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At least 559 records · Page 31Linked to original sources

SCID mouse model for lethal Q fever.

Q fever, a worldwide zoonosis caused by Coxiella burnetii, has many manifestations in humans. Endocarditis is the most serious complication of Q fever. Animal models are limited to acute pulmonary or hepatic disease and reproductive disorders. An appropriate experimental animal model for Q fever endocarditis does not yet exist. In this study, severe combined immunodeficient (SCID) mice infected with C. burnetii showed persistent clinical symptoms and died, whereas immunocompetent mice similarly infected became asymptomatic and survived. The SCID mice examined in this study had severe chronic lesions in their primary organs: the heart, lung, spleen, liver, and kidney. The heart lesions of the SCID mice were similar to those in humans with chronic Q fever endocarditis: they had focal calcification and expanded macrophages containing C. burnetii. The 50% lethal dose of C. burnetii in SCID mice was at least 10(8) times less than that in immunocompetent mice. The SCID mouse is highly susceptible to C. burnetii, and the immunodeficiency of the host enhances the severity of Q fever. This animal model could provide a new tool for the study of chronic Q fever and Q fever in immunodeficient hosts.

Animals↗

Effectiveness of pergolide mesylate in long term treatment of hyperprolactinaemia.

Twenty five patients with hyperprolactinaemia were treated with pergolide mesylate, a new dopamine receptor agonist. Twenty three received treatment for six to 20 months, and in all serum prolactin concentrations were considerably reduced. In most patients prolactin concentrations were maintained in the normal range by a low, once daily dose of pergolide and reversal of associated reproductive disorders was observed. Tumour volume as assessed by computed tomography decreased considerably during treatment in three out of four patients with a pituitary tumour. The drug was well tolerated. Side effects were similar to those of bromocriptine, but four out of eight patients who had been forced to stop taking bromocriptine because of untoward effects were subsequently able to tolerate treatment with pergolide. Pergolide mesylate promises to be a useful addition to the currently available long acting dopamine agonists in the management of hyperprolactinaemia.

Adult↗

Assessment of exposure to solvents among hairdressers: reliability of a classification scheme and questionnaire.

OBJECTIVES: To assess the reliability of a classification scheme and interview questions to be used for retrospective expose assessment in a study on reproductive disorders among hairdressers. Based on the presence of an air cleaning device (yes or no) and setting waves (yes or no), this scheme divides hairdressers into groups with potentially high and low exposure to solvents. The reliability of this and other schemes was assessed. Also; the reliability of self reports on other job characteristics was evaluated. METHODS: The monitored hairdressers were interviewed one or two years after measurements were performed. Based on the interview information, hairdressers were classified into exposure groups according to the original and other classification schemes. Measured ethanol concentrations were compared between the classified exposure groups. Furthermore, the interview answers were compared with the registered information one to two years ago. RESULTS: Using self reports, the original scheme resulted in mean ethanol concentrations (used as indicator variable) of 11.8 and 7.4 mg/m3 for the high and low exposure groups, respectively. The resolution was slightly less than for the original classification based on observations (15.0 and 7.1 mg/m3). Surprisingly, the self reported presence of any ventilation device resulted in more contrast in mean exposure concentration between the groups (17.4 and 7.5 mg/m3, respectively). Hairdressers reported validly on salon characteristics such as the type of salon, the number of hairdressers that worked in the salon, and the presence of ventilation devices, but could not make a distinction between different kinds of ventilation devices. The numbers of customers and tasks performed were largely overreported, but most variables correlated significantly with the information registered during the measurements. CONCLUSION: The self reported presence of any ventilation device is most predictive for the level of exposure to ethanol in the hairdressing salon. Questionnaire data on work characteristics should be treated with caution.

Air Pollutants, Occupational↗

Significance of the vaginal bacterial flora in the bitch: a review.

