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1.
Domest Anim Endocrinol ; 72: 106476, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32380311

RESUMEN

Age, neurodegenerative disorders, and dysfunction of insulin secretion may be correlated with increased systemic concentrations of acute phase markers. Thus, the study aimed to determine the effect of age, pituitary pars intermedia dysfunction (PPID), and insulin dysregulation (ID) associated with PPID, on markers of the acute phase reaction. Twenty-nine mix-breed horses of both sexes were classified into groups: (1) healthy adult controls, (2) healthy non-PPID geriatric horses, (3) PPID ID+ horses, and (4) PPID ID- horses. Whole blood proinflammatory cytokine gene expression and serum concentrations of pro- and anti-inflammatory cytokines and acute phase proteins were measured. The data were analyzed using the Mann-Whitney U-test, and correlations between groups of data were assessed using Spearman's correlation coefficient. The tests were statistically significant if P < 0.05. No differences in the whole blood cytokine gene expression, serum cytokine concentrations, or acute phase proteins were noted between the groups. In the PPID ID group, there was a strong correlation between the ACTH concentration after the administration of thyrotropin-releasing hormone and the expression of IL-8 (r = 0.941; P = 0.0321). In the PPID ID+ group, there was a strong correlation between basal insulin concentrations and serum amyloid A (SAA; r = 0.936; P = 0.0083) as well as between postprandial insulin concentrations and SAA (r = 0.965; P = 0.001). These data suggest that neurodegeneration in horses moderately affects circulating markers of inflammation and that ID in horses with PPID influences acute phase inflammatory markers.


Asunto(s)
Reacción de Fase Aguda/veterinaria , Envejecimiento , Enfermedades de los Caballos/metabolismo , Enfermedades de la Hipófisis/veterinaria , Adenohipófisis Porción Intermedia/patología , Reacción de Fase Aguda/metabolismo , Animales , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica , Enfermedades de los Caballos/sangre , Caballos , Inflamación/sangre , Inflamación/metabolismo , Inflamación/veterinaria , Masculino , Enfermedades de la Hipófisis/metabolismo , Adenohipófisis Porción Intermedia/metabolismo
2.
Domest Anim Endocrinol ; 72: 106448, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32247989

RESUMEN

Obesity and metabolic disorders are associated with systemic low-grade chronic inflammation, both in humans and animals. The aim of the study is to assess the effects of obesity and hyperinsulinemia on individual components of the acute-phase reaction in equine metabolic syndrome (EMS) horses. Eight mixed-breed EMS and six control, age-matched horses of both sexes were included in the study. Animals were classified as EMS or control based on the assessment of BCS, cresty neck score, and basal insulin >50 µU/mL and/or insulin responses to the oral sugar test (OST) >60 µU/mL. Peripheral venous blood was collected. The expression of proinflammatory cytokines, the concentration of circulating cytokines, and acute-phase proteins (serum amyloid A, C-reactive protein, haptoglobin, activin A, and procalcitonin) were measured. The data were analyzed using the Mann-Whitney test, whereas correlations were examined using Spearman's correlation coefficient. The tests were statistically significant if P ≤ 0.05. There were no differences in cytokine gene expression, circulating cytokine concentrations, or concentrations of acute-phase proteins between the EMS and the control groups. There was a strong correlation between the basal concentration of insulin and the serum concentrations of IL-6 (r = 0.71, P < 0.05). Activin A was positively correlated with post-OST insulin concentrations (r = 0.707, P = 0.05), indicating that this marker of inflammation could warrant further investigation in horses with EMS.


Asunto(s)
Proteínas de Fase Aguda/metabolismo , Enfermedades de los Caballos/metabolismo , Inflamación/veterinaria , Síndrome Metabólico/veterinaria , Proteínas de Fase Aguda/genética , Tejido Adiposo/metabolismo , Animales , Biomarcadores/sangre , Estudios de Casos y Controles , Citocinas/genética , Citocinas/metabolismo , Femenino , Enfermedades de los Caballos/sangre , Caballos , Inflamación/metabolismo , Insulina/metabolismo , Masculino , Síndrome Metabólico/metabolismo
3.
J Anim Sci ; 95(3): 1071-1079, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28380523

