RESUMEN
Seaweed (Ascophyllum nodosum) is a known source of plant growth regulators, and application to turfgrasses has increased activity of the antioxidant superoxide dismutase (SOD) and specific vitamin precursors. Increased antioxidant activity in both plants and animals diminishes oxidative stress. Two pasture experiments investigated effects of Tasco-Forage (a proprietary seaweed-based product) applied to tall fescue (Festuca arundinacea) on antioxidant activity in plants and in ruminants that grazed the forage. In Exp. 1, fescue was 70 to 100% infected with the endophyte fungus Neotyphodium coenophialum ([Morgan-Jones and Gams] Glenn, Bacon, and Hanlin). Twenty-four wether lambs (initial BW 41 kg; SD = 5) grazed fescue treated with 0, 1.7, or 3.4 kg Tasco/ha applied in April and July, 1994, with four replications per treatment. Grazing occurred for 26 d beginning April 21 and for 22 d beginning July 19. In July, there was a linear increase in daily gains (P < 0.05), and serum vitamin A (P < 0.13) and whole-blood Se (P < 0.10) tended to increase in lambs grazing Tasco-treated fescue. In Exp. 2,48 Angus and Angus x Hereford steers (initial BW 245 kg; SD = 20) grazed infected or uninfected tall fescue in Virginia that was treated (3.4 kg/ ha) or untreated with Tasco in April and July, 1995. Steers that grazed infected tall fescue had lower (P < 0.02) serum vitamin A and E and tended (P < 0.07) to have lower whole-blood Se in September compared with steers that grazed uninfected tall fescue. Tasco decreased (P < 0.06) serum vitamin E but tended to increase whole-blood Se (P < 0.10) in September and serum vitamin A in July (P < 0.12). During 1996 and 1997, the experiment was repeated in Virginia with Angus steers and was replicated at Prairie, MS, where 1/4 Brahman x 3/4 Angus steers were used. Forty-eight steers were included at each location in each year (n = 192 total steers for 1996 and 1997). Steers that grazed infected tall fescue in Mississippi had lower (P < 0.05) serum vitamin E by the end of the grazing season. At both locations Tasco increased (P < 0.05) activity of superoxide dismutase in both infected and uninfected fescue. The endophyte in tall fescue seemed to decrease antioxidant activity in grazing steers, whereas Tasco seemed to increase antioxidant activity in both the forage and the grazing ruminant. Tasco may provide opportunities to reduce oxidative stress in plants and animals.
Asunto(s)
Alimentación Animal , Antioxidantes/farmacología , Enfermedades de los Bovinos/prevención & control , Extractos Vegetales/farmacología , Poaceae/efectos de los fármacos , Poaceae/microbiología , Algas Marinas , Enfermedades de las Ovejas/prevención & control , Estrés Fisiológico/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/metabolismo , Hypocreales , Masculino , Estrés Oxidativo , Estaciones del Año , Ovinos , Enfermedades de las Ovejas/metabolismo , Estrés Fisiológico/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Effects of applying Tasco-Forage, an Ascophyllum nodosum seaweed-based product prepared by a proprietary process, to endophyte (Neotyphodium coenophialum [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin)-infected and endophyte-free tall fescue (Festuca arundinacea Schreb.) were studied in each of 3 yr (1995, 1996, and 1997) in Virginia and in 1996 and 1997 in Mississippi. There were 48 steers at each location in each year (n = 240) in a 2 x 2 x 2 factorial arrangement with two replications at each location. Steers in Virginia were Angus and Angus x Hereford with initial weights of 245 kg (SD = 20), 234 kg (SD = 9), and 265 kg (SD = 5) in yr 1, 2, and 3, respectively. Steers in Mississippi were 3/4 Angus and 1/4 Brahman and weighed 230 kg (SD = 8) and 250 kg (SD = 2) in yr 2 and 3, respectively. Tasco (3.4 kg/ha) was dissolved in water and applied to pastures in April before grazing was begun and again in July at the same rate. The grazing period was from mid-April to late September or mid-October. Total gains were higher (P < 0.05) for steers grazing uninfected than for those grazing endophyte-infected tall fescue. Rectal temperatures were increased (P < 0.05) due to endophyte infection at both locations; Tasco application decreased temperature of steers grazing infected fescue in Virginia (interaction, P < 0.07) but increased temperatures of steers grazing infected fescue in Mississippi (interaction, P < 0.05). Presence of the endophyte resulted in rough hair coats and loss of hair color, but the effect was partially offset (P < 0.05) by Tasco application in Virginia in 1995. Both monocyte phagocytic activity (all years and locations) and major histocompatibility complex class II expression (1995 only) were decreased (P < 0.05) in steers due to endophyte infection, but this effect was reversed (P < 0.05) by application of Tasco to pastures. Application of the extract from A. nodosum seems to have use in alleviating adverse effects of endophyte on immune function and may improve hair coat condition in cattle grazing infected fescue, but effects on rectal temperature varied due to location.