The literature on the bacterial flora in the vagina of the bitch is reviewed. The bacterial flora in the vagina of healthy bitches is compared with the flora of infertile bitches and bitches with vaginitis, and the role of Brucella canis as a cause of infertility is evaluated. Several investigators have recommended that bitches with reproductive disorders be treated with antibacterial drugs, but there is very little knowledge of the effect of this therapy on the bacterial flora in the vagina.

Animals↗

Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI.

Risk for cardiovascular disease due to atherosclerosis increases with increasing concentrations of low-density lipoprotein (LDL) cholesterol and is inversely proportional to the levels of high-density lipoprotein (HDL) cholesterol. The receptor-mediated control of plasma LDL levels has been well understood for over two decades and has been a focus for the pharmacologic treatment of hypercholesterolemia. In contrast, the first identification and characterization of a receptor that mediates cellular metabolism of HDL was only recently reported. This receptor, called scavenger receptor class B type I (SR-BI), is a fatty acylated glycoprotein that can cluster in caveolae-like domains on the surfaces of cultured cells. SR-BI mediates selective lipid uptake from HDL to cells. The mechanism of selective lipid uptake is fundamentally different from that of classic receptor-mediated endocytic uptake via coated pits and vesicles (e.g. the LDL receptor pathway) in that it involves efficient receptor-mediated transfer of the lipids, but not the outer shell proteins, from HDL to cells. In mice, SR-BI plays a key role in determining the levels of plasma HDL cholesterol and in mediating the regulated, selective delivery of HDL-cholesterol to steroidogenic tissues and the liver. Significant alterations in SR-BI expression can result in cardiovascular and reproductive disorders. SR-BI may play a similar role in humans; thus, modulation of its activity may provide the basis of future approaches to the treatment and prevention of atherosclerotic disease.

Animals↗

Mechanisms of abnormal puberty in coeliac disease.

Coeliac disease (CD) is one of the most frequent chronic diseases in childhood. The clinical spectrum has changed; in addition to the classical gastrointestinal form, other clinical manifestations have been described, such as hypogonadism and the consequent delay in onset of puberty. Recent studies reported not only a significantly retarded menarche in untreated CD girls as compared with girls following a gluten-free diet, but also in treated CD a negative effect on pregnancy, resulting in lower birth weight and shorter duration of pregnancy. In boys, there is a reduced serum level of dihydrotestosterone and an increased serum level of luteinizing hormone, an abnormality pattern suggesting androgen resistance. The pathogenesis of CD-related reproductive disorders is still unclear. Some hypotheses may be tried; for example, in CD there is a high level of autoantibodies directed against self-antigens, so there could be antibodies directed against hormones or organs critical for pubertal development. Moreover, in CD there could be a selective malabsorption of micronutrients essential for the metabolism of carrier or receptor proteins for sex hormones.

Autoantibodies↗

Effects of endotoxin on in vitro release of LHRH and amino acid neurotransmitters by preoptic mediobasal hypothalamic fragments.

Alterations in the immune system are often accompanied by reproductive disorders. The bacterial endotoxin lipopolysaccharide (LPS) has central inflammatory effects, and activates the release of cytokines (immune system mediatory factors) in the hypothalamus, where the LHRH neurons are located. Therefore, these studies were designed to investigate a possible effect of the LPS and LHRH secretion and the possible interaction with excitatory and inhibitory amino acids. Animals were decapitated at 09.00 h, and the preoptic mediobasal hypothalamic area (PO/MBH) dissected and superfused. Superfusate fractions were collected at 15-min intervals. After a stabilization superfusion period of 60 min four fractions were collected; LPS (100 ng/ml) was then added to the superfusion medium for the duration of 1 h. This was followed by a washout period of 60 min. The PO/MBH fragments were then subjected to a 56 mM K+ stimulus. Control PO/MBH fragments were continuously superfused with Earle's balanced salt solution. LHRH release was significantly (p < 0.05) reduced during and following exposure to LPS. At this time GABA and taurine concentrations increased in the superfusion medium, while glutamate decreased significantly compared with the control group. These observations indicate that LPS inhibits LHRH and glutamate release, but stimulates taurine and GABA secretion. These effects may be explained by the stimulation of cytokines of neuronal and/or glial source which may interact with the excitatory and inhibitory amino acids.

