RESUMEN

A study was conducted in Argentina, to investigate the period of protection of a single injection of doramectin administered subcutaneously (s.c.) at 200 micrograms kg-1 (1 ml/50 kg) compared with single treatments of ivermectin (200 micrograms kg-1 s.c.) and fenbendazole (5 mg kg-1 p.o.), against field infections of gastrointestinal parasites of cattle. Eighty-three animals were selected and ranked on the basis of serial fecal egg counts (e.p.g.'s). From this group, three animals were slaughtered before treatment and their lungs, abomasum, small and large intestines, were processed for parasite counts and identification. The remaining 80 animals were allocated in ranked groups of four to a control or one of three treated groups. Animals of the four groups were grazed together in the same pasture for the duration of the study. Treatments were administered on Day 0. Individual fecal samples were collected at weekly intervals for the first 49 days post-treatment and twice a week from Day 52 to Day 84 (end of study). At each collection day fecal samples were pooled for coprocultures. On Day 28 and 56, two animals from each group, previously identified on Day 0, were killed and their parasite burdens determined. The duration of protection of a single injection of doramectin was longer than ivermectin or fenbendazole treatment. On Day 56, the total number of parasites found in doramectin-treated animals was significantly (P < 0.05) lower than parasite burdens found in either ivermectin- or fenbendazole-treated animals. The longer persistent activity of doramectin was expressed by the lower number of adults and L4 stages of Ostertagia ostertagi. Data from this experiment demonstrated the limitations of using fecal egg counts to evaluate the persistent efficacy of anthelmintics. The duration of activity of doramectin was demonstrated more accurately by parasite counts in cattle from each group since decreasing e.p.g.'s were seen in non-medicated animals without changes in total parasite burdens.

Asunto(s)

Antihelmínticos/uso terapéutico , Enfermedades de los Bovinos , Fenbendazol/uso terapéutico , Enfermedades Gastrointestinales/veterinaria , Ivermectina/análogos & derivados , Ivermectina/uso terapéutico , Infecciones por Nematodos/veterinaria , Animales , Antihelmínticos/administración & dosificación , Bovinos , Heces/parasitología , Femenino , Fenbendazol/administración & dosificación , Enfermedades Gastrointestinales/parasitología , Enfermedades Gastrointestinales/prevención & control , Inyecciones Subcutáneas , Ivermectina/administración & dosificación , Masculino , Infecciones por Nematodos/prevención & control , Orquiectomía , Recuento de Huevos de Parásitos

RESUMEN

Experiments were designed to characterize endothelin receptors in arteries after chronic increases in blood flow. A fistula was created between the femoral artery and vein in one hindlimb of dogs; contralateral blood vessels were sham operated. Sham- and fistula-operated arteries were removed 6 wk postoperatively. Some arteries were prepared for measurement of isometric force or for isolation of membrane proteins. Other arteries were used for histological staining with an endothelin-B (ETB) receptor antibody. In arteries suspended for the measurement of isometric force, endothelin-1 produced concentration-dependent increases in tension that were significantly greater in fistula- than in sham-operated arteries without endothelium. The ETB-receptor-selective peptide sarafotoxin S6c produced concentration-dependent increases in tension only in fistula-operated arteries. In receptor-binding studies of membrane proteins, Scatchard analysis of saturation binding with 125I-labeled endothelin-1 (125I-endothelin-1) indicated that the total number of receptors was greater in fistula-operated arteries; affinity was threefold less in fistula- than in sham-operated arteries. Competitive displacement of 125I-endothelin-1 by endothelin-3 was significant for a two-site model in membranes prepared from sham-and fistula-operated arteries. Competitive inhibition of 125I-endothelin-1 binding by sarafotoxin S6c was significant for a one-site binding model in all arteries. Sarafotoxin S6c binding sites were elevated significantly in fistula-operated arteries. Immunohistochemical staining for the ETB receptor was significantly greater in both the endothelium and smooth muscle of fistula- than in sham-operated arteries. These results suggest that chronic increases in blood flow upregulate endothelin receptors, including ETB receptors in arterial smooth muscle.

