RESUMEN
BACKGROUND: There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. METHODS: This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. RESULTS: A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. CONCLUSIONS: There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.
Asunto(s)
Trastornos Migrañosos , Adulto , Australia/epidemiología , Femenino , Cefalea , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/epidemiología , Estudios Prospectivos , Estudios Retrospectivos , EspañaRESUMEN
Developing embryos are more vulnerable than adults to acute cholinergic intoxication by anticholinesterases, including organophosphorus pesticides. These agents affect the process of neural development itself, leading to permanent deficits in the architecture of the nervous system. Recent evidence on direct roles of acetylcholinesterase (AChE) on neuronal differentiation provides additional grounds for investigating the developmental toxicity of anticholinesterases. Therefore, the effect of the organophosphate diazinon on the development of chick retinal differentiation was studied by an in vitro reaggregate approach. Reaggregated spheres from dissociated retinal cells of the E6 chick embryo were produced in rotation culture. During the whole culture period of 10 days, experimental cultures were supplemented with different concentrations of the pesticide, from 20 to 120 microM diazinon. The pesticide-treated spheres were reduced in size, and their outer surface was irregular. More importantly, inner structural distortions could be easily traced because the structure of control spheroids can be well characterized by a histotypical arrangement of laminar parts homologous to the normal retina. Acetylcholinesterase activity in diazinon-treated spheres was reduced when compared with controls. As a dramatic effect of exposure to the pesticide, inner plexiform layer (IPL)-like areas in spheroids were not distinguishable anymore. Similarly, photoreceptor rosettes and Müller radial glia were strongly decreased, whereas apoptosis was stimulated. The expression of transcripts for choline-acetyltransferase and muscarinic receptors was affected, revealing an effect of diazinon on the cholinergic system. This further proves the significance of cholinesterases and the cholinergic system for proper nervous system development and shows that further studies of debilitating diazinon actions on development are necessary.
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Inhibidores de la Colinesterasa/toxicidad , Diazinón/toxicidad , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Insecticidas/toxicidad , Retina/efectos de los fármacos , Esferoides Celulares/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Animales , Células Cultivadas , Embrión de Pollo , Colina O-Acetiltransferasa/genética , Colina O-Acetiltransferasa/metabolismo , Relación Dosis-Respuesta a Droga , Neuroglía/efectos de los fármacos , Neuroglía/patología , Células Fotorreceptoras/efectos de los fármacos , Células Fotorreceptoras/patología , ARN Mensajero/metabolismo , Receptores Muscarínicos/genética , Receptores Muscarínicos/metabolismo , Retina/embriología , Retina/patología , Esferoides Celulares/enzimología , Esferoides Celulares/patologíaAsunto(s)
Linfocitos T CD4-Positivos/inmunología , Quimiotaxis de Leucocito/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Selectinas/inmunología , Animales , Linfocitos T CD4-Positivos/metabolismo , Humanos , Inflamación/inmunología , Ligandos , Glicoproteínas de Membrana/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Selectinas/metabolismoRESUMEN
Eighteen male Beagle dogs were randomized to oral (p.o.) or subcutaneous (s.c.) carprofen administration in a two-sequence, two-period crossover design with a 10-day washout between periods. Twenty-five milligrams of carprofen was administered p.o. or s.c. every 12 h for 7 days. Plasma concentrations of carprofen collected after the first and last treatments were determined by high-performance liquid chromatography. Carprofen concentration data were natural log transformed and geometric means were calculated for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0--12) following the first dose and Cmax and AUC0--12 following administration of the last dose. Formulations were considered bioequivalent if the 90% confidence interval (CI) of the mean difference for each variable between formulations were within -20% and 25% of the oral formulation. The mean Cmax and AUC0--12 were 16.9 microg/mL and 73.1 microg. h/mL, respectively, following a single oral dose and 8.0 microg/mL and 64.3 microg x h/mL, respectively, following a single s.c. injection. The 90% CI for Cmax (-56.8 to -48.7%) was outside of the bioequivalence criteria whereas the 90% CI for AUC0--12 (-16.3 to -7.5%) was within the bioequivalence criteria. At steady-state, the mean Cmax and AUC0--12 were 18.7 microg/mL and 101.9 microg x h/mL, respectively, following p.o. administration and 14.7 microg/mL and 111.0 microg x h/mL, respectively, following s.c. injection. The 90% CI was outside the bioequivalence criteria for Cmax (-30.8 to -10.8) but within the bioequivalence criteria for AUC0--12 (2.3-15.9%). The results of this study indicate that peak plasma concentrations of carprofen differ when administered p.o. and s.c., but that total drug exposure following a single dose and at steady-state are bioequivalent.
