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Vitamin D3 (25-hydroxyvitamin D3 (VD)) and vitamin E (VE) have proven to have immunomodulatory and antioxidant functions along with capacities to improve the reproductive function in chickens. Coccidiosis in laying hens at different stages of growth has been shown to negatively affect performance, immune response, and oxidative status, thus increasing the cost of production. A study was conducted to evaluate the influence of dietary VD or VE on performance, gut health, immune response, and oxidative status of laying hens at peak production. Laying hens (23 wk-of-age, n = 225) were randomly allocated into 5 treatment groups (n = 9 hens/replicate) with 5 replicate groups each: 1) unchallenged control (UC), 2) pair-fed control (PF), 3) challenged control (CC), 4) challenged control top-dressed with 5,000 IU of 25-hydroxyvitamin D3 (VD) per kg of diet, and 5) challenged control top-dressed with 100 IU of DL-α-tocopherol (VE). At 25 wk-of-age, hens grouped in CC, VD, and VE were challenged with mixed Eimeria spp. to induce coccidiosis. VD or VE supplemented hens did not impact bird body weight; however, egg production increased by 10.36% and 13.77%, respectively (P < 0.0001). Furthermore, the gut health of the hens was improved with either VD or VE supplementation, as indicated by lowered gut permeability and intestinal lesion scores (P < 0.05). VE significantly reduced the heterophil count (P = 0.0490) alongside numerically increasing the peripheral CD4+ and CD8+ T cells and monocyte counts (P > 0.05). Both VD or VE increased the TAC at 14 DPI compared to UC (P<0.05). Preliminary findings suggest that dietary VD or VE supplementation has the potential to improve gut health, modulate the immune response, and increase egg production in coccidiosis-infected laying hens.
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Alimentación Animal , Calcifediol , Pollos , Coccidiosis , Dieta , Suplementos Dietéticos , Enfermedades de las Aves de Corral , Vitamina E , Animales , Pollos/inmunología , Pollos/fisiología , Coccidiosis/veterinaria , Coccidiosis/parasitología , Coccidiosis/inmunología , Femenino , Alimentación Animal/análisis , Dieta/veterinaria , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/inmunología , Suplementos Dietéticos/análisis , Calcifediol/administración & dosificación , Calcifediol/farmacología , Vitamina E/administración & dosificación , Vitamina E/farmacología , Distribución Aleatoria , Eimeria/fisiología , Vitaminas/administración & dosificación , Vitaminas/farmacología , Estrés Oxidativo/efectos de los fármacosRESUMEN
Injuries of the sternum and humerus are an important welfare concern in domestic chickens (Gallus domesticus), especially laying hens. Published anatomic references using standardized terminology from the Nomina Anatomica Avium (NAA) are lacking. Objectives of the current retrospective, descriptive study were to provide a user-friendly hierarchical table of NAA-compliant anatomic terms and labeled images illustrating anatomic structures for the sternum and humerus of domestic chickens. Three-dimensional model images were downloaded from a publicly accessible platform, labeled in consultation with a veterinary anatomist, and enhanced by a medical illustrator. Findings can serve as a resource for future clinical and research applications.
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Crianza de Animales Domésticos , Pollos , Animales , Femenino , Pollos/lesiones , Estudios Retrospectivos , Crianza de Animales Domésticos/métodos , Esternón/lesiones , Húmero/diagnóstico por imagenRESUMEN
Working dogs are widely used by service professionals and the military for diverse roles that include sentry, patrol, messenger, tracking, search and rescue, law enforcement, apprehension, as well as explosives and narcotics detection. The expected tasks performed are in many ways determined by the breed, which is customarily a German Shepherd, Dutch Shepherd, Golden Retriever, Border Collie, Labrador Retriever, Beagle, or Belgium Malinois. Working dogs may be subject to injury from dangerous work environments or harmful agent exposure. Personal protective equipment (PPE) has been developed for such dogs, but may impede performance of duties or be poorly tolerated. Canine-specific field-use ready decontamination techniques and kits are therefore needed for use on working dogs that have encountered a harmful agent exposure. This report briefly reviews the development of the military working dog and examines personal protective equipment and decontamination techniques for working dogs after exposure to harmful biologic or chemical agents.