Animals↗

Intimate partner violence and physical health consequences: policy and practice implications.

Extensive research indicates that intimate partner violence (IPV) poses a significant risk to the physical health of women. IPV is associated with increased mortality, injury and disability, worse general health, chronic pain, substance abuse, reproductive disorders, and poorer pregnancy outcomes. IPV is also associated with an overuse of health services and unmet need for services, as well as strained relationships with providers. The body of IPV research has several critical gaps. There are almost no longitudinal studies of IPV and health. Most studies are clustered into a few specialties, with almost no research in the areas of allied health, dentistry, or management. A common definition of IPV is still not used. Finally, with some notable exceptions, there has been little success in moving the health care system to routinely screen women for IPV.

Battered Women↗

Evaluation of a porcine circovirus type 2-specific antigen-capture enzyme-linked immunosorbent assay for the diagnosis of postweaning multisystemic wasting syndrome in pigs: comparison with virus isolation, immunohistochemistry, and the polymerase chain reaction.

Quantitative virus isolation, immunohistochemistry, polymerase chain reaction (PCR) assay, and a porcine circovirus 2 (PCV2)-specific antigen-capture enzyme-linked immunosorbent assay (ELISA) were used for differentiation between clinical and subclinical PCV2 infections of swine. Tissue samples from pigs experimentally infected with PCV2 and field cases of postweaning multisystemic wasting syndrome and PCV2-associated reproductive disorders were used in this evaluation. In initial studies on 6 PCV2 pools using 3 previously published PCR protocols for PCV2 detection, quantitative virus isolation, and antigen-capture ELISA, substantial differences in sensitivity were identified among these procedures. Examination of tissue samples from diseased and clinically normal pigs indicated that immunohistochemistry, quantitative virus isolation, and antigen-capture ELISA could be used to differentiate between clinical and subclinical PCV2 infections, but the PCR assay could not. Because subclinical infections of pigs with PCV2 are common, the use of nonquantitative PCR as a diagnostic tool for PCV2-related diseases should be discouraged and the PCV2-specific antigen-capture ELISA evaluated further.

Animals↗

A sequential study of experimental porcine paramyxovirus (LPMV) infection of pigs: immunostaining of cryostat sections and virus isolation.

La Piedad Michoacan Paramyxovirus (LPMV) is a recently recognized paramyxovirus infecting pigs throughout Mexico. Disease syndromes observed in field cases associated with LPMV infection include neurologic, respiratory, and reproductive disorders. Clinical signs and the distribution of LPMV virus and antigen in tissue samples from pigs experimentally infected with LPMV by natural routes were studied. Severe neurologic disease and death occurred following experimental inoculation of 3- and 17-day-old pigs. All of the pigs inoculated at 3 days of age were either dead or moribund by 8 days after inoculation, whereas 30% of the pigs inoculated at 17 days of age were affected. Virus was consistently recovered from or demonstrated in tissues from the respiratory tract of both groups of pigs. LPMV and antigen were also demonstrated in central nervous system (CNS) tissues from these pigs; however, differences in virus distribution within the CNS were demonstrated in the 2 groups. In the pigs inoculated at 17 days of age, isolation of LPMV was restricted to the olfactory bulb and midbrain. In contrast, in the pigs inoculated at 3 days of age, isolation of LPMV was more widespread throughout the CNS tissue examined. Virus excretion studies indicated that nasal spread of LPMV was more important than fecal spread. Comparatively large quantities of infectious LPMV were consistently recovered from urine samples of experimentally infected pigs.