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Antiinflamatorios no Esteroideos/farmacocinética , Carbazoles/farmacocinética , Perros/metabolismo , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/sangre , Área Bajo la Curva , Carbazoles/administración & dosificación , Carbazoles/sangre , Estudios Cruzados , Inyecciones Subcutáneas/veterinaria , Masculino , Equivalencia TerapéuticaRESUMEN
We investigated the functional role of glia cells during retinogenesis using the rotation culture system. Reaggregating cells from the embryonic chick retina have the unique capacity to reassemble into laminated cellular spheres. These spheres are composed of several compartments holding the constituents of many retinal layers in a topologically correct, yet inverse orientation. However, when these spheres are cultured in the presence of conditioned media derived from monolayers of cerebellar glia cells, the reassembling retinal cells behave totally differently. The anlage of the originally reversed lamina polarity is progressively transformed within a week into a sphere with a compound and correctly laminated orientation. Conditioned media from fibroblasts, other glia cells (except Müller cells) or a set of already characterized retinogenetic factors are not able to produce this dramatic transformation. Additionally, we were able to show that only retinal cells are able to respond with a reorganization process. Reaggregating cells from the chick cerebellum also form spheroids; however, neither in the presence of cerebellar glia cell-derived conditioned medium nor their control counterparts are they able to reassemble histotypically. This indicates that cerebellar glia cells produce diffusible factors to which retinal cells can respond and that these factors can act as important determinants for the correct establishment of the retinal polarity. Since all types of laminar disorganization are of great clinical significance, the knowledge of factors which determine and sustain the normal retinal architecture are biomedically highly relevant.
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Cerebelo/citología , Neuroglía/metabolismo , Retina/embriología , Animales , Agregación Celular , Células Cultivadas , Cerebelo/embriología , Embrión de Pollo , Medios de Cultivo Condicionados/metabolismo , Esferoides Celulares/metabolismo , Factores de TiempoRESUMEN
The objective of this study was to identify the active form of the feline calicivirus (FCV) RNA-dependent RNA polymerase (RdRP). Multiple active forms of the FCV RdRP were identified. The most active enzyme was the full-length proteinase-polymerase (Pro-Pol) precursor protein, corresponding to amino acids 1072 to 1763 of the FCV polyprotein encoded by open reading frame 1 of the genome. Deletion of 163 amino acids from the amino terminus of Pro-Pol (the Val-1235 amino terminus) caused a threefold reduction in polymerase activity. Deletion of an additional one (the Thr-1236 amino terminus) or two (the Ala-1237 amino terminus) amino acids produced derivatives that were 7- and 175-fold, respectively, less active than Pro-Pol. FCV proteinase-dependent processing of Pro-Pol in the interdomain region preceding Val-1235 was not observed in the presence of a catalytically active proteinase; however, processing within the polymerase domain was observed. Inactivation of proteinase activity by changing the catalytic cysteine-1193 to glycine permitted the production and purification of intact Pro-Pol. Biochemical analysis of Pro-Pol showed that this enzyme has properties expected of a replicative polymerase, suggesting that Pro-Pol is an active form of the FCV RdRP.