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Student application packages for admission to the University of Georgia College of Veterinary Medicine currently include the following information: undergraduate grade point average (GPA), GPA in science courses, GPA in non-science courses, GPA for the last 45 hours (GPALast45hrs), Graduate Record Examination Quantitative and Verbal Reasoning (GRE-QV) score, GRE Analytical Writing (GRE-AW) score, and grades for 10 required prerequisite courses. From these data, an academics score of up to 70 points is calculated. Faculty reviewers also score each applicant up to a maximum of 30 points (FileScore), giving a total possible score of 100 points. Previous analyses demonstrated that the file score and academic variables are significantly related to first-year GPA of veterinary students; however, it is unknown how these variables relate to performance in clinical rotations. The present study pooled the two most recent graduating classes to compare each academic score component to student clinical rotation grades received during year 4 (CGrYr4) in the teaching hospital. Only one component of the student application packages-the pre-admission GRE-QV score-significantly correlated with CGrYr4.
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Educación en Veterinaria , Animales , Universidades , ComunicaciónRESUMEN
Rabbits have been a popular pet and research species world-wide. In many clinical and research situations, controlling inflammation is necessary for the health of these animals. One of the first drugs commonly employed in veterinary medicine to suppress inflammatory responses is corticosteroids. Unfortunately, steroid use in rabbits is not universally accepted as they are perceived, based on their potent immunosuppressant activity, to negatively impact quality of life. This is may be due, in part, to the lack of well-developed dosing protocols in these animals. This study evaluated the impact of a 5-day IM dexamethasone (Dex, 0.5 mg/kg) protocol on the immunity and clinical health of the New Zealand rabbit. Through two experiments separated by a 10-day washout period, experiment 1 comprised 5-days of dosing with bleedings on day 0, 3, 5 and 7, where experiment 2 consisted of 5-days of dosing with bleedings on day 0, 3 and 5. Animals were monitored twice daily for changes in clinical health. Hematology, T cell subset phenotype, leukocyte cell cycle, histopathology, phagocytosis and oxidative formation were evaluated. Consistent with other species, 5-day dosing with Dex suppressed leukocytes, in particular the T cells (p ≤ 0.003). Interestingly, rabbits failed to show any adverse clinical signs throughout the entire study. This would imply that a 5-day IM Dex (0.5 mg/kg) dosing protocol is well tolerated by New Zealand white rabbits and could be used in rabbits suffering from inflammatory conditions or disease as long as the animal's immune status is closely monitored.
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Antiinflamatorios/efectos adversos , Dexametasona/efectos adversos , Conejos/fisiología , Animales , FemeninoRESUMEN
Student applications for admission to the University of Georgia College of Veterinary Medicine include the following information: undergraduate grade point average (GPA), GPA in science courses (GPAScience), GPA for the last 45 credit hours (GPALast45hrs), results for the Graduate Record Examination Quantitative and Verbal Reasoning Measures (GRE-QV), results for the GRE Analytical Writing Measure (GRE-AW), and grades received for 10 required prerequisite courses. In addition, three faculty members independently review and score subjective information in applicants' files (FileScore). The admissions committee determines a composite Admission Score (AdmScore), which is based on GPA, GPAScience, GPALast45hrs, GRE-QV, GRE-AW, and the FileScore. The AdmScore is generally perceived to be a good predictor of class rank at the end of year 1 (CREY1). However, this has not been verified, nor has it been determined which components of the AdmScore have the strongest correlation with CREY1. The present study therefore compared each component of the AdmScore for correlation with CREY1, for the three classes admitted in 2015, 2016 and 2017 (Class15, Class16, Class17). Results suggest that only a few components of the application file are needed to make strong predictive statements about the academic success of veterinary students during the first year of the curriculum.