Asunto(s)

Arterias/metabolismo , Circulación Sanguínea/fisiología , Músculo Liso Vascular/metabolismo , Receptores de Endotelina/metabolismo , Regulación hacia Arriba , Animales , Sitios de Unión , Unión Competitiva , Perros , Endotelina-1/metabolismo , Femenino , Inmunohistoquímica , Masculino , Técnicas de Cultivo de Órganos/métodos , Receptor de Endotelina B , Análisis de Regresión , Factores de Tiempo , Venenos de Víboras/metabolismo

RESUMEN

The anticoccidial efficacies of semduramicin and salinomycin against five field isolates of Eimeria maxima in broiler chickens were compared in five trials. Uninfected, unmedicated; infected, unmedicated; infected, 25 ppm semduramicin; and infected, 66 ppm salinomycin treatments were assigned to battery cages using a randomized, complete block design. Two levels of inocula, 10(3) and 10(4) oocysts per bird, were used in each trial in the infected treatments, creating a total of seven treatments per trial. Each treatment consisted of five replicate cages of eight broiler cockerels each. Medications were given in the feed continuously for 7 d beginning 24 h before inoculation. Response variables measured included bird weight gain by pen, feed consumption, feed conversion, plasma carotenoid concentrations, and coccidial lesion score. By using two levels of inocula it was demonstrated that the efficacy of each anticoccidial was equal to or greater than 90% in controlling these E. maxima isolates. It was also demonstrated that 25 ppm semduramicin was more efficacious than 66 ppm salinomycin based on improvements in weight gain, feed conversion, plasma carotenoid concentrations, and coccidial lesion control.

Asunto(s)

Antibacterianos/uso terapéutico , Pollos/parasitología , Coccidiosis/veterinaria , Coccidiostáticos/uso terapéutico , Eimeria/efectos de los fármacos , Nigericina/análogos & derivados , Enfermedades de las Aves de Corral/tratamiento farmacológico , Piranos/uso terapéutico , Animales , Antibacterianos/normas , Carotenoides/sangre , Pollos/sangre , Pollos/fisiología , Coccidiosis/tratamiento farmacológico , Coccidiostáticos/normas , Ingestión de Alimentos/fisiología , Eimeria/aislamiento & purificación , Masculino , Nigericina/normas , Nigericina/uso terapéutico , Piranos/normas , Aumento de Peso/efectos de los fármacos , Aumento de Peso/fisiología

RESUMEN

Experiments were designed to characterize endothelin receptors in canine femoral veins and to determine whether their distribution or sensitivity could be altered by chronic changes in blood flow and oxygen tension in veins proximal to an arteriovenous fistula. Endothelium was removed from unoperated or fistula-operated femoral veins of anesthetized dogs. Veins were cut into rings and suspended in organ chambers for the measurement of isometric force or frozen for isolation of membrane proteins. Endothelin-1, endothelin-3, and sarafotoxin S6c caused concentration-dependent increases in tension in all rings. In rings of unoperated veins, maximal tensions were significantly less to endothelin-3 and sarafotoxin S6c than to endothelin-1. In rings of fistula-operated veins, maximal tensions to endothelin-1 and endothelin-3 were the same. Contractions to endothelin-1 or endothelin-3 in unoperated veins were not inhibited by an antagonist of endothelin-A receptors, BQ-123. Binding of 125I-labeled endothelin-1 (125I-endothelin-1) to membranes from veins without endothelium increased as a function of membrane protein. Affinity of receptors, as determined by competitive inhibition of 125I-endothelin-1 was as follows: endothelin-1 > endothelin-3 > sarafotoxin S6c. Competitive inhibition of 125I-endothelin-1 by endothelin-3 and sarafotoxin S6c was significant for a two-site binding model in all veins. The total number of binding sites was reduced significantly in fistula-operated veins; the relative proportions of high- and low-affinity binding sites did not change. Affinity of high- and low-affinity receptors increased in fistula-operated veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Endotelinas/farmacología , Vena Femoral/fisiología , Contracción Muscular/efectos de los fármacos , Receptores de Endotelina/fisiología , Acetilcolina/farmacología , Animales , Derivación Arteriovenosa Quirúrgica , Unión Competitiva , Membrana Celular/fisiología , Dinoprost/farmacología , Perros , Relación Dosis-Respuesta a Droga , Antagonistas de los Receptores de Endotelina , Endotelinas/metabolismo , Endotelio Vascular/fisiología , Femenino , Vena Femoral/efectos de los fármacos , Técnicas In Vitro , Indometacina/farmacología , Cinética , Masculino , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Norepinefrina/farmacología , Péptidos Cíclicos/farmacología , Fentolamina/farmacología , Propranolol/farmacología , Vasoconstrictores/farmacología , Venenos de Víboras/farmacología