Asunto(s)
Calicivirus Felino/enzimología , Endopeptidasas/metabolismo , Precursores Enzimáticos/metabolismo , ARN Polimerasa Dependiente del ARN/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Endopeptidasas/química , Endopeptidasas/aislamiento & purificación , Precursores Enzimáticos/química , Precursores Enzimáticos/aislamiento & purificación , Manganeso/farmacología , Datos de Secuencia Molecular , ARN Viral/biosíntesisRESUMEN
We investigated the developmental role of alpha(1-6)-linked fucose, applying Aleuria aurantia lectin to a specific retinal regeneration system. Thereby, dissociated retinal cells of chicken embryos reaggregate, proliferate, and differentiate in vitro into histotypical spheres, so-called retinospheroids. Under the influence of A. aurantia lectin, processes of proliferation, differentiation and histogenesis of retinospheroids were disturbed. Extending these in vitro studies, we here show that A. aurantia lectin treatment decreases cells of the inner half retina and their processes into inner plexiform layer areas, as revealed by quantitative enzyme histochemistry for butyryl- and acetylcholinesterase, and immunohistochemistry using antibodies to acetylcholinesterase, Pax-6, calbindin-D, and F11. Concomitantly, the number of rod and red/green photoreceptors dramatically increases, using the antibodies rho4D2 and CERN901 (both specific for rods) and CERN906 (specific for red/green cones). These findings show that glycoproteins exhibiting fucose in alpha(1-6)-linkage are involved in processes determining retinal cell fate, strongly shifting the relative ratio of cells of the inner towards cells of the outer retina.
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Agregación Celular/fisiología , Diferenciación Celular/fisiología , Fucosa/antagonistas & inhibidores , Glicoproteínas/metabolismo , Células Fotorreceptoras/metabolismo , Retina/embriología , Esferoides Celulares/citología , Acetilcolinesterasa/metabolismo , Células Amacrinas/citología , Células Amacrinas/efectos de los fármacos , Células Amacrinas/metabolismo , Animales , Butirilcolinesterasa/metabolismo , Calbindinas , Agregación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , División Celular/fisiología , Embrión de Pollo , Proteínas del Ojo , Fucosa/metabolismo , Proteínas de Homeodominio/metabolismo , Inmunohistoquímica , Lectinas/farmacología , Neuritas/efectos de los fármacos , Neuritas/metabolismo , Neuritas/ultraestructura , Factor de Transcripción PAX6 , Factores de Transcripción Paired Box , Células Fotorreceptoras/citología , Células Fotorreceptoras/efectos de los fármacos , Proteínas Represoras , Retina/citología , Retina/efectos de los fármacos , Células Ganglionares de la Retina/citología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Opsinas de Bastones/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismoRESUMEN
Our objective was to develop a rapid and safe liver biopsy technique that could be repeated on multiple occasions in individual neonatal calves. A pilot study was performed to verify the efficacy of sedation and restraint procedures and to evaluate different biopsy instruments. Following the pilot experiment, a biopsy trocar was fabricated and an experiment was conducted using this procedure. Liver biopsies were performed in neonatal calves on d 4, 9, 15, 21, and 28 of life to evaluate the effect of vitamin A intake on liver vitamin A concentrations. On these days, a single injection of ceftiofur sodium was administered i.m. 1 to 2 h prior to the procedure. Calves were lightly sedated with xylazine and placed on a surgical table in left-lateral recumbency. The right caudo-thoracic area was clipped and scrubbed with an iodophor agent. Following administration of a local anesthetic (lidocaine), a small incision was made in the skin between the 12th and 13th ribs approximately 15 cm from the dorsal midline. The biopsy trocar was inserted through the body wall and peritoneum and introduced into the liver parenchyma, and a liver sample was collected. Following the biopsy, the cutaneous incision was sutured and an antiseptic agent was applied to prevent infection. An i.m. injection of an analgesic was administered 1 h following the procedure to alleviate postsurgical discomfort. Most calves were able to stand within 2 h after the biopsy. The entire procedure, which could be performed by a single individual, usually required about 20 min from initial sedation until skin closure. Although liver samples of up to 500 mg were obtained, most samples weighed 75 to 150 mg (wet weight). A total of 156 liver biopsies were performed on 33 calves. Complications due to the biopsy procedure were observed in only two calves. Therefore, this procedure can be useful for studies designed to monitor changes in liver composition or enzyme activities over time.