RESUMEN

Equine obesity can cause life-threatening secondary chronic conditions, similar to those in humans and other animal species. Equine metabolic syndrome (EMS), primarily characterized by hyperinsulinemia, is often present in obese horses and ponies. Due to clinical similarities to conditions such as pituitary pars intermedia dysfunction (formerly equine Cushing's disease), conclusive diagnosis of EMS often proves challenging. Aside from changes in diet and exercise, few targeted treatments are available for EMS, emphasizing the need for early identification of at-risk individuals to enable implementation of preventative measures. A genomewide association study (GWAS) using Arabian horses with a history of severe laminitis secondary to EMS revealed significant genetic markers near a single candidate gene () that may play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T > C), was correlated with elevated insulin values and increased frequency of laminitis ( = 0.0024 and = 9.663 × 10, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values ( = 0.0056) and BCS ( = 0.0063). Screening of the predicted coding regions by sequencing identified a polymorphic guanine homopolymer and 5 haplotypes in the 3' untranslated region (UTR). An 11 guanine (11-G) allele at was correlated with elevated insulin values in the GWAS population ( = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 ( = 0.0055 and = 0.0162, respectively). The BIEC2-263524-C and the 3' UTR -11(G) polymorphisms were correlated at a 98% frequency, indicating strong linkage disequilibrium across this 150-kb haplotype. Assays for these markers could diagnose horses with a genetic predisposition to develop obesity. Additionally, discovery of FAM174A function may improve our understanding of the etiology of this troubling illness in the horse and warrants investigation of this locus for a role in metabolic- and obesity-related disorders of other species.


Asunto(s)
Estudio de Asociación del Genoma Completo , Enfermedades de los Caballos/genética , Síndrome Metabólico/veterinaria , Obesidad/veterinaria , Animales , Predisposición Genética a la Enfermedad , Caballos , Síndrome Metabólico/genética , Síndrome Metabólico/metabolismo , Obesidad/genética
4.
Domest Anim Endocrinol ; 60: 1-8, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28254632

RESUMEN

Extracts derived from the leaves of the stevia plant (stevioside) are commonly used as sweeteners for humans and horses. Stevioside appears to be safe for human consumption, including for individuals with insulin dysregulation. In the horse, the safety or metabolic effects of stevioside on normal animals or on those with metabolic dysfunction are unknown. Furthermore, the inflammatory response to a glycemic challenge or to stevioside in horses is not well defined. Therefore, the objective of this study was to measure the effects of stevioside and a glycemic challenge on insulin, glucose, and inflammatory responses in horses with a common metabolic dysfunction (equine metabolic syndrome or EMS) compared with non-EMS controls. To accomplish this, 15 horses were selected; 8 EMS and 7 age-matched controls. An oral sugar test was performed using Karo corn syrup (karo) or stevioside in a random crossover design. Horses were given 0.15 mL/kg body weight of karo or its equivalent grams of sugar in stevia dissolved in water. Blood samples were collected by jugular venipuncture before administration of either stevia or karo and at 60 and 240 min after administration. Serum was used for glucose and insulin determination and plasma for isolation of peripheral blood mononuclear cells (PBMCs) for inflammatory cytokine analysis via flow cytometry and reverse transcription PCR (RT-PCR). Stevia appeared to stimulate lower glycemic and insulinemic responses when compared to karo, in particular in EMS horses. EMS and control horses had inverse inflammatory responses to administration of either stevia or karo with EMS horses having a proinflammatory response (P ≤ 0.05). These data provide evidence as to why horses with EMS may be predisposed to developing laminitis, potentially as a result of an exaggerated inflammatory response to glycemic and insulinemic responses. Furthermore, the data provide new avenues for exploring mechanisms behind the syndrome, in particular when using a glycemic challenge.


Asunto(s)
Glucemia/efectos de los fármacos , Diterpenos de Tipo Kaurano/farmacología , Glucósidos/farmacología , Enfermedades de los Caballos/sangre , Inflamación/veterinaria , Síndrome Metabólico/veterinaria , Animales , Estudios de Casos y Controles , Diterpenos de Tipo Kaurano/efectos adversos , Glucósidos/efectos adversos , Caballos , Inflamación/tratamiento farmacológico , Insulina/sangre , Síndrome Metabólico/sangre , Edulcorantes/efectos adversos , Edulcorantes/farmacología
5.
J Vet Intern Med ; 29(3): 877-81, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25858585

RESUMEN

OBJECTIVE: To determine if concentrations of free thyroxine (FT4) measured by semi-automated chemiluminescent immunoassay (CLIA) correspond to FT4 determined by equilibrium dialysis (ED) in hypothyroid dogs positive for thyroglobulin antibody (TGA). ANIMALS: Thirteen TGA-positive dogs classified as hypothyroid based on subnormal FT4 concentrations by ED. METHODS: Qualitative assessment of canine TGA was performed using an enzyme-linked immunosorbent assay. Serum total thyroxine and total triiodothyronine concentrations were measured by radioimmunoassay. Serum FT4 concentration was determined by ED, and also by semi-automated CLIA for human FT4 (FT4h) and veterinary FT4 (FT4v). Canine thyroid stimulating hormone concentration was measured by semi-automated CLIA. RESULTS: Each dog's comprehensive thyroid profile supported a diagnosis of hypothyroidism. For detection of hypothyroidism, sensitivities of CLIA for FT4h and FT4v were 62% (95% CI, 32-85%) and 75% (95% CI, 36-96%), respectively, compared to FT4 by ED. Five of 13 (38%) dogs had FT4h and 2 of 8 (25%) dogs had FT4v concentrations by CLIA that were increased or within the reference range. Percentage of false-negative test results for FT4 by CLIA compared to ED was significantly (P < .0001 for FT4h and P < .001for FT4v) higher than the hypothesized false-negative rate of 0%. CONCLUSIONS AND CLINICAL IMPORTANCE: Caution should be exercised in screening dogs for hypothyroidism using FT4 measured by CLIA alone. Some (25-38%) TGA-positive hypothyroid dogs had FT4 concentrations determined by CLIA that did not support a diagnosis of hypothyroidism.