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Spatial visualization ability is defined as the ability to mentally rotate two- and three-dimensional figures. Visual reasoning is the ability to manipulate mental images of an object to reach a certain conclusion and has been linked to spatial ability. There is currently limited information about how entry-level spatial and visual reasoning abilities may be enhanced with progression through the rigorous veterinary medical curriculum. The present study made use of two tests that measure spatial ability and one test that measures non-verbal general reasoning ability in female veterinary students: Guay's Visualization of Views Test, Adapted Version (VVT), Mental Rotations Test (MRT), and Raven's Advanced Progressive Matrices Test, short form (APMT). Tests were given immediately before commencing the integrated veterinary medical curriculum (T0), at week 32 (T1), and at week 64 (T2) into the program. Results showed improved spatial visualization ability as measured by VVT and MRT and improved non-verbal general reasoning ability as measured by APMT at both 32 and 64 weeks. The spatial ability scores measured by VVT and MRT showed a positive correlation with non-verbal general reasoning ability scores (APMT), supporting the idea that these abilities are linked.
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There is currently limited available information, but growing interest, in possible relationships between spatial visualization skills in medical students and their academic performance in select areas of the curriculum such as radiographic interpretation and anatomy. There is very limited comparable information on how entry-level spatial visualization skills may correlate with macroscopic anatomy performance in veterinary medical students exposed to an integrated curriculum. The present study made use of a battery of two short tests that measure spatial ability: Guay's visualization of views test (VVT) and mental rotation test (MRT) and, one test that measures general non-verbal reasoning abilities: Raven's Advanced Progressive Matrices Test, short form (APMT). Tests were given to 1st-year veterinary medical students (n = 124) immediately before commencing the integrated veterinary medical curriculum. Results show there is a positive correlation between entry-level spatial ability and non-verbal general reasoning scores confirming these abilities are linked (r: +0.22 and +0.3 for VVT/APMT and MRT/APMT respectively). The dispersion and inconsistency of significant positive correlation between anatomy practical exams grade and spatial and general reasoning scores suggest these abilities either do not correlate with anatomy practical exams grade or, are overcome with progression through the anatomy courses. Males scored higher than females in the spatial ability tests: 16.59 vs. 12.06 for VVT (p = 0.01) and 19.0 vs. 14.68 for MRT (p = 0.01). Scores for APMT did not show a significant difference by gender.
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Lead is a persistent inorganic environmental pollutant that affects humans and animals worldwide. Avian species are especially susceptible to lead exposure through consumption of lead ammunition, lead fishing tackle, and other contaminated food sources such as aquatic species ingesting lead contaminated sediments in mining areas. Even with government regulations on the use of lead ammunition in many countries, including the United States, terrestrial, aquatic, predatory, and scavenger avian species are still at risk of exposure to potentially lethal concentrations of lead. The toxicities seen in these avian species include increased oxidative stress and decreased anti-oxidant enzymes in hepatic and renal tissue. The avian immune system is also a target of lead and displays a number of altered functions suggestive of immune suppression; however, studies in wildlife and laboratory species remain too limited for definitive statements with regard to population risk. In contrast, lead clearly inhibits reproductive capabilities in adult birds, and alters growth and development of hatchlings. Environmental remediation for lead removal, which would lower toxic exposure in wildlife, presently is a monumental and prohibitively expensive effort. Wildlife exposure will therefore continue in contaminated areas, necessitating development of new remediation practices. These plans should aim toward limiting more widespread or heavier contamination of wildlife habitats. This chapter reviews presently available information of lead toxicity in wild bird species, and suggests continued monitoring and reduction strategies to reduce lead exposure for at-risk avian populations.