Asunto(s)
Animales Recién Nacidos , Biopsia/veterinaria , Bovinos/anatomía & histología , Hígado/patología , Animales , Biopsia/instrumentación , Biopsia/métodosRESUMEN
OBJECTIVE: To determine risk factors for development of sequestra in cattle and identify factors associated with a successful outcome. DESIGN: Retrospective study. ANIMALS: 110 cattle. PROCEDURE: Medical records of cattle treated at veterinary teaching hospitals in North America were reviewed. To determine risk factors for osseous sequestration, breed, age, and sex of cattle with osseous sequestration were compared with breed, age, and sex of all other cattle admitted during the study period. RESULTS: 110 cattle were included in the study. Three had 2 sequestra; thus, 113 lesions were identified. Most sequestra were associated with the bones of the extremities, most commonly the third metacarpal or third metatarsal bone. Ninety-two animals were treated surgically (i.e., sequestrectomy), 7 were treated medically, 3 were initially treated medically and were then treated surgically, and 8 were not treated. Follow-up information was available for 65 animals treated surgically and 6 animals treated medically. Fifty-one (78%) animals treated surgically and 5 animals treated medically had a successful outcome. Cattle that were 6 months to 2 years old had a significantly increased risk of developing a sequestrum, compared with cattle < 6 months old. Cattle in which sequestrectomy was performed with the aid of local anesthesia were significantly more likely to undergo 2 or more surgical procedures than were cattle in which sequestrectomy was performed with the aid of general anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that sequestrectomy will result in a successful outcome for most cattle with osseous sequestration.
Asunto(s)
Enfermedades Óseas/veterinaria , Enfermedades de los Bovinos/epidemiología , Factores de Edad , Animales , Enfermedades Óseas/epidemiología , Enfermedades Óseas/cirugía , Cruzamiento , Bovinos , Enfermedades de los Bovinos/etiología , Enfermedades de los Bovinos/cirugía , Femenino , Estudios de Seguimiento , Masculino , Registros/veterinaria , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Heridas y Lesiones/complicaciones , Heridas y Lesiones/veterinariaRESUMEN
CD26 or dipeptidylpeptidase IV (DPP IV) is a cell surface protease involved in T cell activation. It is a type II transmembrane glycoprotein consisting of a large extracellular part, a single transmembrane region and a short cytoplasmic tail without any common signalling motifs. To eluciate the mechanisms involved in CD26-mediated signalling we have constructed C-terminal deletion mutants of the human CD26 molecule and transfected them into murine T cell hybridomas. Stimulation experiments show that most of the extracellular part of CD26 can be deleted without affecting its costimulatory activity. The membrane proximal glycosylation rich region of CD26 is sufficient to transduce costimulatory signals. Activation of T cells via CD26, however, is not mediated by the important T cell receptor associated adaptor proteins LAT and TRIM as shown in colocalization assays.
Asunto(s)
Dipeptidil Peptidasa 4/fisiología , Transducción de Señal/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Animales , Antígenos CD/biosíntesis , Antígenos de Diferenciación de Linfocitos T/biosíntesis , Biomarcadores/análisis , Dipeptidil Peptidasa 4/inmunología , Dipeptidil Peptidasa 4/metabolismo , Glicosilación , Humanos , Lectinas Tipo C , Activación de Linfocitos , Proteínas de la Membrana/biosíntesis , Ratones , Ratones Endogámicos AKR , Mutagénesis Sitio-Dirigida , Receptores de Antígenos de Linfocitos T/biosíntesis , Receptores de Antígenos de Linfocitos T gamma-delta/biosíntesis , Células Tumorales Cultivadas , Regulación hacia Arriba/inmunología , Proteínas ras/fisiologíaRESUMEN
Beef heifers were assigned to three groups: (1) untreated controls (n=4), (2) Syncro-Mate B(R) (SMB)-treated (n=5), and (3) hysterectomized and SMB-treated (n=4). SMB was administered 8 or 9 days after oestrus, approximately 30 days after hysterectomy. This study was conducted to determine if the uterus was necessary for SMB to induce luteolysis. SMB induced premature luteolysis as only 20% of the intact SMB-treated heifers had >/=0.75 ng/ml of progesterone 7 days after the time of SMB treatment, compared to all (100%) of the untreated heifers (p<0.05). By 9 days after the time of SMB treatment, 25% of the untreated heifers and none (0%) of the intact SMB-treated heifers had >/=0.75 ng/ml of progesterone; however, all (100%) of the hysterectomized SMB-treated heifers had >/=0.75 ng/ml of progesterone (p<0.05). Therefore, SMB-induced luteolysis required the involvement of the uterus. The luteolysin, prostaglandin F(2alpha), is probably the secretion from the uterus that mediates the SMB-induced luteolysis. SMB treatment, however, required 7-8 days to induce luteolysis.