Asunto(s)
Autoanticuerpos/inmunología , Enfermedades de los Perros/sangre , Hipotiroidismo/veterinaria , Mediciones Luminiscentes/veterinaria , Tiroglobulina/inmunología , Tiroxina/sangre , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/inmunología , Perros , Ensayo de Inmunoadsorción Enzimática/veterinaria , Reacciones Falso Positivas , Femenino , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/veterinaria , Hipotiroidismo/sangre , Hipotiroidismo/diagnóstico , Hipotiroidismo/inmunología , Mediciones Luminiscentes/métodos , Masculino , Tiroiditis Autoinmune/sangre , Tiroiditis Autoinmune/diagnóstico , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/veterinaria , Tirotropina/sangre , Triyodotironina/sangre
6.
J Vet Intern Med ; 24(3): 650-4, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20384949

RESUMEN

BACKGROUND: Determination of adrenocorticotropic hormone (ACTH) concentration is a commonly used test in the evaluation of endocrine causes of equine laminitis, but the concentration in healthy horses can be high at certain times of year, which alters the specificity of the ACTH test. OBJECTIVE: To determine if circulating concentrations of ACTH, cortisol, glucose, insulin, and thyroxine vary month to month in healthy horses and in horses with equine metabolic syndrome (EMS). ANIMALS: Nine healthy adult horses were studied on their farm/stable over the course of 1 year. After the diagnosis of EMS, 10 laminitic horses residing at the same farm/stable were also studied. METHODS: Prospective study of healthy and laminitic horses. Plasma/serum samples were analyzed for concentrations of hormones and glucose. RESULTS: ACTH was the only analyte to show a discrete seasonal pattern, with concentrations in healthy and EMS horses frequently outside of the reference range (9-35 pg/mL) in August through October. Insulin was elevated (>40 microIU/mL) in EMS horses during most months and median serum glucose was generally higher in EMS horses (100 mg/dL, range, 76-163 mg/ dL) than in controls (94 mg/dL, range, 56-110 mg/dL), but no seasonal patterns for insulin or glucose were found. CONCLUSIONS AND CLINICAL IMPORTANCE: An increased ACTH concentration in horses in late summer or autumn should be interpreted with caution. In contrast, insulin concentration is maintained within the reference range throughout the year in healthy horses, thus an increased insulin concentration at any time of year should raise suspicions of EMS, ECD, or both.


Asunto(s)
Hormona Adrenocorticotrópica/sangre , Glucemia , Enfermedades de los Caballos/sangre , Hidrocortisona/sangre , Insulina/sangre , Tiroxina/sangre , Animales , Enfermedades del Pie/sangre , Enfermedades del Pie/metabolismo , Pezuñas y Garras/patología , Enfermedades de los Caballos/metabolismo , Caballos , Síndrome Metabólico/sangre , Síndrome Metabólico/veterinaria , Estaciones del Año , Tiempo
7.
Biotech Histochem ; 82(1): 17-22, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17510810

RESUMEN

Fetuses develop in a marked hypoxic environment in utero. Premature infants often require high concentrations of oxygen to survive and develop in an environment that would be considered an oxygen stress for the fetus. Postnatal hyperoxia alters organ development, but there is minimal research regarding the role of hyperoxia in intestinal development. We attempted to determine whether postnatal hyperoxia exposure alters intestinal growth and function by using a reliable, objective and sensitive set of methods to study region-specific postnatal intestinal maturation. Rat pups born naturally were placed in continual exposure to room air (normoxia) or 85% oxygen (hyperoxia) immediately after birth. Pups were sacrificed at 1 and 2 weeks of age. Intestines were removed and fixed in formalin. Average mucosal, submucosal, and muscularis thicknesses were measured on hematoxylin and eosin stained sections. Immunohistochemistry was performed using antibodies against NOS II. The staining intensity was determined and quantified for site-specific regions of intestinal sections. No differences in mucosal thickness, submucosal thickness, or muscularis thickness were measured in the duodenum, jejunum or colon at any age. At two weeks of age, the thickness of the ileal mucosa was significantly greater in the group reared in 85% oxygen, and the group exposed to room air demonstrated significantly greater NOS II protein concentration than the hyperoxia group within the distal villus, proximal villus/crypts, submucosa, and muscularis in the distal small intestine.