RESUMEN

The in vitro susceptibility of 839 isolates of Actinobacillus pleuropneumoniae, 969 isolates of Pasteurella multocida and 104 isolates of Salmonella choleraesuis from pigs to the fluoroquinolone danofloxacin, and eight other commonly used antimicrobial drugs was determined by veterinary diagnostic laboratories in Europe, Japan, South Africa and North America between 1989 and 1991, by using a broth microdilution technique. The minimum inhibitory concentrations of danofloxacin, amoxycillin, ceftiofur, erythromycin, gentamicin, lincomycin, oxytetracycline, spectinomycin and trimethoprim:sulphamethoxazole (ratio 1:19) that prevented the growth of 90 per cent of the bacteria were 0.125, < or = 0.5, < or = 0.125, 8, 8, 32, 32, 64 and < or = 0.25 microgram/ml for A pleuropneumoniae, 0.06, 1, < or = 0.125, 8, 4, 64, 8, 32 and 8 micrograms/ml for P multocida, and 0.125, > 64, < or = 1, > 64, 1, > 64, > 64, 64 and < or = 0.25 microgram/ml for S choleraesuis. These data confirm the high in vitro potency of danofloxacin against field isolates that show significant resistance to several other antibacterial drugs.

Asunto(s)

Actinobacillus pleuropneumoniae/efectos de los fármacos , Antibacterianos/farmacología , Pasteurella multocida/efectos de los fármacos , Salmonella/efectos de los fármacos , Enfermedades de los Porcinos/microbiología , Infecciones por Actinobacillus/microbiología , Infecciones por Actinobacillus/veterinaria , Actinobacillus pleuropneumoniae/aislamiento & purificación , Animales , Farmacorresistencia Microbiana , Pruebas de Sensibilidad Microbiana/veterinaria , Técnicas Microbiológicas/veterinaria , Infecciones por Pasteurella/microbiología , Infecciones por Pasteurella/veterinaria , Pasteurella multocida/aislamiento & purificación , Salmonella/aislamiento & purificación , Salmonelosis Animal/microbiología , Porcinos

RESUMEN

The relationships between nucleotide (ATP, ADP, AMP, NADPH, NADP(+), NADH and NAD(+)) concentrations and the metabolism of the hepatocarcinogen 2,6-dinitrotoluene (2,6-DNT) in cultured slices of rat liver were investigated. ATP, NADPH and NADH concentrations in freshly prepared rat liver slices at the beginning of culture were 48-67% lower than those measured in freeze-clamped rat liver (in vivo values). ATP concentrations in cultured liver slices increased with time of incubation, and after 4 hr ATP concentrations in liver slices were 25% greater than in vivo values. In contrast, NADPH and NADH concentrations did not recover with time of culture, and after 4 hr NADPH and NADH concentrations in liver slices were 50 and 24% of in vivo values, respectively. The addition of ethanol (50 mm) to cultured liver slices increased NADH concentrations by 132%, relative to untreated liver slices. Treatment of liver slices with ammonium chloride (10 mm), 6-aminonicotinamide (1 mm), or the substitution of fructose for glucose in the incubation medium significantly decreased NADPH concentrations by 64, 44 and 63%, respectively. All treatments significantly decreased ATP concentrations; fructose was the most effective agent tested and decreased liver slice ATP concentrations by 69%. These results indicate that the changes in liver slice nucleotide concentrations that occur during culture are not irreversible, and we suggest that these changes are a homoeostatic response to culture conditions and not a reflection of tissue damage or cytotoxicity. Rates of 2,6-dinitrotoluene metabolism by rat liver slices were unaffected by fructose or ammonium chloride, despite the decrease in NADPH concentrations produced by these agents. These results suggest that NADPH concentrations are not rate-limiting to 2,6-DNT metabolism by rat liver slices.