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Bovinos/sangre , Estradiol/análogos & derivados , Estrógenos Conjugados (USP)/farmacología , Sincronización del Estro , Luteólisis/efectos de los fármacos , Pregnenodionas/farmacología , Congéneres de la Progesterona/farmacología , Útero/efectos de los fármacos , Animales , Estradiol/farmacología , Femenino , Histerectomía , Progesterona/sangreRESUMEN
CD26 or dipeptidyl peptidase IV (DPP-IV) is a cell surface protease involved in T cell activation. Monoclonal antibodies (mAbs) directed against the CD26 molecule are able to stimulate CD26-expressing T cells. Although many different CD26-specific mAbs exist which are able to provide a triggering signal in T cells, little is known about their specific epitopes on the CD26 molecule. Whereas some mAbs were shown to compete with each other and to inhibit the association of adenosine deaminase (ADA) and human immunodeficiency virus 1 (HIV-1)-derived Tat protein with CD26, other CD26-specific mAbs obviously bind to distinct regions on DPP-IV. In the present study we have generated truncated versions of the human CD26 molecule and expressed them in COS-1 cells to study the binding pattern of a panel of 14 CD26-specific mAbs in confocal microscopy and, thus, correlated the CD26-specific mAbs epitopes with the binding region of ADA. We show that the majority of anti-CD26 mAbs is directed against the glycosylation-rich region of the molecule whereas the ADA-binding site could be located in the cysteine-rich region of DPP-IV. In contrast to binding experiments with purified ADA, which revealed a specific association with CD26 on CD26-positive Jurkat cells, HIV-derived Tat protein did not interact specifically with CD26 on transfected Jurkat cells, nor could Tat binding be competed by anti-CD26-specific mAbs.
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Adenosina Desaminasa/metabolismo , Dipeptidil Peptidasa 4/inmunología , Epítopos de Linfocito B/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Sitios de Unión , Células COS , Cisteína/metabolismo , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Productos del Gen tat/metabolismo , Glicosilación , VIH-1/metabolismo , Humanos , Células Jurkat , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
OBJECTIVE: To determine whether anesthesia consisting of sedation induced by intramuscular administration of xylazine hydrochloride and lumbosacral analgesia induced by epidural administration of lidocaine and xylazine is useful for umbilical surgery in neonatal calves. DESIGN: Prospective study. ANIMALS: 6 neonatal male dairy calves. PROCEDURE: Calves were sedated with xylazine (0.1 mg/kg [0.045 mg/lb] of body weight, i.m.), and 5 minutes later a 2% solution of lidocaine (0.18 to 0.24 ml/kg [0.08 to 0.11 ml/lb]) and xylazine (0.05 mg/kg [0.022 mg/lb]) were administered into the lumbosacral epidural space. Calves were positioned in dorsal recumbency, and the umbilical structures were resected. Local infusion of lidocaine, cranial to the umbilicus, was required in 5 of 6 calves to provide adequate analgesia. Xylazine sedation was reversed with tolazoline (1 mg/kg [0.45 mg/lb], i.v.). RESULTS: Calves maintained adequate cardiac output and oxygen delivery throughout the procedure but were hypotensive. Reversal of xylazine-induced sedation with tolazoline caused transient sinus bradycardia and sinus arrest, accompanied by severe systemic arterial hypotension. All calves regained a suckle reflex within 10 minutes and were able to stand within 90 minutes. CLINICAL IMPLICATIONS: Intramuscular administration of xylazine for sedation and epidural administration of lidocaine and xylazine for analgesia failed to provide satisfactory analgesia for umbilical resection without supplemental local infiltration of lidocaine. The anesthetic protocol is most useful when respiratory compromise or cost are concerns and the surgical procedure can be completed in < 1 hour. Caution should be exercised when tolazoline is administered intravenously to reverse xylazine-induced sedation in calves.