Asunto(s)
Alimentación Animal , Enfermedades de los Bovinos/prevención & control , Monocitos/inmunología , Micotoxicosis/veterinaria , Extractos Vegetales/farmacología , Poaceae/efectos de los fármacos , Poaceae/microbiología , Algas Marinas , Estrés Fisiológico/veterinaria , Animales , Temperatura Corporal , Bovinos , Enfermedades de los Bovinos/inmunología , Cabello , Hypocreales , Masculino , Mississippi , Monocitos/efectos de los fármacos , Micotoxicosis/inmunología , Micotoxicosis/prevención & control , Fagocitosis , Estaciones del Año , Estrés Fisiológico/inmunología , VirginiaRESUMEN
Tall fescue (Festuca arundinacea Schreb.) infected with the endophyte Neotyphodium coenophialum ([Morgan-Jones and Gams] Glenn, Bacon, and Hanlin) causes fescue toxicosis in cattle grazing the forage, but effects of the endophyte were considered to be abated soon after removal of the animals from pastures. Tasco-Forage, a proprietary extract from the brown seaweed Ascophyllum nodosum, is a known source of cytokinins and has increased antioxidant activity in both plants and the animals that graze the forage. Tasco was applied at 0 and 3.4 kg/ha to infected and uninfected tall fescue pastures in Virginia and Mississippi. Forty-eight steers grazed the pastures at each location during each of 2 yr (n = 192) before being transported to Texas for feedlot finishing. On arrival at the feedlot, steers from Tasco-treated pastures had higher (P < 0.01) monocyte phagocytic activity and tended (P < 0.07) to have higher major histocompatibility complex class II expression than steers that grazed the untreated pastures. A depression (P < 0.05) in monocyte immune cell function due to grazing infected fescue was detected throughout the feedlot finishing period but was reversed by Tasco. Rectal temperatures were elevated (P < 0.07) in steers that had grazed the infected tall fescue when they arrived in Texas, but by d 14 no difference was detected. However, by d 28 the temperature effects of infected tall fescue were reversed. Steers that had grazed infected fescue had lower (P < 0.01) rectal temperatures on d 112 of the feedlot period, demonstrating a much longer-lasting effect of the endophyte on thermoregulatory mechanisms than previously thought. Steers that had grazed Tasco-treated pastures had higher (P < 0.01) rectal temperatures on d 56 than steers that had grazed untreated fescue. Steers that had grazed the Tasco-treated pastures had higher marbling scores (P < 0.05) regardless of the endophyte, but no effect of Tasco or endophyte on gain was measured. Our data suggest that Tasco application to tall fescue pastures alleviated some of the negative effects of tall fescue toxicity.
Asunto(s)
Alimentación Animal , Composición Corporal/efectos de los fármacos , Enfermedades de los Bovinos/prevención & control , Monocitos/inmunología , Micotoxicosis/veterinaria , Extractos Vegetales/farmacología , Poaceae/efectos de los fármacos , Poaceae/microbiología , Algas Marinas , Estrés Fisiológico/veterinaria , Animales , Temperatura Corporal , Bovinos , Enfermedades de los Bovinos/inmunología , Cabello , Hypocreales , Masculino , Mississippi , Monocitos/efectos de los fármacos , Micotoxicosis/inmunología , Micotoxicosis/prevención & control , Fagocitosis , Estaciones del Año , Estrés Fisiológico/inmunología , VirginiaRESUMEN
Two field studies were conducted in the USA to determine the efficacy of a single strategically-timed dose of doramectin pour-on in the control of gastrointestinal nematodosis in beef cow-calf herds and the resultant effects on calf productivity. One study was carried out between May and October 1996 in a spring-calving herd at a site located in Idaho (ID) and the other between January and July 1997 in a fall-calving herd at a site located in Mississippi (MS). In each study, cow-calf pairs were randomly allotted by sex of calf to pastures and one of two treatment groups (doramectin pour-on at the recommended dose rate of 500 microg/kg body weight or untreated control). There were four pasture replicates per treatment at each site. Each pasture contained 12 cow-calf pairs at the ID site and 15 cow-calf pairs at the MS site. Treatment was administered to cows and calves on 21 May 1996 (ID) or 23 January 1997 (MS). Following treatment, cow-calf pairs were assigned to their designated pastures where they remained until the calves were weaned 140 (ID) or 168 (MS) days later. Cow and calf fecal egg counts and calf body weights were recorded on treatment day and then at monthly intervals until study termination. Doramectin treatment reduced nematode egg output in cows and calves over the entire grazing season compared to untreated controls and resulted in calf weight gain improvements of 9.8kg (p=0.295) at the ID site and 17.4kg (p=0.0002) at the MS site.