Asunto(s)
Hiperoxia , Íleon/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Femenino , Hiperoxia/fisiopatología , Íleon/anatomía & histología , Íleon/efectos de los fármacos , Inmunohistoquímica , Morfogénesis/efectos de los fármacos , Oxígeno/farmacología , Embarazo , Ratas , Ratas Sprague-Dawley
8.
Acta Diabetol ; 42(3): 147-52, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16258738

RESUMEN

Urinary bladder dysfunction is a major complication in diabetes mellitus and its mechanism has been attributed to altered neurological function (autonomic and/or peripheral neuropathy). Previous studies have demonstrated impaired nerve deficiencies, including either loss of nerve function and/or anatomical loss of neuromuscular nerve terminals. While the phenomenon of diabetes-related neurological injury is well recognised, its pathogenesis is not well understood. Using a well established rat model of diabetes (streptozotocin model), we investigated the prevalence of sympathetic and parasympathetic nerves and relative prevalence of connexin isoforms (gap junction proteins) during diabetes-related bladder dysfunction. Immunohistochemistry and digital image analysis was used to detect the prevalence of postsynaptic neuronal markers, NOS1 and connexin isoform expressions. Immunohistochemistry showed significant increases in tyrosine hydroxylase (marker of sympathetic innervation) and decreased vesicular acetylcholine transporter (marker of parasympathetic innervation), predominantly in the smooth muscle layer, 3 days after diabetes induction, when compared to age-matched controls. Time-dependent and cell-specific decreases in the connexin 43 isoform, but transient increases in connexin 32 and 26, were also observed in diabetic rats vs. controls (p<0.05). These data suggest that selective and time-dependent expression of gap junction proteins and altered prevalence of sympathetic/parasympathetic innervation are early events during diabetes-related bladder dysfunction and remodelling.


Asunto(s)
Conexinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Neuropatías Diabéticas/metabolismo , Vejiga Urinaria/metabolismo , Animales , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Óxido Nítrico Sintasa de Tipo I/metabolismo , Isoformas de Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa/metabolismo , Vejiga Urinaria/inervación , Proteínas de Transporte Vesicular de Acetilcolina/metabolismo
9.
Equine Vet J ; 34(7): 679-85, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12455838

RESUMEN

Plasma ACTH levels have been variable in horses with a positive clinical response for therapy for equine Cushing's Disease (ECD). Therefore, our purpose was to determine the value of monitoring plasma adrenocorticotropin (ACTH) levels during treatment of equine Cushing's disease (ECD) with either cyproheptadine (n = 32) or pergolide (n = 10). First, we validated the chemiluminescent ACTH assay (specificity, precision, accuracy, intra-assay and interassay variations) and tested methods of handling the whole blood from the time of collection to when the ACTH was assayed. The sensitivity and specificity of high plasma ACTH levels for detecting ECD was determined in a retrospective study on hospitalised horses (n = 68). Surveys were sent to veterinarians who submitted equine ACTH levels that were high initially and had at least 2 ACTH samples to determine the value of monitoring ACTH levels during therapy of ECD. The ACTH chemiluminescent assay was valid. The ACTH was stable when whole blood was collected and held in plastic tubes for 8 h before separating the plasma. The sensitivity and specificity of plasma ACTH levels for detecting ECD were 84% (n = 19,95% CI 60,97) and 78% (n = 49,95% CI 63,88), respectively. Treated horses generally showed a decrease in plasma ACTH. Plasma ACTH levels may be helpful when monitoring therapy of ECD, although improvement in clinical signs should be considered most important. There were no differences between cyproheptadine and pergolide in terms of improvements in any of the clinical signs.


Asunto(s)
Hormona Adrenocorticotrópica/sangre , Síndrome de Cushing/veterinaria , Ciproheptadina/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológico , Pergolida/uso terapéutico , Animales , Síndrome de Cushing/sangre , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/tratamiento farmacológico , Monitoreo de Drogas/veterinaria , Femenino , Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/diagnóstico , Caballos , Mediciones Luminiscentes , Masculino , Estudios Retrospectivos , Sensibilidad y Especificidad
10.
J Neurosci ; 21(11): RC149, 2001 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-11344255