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Analgesia Epidural/veterinaria , Anestésicos Locales , Bovinos/fisiología , Hipnóticos y Sedantes , Lidocaína , Ombligo/cirugía , Xilazina , Agonistas alfa-Adrenérgicos/administración & dosificación , Antagonistas Adrenérgicos alfa/farmacología , Anestésicos Locales/administración & dosificación , Animales , Bovinos/cirugía , Frecuencia Cardíaca , Hemodinámica/efectos de los fármacos , Hipotensión/inducido químicamente , Hipotensión/veterinaria , Lidocaína/administración & dosificación , Masculino , Respiración , Tolazolina/farmacología , Xilazina/administración & dosificación , Xilazina/antagonistas & inhibidoresRESUMEN
CD26 is a proteolytic enzyme (dipeptidyl-peptidase IV) with a wide tissue distribution and a unique specificity that was already described 27 years ago. CD26 is expressed on a fraction of resting T cells at low density but is strongly upregulated following T-cell activation. Recent results indicate that CD26 is a multifunctional molecule that may have important functions on T cells and in the immune system. It is associated with molecules of immunological importance such as the protein tyrosine phosphatase CD45 and adenosine deaminase (ADA) on the cell surface. Synthetic inhibitors of the enzymatic activity of CD26 have been shown to suppress certain immune reactions in vitro and in vivo. An interesting feature of CD26 is its ability to transmit a transmembrane signal to trigger functional programs in T cells. This triggering requires crosslinking of CD26 on a cell membrane. The enzymatic activity of CD26 is not obligatory for the activation of T cells via CD26. Since CD26 is a type II membrane protein with only six intracellular amino acids, it must deliver its signal via a signal-transducing molecule. Signaling is dependent on the expression of the T-cell receptor (TCR) complex with a special need for a functional zeta-chain. In this context the zeta-chain of the TCR complex is required for CD26-mediated signaling but, in contrast to other co-stimulatory molecules such as the CD2 molecule, is not sufficient for triggering the T cell.
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Dipeptidil Peptidasa 4/inmunología , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Animales , Humanos , Sistema Inmunológico/inmunologíaRESUMEN
Electromyographic (EMG) recordings of the abomasal corpus, pyloric antrum and proximal duodenum were made from six goats for 2 h periods before and after administration of 0.5 mg/kg metoclopramide intravenously or intramuscularly. Analog EMG signal was transformed via a computer program to digital data. The percentage change in electrical activity was determined by comparing the electrical activity following administration of IV or IM metoclopramide with the electrical activity of the control periods for the abomasal corpus, pyloric antrum and proximal duodenum. Metoclopramide caused a significant, time-dependent increase in duodenal electrical activity following either route of administration. This increase in duodenal electrical activity coincided with peak plasma levels of metoclopramide until its decline below 100 ng/ml in plasma. There was a significant biphasic increase in electrical activity of the abomasal corpus and pyloric antrum following IM administration of metoclopramide. The first phase lasted approximately 5 min and was followed by a longer period (approximately 20 min) of diminished electrical activity. A second phase of increased electrical activity occurred approximately 40-60 min after initial IM injection of metoclopramide. It is uncertain whether this increase was drug-mediated or endogenously-triggered. Similar increases in corpus and antral electrical activity were present following IV metoclopramide administration, though early increases were not statistically significant. Overall, the percentage changes in electrical activity correlated well with predicted peak plasma levels of metoclopramide only in the duodenum. This correlation was limited to approximately 5 min after IV and 15 min after IM metoclopramide administration.