RESUMEN

Liver slice tissue culture was used to compare human and rat liver metabolism of 2,6-dinitrotoluene (2,6-DNT). Oxidative metabolism of the 2,6-DNT side-chain methyl moiety produced 2,6-dinitrobenzylalcohol and the glucuronide conjugate of 2,6-dinitrobenzylalcohol, and reductive metabolism of the 2,6-DNT nitro groups produced 2-amino-6-nitrotoluene. Metabolites derived from side-chain oxidation accounted for 90-95% of the 2,6-DNT metabolites produced by rat liver slices under ambient oxygen concentrations of 25-100%; however, under 0% oxygen (100% nitrogen) atmospheres 2-amino-6-nitrotoluene accounted for 96% of the total metabolites. An increase in slice thickness from 0.3 to 0.8 mm decreased the ratio of oxidized to reduced 2,6-DNT metabolites produced by rat liver from 9:1 to 1:1. Under 100% oxygen and in liver slices approximately 0.3 mm thick, average rates of 2,6-DNT oxidative metabolism by human (five subjects) and rat liver were 1.0 and 2.1 nmol/min/g liver, respectively. K(m) and V(max) for the oxidative metabolism of 2,6-DNT by rat liver slices were 0.38 mm and 12 nmol/min/g liver, respectively. The average K(m) and V(max) for the oxidative metabolism of 2,6-DNT by two human subjects were 0.019 mm and 0.91 nmol/min/g liver, respectively.

RESUMEN

The in vitro susceptibility of Escherichia coli and Pasteurella multocida isolated from poultry was determined to danofloxacin, a novel fluoroquinolone, and five other commonly used antimicrobials. A total of 1737 E. coli field isolates and 107 P. multocida isolates were tested by veterinary diagnostic laboratories in Europe, Japan, South Africa, and North America during the period 1989-91. The antimicrobial susceptibility of these isolates was determined using the Sensititre broth microdilution technique. The minimum inhibitory concentrations (MIC) of danofloxacin, furaltadone, lincomycin, oxytetracycline, spectinomycin, and trimethoprim:sulfamethoxazole that prevented growth of 90% of the bacteria were 0.25 > 64, > 64, > 64, > 128, and > 16 micrograms/ml, respectively, against E. coli isolates and 0.25, 64, 64, 16, 128, and 8 micrograms/ml, respectively, against P. multocida isolates. Danofloxacin demonstrated considerable in vitro potency against these important poultry pathogens, many of which showed extensive resistance to the other antimicrobials tested.

Asunto(s)

Antibacterianos/farmacología , Pollos/microbiología , Escherichia coli/efectos de los fármacos , Fluoroquinolonas , Pasteurella multocida/efectos de los fármacos , Quinolonas/farmacología , Animales , Pruebas de Sensibilidad Microbiana/veterinaria , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/microbiología

RESUMEN

1. 2,6-Dinitrotoluene (2,6-DNT) metabolism by human liver and male Fischer F344 rat liver subcellular fractions under aerobic (100% oxygen) and anaerobic (100% nitrogen) incubation conditions was examined. Under aerobic conditions the major 2,6-DNT metabolite formed by hepatic microsomes was 2,6-dinitrobenzyl alcohol (2,6-DNBalc); under anaerobic conditions 2-amino-6-nitrotoluene (2Am6NT) was the major metabolite. 2. Rates of 2,6-DNBalc formation by human and rat liver microsomes under aerobic conditions were 247 and 132 pmol/min per mg protein, respectively. Rates of 2Am6NT formation by human and rat liver microsomes under anaerobic conditions were 292 and 285 pmol/min per mg protein, respectively. Anaerobic reduction of 2,6-DNT to 2Am6NT by rat and human liver microsomes was inhibited by carbon monoxide and metyrapone, which indicates that microsomal metabolism of 2,6-DNT to 2Am6NT is mediated by cytochrome P-450. 3. Liver cytosolic fractions also metabolized 2,6-DNT to 2Am6NT under anaerobic conditions. Formation of 2Am6NT by human and rat liver cytosols was supported by hypoxanthine, NADPH and NADH. Allopurinol inhibited the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by rat, but not human, liver cytosol. Dicumarol inhibited the NADPH-supported anaerobic metabolism of 2,6-DNT by human, but not rat, liver cytosol. These results indicate that xanthine oxidase contributes to the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by human liver cytosol.