RESUMEN

Peroxynitrite formation has been demonstrated in several neurodegenerative disorders; thus far, protein nitration and consequent alterations in protein function are implicated as mechanistic events. Free 3-nitrotyrosine (free-3NT) is also elevated in these settings; a neurotoxic role for this modified amino acid has not been investigated. We tested the hypothesis that free-3NT is neurotoxic in vivo, using a mouse model of striatal degeneration. The neurodegenerative effects of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) (unilateral intrastriatal injection, 64 nmol) were compared with free-3NT (32 nmol) or free-tyrosine (free-TYR) (32 nmol). 6-OHDA-treated mice exhibited significant ipsilateral turning behavior after d-amphetamine challenge, indicative of unilateral striatal injury (ipsilateral-contralateral turning differential, 21.1 +/- 6.8). Significant turning behavior was also observed in free-3NT-treated mice but not in free-tyrosine-treated mice (free-3NT, 16.0 +/- 3.9; free-TYR, 1 +/- 2.7; p < 0.01). Immunohistochemistry was used to evaluate striatal tyrosine hydroxylase (TH) content. 6-OHDA or free-3NT treatment caused severe reductions in TH immunoreactivity in injected striata compared with the contralateral hemisphere (injected/contralateral immunoreactivity ratio: 6-OHDA, 0.23 +/- 0.07; free-3NT, 0.49 +/- 0.02). Free-tyrosine treatment had no effect (1.03 +/- 0.09). Turning behavior was correlated with striatal TH ratio (p < 0.01). Furthermore, we observed a striking unilateral reduction in TH-positive cell body counts in the substantia nigra pars compacta of 6-OHDA- and free-3NT-treated mice (injected/contralateral cell count ratio: 6-OHDA, 0.40 +/- 0.04; free-3NT, 0.59 +/- 0.02). Free-tyrosine treatment had no effect (1.05 +/- 0.04). No evidence for increased striatal protein incorporation of 3NT was observed in any treatment group. These data represent the first evidence that free-3NT can elicit neurodegenerative effects in vivo; free-3NT may have a causal role in neurodegenerative conditions.


Asunto(s)
Cuerpo Estriado/efectos de los fármacos , Enfermedades Neurodegenerativas/inducido químicamente , Tirosina/análogos & derivados , Tirosina/toxicidad , Animales , Recuento de Células , Cuerpo Estriado/enzimología , Cuerpo Estriado/patología , Dextroanfetamina/farmacología , Modelos Animales de Enfermedad , Inmunohistoquímica , Ratones , Actividad Motora/efectos de los fármacos , Enfermedades Neurodegenerativas/enzimología , Enfermedades Neurodegenerativas/patología , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Oxidopamina/administración & dosificación , Oxidopamina/toxicidad , Sustancia Negra/efectos de los fármacos , Sustancia Negra/enzimología , Sustancia Negra/patología , Tirosina/administración & dosificación , Tirosina 3-Monooxigenasa/análisis , Tirosina 3-Monooxigenasa/metabolismo
11.
Cardiovasc Res ; 49(4): 798-807, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11230979

RESUMEN

OBJECTIVE: Oxidative stress is implicated in the initiation and progression of congestive heart failure, but the putative reactive species and cellular targets involved remain undefined. We have previously shown that peroxynitrite (ONOO(-), an aggressive biological oxidant and nitrating agent) potently inhibits myofibrillar creatine kinase (MM-CK), a critical controller of contractility known to be impaired during heart failure. Here we hypothesized that nitration and inhibition of MM-CK participate in cardiac failure in vivo. METHODS: Heart failure was induced in rats by myocardial infarction (left coronary artery ligation) and confirmed by histological analysis at 8 weeks postinfarct (1.3+/-1.4 vs. 37.7+/-3.2% left ventricular circumference; sham control vs. CHF, n=10 each). RESULTS: Immunohistochemistry demonstrated significantly increased protein nitration in failing myocardium compared to control (optical density: 0.58+/-0.06 vs. 0.93+/-0.09, sham vs. CHF, P<0.05). Significant decreases in MM-CK activity and content were observed in failing hearts (MM-CK k(cat): 6.0+/-0.4 vs. 3.0+/-0.3 micromol/nM M-CK/min, P<0.05; 6.8+/-1.3 vs. 4.7+/-1.2% myofibrillar protein, P<0.05), with no change in myosin ATPase activity. In separate experiments, isolated rat cardiac myofibrils were exposed to ONOO(-) (2-250 microM) and enzyme studies were conducted. Identical to in vivo studies, selective reductions in MM-CK were observed at ONOO(-) concentrations as low as 2 microM (IC(50)=92.5+/-6.0 microM); myosin ATPase was unaffected with ONOO(-) concentrations as high as 250 microM. Concentration dependent nitration of MM-CK occurred and extent of nitration was statistically correlated to extent of CK inhibition (P<0.001). Immunoprecipitation of MM-CK from failing left ventricle yielded significant evidence of tyrosine nitration. CONCLUSION: These data demonstrate that cardiac ONOO(-) formation and perturbation of myofibrillar energetic controllers occur during experimental heart failure; MM-CK may be a critical cellular target in this setting.