Asunto(s)
Antihelmínticos/uso terapéutico , Enfermedades de los Bovinos/prevención & control , Ivermectina/análogos & derivados , Infecciones por Nematodos/veterinaria , Animales , Antihelmínticos/administración & dosificación , Bovinos , Femenino , Idaho , Ivermectina/administración & dosificación , Ivermectina/uso terapéutico , Masculino , Mississippi , Infecciones por Nematodos/prevención & control , Recuento de Huevos de Parásitos/veterinaria , Embarazo , Estaciones del Año , Aumento de PesoRESUMEN
Although significant pharmacologic and nonpharmacologic advances in treating hypertension during the last decade have reduced mortality and morbidity, hypertension continues to be a major health concern worldwide. Therefore, the search continues for newer specific pharmacologic treatment of this disorder. This review focuses on pharmacologic agents or classes of agents either recently approved or under clinical development for the treatment of hypertension.
Asunto(s)
Antihipertensivos/farmacología , Drogas en Investigación/farmacología , Animales , Antihipertensivos/clasificación , Cardiología/tendencias , HumanosRESUMEN
A 21-year-old multiparous female exhibiting 31-41 day menstrual cycles was given hFSH (225 IU/day, Metrodin 75, from cycle day 3 through 9 (menses = day 1) and hCG (10,000 IU, Profasi, on day 10 to stimulate follicular development. At 35 h after hCG, under isoflurane (AErrane) anesthesia, follicles were aspirated by controlled suction under transvaginal ultrasound guidance. Metaphase II oocytes (n = 11) were placed in modified human tubal fluid (mHTF, 100 microliters) medium under oil at 37 degrees C in humidified 5% CO2. Frozen semen, collected by voluntary ejaculation, was thawed (70 degrees C H2O bath, 6 sec), diluted slowly, centrifuged, and resuspended in mHTF, and 160,000 motile spermatozoa/ml were added at 6 h after oocyte recovery. At 21 h postinsemination (p.i.) eight oocytes were at the two-cell stage, five were cryopreserved, and three were cultured to the six- to eight-cell stage in mHTF with granulosa cells before transcervical uterine transfer at 47 h p.i. using a Teflon catheter. Micronized progesterone (400 mg/d) was orally administered for 10 weeks posttransfer (p.t.). Ultrasound examination revealed a single fetus at 15 weeks p.t., and unassisted delivery of a live 1.37 kg female infant occurred at 29 weeks. Am. J. Primatol. 41:247-260, 1997.
Asunto(s)
Transferencia de Embrión/veterinaria , Fertilización In Vitro/veterinaria , Gorilla gorilla , Animales , Criopreservación/veterinaria , Transferencia de Embrión/métodos , Femenino , Fertilización In Vitro/métodos , Hormona Folículo Estimulante/administración & dosificación , Ciclo Menstrual/fisiología , Oocitos , Preservación de Semen/veterinariaRESUMEN
The efficacy of erodible norgestomet implants for preventing pregnancy in postpubertal heifers was evaluated in two experiments at five locations each. Heifers (n = 896) within each study location were stratified by weight and allotted randomly to receive an ear implant containing either 0, 24, 36, or 48 mg of norgestomet (d 0). Heifers were exposed to fertile bulls immediately after implantation for 75 d (d 0 to 74) in Exp. 1 (n = 476) or for 80 d (d 75 to 154) in Exp. 2 (n = 420). Weights were recorded on d 0 and 74 (Exp. 1 and 2) and d 154 (Exp. 2). Each heifer was palpated rectally for pregnancy at the end of each experiment. Pregnancy rates were higher (P < .01) for control heifers (0 mg implant) than for heifers that received 24, 36, or 48 mg of norgestomet. In Exp. 1, pregnancy rates were 96, 29, 6, and 4% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. In Exp. 2, pregnancy rates were 85, 36, 19, and 9% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. Estrous activity during the first 3 wk of bull exposure was reduced (P < .05) among heifers that received norgestomet implants compared to control heifers but was not completely abolished at any dosage in Exp. 1. During the first 75 d of Exp. 1 and 2, heifers treated with 36 or 48 mg norgestomet implants gained weight faster (P < .05) than control heifers. Combined across both experiments, ADG during the first 74 d were .53, .56, .59, and .60 kg/d for heifers treated with 0, 24, 36, and 48 mg implants of norgestomet, respectively. These data indicate that norgestomet implants increased rate of weight gain, reduced estrous activity, and reduced the occurrence of pregnancy in heifers on pasture.