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Animales Salvajes/metabolismo , Aves/metabolismo , Contaminantes Ambientales/toxicidad , Plomo/toxicidad , Animales , Monitoreo del Ambiente , Contaminantes Ambientales/metabolismo , Armas de Fuego , Plomo/metabolismo , Especificidad de Órganos , Reproducción/efectos de los fármacos , Distribución TisularRESUMEN
Many aquatic and terrestrial avian species inadvertently ingest lead (Pb) in the form of spent or fragmented ammunition, mistaking it for food or grit. Previous studies in our laboratory have shown that ingestion of even a single 45-mg pellet can significantly increase blood-Pb levels and significantly inhibit the enzyme delta aminolevulinic-acid dehydratase (δ-ALAD) for a period of greater than 4 weeks. In the current study, proven breeder pairs of domestic Roller pigeons were housed in individual cages. The hens were orally gavaged with dH2O vehicle, a single #9 Pb pellet (2.0 mm/45 mg) or a single #7.5 Pb pellet (2.3 mm/95 mg), placed back with the cock bird and allowed to mate for two consecutive clutches. The eggs were monitored for fertilization, shell damage, egg weight, and length during the 16- to 18-day incubation period. Hatchlings remained with the hen and cock through the weaning period (28-35 days post hatch) and were monitored for weight, development, and mortality. Weanling blood was collected for blood-Pb levels, δ-ALAD activity, red blood cell counts, total protein, and packed cell volume. Following euthanasia, weanling liver, spleen, kidney, sciatic nerve, thymus, and brain were collected for histopathology. Egg weight and length were significantly decreased in the #7.5 Pb pellet treatment group for the first clutch, and hatchling weight 7 days post hatch also was significantly less in the #7.5 Pb pellet treatment group during the first clutch. Histopathologic analysis showed increased lesions in liver, kidney, spleen, and thymus of the Pb-treated weanlings, during both the first and second clutch compared with the non-Pb-treated weanlings. These data suggest that maternal consumption of a single 95-mg Pb pellet can adversely impact egg size and hatchling organ development.
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Columbidae/fisiología , Sustancias Peligrosas/toxicidad , Plomo/toxicidad , Óvulo/fisiología , Animales , FemeninoRESUMEN
Spatial visualization ability refers to the human cognitive ability to form, retrieve, and manipulate mental models of spatial nature. Visual reasoning ability has been linked to spatial ability. There is currently limited information about how entry-level spatial and visual reasoning abilities may predict veterinary anatomy performance or may be enhanced with progression through the veterinary anatomy content in an integrated curriculum. The present study made use of two tests that measure spatial ability and one test that measures visual reasoning ability in veterinary students: Guay's Visualization of Views Test, adapted version (GVVT), the Mental Rotations Test (MRT), and Raven's Advanced Progressive Matrices Test, short form (RavenT). The tests were given to the entering class of veterinary students during their orientation week and at week 32 in the veterinary medical curriculum. Mean score on the MRT significantly increased from 15.2 to 20.1, and on the RavenT significantly increased from 7.5 to 8.8. When females only were evaluated, results were similar to the total class outcome; however, all three tests showed significant increases in mean scores. A positive correlation between the pre- and post-test scores was found for all three tests. The present results should be considered preliminary at best for associating anatomic learning in an integrated curriculum with spatial and visual reasoning abilities. Other components of the curriculum, for instance histology or physiology, could also influence the improved spatial visualization and visual reasoning test scores at week 32.
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Educación en Veterinaria/métodos , Solución de Problemas , Percepción Espacial , Estudiantes de Medicina/psicología , Percepción Visual , Curriculum , Femenino , Humanos , Masculino , Evaluación de Programas y Proyectos de SaludRESUMEN
A German shepherd puppy presented for evaluation of a suspected arteriovenous fistula on the distal aspect of the right pelvic limb. Radiographs demonstrated expansion and resorption of the tarsal and metatarsal bones, and ultrasound detected a vascular abnormality. Using computed tomographic angiography, a complex arteriovenous malformation (AVM) involving the distal tibia, tarsus, and the metatarsus and an osteochondritis dissecans (OCD) lesion of the talus were identified. Based on these findings, therapeutic limb amputation was performed. Fluoroscopic angiography, vascular casting, and dissection were then used to further characterize features of this previously unreported AVM with concurrent bony lesions and OCD.