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Abomaso/fisiología , Antieméticos/farmacología , Duodeno/fisiología , Cabras/fisiología , Metoclopramida/farmacología , Abomaso/efectos de los fármacos , Animales , Antieméticos/sangre , Antieméticos/farmacocinética , Relación Dosis-Respuesta a Droga , Duodeno/efectos de los fármacos , Electromiografía/métodos , Electromiografía/veterinaria , Femenino , Inyecciones Intramusculares/veterinaria , Inyecciones Intravenosas/veterinaria , Masculino , Metoclopramida/sangre , Metoclopramida/farmacocinética , Antro Pilórico/efectos de los fármacos , Antro Pilórico/fisiología , Factores de TiempoRESUMEN
Systematic review of published cases and a hospital-based case-control study were completed to evaluate breed as a risk factor for atresia coli in cattle. Systematic review of 37 published studies indicated that atresia coli has been diagnosed in 10 cattle breeds and 12 countries, with the marked preponderance of cases occurring in Holstein-Friesian calves (485/514 cases, 94%). Epidemiologic analysis based on 28,373 cattle < 2 mo of age admitted to North American veterinary schools between 1964 and 1993 identified 291 cases of atresia coli in 13 breeds, with the marked preponderance of cases occurring in Holstein-Friesian calves (228/291, 78%). Holstein-Friesian cattle were at significantly greater risk for the condition than all other dairy cattle breeds (crude odds ratio 4.55, P < 0.0001) and all other cattle breeds (crude odds ratio 7.12, P < 0.0001), whereas there was no difference in the odds ratio between dairy cattle (not Holstein-Friesian) and beef cattle (crude odds ratio 1.68, P = 0.11). Atresia coli probably occurs secondary to vascular insufficiency of the developing colon. Holstein-Friesian cattle may be genetically predisposed to atresia coli, possibly because their developing colon grows at a faster rate and/or to a greater extent than that in other cattle breeds. Early or vigorous palpation per rectum of the amniotic vesicle appears to increase the risk of atresia coli in a genetically predisposed fetus, probably through palpation-induced damage to the developing colonic vasculature.
RESUMEN
UNLABELLED: Although sporadic colorectal cancer (CRC) is relatively uncommon in the young, it may constitute an elevated genetic risk for CRC in these individuals. PURPOSE: This study was designed to determine extent of colorectal cancer in families of probands under 40 years of age. METHODS: Medical records of all consecutive patients, 40 years of age or younger at the time of CRC surgery, during the time period 1986 to 1994 were examined. Cases of familial adenomatous polyposis and ulcerative colitis were excluded. Via interviews of surviving probands or nearest relatives, dates of birth and death, causes of death, and diagnosis of cancer were recorded on all first-degree relatives (parents, siblings, and offspring), second-degree relatives (grandparents, aunts, and uncles), and any other relatives. RESULTS: A total of 128 patients, 40 years of age or less at time of CRC resection, were identified. Of these, 45 probands/families were reached by phone, and 45 detailed family histories were obtained. Age range of these 45 probands was 19 to 40 (mean, 33.1) years. In 25 families there was no history of CRC in first-degree, second-degree, or third-degree relatives. Eight of 45 probands (17.8 percent) had at least one first-degree relative with CRC, and three of these eight families fulfilled the Amsterdam criteria for hereditary nonpolyposis colorectal cancer (HNPCC). In all three families, inheritance of CRC appeared to segregate with the maternal side of the family. In addition, 5 of 43 non-HNPCC probands had at least one first-degree, second-degree, or third-degree relative less than 40 years of age, at time of CRC diagnosis. CONCLUSION: Ascertainment of a detailed family history in early age of onset CRC patients identifies frequent familial clustering of CRC and HNPCC in 17.8 percent of cases.
Asunto(s)
Neoplasias Colorrectales/genética , Adulto , Análisis por Conglomerados , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Femenino , Humanos , Masculino , LinajeRESUMEN
Electromyographic (EMG) recordings of the reticulum, abomasal corpus, pyloric antrum and duodenum of six dairy cows with left displacement of the abomasum (LDA) were made in order to substantiate abomasal atony as a prerequisite to abomasal displacement. EMG recordings were made when LDA was present as well as when absent. Mean values were determined in five of six cows for the maximum peak or amplitude, mean peak values, peak-to-peak interval and count of the electrical response activity (ERA) for each 15 min segment of the waveform recordings. Segments containing phase III migrating myoelectric activity were not analysed. LDA positive periods were compared to LDA negative periods in each cow. The 6 h period (transition period) prior to the diagnosis of LDA was analysed separately. Paired t-tests were applied to group values with statistical significance established at the P = 0.05 level. There was a significant decrease in the ERA count during the LDA positive periods in the abomasal corpus (-1.40% to -7.88%, P = 0.0217) and in the pyloric antrum (-2.05% to -11.98%, P = 0.0430). A corresponding significant increase occurred in the peak-to-peak interval. During the transition period spike activity in the duodenum increased 0.5% to 48.31% (P = 0.0474) and the peak-to-peak interval was significantly decreased. No extended periods of atony were observed in the abomasum during this study.