Asunto(s)
Creatina Quinasa/metabolismo , Insuficiencia Cardíaca/metabolismo , Miofibrillas/metabolismo , Nitratos/farmacología , Oxidantes/farmacología , Tirosina/análogos & derivados , Animales , Forma MM de la Creatina-Quinasa , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Isoenzimas/metabolismo , Masculino , Miofibrillas/efectos de los fármacos , Miosinas/metabolismo , Ratas , Ratas Sprague-Dawley , Tirosina/análisis
12.
Anal Cell Pathol ; 21(1): 41-8, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11254224

RESUMEN

Primary defects in mitochondrial function have been implicated in over 100 diverse diseases. In situ, mitochondria possess unique and well-defined morphology in normal healthy cells, but diseases linked to defective mitochondrial function are characterized by the presence of morphologically abnormal and swollen mitochondria with distorted cristae. In situ study of mitochondrial morphology is established as an indicator of mitochondrial health but thus far assessments have been via subjective evaluations by trained observers using discontinuous scoring systems. Here we investigated the value of digital imaging analysis to provide for unbiased, reproducible, and convenient evaluations of mitochondrial ultrastructure. Electron photomicrographs of ileal mucosal mitochondria were investigated using a scoring system previously described by us, and also analyzed digitally by using six digital parameters which define size, shape, and electron density characteristics of over 700 individual mitochondria. Statistically significant changes in mitochondrial morphology were detected in LPS treated animals relative to vehicle control using both the subjective scoring system and digital imaging parameters (p < 0.05). However, the imaging approach provided convenient and high throughput capabilities and was easily automated to remove investigator influences. These results illustrate significant changes in ileal mucosal mitochondrial ultrastructure during sepsis and demonstrate the value of digital imaging technology for routine assessments in this setting.


Asunto(s)
Endotoxemia/patología , Endotoxinas/toxicidad , Íleon/ultraestructura , Procesamiento de Imagen Asistido por Computador/métodos , Mucosa Intestinal/ultraestructura , Mitocondrias/ultraestructura , Conversión Analogo-Digital , Animales , Gatos , Íleon/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Microscopía Electrónica , Mitocondrias/efectos de los fármacos , Insuficiencia Multiorgánica/inducido químicamente
13.
Clin Transpl ; : 207-19, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-8794267

RESUMEN

Overall, patient and renal allograft survivals after cadaveric transplantation have improved significantly since the incorporation of CsA into the standard immunosuppressive regimen. Overall, patient and renal allograft survivals were significantly better for non-diabetic recipients when compared to diabetic recipients after cadaveric transplantation. Living-donor renal transplant recipients have a better outcome than cadaveric transplant recipients. Cardiovascular disease is the leading cause of death after renal transplantation. Death on dialysis accounted for the second largest number of posttransplant mortalities. Sepsis and malignancy remained the next most important causes of death after renal transplantation.


Asunto(s)
Trasplante de Riñón , Centros Médicos Académicos , Adolescente , Adulto , Anciano , Cadáver , Causas de Muerte , Niño , Preescolar , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/cirugía , Femenino , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Iowa , Trasplante de Riñón/mortalidad , Trasplante de Riñón/tendencias , Donadores Vivos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Factores de Tiempo , Donantes de Tejidos
14.
J Androl ; 15(1): 29-35, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7910599

RESUMEN

Pituitaries were collected from intact rams and rams that had been rendered bilaterally cryptorchid by surgery to examine the effects of cryptorchidism on gonadotropin heterogeneity, levels of uncombined luteinizing hormone (LH) subunits, and the apparent molecular sizes of LH and follicle-stimulating hormone (FSH). Cryptorchid rams had higher pituitary contents of LH and FSH as well as reduced testicular weights. The levels of uncombined LH subunits, their apparent molecular weights, and the apparent molecular weights of intrapituitary LH were similar in control and cryptorchid rams. However, the apparent molecular weight of intrapituitary FSH was slightly larger in cryptorchid rams. Cryptorchidism altered the pattern of gonadotropin heterogeneity by shifting the distribution of LH isoforms towards basic components and shifting the distribution of FSH isoforms towards acidic components. Thus, it appears that the altered gonadal feedback mechanisms resulting from cryptorchidism modify the pattern of both LH and FSH heterogeneity by shifting the distribution of isoforms in opposite directions.


Asunto(s)
Criptorquidismo/veterinaria , Hormona Folículo Estimulante/análisis , Hormona Luteinizante/análisis , Hipófisis/química , Enfermedades de las Ovejas/metabolismo , Ovinos/metabolismo , Animales , Criptorquidismo/metabolismo , Hormona Folículo Estimulante/química , Hormona Folículo Estimulante/genética , Hormona Luteinizante/química , Hormona Luteinizante/genética , Masculino , Peso Molecular , Hipófisis/metabolismo , Radioinmunoensayo
15.
J Reprod Fertil ; 99(1): 231-5, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8283443