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Malformaciones Arteriovenosas/veterinaria , Perros/anomalías , Miembro Posterior/anomalías , Animales , Malformaciones Arteriovenosas/diagnóstico por imagen , Femenino , Fluoroscopía/veterinaria , Miembro Posterior/diagnóstico por imagen , Osteocondritis Disecante/diagnóstico por imagen , Osteocondritis Disecante/veterinaria , Huesos Tarsianos/diagnóstico por imagen , Huesos Tarsianos/patología , Tibia/diagnóstico por imagen , Tibia/patología , Tomografía por Rayos X/veterinariaRESUMEN
Crocodilians are important keystone species and indicators of environmental health. Much remains unknown, however regarding utility of field-collected crocodilian blood samples for ecologic assessments. Field sampling sites are also often distant to analysis centers, necessitating development of new techniques and panels of assays that will yield environmentally relevant data. Stability and viability of hematological and immunological indices have been of particular interest for linking ecosystem health to biomarkers in resident species. In this study, we investigated the effect of time at analysis post-blood sampling at 4 and 24 hr on a panel of potential biomarkers in alligator blood. Our results suggest alligator blood samples can be reliably evaluated for both hematologic and immunologic profile 24 hr after sampling.
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Caimanes y Cocodrilos/sangre , Caimanes y Cocodrilos/inmunología , Biomarcadores/sangre , Manejo de Especímenes , AnimalesRESUMEN
Estrogen has potent immunomodulatory effects on proinflammatory responses, which can be mediated by serine proteases. We now demonstrate that estrogen increased the extracellular expression and IL-12-induced activity of a critical member of serine protease family Granzyme A, which has been shown to possess a novel inflammatory persona. The inhibition of serine protease activity with inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride significantly diminished enhanced production of proinflammatory interferon-γ, IL-1ß, IL-1α, and Granzyme A activity even in the presence of a Th1-inducing cytokine, IL-12 from splenocytes from in vivo estrogen-treated mice. Inhibition of serine protease activity selectively promoted secretion of Th2-specific IL-4, nuclear phosphorylated STAT6A, signal transducer and activator of transcription (STAT)6A translocation, and STAT6A DNA binding in IL-12-stimulated splenocytes from estrogen-treated mice. Inhibition with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride reversed the down-regulation of Th2 transcription factors, GATA3 and c-Maf in splenocytes from estrogen-exposed mice. Although serine protease inactivation enhanced the expression of Th2-polarizing factors, it did not reverse estrogen-modulated decrease of phosphorylated STAT5, a key factor in Th2 development. Collectively, data suggest that serine protease inactivity augments the skew toward a Th2-like profile while down-regulating IL-12-induced proinflammatory Th1 biomolecules upon in vivo estrogen exposure, which implies serine proteases as potential regulators of inflammation. Thus, these studies may provide a potential mechanism underlying the immunomodulatory effect of estrogen and insight into new therapeutic strategies for proinflammatory and female-predominant autoimmune diseases.
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Estrógenos/fisiología , Granzimas/fisiología , Mediadores de Inflamación/fisiología , Interleucina-12/fisiología , Inhibidores de Serina Proteinasa/farmacología , Células Th2/metabolismo , Animales , Citocinas/metabolismo , Femenino , Factor de Transcripción GATA3/metabolismo , Granzimas/metabolismo , Interleucina-4/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-maf/metabolismo , Factor de Transcripción STAT5/metabolismo , Factor de Transcripción STAT6/metabolismo , Sulfonas/farmacología , Células Th2/enzimología , Regulación hacia Arriba/fisiologíaRESUMEN
Parabens, alkyl esters of p-hydroxybenzoic acid, are widely used in cosmetics, pharmaceuticals, personal care products and as food additives to inhibit microbial growth and extend product shelf life. Consumers of these compounds are frequently exposed via the skin, lips, eyes, oral mucosa, nails, and hair. Parabens are estrogenic molecules but exert weaker activity than natural estrogens, which would imply a low risk. Consistent with this idea, a number of recent commission reports from different countries suggested that parabens pose a negligible endocrine-disrupting risk at the recommended doses. However, individuals are not routinely exposed to a single paraben, and most of the available paraben toxicity data, reviewed in these reports, are from single-exposure studies. Further, assessing the additive and cumulative risk of multiple paraben exposure from daily use of multiple cosmetic and/or personal care products is presently not possible based on current studies. In this review, current and recent studies of paraben exposure and public health policies as well as critical gaps in the knowledge are discussed and new research directions regarding multiple exposures and novel target cohorts are recommended.