Asunto(s)
Alimentación Animal , Bovinos/fisiología , Preñez/efectos de los fármacos , Pregnenodionas/farmacología , Congéneres de la Progesterona/farmacología , Animales , Relación Dosis-Respuesta a Droga , Implantes de Medicamentos , Estro/efectos de los fármacos , Estro/fisiología , Femenino , Fertilidad/efectos de los fármacos , Fertilidad/fisiología , Masculino , Embarazo , Índice de Embarazo , Preñez/fisiología , Pregnenodionas/administración & dosificación , Congéneres de la Progesterona/administración & dosificación , Distribución Aleatoria , Aumento de Peso/efectos de los fármacos , Aumento de Peso/fisiologíaRESUMEN
The composition of, and seasonal changes in, populations of gastrointestinal parasites of calves in northeast Mississippi were determined for 10 months post-weaning. After weaning on 15 October, 20 mixed breed beef steers were grazed together on a 4 ha fescue/bermudagrass pasture. From November through August of the following year, two of the calves were removed each month for necropsy and counting of gastrointestinal nematodes. Eight species of worms were found: Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Bunostomum phlebotomum, Cooperia spp., Trichostrongylus colubriformis, Oesophagostomum spp., and Trichuris ovis. During all months, Ostertagia ostertagi and Cooperia spp. combined comprised at least 89% of gastrointestinal nematode burdens. Cooperia spp. represented 92.6% of the total worm burden of calves in November but declined to about 56% in January and February. From March through August, Ostertagia ostertagi comprised at least 79% of the worms from calves. Numbers of inhibited Ostertagia ostertagi increased markedly from February to March and remained at high levels prior to resumption of development in August. The proportion of Trichostrongylus axei remained about 4% throughout the year, but the highest numbers were recorded in the summer months. Other species were minor components of the worm population. These data indicate that with respect to Ostertagia ostertagi, northeast Mississippi can be considered a summer inhibition zone.
Asunto(s)
Enfermedades de los Bovinos/epidemiología , Parasitosis Intestinales/veterinaria , Ostertagiasis/veterinaria , Abomaso/parasitología , Animales , Bovinos , Parasitosis Intestinales/epidemiología , Masculino , Mississippi/epidemiología , Infecciones por Nematodos/epidemiología , Infecciones por Nematodos/veterinaria , Ostertagiasis/epidemiología , Estaciones del AñoRESUMEN
The epidemiology of gastrointestinal nematodes was studied in a spring calving herd in northeast Mississippi. Pregnant, mixed breed beef cows (n = 15) were placed on a 10 ha fescue/bermuda grass pasture from January 1990-February 1992. In both years, calves were born from February-April and were weaned and removed from the pasture in mid-October. Fecal egg counts (EPG) and generic composition of nematodes in fecal cultures were determined monthly for cows and calves. Estimation of numbers of third-stage larvae on herbage also was determined monthly from March 1990-February 1992. Worm-free tracer calves (2-3 per month) were allowed to graze for 1 month periods and slaughtered for counting and identification of gastrointestinal nematodes. The mean monthly EPG of cows was consistently low (0.23-3.41); EPG of calves increased from spring through fall of both years. Five nematode genera were identified from fecal cultures of cows and calves. Ostertagia and Trichostrongylus spp. were the predominant nematodes in cows, while Ostertagia and Cooperia spp. were predominant in calves. Numbers of third-stage larvae on herbage declined from spring through summer and remained at low levels until late fall/winter, when numbers increased markedly. Eleven nematode species were identified from tracers, but O. ostertagi and Cooperia spp. predominated in most months. Seasonal changes in tracer worm counts coincided with similar changes in counts of third-stage larvae on herbage. Inhibition of O. ostertagi occurred in tracer calves during spring, but did not give rise to a marked increase in egg production in cows during fall.