RESUMEN

The role of LHRH in modulating intrapituitary LH content as well as the distribution of LH among its isoforms was examined in sheep. Rams (n = 3) and wethers (n = 6) were actively immunized against an LHRH-human serum globulin conjugate. Pituitaries collected from these animals plus pituitaries from corresponding numbers of nonimmunized rams and wethers were extracted with a buffered saline solution containing protease inhibitors. Immunization markedly reduced total amounts of immunoreactive LH in the pituitary. An aliquot of each pituitary extract was desalted by flow dialysis against water and chromatofocused on a pH 10.5-7.0 gradient. Concentrations of LH in chromatofocusing fractions were determined by radioimmunoassay. LH in pituitary extracts resolved into nine peaks during chromatofocusing which were coded with letters beginning with the most basic isoform. The percentage of LH as the two most basic isoforms, A' and B, was similar (P > 0.05) in all treatment groups. Isoform H constituted a higher percentage (P < 0.05) of the LH in both castrate groups. Nonimmunized wethers had higher percentages of isoforms C, D and E (P < 0.05) and lower percentages (P < 0.05) of the acidic isoforms (coded as peak Z herein) than did other treatment groups. Thus, castration shifted the pattern of intrapituitary isohormones towards the more basic forms. Nonimmunized rams had a higher percentage (P < 0.05) of isoform G than did other groups. Isoform F, the most abundant isoform, was present as a higher percentage (P < 0.05) in immunized rams and wethers than in nonimmunized animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Hormona Liberadora de Gonadotropina/fisiología , Hormona Luteinizante/química , Hipófisis/metabolismo , Ovinos/metabolismo , Animales , Cromatografía , Hormona Liberadora de Gonadotropina/inmunología , Hormona Luteinizante/biosíntesis , Masculino , Orquiectomía , Hipófisis/química , Radioinmunoensayo , Vacunación
16.
Biol Reprod ; 47(5): 776-81, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1477203

RESUMEN

Ovariectomized beef cows were actively immunized against LHRH to test the hypothesis that decreased stimulation of gonadotropes would alter the distribution of LH isoforms and amounts of mRNA for subunits of LH in the pituitary. Eight long-term (3 yr) ovariectomized beef cows were randomly assigned to one of two treatments: immunization against LHRH conjugated to human serum globulin (n = 4) and nonimmunization (control, n = 4). Mean concentration of serum LH in cows immunized against LHRH (1.0 +/- .83 ng/ml) was less (p = 0.01) than in control cows (5.0 +/- 0.83 ng/ml). Amounts of alpha- (p = 0.13) and LH beta-subunit (p = 0.10) mRNA tended to be reduced in cows immunized against LHRH compared to control cows. However, weight of the anterior pituitary and concentrations of LH in this gland did not differ (p = 0.90) among cows from the two groups. Pituitary extracts were chromatofocused on pH 10.5-7.0 gradients, and concentrations of LH in eluent fractions were determined by RIA. Extracts of all pituitaries resolved into nine isoforms (designated A through H and Z beginning with the most basic form). Only isoform F (mid-alkaline elution, pH = 8.8) was influenced by treatment (p = 0.05). Cows immunized against LHRH had a greater relative amount of isoform F (42.1 +/- 1.4%) than controls (37.2 +/- 1.4%). In summary, immunization of cows against LHRH altered 1) circulating concentrations of LH, 2) amounts of mRNA for the subunits of LH, and 3) distribution of intrapituitary LH isoforms without changing the concentrations of LH in the anterior pituitary.


Asunto(s)
Hormona Liberadora de Gonadotropina/fisiología , Isoenzimas , Hormona Luteinizante/biosíntesis , Hipófisis/metabolismo , ARN Mensajero/biosíntesis , Animales , Northern Blotting , Bovinos , Femenino , Regulación de la Expresión Génica , Hipotálamo/fisiología , Tamaño de los Órganos , Ovariectomía , Hipófisis/anatomía & histología , Radioinmunoensayo , Vacunación
17.
J Reprod Fertil ; 94(1): 107-14, 1992 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1552470

RESUMEN

Changes in plasma and follicular fluid concentrations of inhibin were examined in sows after weaning at 28-32 days post partum. From 0 to 48 h after weaning, inhibin concentrations were 200-300 times higher in follicular fluid from small (less than 4 mm) and medium-large (greater than or equal to 4 mm) follicles than in ovarian venous plasma. Inhibin concentrations increased in follicular fluid from medium-large follicles at 24 and 48 h after weaning; concentrations in ovarian venous plasma were positively correlated with the number of medium-large follicles (r = 0.40) and with ovarian venous plasma concentrations of oestradiol (r = 0.61). Blood samples were collected for 30 days from sows (n = 6) that exhibited oestrus within 5 days after weaning and from sows (n = 5) that remained anoestrous for 11 days after weaning. Plasma inhibin concentrations rose in oestrous and anoestrous sows by 12 h and continued to rise for 60 h after weaning. Plasma inhibin concentrations rose further and were higher at 3.5-4.5 days after weaning in oestrous sows than in sows that remained anoestrous. After oestrus, plasma inhibin concentrations declined. At weaning, plasma concentrations of follicle-stimulating hormone (FSH) were higher in sows that subsequently exhibited oestrus than in sows that remained anoestrous. After weaning, plasma concentrations of FSH declined in both groups, reached a nadir at 2.5 days, and increased gradually in anoestrous sows; oestrous sows exhibited an FSH surge at oestrus. Plasma FSH returned to preweaning concentrations in both groups of sows at Days 7-8.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Estro/sangre , Líquido Folicular/química , Inhibinas/análisis , Porcinos/metabolismo , Destete , Animales , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Fase Folicular/fisiología , Inhibinas/sangre , Ovario/irrigación sanguínea , Progesterona/sangre
18.
J Reprod Fertil ; 94(1): 57-69, 1992 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1552493