Asunto(s)

Citosol/metabolismo , Dinitrobencenos/metabolismo , Hígado/metabolismo , Microsomas Hepáticos/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Humanos , Masculino , NADP/metabolismo , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Tritio

RESUMEN

Previous studies indicate that tris(2-chloroethyl)phosphate (TCP) preferentially produces hippocampal brain lesions in female versus male rats, and the expression of these lesions is inversely related to the in vivo rate of TCP metabolism. In the present studies, TCP (0.17 mM in all incubations) was metabolized in vitro by liver slices and microsomes from human and Fischer 344N rat liver to bis(2-chloroethyl) hydrogen phosphate (BCP), 2-chloroethanol (CE), and three unidentified metabolites. The rate of TCP metabolism by male rat liver microsomes and liver slices was 0.049 nmol/min/mg protein and 2.53 nmol/min/g liver, respectively. TCP metabolism by male rat liver microsomes was inhibited by 10 microM diisopropyl fluorophosphate, 10 microM paraoxon and carbon monoxide. TCP did not appear to be metabolized by female rat liver microsomes, but female rat liver slices metabolized TCP at a rate of 1.51 nmol/min/g liver. TCP was metabolized by male and female rat plasma at a rate of 0.156 and 0.169 nmol/ml plasma, respectively. TCP was metabolized by male and female human liver microsomes at a rate of 0.027 and 0.031 nmol/min/mg protein, respectively. TCP was metabolized by male and female human liver slices at a rate of 1.37 and 1.82 nmol/min/g liver, respectively. BCP and CE were the major metabolites formed in all studies, except for liver slices and microsomes from two human male subjects in which an unidentified metabolite constituted 29 to 38% of the total TCP metabolism. TCP was not metabolized by plasma or whole blood from male or female human subjects. These results support the previously reported sex-specific difference in TCP metabolism by male and female Fischer 344N rats. However, no sex-specific difference in rates of TCP metabolism by male and female human liver microsomes or slices was observed.

Asunto(s)

Retardadores de Llama/metabolismo , Hígado/metabolismo , Organofosfatos/metabolismo , Adulto , Anciano , Animales , Biotransformación , Cromatografía Líquida de Alta Presión , Citosol/metabolismo , Femenino , Humanos , Masculino , Microsomas Hepáticos/metabolismo , Persona de Mediana Edad , Organofosfatos/sangre , Ratas , Ratas Endogámicas F344 , Factores Sexuales , Especificidad de la Especie

RESUMEN

Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5 patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80-120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations greater than 140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course.

Asunto(s)

Diarrea/sangre , Péptido Intestinal Vasoactivo/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Cromatografía en Gel , Enfermedad Crónica , Diarrea/etiología , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Radioinmunoensayo

RESUMEN

The in vitro metabolism of [14C]toluene by liver microsomes and liver slices from male Fischer F344 rats and human subjects has been compared. Rat liver microsomes produced only benzyl alcohol from toluene. Liver microsomes from human subjects metabolized toluene to benzyl alcohol, benzaldehyde, and benzoic acid. Liver microsomes from one human donor also produced p-cresol and o-cresol. The overall rate of toluene metabolism by human liver microsomes was 9-fold greater than by rat liver microsomes. Human liver microsomal metabolism of benzyl alcohol to benzaldehyde required NADPH and was inhibited by carbon monoxide and high pH (pH 10). but was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P-450, rather than alcohol dehydrogenase, was responsible for the metabolism of benzyl alcohol to benzaldehyde. Human and rat liver slices metabolized toluene to hippuric acid and benzoic acid. The overall rate of toluene metabolism by human liver slices was 1.3-fold greater than by rat liver slices. Cresols and cresol conjugates were not detected in human or rat liver slice incubations. Covalent binding of [14C]toluene to human liver microsomes and slices was 21-fold and 4-fold greater than to the comparable rat liver preparations. Covalent binding did not occur in the absence of NADPH, was significantly decreased by coincubation with cysteine, glutathione, or superoxide dismutase, and was unaffected by coincubation with lysine. Protease and ribonuclease digestion decreased the amount of toluene covalently bound to human liver microsomes by 78% and 27% respectively. Acid washing of human liver microsomes had no effect on covalent binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Hígado/metabolismo , Microsomas Hepáticos/metabolismo , Tolueno/metabolismo , Consumo de Bebidas Alcohólicas , Animales , Alcohol Bencilo , Alcoholes Bencílicos/metabolismo , Cromatografía Líquida de Alta Presión , Humanos , Hidrólisis , Técnicas In Vitro , Riñón/metabolismo , Unión Proteica , Ratas , Ratas Endogámicas F344 , Fumar/metabolismo , Espectrofotometría Ultravioleta