Animals↗

A comparative study on the use of virus and antibody detection techniques for the diagnosis of La Piedad Michoacan paramyxovirus (LPMV) infection in pigs.

La Piedad Michoacan paramyxovirus (LPMV) is newly recognized paramyxovirus that has been associated with neurologic and reproductive disorders in pigs in Mexico. To date, no comparative study of methods for the diagnosis of infection with this virus has been published. In this study, we identified tissues containing maximum virus load to optimize virus isolation procedures, and we compared this method to a rapid diagnostic test employing immunostaining of impression smears for LPMV antigens. In addition, several of the available tests for detecting LPMV antibodies were compared for their sensitivity in detecting seroconversion. Pigs used for the study of virus load in tissues and serologic studies were inoculated at 17 days of age with 10(7.00) TCID50 of LPMV. Serial blood samples were collected from selected pigs, and selected pigs were necropsied over a 14-day period. Pigs used in the investigation comparing standard virus isolation techniques to immunostaining of impression smears were inoculated at 3 days of age as described above and necropsied over an 8-day period. The results demonstrate that in the 17-day-old pigs maximum virus titers were detected in olfactory bulb at 5 days postinoculation (PI) and in midbrain at 9 days PI. In addition, the most consistent recovery of high titer virus was from tonsil (3-9 days PI) and olfactory bulb (4-9 days PI). Immunostaining of impression smears was as sensitive as virus isolation when selected tissues (lung, midbrain, olfactory bulb) were compared, with virus detected by both methods in 11/13 samples and in 1 sample each by immunostaining and virus isolation, respectively. All of the serology tests investigated detected seroconversion in pigs by 8 days PI. The identification of target organs where highest virus titers are found combined with immunofluorescent methods for the detection of LPMV antigens and a comparative study of the available serologic tests should facilitate the selection of techniques suitable for any laboratory to diagnose LPMV infection in pigs.

Animals↗

Plasma vitamin E and blood selenium concentrations in Norwegian dairy cows: regional differences and relations to feeding and health.

Plasma alpha-tocopherol (vit E) and blood selenium (Se) concentrations in February were determined in samples from 314 dairy cows in Norway, selected to provide a representative subset of the Norwegian dairy cow population. Each sample was followed by a questionnaire with information about feeding of the cow at the time of sampling. The results were correlated to herd data and to calving and health data for each cow from the Norwegian Dairy Herd Recording System and the Norwegian Cattle Health Recording System. The mean concentrations were 6.9 microg vit E per ml plasma and 0.16 microg Se per g blood. Both levels were highest in mid lactation. Plasma vit E varied with the amount of silage fed to the cow, while blood Se varied with the amount of concentrates and mineral supplements, and with geographical region. No differences in vit E or Se levels were found between cows with recorded treatments for mastitis, parturient paresis or reproductive disorders in the lactation during or immediately prior to sampling, and those without such treatments. For ketosis, a small difference in blood Se was found between the groups with or without recorded treatments. It is concluded that winter-fed lactating cows in Norway had an adequate plasma level of vit E and a marginal-to-adequate level of Se.

