and prepared for skeletal analysis by using Alizarin Red S staining. RESULTS: No significant gross external malformations were observed in any of the study groups. Fetal weights were significantly reduced in most study groups. Resorption rates were significantly increased only in the 2,000-mg/kg/day LEV group. The overall incidence of skeletal abnormalities and specifically of hypoplastic phalanges was significantly increased in both PBA treatments and in the intermediate 1,200-mg/kg/day LEV group. In contrast to that in humans, 24-h urinary excretion analysis in mice showed that 65-100% of the LEV doses were excreted unchanged, whereas only 4% was excreted as the metabolite PBA. CONCLUSIONS: Results of this study demonstrate that both LEV and its major metabolite in humans, PBA, do not induce major structural malformations in developing SWV/Fnn embryos and suggest that they provide a margin of reproductive safety for the pregnant epileptic population when compared with other AEDs tested in this mouse model.

Animals↗
PubMed1979

Immediate postpartum insertion of a copper-wired intrauterine contraceptive device, the MLCu250.

The MLCu250, a copper-wired intrauterine contraceptive device, was inserted in 600 women immediately after delivery of the placenta. Thirty months after insertion, 9843 woman months of experience were computerized and the data analysed according to the life-table method. The gross cumulative pregnancy and expulsion rates were 1.3 and 6.0 respectively. No serious complications were observed and the puerperium was uncomplicated.

Adult↗
PubMed2003

The effect of feeding frequency on consumption of food, absorption efficiency, and gonad production in the sea urchin Lytechinus variegatus.

The frequency of feeding in the field is variable in sea urchins, ranging from nearly continuous to diel or intermittent. It is essential to know the effect of feeding interval on physiological and metabolic processes to understand the basis for production. Lytechinus variegatus (50 mm horizontal diameter) were collected in January 1999 and held in closed-circuit aquaria at 25 degrees C and 35 per thousand salinity. After 9 days without food, individuals were fed one of three treatments: food available ad libitum, food available for 1 day every 2 days or food available for 1 day every 4 days for 28 days. The rate of food consumption per day of all individuals was high the first week of feeding. It then decreased to a lower, constant rate in those fed ad libitum but remained high in those fed one day every 2 or 4 days. The total amount eaten was directly related to frequency of feeding. The apparent dry matter digestibility (absorption efficiency) did not vary with frequency of feeding. As the total amount of energy absorbed was directly related to the frequency of feeding, the increase in the rate of food consumption does not compensate for a decrease in frequency of feeding. Gonad production efficiency was directly related to frequency of feeding. Gonad gross production (assimilation) efficiencies were 8.4, 3.9 and 3.4% for individuals fed every day, or fed one day every 2 and 4 days, respectively. The corresponding gonad net assimilation efficiencies were 12.5, 5.5, and 4.8%. A decrease in frequency of food availability results in use of a greater proportion of the food consumed for maintenance and less for gonad production.

Animal Feed↗
PubMed2004

The effect of treatment on pathogen virulence.

The optimal virulence of a pathogen is determined by a trade-off between maximizing the rate of transmission and maximizing the duration of infectivity. Treatment measures such as curative therapy and case isolation exert selective pressure by reducing the duration of infectivity, reducing the value of duration-increasing strategies to the pathogen and favoring pathogen strategies that maximize the rate of transmission. We extend the trade-off models of previous authors, and represents the reproduction number of the pathogen as a function of the transmissibility, host contact rate, disease-induced mortality, recovery rate, and treatment rate, each of which may be influenced by the virulence. We find that when virulence is subject to a transmissibility-mortality trade-off, treatment can lead to an increase in optimal virulence, but that in other scenarios (such as the activity-recovery trade-off) treatment decreases the optimal virulence. Paradoxically, when levels of treatment rise with pathogen virulence, increasing control efforts may raise predicted levels of optimal virulence. Thus we show that conflict can arise between the epidemiological benefits of treatment and the evolutionary risks of heightened virulence.

Communicable Diseases↗
PubMed2004

Habitat quality as a predictor of spatial variation in blue tit reproductive performance: a multi-plot analysis in a heterogeneous landscape.

Vertebrate studies have rarely investigated the influence of spatial variation in habitat richness on both short-term (breeding) and long-term (offspring recruitment) reproductive performance using simultaneously multi-patch, multi-habitat type and multi-year approaches at landscape level. Here we present results of such an approach using the influence of two oak tree (Quercus ilex, Q. humilis) species on reproductive performance in Corsican blue tits (Parus caeruleus ogliastrae) as a model system. We found that blue tits breeding in rich broad-leaved deciduous patches consistently laid eggs earlier in the season, and produced larger clutches and more fledglings of higher quality, than those breeding in poor evergreen patches. Also, parents, especially males, were in better physical condition in the broad-leaved deciduous than in the evergreen patches. Surprisingly, estimates of long-term effects of reproduction, such as recruitment rates of locally born offspring, did not differ between the two habitat types. Our results suggest that short-term breeding performance and phenotypic quality of both chicks and parents do not necessarily provide reliable information about contributions to following generations at a scale larger than that of the local study plot. Differences in reproductive performance between the two oak habitat types could not be attributed to density-dependent effects, differences in levels of nest predation, or differences in age structure of the birds. We suggest that habitats that are optimal for breeding are not necessarily optimal for survival after the breeding season.

Animals↗