RESUMEN

The distribution of galanin-like immunoreactivity in various regions of the central nervous system was assessed in three mammalian species, pig, rat, and human, by radioimmunoassay. Galanin concentrations were highest in the hypothalamus and pituitary region. In spinal cord, there was a rostrocaudal/dorsoventral gradient with highest levels observed in the sacral dorsal horn. Serial dilutions of porcine tissue extracts diluted parallel to the porcine standard curve, while the rat and human tissue extracts did not. In all tissues examined by high pressure liquid chromatography, the principal peak of immunoreactivity coeluted with the authentic porcine galanin standard and was decreased by trypsin cleavage. These results suggest a role for galanin in the central nervous system and support species differences in the structure of galanin.

Asunto(s)

Sistema Nervioso Central/química , Neuropéptidos/análisis , Péptidos/análisis , Animales , Especificidad de Anticuerpos , Cromatografía Líquida de Alta Presión , Galanina , Humanos , Radioinmunoensayo , Ratas , Especificidad de la Especie , Porcinos

RESUMEN

Concentrations of gastrointestinal neuropeptides in serial human milk samples from 28 women were determined over the first 6 postpartum mo. All gut neuropeptides were present during the first postpartum week. Gastric inhibitory peptide (GIP) concentration remained constant but the others decreased by 6 wk. Bombesin concentration in breast milk was threefold greater than concurrent plasma concentration (p less than 0.001); all other neuropeptides were at the same or lower concentrations in milk than in plasma. At 36 wk gestation plasma concentrations of GIP were lower and concentrations of vasoactive intestinal peptide were higher than concentrations in age-matched control subjects. Concentrations of gastrin and cholecystokinin, bombesin, peptide histidine methionine, peptide YY, and neurotensin in plasma were similar in pregnant and nonpregnant women. These gut neuropeptides in milk may be important for growth and maturation of the gastrointestinal system in neonates. Bombesin may contribute to neonatal hypergastrinemia.

Asunto(s)

Polipéptido Inhibidor Gástrico/análisis , Leche Humana/análisis , Neuropéptidos/análisis , Periodo Posparto , Adulto , Bombesina/análisis , Colecistoquinina/análisis , Femenino , Polipéptido Inhibidor Gástrico/sangre , Gastrinas/análisis , Humanos , Neuropéptido Y/análisis , Neuropéptidos/sangre , Neurotensina/análisis , Péptido PHI/análisis , Embarazo , Péptido Intestinal Vasoactivo/análisis

RESUMEN

The sequence for peptide histidine-methionine is present within the same preprohormone as vasoactive intestinal polypeptide. Since our previous study using radioimmunoassay had demonstrated significantly decreased colonic concentrations of vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis compared to normal colon, we determined the distribution and quantitation of peptide histidine-methionine. Fresh surgical specimens were dissected into mucosal-submucosal and muscularis externa layers prior to acid extraction and specific radioimmunoassay. One immunoreactive species that appeared to coelute with peptide histidine-methionine was separated by reverse-phase high-performance liquid chromatography. Mucosal-submucosal concentrations of peptide histidine-methionine were significantly decreased in ulcerative colitis and Crohn's colitis, compared to those in normal colon. In normal ileum and colon, linear correlation analysis showed no relationship between patient age and tissue concentrations of peptide histidine-methionine. However, a parallel decrease in molar concentrations of peptide histidine-methionine and vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis was demonstrated by linear correlation analysis. These results are consistent with the hypothesis that peptide histidine-methionine and vasoactive intestinal polypeptide are colocalized within the same neural structures that have been altered in the idiopathic inflammatory bowel diseases.