RESUMEN

Twelve non-implanted crossbred bull calves served as controls and 30 crossbred bull calves (10/treatment) were implanted for 82 days, beginning at 34 days of age, to determine the influence of testosterone propionate (TP), dihydrotestosterone propionate (DHTP) and oestradiol-17 beta (E2) on prepubertal and pubertal pituitary-testicular function and on postpubertal social and sexual behaviour. Compared with control bulls, concentrations of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin concentrations were suppressed (P less than 0.01) in all implanted bulls. Testosterone (T) concentration increased (P less than 0.001) in TP-implanted, but decreased (P less than 0.01) in DHTP and E2 bulls during the implant period. LH response to gonadotrophin-releasing hormone (GnRH) challenge during the implant period (2.5 months of age) was less (P less than 0.01) in TP, E2 and DHTP bulls than in controls. A small but significant T response to GnRH occurred in control bulls at 2.5 months of age. LH and T responses to GnRH challenge at 7 months of age (100 days after implant removal) was similar (P greater than 0.20) in control and implanted bulls. Steroid implants administered prepubertally had no effect (P greater than 0.10) on postpubertal social and sexual behaviours, including number of flehmen responses, abortive mounts, services and competitive order score. Body weight did not differ (P greater than 0.10) between treatment groups, but testis size was reduced (P less than 0.01) during the implant period and up to 10 months of age in treated bulls compared with controls. Testes remained smaller in E2-treated bulls up to the end of the study (23 months of age), but daily sperm production and epididymal weight did not differ (P greater than 0.10) between treatment groups at slaughter. Control bulls reached puberty earlier (P less than 0.01; 270 +/- 11 days of age) than did TP (302 +/- 11 days), DHTP (309 +/- 11 days) or E2 (327 +/- 11 days) bulls. Although puberty was delayed in all implant groups, there was no difference in scrotal circumference at puberty (average 28.4 +/- 0.4 cm) between treatment groups. Our findings indicate that TP, DHTP and E2 implants administered prepubertally result in acute suppression of serum LH, FSH and inhibin during the implant period and in post-implant suppression of testis size and delayed puberty in bulls. The lack of treatment effect on behaviour suggests that steroidal programming of sexual behaviour occurs before 1 month of age in bulls.


Asunto(s)
Hormonas Esteroides Gonadales/farmacología , Hipófisis/efectos de los fármacos , Conducta Sexual Animal/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Conducta Social , Testículo/efectos de los fármacos , Animales , Bovinos , Dihidrotestosterona/farmacología , Implantes de Medicamentos , Estradiol/farmacología , Hormona Folículo Estimulante/sangre , Inhibinas/sangre , Hormona Luteinizante/sangre , Masculino , Testosterona/farmacología
19.
Meat Sci ; 32(4): 387-96, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-22059889

RESUMEN

One-hundred and forty-four weanling bulls of Angus (A, n = 48), Simmental x Hereford (SH, n = 8) and Simmental (S, n = 48) breeding were either castrated, left intact, left intact and implanted with Ralgro or left intact and implanted with Synovex S. Cattle were slaughtered after 190, 246 or 315 days of high-energy feeding. The right side of each carcass was electrically stimulated. Steers were inferior to intact treatments for most performance and carcass cutability traits, but steers were superior in marbling and lean quality (P < 0·05). There were no differences (P>0·05) in dressing percentage or ribeye area per 100 kg of carcass weight among treatments. Relative to intact bulls, Ralgro and Synovex S increased carcass masculinity. Implanted intact treatments did not differ from nonimplanted intacts for feed conversion, average daily gain, yield grade characteristics, percent longissimus dorsi chemical fat and 9-10dash11th rib composition (P >0·05).

20.
Meat Sci ; 32(4): 397-405, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-22059890

RESUMEN

One-hundred and forty four weanling bulls of Angus (A, n = 48), Simmental x Hereford (SH, n = 48) and Simmental (S, n = 48) breeding were either castrated, left intact, left intact and implanted with Ralgro or left intact and implanted with Synovex S. Cattle were slaughtered after either 190, 246 or 315 days of high-energy feeding, and the right side of each carcass was electrically stimulated. Sensory analysis was conducted on longissimus dorsi steaks after 5 days aging and Warner-Bratzler shear force (WBS) was measured after 5, 10 and 15 days aging. Steers had lower (P < 0·05) WBS and more desirable sensory panel scores for juiciness, ease of fragmentation, amount of connective tissue and overall tenderness than all intact treatments. The implanting of weanling bulls with synthetic steroid hormone compounds did not make a practical improvement in beef tenderness.

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