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Parabenos/toxicidad , Receptores de Estrógenos/efectos de los fármacos , Adulto , Cosméticos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Desarrollo Fetal/efectos de los fármacos , Humanos , Masculino , Neoplasias/inducido químicamente , Embarazo , Conservadores Farmacéuticos/toxicidadRESUMEN
Avian wildlife species commonly ingest lead (Pb) spent shot or bullet fragments as grit or mistakenly as food. In previous studies in our laboratory and others, the toxicity varied based on the diet as well as type and quantity of Pb ingested. In the current study, domestic pigeons were gavaged with 1, 2, or 3 Pb pellets and then followed with weekly radiographs and blood physiologic endpoints for 28 days. Pellet retention decreased by roughly 50 % per week as pellets were either absorbed or excreted, except for week 4 where pellet number no longer was diminished. Size of retained pellets visually decreased over retention time. Birds dosed with a single #9 pellet showed mean blood Pb levels over 80 times higher than those of the controls, verifying Pb pellet absorption from the gut. A single Pb pellet also reduced plasma δ-aminolevulinic acid dehydratase (δ-ALAD) activity by over 80 % compared to controls, suggesting the potential for population injury in Pb pellet-exposed pigeons.
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Columbidae/metabolismo , Contaminantes Ambientales/toxicidad , Plomo/toxicidad , Porfobilinógeno Sintasa/metabolismo , Animales , Columbidae/sangre , Contaminantes Ambientales/sangre , Contaminantes Ambientales/farmacocinética , Femenino , Plomo/sangre , Plomo/farmacocinética , Masculino , Distribución AleatoriaRESUMEN
Two immunologically different mouse strains, C57BL/6 and SNF(1), were exposed to a mid-gestation dose of TCDD. The C57BL/6 mouse has a high-affinity aryl hydrocarbon receptor (AhR) and is sensitive to TCDD. The SNF(1) mouse has a low-affinity AhR but spontaneously develops autoimmune nephritis. Autoreactive Vß(+)CD4(+)17a and Vß(+)CD3(+) T cells were increased at 24-weeks-of-age in offspring of C57BL/6 mice, more so in females than males. The cytokine IFN-γ was elevated in the females, while IL-10 was elevated in males. Phenotypic changes in B-lineage cells were present in bone marrow and spleen, and circulating autoantibodies were increased after prenatal TCDD. Kidneys of males showed significant anti-IgG and anti-C3 deposition, suggesting early-stage autoimmune disease. The SNF(1) offspring similarly showed increased peripheral Vß(+) cells in the females, increased autoantibody production in both sexes, and increased IFN-γ production in females. Male SNF(1) mice had increased anti-IgG and anti-C3 deposition in kidneys. Both mouse models therefore showed clear signatures of enhanced autoimmunity after prenatal TCDD.
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Enfermedades Autoinmunes/inducido químicamente , Contaminantes Ambientales/toxicidad , Exposición Materna/efectos adversos , Nefritis Intersticial/inducido químicamente , Dibenzodioxinas Policloradas/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Femenino , Antígenos de Histocompatibilidad Clase II/inmunología , Interferón gamma/sangre , Interleucina-10/sangre , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/patología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Nefritis Intersticial/inmunología , Nefritis Intersticial/patología , Embarazo , Factores Sexuales , Bazo/efectos de los fármacos , Bazo/metabolismo , Bazo/patología , Linfocitos T/inmunología , Linfocitos T/patología , Timo/efectos de los fármacos , Timo/metabolismoRESUMEN
Pregnant mice (n = 3) were exposed to BPA by intraperitoneal injection, from gestation day 9.5 until end of lactation. Male offspring were evaluated for cytokine production at 20 wk-of-age. One pregnant control mouse produced no males, precluding statistical analysis. However, recurring shifts in cytokines were suggested in the adult BPA offspring. Serum showed a numeric increase in 16 of 21 basal cytokine levels. ConA-stimulated splenocytes showed a numeric increase in 17 of 21 cytokines, and LPS-stimulated splenocytes an increase in 18 of 21 cytokines. The cytokine profile was one of T(H)1 up-regulation more than T(H)2, and with skewing toward T(H)17 responses.