Animal Feed↗

Non-syndromic premature ovarian insufficiency associated with monoallelic LIG4 mutation via haploinsufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is a heterogeneous reproductive disorder, with genetic factors, particularly defects in DNA damage response pathways, increasingly implicated in its pathogenesis. DNA ligase IV (LIG4) is a key enzyme in the non-homologous end joining (NHEJ) pathway responsible for repairing DNA double-strand breaks (DSBs). However, its role in non-syndromic POI remains unclear. This study aimed to investigate the potential contribution of LIG4 variants to non-syndromic POI. RESULTS: Whole-exome sequencing identified a heterozygous frameshift variant in LIG4 (c.1271_1275del) in a three-generation Han Chinese family with non-syndromic POI, which co-segregated with affected individuals. AlphaFold-based structural modeling predicted truncation of the C-terminal XRCC4 interaction region. Functional experiments demonstrated that the mutant LIG4 protein showed reduced stability and was predominantly mislocalized to the cytoplasm of cells. In ovarian KGN cells, LIG4 depletion reduced cell viability, induced stress-associated cellular senescence, and impaired DNA damage repair capacity. In LIG4 knockout 293T cells, co-transfection of wild-type and mutant constructs revealed dose-dependent functional impairment, resulting in increased apoptosis under basal conditions and after phleomycin induced DNA damage, together with delayed repair of DSBs. Reanalysis of public single-cell RNA sequencing data further showed stage specific upregulation of LIG4 during oocyte maturation. Co-expression network analysis revealed enrichment in the Fanconi anemia pathway, phosphatidylinositol 3-kinase signaling pathway, and glycan metabolism. CONCLUSIONS: Our findings suggest that monoallelic LIG4 mutations may represent a potential genetic etiology for non-syndromic POI with sex-limited penetrance. While further validation in more physiologically relevant models is warranted, our data indicate that LIG4 haploinsufficiency may impair DSB repair and disrupt molecular pathways crucial for oocyte maturation and survival, highlighting a potential role of the NHEJ pathway in maintaining human ovarian function.

Humans↗

Local epidemiosurveillance in swine diseases in Northern Vietnam: description and preliminary results.

The REMAPORC is an epidemiosurveillance network in swine diseases and an organizational model for local veterinary services in one district of Northern Vietnam. A strong concern was done on quality of the sanitary information chain from field and feedback to local agents. Based on 4,000 declarations provided by veterinarians and animal health workers involved, preliminary results highlighted the major incidence of porcine respiratory disease complex; digestive affections in piglets, and reproductive disorders in newly raised exotic sows have been also noticed.

Animals↗

Bartonella infection in domestic cats and wild felids.

Bartonella are vector-borne, fastidious Gram-negative bacteria causing persistent bacteremia in their reservoir hosts. Felids represent a major reservoir for several Bartonella species. Domestic cats are the main reservoir of B. henselae, the agent of cat-scratch disease. Prevalence of infection is highest in warm and humid climates that are optimal for the survival of cat fleas, as fleas are essential for the transmission of the infection. Flea feces are the likely infectious substrate. Prevalence of B. henselae genotypes among cat populations varies worldwide. Genotype Houston I is more prevalent in the Far East and genotype Marseille is dominant in western Europe, Australia, and the western United States. Cats are usually asymptomatic, but uveitis, endocarditis, neurological signs, fever, necrotic lesions at the inoculation site, lymphadenopathy, and reproductive disorders have been reported in naturally or experimentally infected cats. Domestic cats are also the reservoir of B. clarridgeiae and co-infection has been demonstrated. B. koehlerae has been isolated from domestic cats, and was identified in cat fleas and associated with a human endocarditis case. B. bovis was isolated from a few cats in the United States and B. quintana DNA was recently identified in a cat tooth. Bartonella spp. have also been isolated from free-ranging and captive wild felids from North America and Africa. Whereas, B. henselae was identified in African lions and a cheetah, some strains specific to these wild cats have also been identified, leading to the concept of a B. henselae group including various subspecies, as previously described for B. vinsonii.

Animals↗

Estrogen receptor beta-mediated inhibition of male germ cell line development in mice by endogenous estrogens during perinatal life.