Asunto(s)
Enfermedades de los Bovinos/epidemiología , Parasitosis Intestinales/veterinaria , Infecciones por Nematodos/veterinaria , Complicaciones Parasitarias del Embarazo/veterinaria , Animales , Bovinos , Heces/parasitología , Femenino , Parasitosis Intestinales/epidemiología , Larva , Masculino , Mississippi/epidemiología , Nematodos/clasificación , Nematodos/aislamiento & purificación , Infecciones por Nematodos/epidemiología , Recuento de Huevos de Parásitos/veterinaria , Embarazo , Complicaciones Parasitarias del Embarazo/epidemiología , Lluvia , Estaciones del Año , TemperaturaRESUMEN
In summary, ET-1 levels were significantly increased in black men compared with white men. This racial difference could have important research implications if increased ET-1 levels are linked to left ventricular hypertrophy and other cardiovascular diseases, and it may serve as a foundation for future studies.
Asunto(s)
Población Negra , Endotelinas/sangre , Caracteres Sexuales , Población Blanca , Adolescente , Adulto , Anciano , Análisis de Varianza , Biomarcadores/sangre , Presión Sanguínea , Estatura , Peso Corporal , Femenino , Cardiopatías/sangre , Humanos , Hipertrofia Ventricular Izquierda/sangre , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
The endothelium represents a potentially critical target for gene therapy because of its anatomical location and its importance in the viability in both normal and malignant tissues. Protecting the endothelium of normal tissues, such as the lungs, from the toxic effects of current antineoplastic agents and the destruction of the tumor vasculature are reasonable goals. As a target, however, the endothelium continues to represent a significant challenge. While gene delivery to cultured endothelial cells is possible, improved delivery systems are required, as well as cell-specific promoters, before in vivo gene therapy to important endothelial populations can be accomplished.
Asunto(s)
Antineoplásicos/toxicidad , Bleomicina/toxicidad , Endotelio Vascular , Neoplasias Experimentales/irrigación sanguínea , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Resistencia a Medicamentos , Técnicas de Transferencia de Gen , Terapia Genética , Ratones , Datos de Secuencia Molecular , Fibrosis Pulmonar/inducido químicamenteRESUMEN
Flavone acetic acid (FAA) is an antineoplastic agent that has undergone extensive study in Phase I trials. Concentration-dependent plasma protein binding has been demonstrated in vitro at concentrations of total drug that are achieved in vivo. Moreover, dose-dependent total systemic clearance has been described when FAA has been administered as a short iv infusion. When administered as a prolonged 24-hr infusion, total FAA (bound plus unbound) plasma pharmacokinetics are well described with a first-order two-compartment model. However, measurement of unbound FAA intra- and post-intravenous infusion in eight patients revealed a twofold increase in fraction of FAA unbound in plasma intrainfusion. We attempted to fit pharmacokinetic structural models of varying complexity to the unbound concentrations alone and simultaneously to the unbound and bound FAA plasma concentrations. The data were adequately described only by a model that incorporated simultaneous saturable plasma protein binding and a Michaelis-Menten process for elimination. A comparison among models is presented, as well as pharmacokinetic parameter estimates for FAA in children. These clinical data are consistent with predictions of the clearance model in which both saturable protein binding (resulting in a dynamically increasing unbound fraction) and saturable elimination (resulting in gradually decreasing unbound intrinsic clearance) are operative.