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Citocinas/sangre , Estrógenos no Esteroides/toxicidad , Linfocitos/metabolismo , Fenoles/toxicidad , Efectos Tardíos de la Exposición Prenatal , Animales , Compuestos de Bencidrilo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Mitógenos , EmbarazoRESUMEN
INTRODUCTION: Pregnancy may be complicated by maternal diabetes. The following experiments were performed in an attempt to produce mouse models of insulin-resistant maternal diabetes. METHODS: CD1 females received 200 mg/kg streptozocin (STZ) to model insulin-dependent diabetes (T1 group). Another group of females (T2 group) was put on a HFD 4 weeks before receiving 100 mg/kg STZ. After 4 additional weeks of HFD, hyperglycemic females were separated and bred. In another experiement, CD1 females were fed a HFD for 4 weeks before receiving an intravenous (GDM1 group) or intraperitoneal (GDM2 group) injection of 100 mg/kg STZ. Females from GDM2 group were bred at the same day of the STZ injection. Females from GDM1 group were bred 4 weeks after the STZ injection. RESULTS AND CONCLUSION: About 25% of the females from T2 group became hyperglycemic after 4 weeks of the injection of STZ. Fifty percent of the females from GDM1 group reached hyperglycemic levels greater than 250 mg/dl during pregnancy. The combination of HFD and moderate STZ in CD1 mice therefore produced hyperglycemic females; however numbers of these mice were somewhat low.
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Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Grasas de la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Embarazo en Diabéticas/metabolismo , Estreptozocina/administración & dosificación , Animales , Glucemia/metabolismo , Peso Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Diabetes Gestacional/sangre , Diabetes Gestacional/etiología , Femenino , Insulina/sangre , Ratones , Embarazo , Embarazo en Diabéticas/sangre , Embarazo en Diabéticas/etiologíaRESUMEN
BACKGROUND: Previous work in our laboratory showed reduced myocardium and dilated ventricular chambers in gestation day (GD) 17 hearts that were collected from hyperglycemic CD1 mouse dams. Pre-breeding maternal immune stimulation, using Freund's complete adjuvant (FCA), diminished the severity of these fetal heart lesions. The following experiments were performed to detect possible changes in fetal heart apoptotic cell death, under hyperglycemic conditions and with or without maternal immune stimulation. METHODS: Female CD1 mice were injected with 200 mg/kg of streptozocin (STZ) to induce insulin-dependent diabetes mellitus. Half of these mice received prior FCA injection. Fetal hearts were collected on GD 17 and myocardial apoptotic cells were quantified using flow cytometry. A panel of apoptosis regulatory genes (Bcl2, p53, Casp3, Casp9, PkCe) was then examined in the fetal myocardium using RT-PCR. RESULTS: Early apoptotic cells and late apoptotic/necrotic cells were significantly increased in fetal hearts from STZ or STZ+FCA dams. Pre-treatment with FCA reduced late apoptotic/necrotic cells to control level, suggesting some cell death protection was rendered by FCA. Paradoxically in the face of such increased cell death, the expression of pro-apoptotic genes Casp3 and Casp9 was decreased by diabetes, while the anti-apoptotic gene Bcl2 was increased. CONCLUSIONS: Maternal hyperglycemia causes dys-regulated apoptosis of fetal myocardial cells. Such effect may be prevented by maternal immune stimulation.