Epidemiological, clinical, and experimental studies have suggested that excessive exposure to estrogens during fetal/neonatal life can lead to reproductive disorders and sperm abnormalities in adulthood. However, it is unknown whether endogenous concentrations of estrogens affect the establishment of the male fetal germ cell lineage. We addressed this question by studying the testicular development of mice in which the estrogen receptor (ER) beta or the ERalpha gene was inactivated. The homozygous inactivation of ERbeta (ERbeta-/-) increased the number of gonocytes by 50% in 2- and 6-d-old neonates. The numbers of Sertoli and Leydig cells and the level of testicular testosterone production were unaffected, suggesting that estrogens act directly on the gonocytes. The increase in the number of gonocytes did not occur during fetal life but instead occurred just after birth, when gonocytes resumed mitosis and apoptosis. It seems to result from a decrease in the apoptosis rate evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method and cleaved caspase-3 immunohistochemical detection. Last, mice heterozygous for the ERbeta gene inactivation behaved similarly to their ERbeta-/- littermates in terms of the number of gonocytes, apoptosis, and mitosis, suggesting that these cells are highly sensitive to the binding of estrogens to ERbeta. ERalpha inactivation had no effect on the number of neonatal gonocytes and Sertoli cells. In conclusion, this study provides the first demonstration that endogenous estrogens can physiologically inhibit germ cell growth in the male. This finding may have important implications concerning the potential action of environmental estrogens.

Animals↗

Regulation of the follicle-stimulating hormone beta gene by the LHX3 LIM-homeodomain transcription factor.

FSH is a critical hormone regulator of gonadal function that is secreted from the pituitary gonadotrope cell. Human patients and animal models with mutations in the LHX3 LIM-homeodomain transcription factor gene exhibit complex endocrine diseases, including reproductive disorders with loss of FSH. We demonstrate that in both heterologous and pituitary gonadotrope cells, specific LHX3 isoforms activate the FSH beta-subunit promoter, but not the proximal LHbeta promoter. The related LHX4 mammalian transcription factor can also induce FSHbeta promoter transcription, but the homologous Drosophila protein LIM3 cannot. The actions of LHX3 are specifically blocked by a dominant negative LHX3 protein containing a Kruppel-associated box domain. Six LHX3-binding sites were characterized within the FSHbeta promoter, including three within a proximal region that also mediates gene regulation by other transcription factors and activin. Mutations of the proximal binding sites demonstrate their importance for LHX3 induction of the FSHbeta promoter and basal promoter activity in gonadotrope cells. Using quantitative methods, we show that the responses of the FSHbeta promoter to activin do not require induction of the LHX3 gene. By comparative genomics using the human FSHbeta promoter, we demonstrate structural and functional conservation of promoter induction by LHX3. We conclude that the LHX3 LIM homeodomain transcription factor is involved in activation of the FSH beta-subunit gene in the pituitary gonadotrope cell.

Activins↗

Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902.

Suppression of the hypothalamic-pituitary-gonadal axis by peptides that act at the GnRH receptor has found widespread use in clinical practice for the management of sex-steroid-dependent diseases (such as prostate cancer and endometriosis) and reproductive disorders. Efforts to develop orally available GnRH receptor antagonists have led to the discovery of a novel, potent nonpeptide antagonist, NBI-42902, that suppresses serum LH concentrations in postmenopausal women after oral administration. Here we report the in vitro and in vivo pharmacological characterization of this compound. NBI-42902 is a potent inhibitor of peptide radioligand binding to the human GnRH receptor (K(i) = 0.56 nm). Tritiated NBI-42902 binds with high affinity (K(d) = 0.19 nm) to a single class of binding sites and can be displaced by a range of peptide and nonpeptide GnRH receptor ligands. In vitro experiments demonstrate that NBI-42902 is a potent functional, competitive antagonist of GnRH stimulated IP accumulation, Ca(2+) flux, and ERK1/2 activation. It did not stimulate histamine release from rat peritoneal mast cells. Finally, it is effective in lowering serum LH in castrated male macaques after oral administration. Overall, these data provide a benchmark of pharmacological characteristics required for a nonpeptide GnRH antagonist to effectively suppress gonadotropins in humans and suggest that NBI-42902 may have clinical utility as an oral agent for suppression of the hypothalamic-pituitary-gonadal axis.

Administration, Oral↗