Asunto(s)
Antineoplásicos/farmacocinética , Flavonoides/farmacocinética , Neoplasias/metabolismo , Antineoplásicos/sangre , Niño , Flavonoides/sangre , Humanos , Cinética , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Neoplasias Experimentales/sangre , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Unión ProteicaRESUMEN
An improved high-performance liquid chromatographic assay is presented for the determination of 7-ethoxycoumarin O-deethylase activity. Following a 30-min microsomal incubation, 7-ethoxycoumarin, 4-methylumbelliferone (internal standard), and the metabolite umbelliferone were extracted with chloroform. Separation was achieved with an isocratic mobile phase using a microBondapak phenyl (300 mm x 3.9 mm I.D.) analytical column. The effluent was monitored by fluorescence detection with an excitation wavelength of 360 nm and an emission wavelength of 470 nm. The intra- and inter-assay coefficients of variation were 10 and 6%, respectively. A detection limit of 0.07 micrograms/ml was achieved, making this method suitable for characterizing P-450 activity of human livers.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cumarinas/análisis , Umbeliferonas/análisis , 7-Alcoxicumarina O-Dealquilasa/análisis , Cumarinas/metabolismo , Humanos , Microsomas Hepáticos/metabolismo , Umbeliferonas/metabolismoRESUMEN
Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Calcio/metabolismo , Homeostasis/efectos de los fármacos , Hipertensión/metabolismo , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Captopril/farmacología , Diltiazem/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Renina/sangreRESUMEN
Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Captopril/uso terapéutico , Diltiazem/uso terapéutico , Epinefrina/sangre , Hipertensión/tratamiento farmacológico , Norepinefrina/sangre , Renina/sangre , Adulto , Anciano , Preparaciones de Acción Retardada , Humanos , Hipertensión/sangre , Persona de Mediana EdadRESUMEN
The antihypertensive activity of a sustained-release preparation of diltiazem (given each 12 hours) was assessed in 96 patients with supine diastolic blood pressure (BP) between 95 and 110 mm Hg in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial comparing optimally titrated doses of diltiazem and placebo. The aim was to assess the onset of action as well as the extent and variability of BP control of this formulation during the 12-hour interval. Diltiazem was titrated from 120 mg bid to 180 mg bid as necessary to lower BP. At baseline, on the first day of titration, and at the end of 8 weeks, BP was evaluated at 0, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dosing. The onset of action was within 2 hours, and the effect was maintained throughout the 12-hour period. Mean BP for the diltiazem group at baseline was 154/101 mm Hg. At week 8, BP was 148/93 mm Hg at hour "0" (P less than .02 and P = .0001 for systolic and diastolic BP vs. placebo), 139/84 mm Hg at the nadir at hour 5 (P = .0001), and 149/91 mm Hg at the end of the 12-hour period (P less than .02 and P = .0001 for systolic and diastolic BP). Diltiazem was significantly more effective than placebo (P = .0001) with 50% of patients controlled to a diastolic pressure of less than 90 mm Hg at 7 of the 10 evaluation points, including the evaluation point of 12 hours post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diltiazem/administración & dosificación , Hipertensión/tratamiento farmacológico , Anciano , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Preparaciones de Acción Retardada , Diltiazem/uso terapéutico , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Postura , Distribución Aleatoria , Factores de TiempoRESUMEN
The effect of diuretics to increase serum glucose, low-density lipoprotein cholesterol and triglycerides, as well as the adverse changes in triglycerides and high-density lipoprotein cholesterol produced by nonselective beta blockers, have been largely ignored in the treatment of hypertension. However, a number of trials have shown that reductions in serum lipids can alter cardiovascular mortality. Calcium antagonists have become major drugs in the treatment of hypertension, and some data suggest that calcium antagonists may increase serum glucose levels. Significantly less data on lipid effects have been published. Lipid and glucose effects were examined in an 8-week antihypertensive study using a sustained-release preparation of diltiazem titrated from 240 to 360 mg/day in a twice-daily regimen in a randomized, double-blind, placebo-controlled parallel trial in 96 patients. Average supine blood pressure at week 8 was 156/98 mm Hg, standing blood pressure with placebo 152/100 mm Hg, and with diltiazem 147/91 and 144/93 mm Hg. There were no statistically significant changes in serum lipids or glucose in the diltiazem or placebo group or between the groups. Mean values (mg/dl) at baseline and week 8 in the diltiazem group were, respectively, for cholesterol 215 and 218, high-density lipoprotein cholesterol 50 and 51, low-density lipoprotein cholesterol 128 and 133, triglycerides 169 and 175, and glucose 113 and 110. Thus, this large and placebo-controlled study shows that diltiazem is among the antihypertensives with no adverse long-term lipid or glucose effects.
Asunto(s)
Glucemia/metabolismo , Diltiazem/farmacología , Hipertensión/tratamiento farmacológico , Lípidos/sangre , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Distribución AleatoriaRESUMEN
From Nov 22, 1983 through May 15, 1984, 36 crossbred steers were allotted into 3 treatment groups (12/group) and were grazed on separate 3.4-hectare pastures. On Nov 22, 1983, the steers were administered a single morantel sustained-release bolus (MSRB), orally (group 1), or a single dose of thiabendazole (TBZ; 66 mg/kg of body weight, orally; group 2), or were left untreated (group 3; controls). Animal weights, nematode egg counts in fecal specimens, and plasma pepsinogen concentrations were monitored monthly. At the termination of the study, 4 steers from each treatment group were slaughtered and necropsied and worm counts were determined. A set of parasite-free tracer calves (3/treatment group) were grazed with each treatment group for 1 month, beginning on Nov 22, 1983; a second set of tracer calves (3/group) were grazed with each treatment group for 1 month, beginning Apr 3, 1984. At the end of their respective grazing periods, tracer calves were held for 3 weeks and then were slaughtered and necropsied and their worm counts were determined. Mean nematode egg counts in fecal specimens of group 1 (MSRB treated) were significantly lower (P less than 0.05) than that of the TBZ-treated or nontreated steers. Differences in worm counts were not found between treatment groups. Differences in worm counts of tracer calves were not found among the 3 groups for November 1983 nor for April 1984. Steers treated with the MSRB had a higher mean weight gain (P less than 0.06) than did the control or TBZ-treated steers.
Asunto(s)
Enfermedades de los Bovinos/parasitología , Enfermedades Gastrointestinales/veterinaria , Morantel/uso terapéutico , Pirimidinas/uso terapéutico , Tiabendazol/uso terapéutico , Animales , Bovinos , Enfermedades de los Bovinos/prevención & control , Preparaciones de Acción Retardada , Enfermedades Gastrointestinales/parasitología , Enfermedades Gastrointestinales/prevención & control , Parasitosis Intestinales/prevención & control , Parasitosis Intestinales/veterinaria , Masculino , MississippiRESUMEN
The antihypertensive effect of enalaprilat (MK-422), an intravenous (IV), nonsulfhydryl converting-enzyme inhibitor, was evaluated in a double-blind study of 14 patients with mild to moderate hypertension. The seven patients in the treatment group initially received IV enalaprilat 1.25 mg q6h for 24 hours. Thereafter, responding patients (diastolic blood pressure [BP] less than or equal to 95 mm Hg) continued receiving this dose q6h for an additional 24 hours, whereas nonresponding patients were increased to IV enalaprilat 5 mg q6h for another 24 hours. Baseline BP for enalaprilat was 161 +/- 5/107 +/- 2 mm Hg (+/- SEM), and for placebo it was 150 +/- 5/103 +/- 2 mm Hg. Within the first 60 minutes, a significant reduction in both systolic and diastolic BP was noted in the enalaprilat group (P less than .05), without significant changes occurring in the placebo group. Although there was a gradual decline in both systolic and diastolic BP throughout the 48-hour study period in the placebo group, systolic and diastolic BP reduction was greater in the enalaprilat group, reaching a maximal decrease of 133 +/- 3/87 +/- 3 mm Hg. Adverse side effects did not occur in any patient.
Asunto(s)
Antihipertensivos/uso terapéutico , Enalapril/análogos & derivados , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Antihipertensivos/efectos adversos , Ensayos Clínicos como Asunto , Método Doble Ciego , Enalapril/efectos adversos , Enalapril/uso terapéutico , Enalaprilato , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución AleatoriaRESUMEN
The effect of enalaprilat (MK-422), a newly synthesized, intravenous, nonsulfhydryl, angiotensin-converting enzyme inhibitor, was studied in seven patients with either severe or malignant hypertension. All subjects initially received a 1 mg bolus injection of enalaprilat followed in 30 minutes by 10 mg. Five subjects received an additional 40 mg. Mean (+/- SE) pretreatment blood pressure for the group was 226 +/- 9/141 +/- 7 mm Hg. Five minutes after the 1 mg enalaprilat dose, blood pressure decreased to 211 +/- 10/131 +/- 9 mm Hg and further fell to 201 +/- 14/123 +/- 11 mm Hg at 30 minutes. The maximal reduction in blood pressure to 169 +/- 14/112 +/- 10 mm Hg occurred 30 minutes after the 10 mg dose. No further blood pressure reduction was observed in those subjects who received the additional 40 mg dose. Within the entire group, five subjects exhibited sustained blood pressure reduction. No adverse side effects or symptomatic hypotension occurred in any subject.