Asunto(s)

Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/metabolismo , Mucosa Intestinal/metabolismo , Péptido PHI/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Cromatografía Líquida de Alta Presión , Colitis Ulcerosa/patología , Colon/metabolismo , Colon/patología , Enfermedad de Crohn/patología , Humanos , Íleon/metabolismo , Íleon/patología , Mucosa Intestinal/patología , Persona de Mediana Edad , Radioinmunoensayo , Péptido Intestinal Vasoactivo/metabolismo

RESUMEN

Levels of substance P (sP), peptide-histidine-isoleucine (PHI), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), neurotensin (NT), bombesin (BOM) and methionine-enkephalin (Met-Enk) like immunoreactivity were measured in cat, dog, primate and sloth cervical, thoracic, lumbar and sacral dorsal and ventral horns and dorsal root ganglia. The levels of peptides in the cat sacral cord and the principal peaks of immunoreactivity on a 10-60% acetonitrile gradient on a C18 reverse phase high performance liquid chromatography (HPLC) were sP (sP1-11: 369 ng/g), PHI (PHI: 271 ng/g), VIP (VIP1-28: 210 ng/g), Met-Enk (Met1-5 and extended forms: 257 ng/g), BOM (BOM1-10 and GRP1-27: 20 ng/g), CCK (CCK-8: 15 ng/g) and NT (NT1-13: 10 ng/g). Consideration of the rostrocaudal levels revealed an approximately even distribution with the exception of VIP and PHI which showed sacral/cervical ratios of 79 and 63. For sP, Met-Enk and BOM dorsal/ventral ratios were greater than 1 at all spinal levels. For VIP, PHI and CCK these ratios were greater than 1 only in the sacral cord. Dorsal root ganglion (DRG) levels of sP, VIP, PHI were readily measurable in single ganglia and covaried with the respective levels in the dorsal cord. Pooled samples of spinal ganglia and the trigeminal ganglia revealed that the relative levels of peptide immunoreactivity were: sP (25 ng/g); VIP (26 ng/g); PHI (28 ng/g); Met-Enk (6 ng/g); CCK (2 ng/g); NT (1 ng/g); and BOM (1 ng/g).

Asunto(s)

Bombesina/análisis , Colecistoquinina/análisis , Encefalina Metionina/análisis , Neurotensina/análisis , Péptido PHI/análisis , Médula Espinal/análisis , Sustancia P/análisis , Péptido Intestinal Vasoactivo/análisis , Animales , Aotus trivirgatus , Gatos , Perros , Macaca mulatta , Especificidad de Órganos , Valores de Referencia , Perezosos

RESUMEN

The application of radioimmunoassay of insulin, C-peptide, gastrin, glucagon, vasoactive intestinal polypeptides (VIP), somatostatin, human pancreatic polypeptides (hPP), substance P and neurotensin to detect endocrine tumors of the pancreas and other organ systems is undoubtedly important in the clinical management of patients suspected of having tumors that secrete these hormones. Radioimmunoassays of the above gut peptides have certain degrees of specificity and sensitivity; however, there are several factors that need to be considered in the interpretation of results since heterogeneity of molecular forms does occur and the varied radioimmunoassay techniques use different antibodies that may yield different results. It is, therefore, important that each laboratory establish its own normal values, determine the molecular species that each assay is detecting, and also determine the false positivity of the methodology. The same endocrine tumor may contain and secrete several detectable peptides, but the syndrome may relate to only one peptide. Although the simultaneous measurement of multiple peptides in patients with benign gastrointestinal disease has yielded information that contributes to our understanding of the complexities of gut neuroendocrine interaction, the pathophysiological role of gut peptides and their clinical relevance need further evaluation.

Asunto(s)

Enfermedades Gastrointestinales/diagnóstico , Hormonas Gastrointestinales/sangre , Animales , Diagnóstico Diferencial , Digestión , Alimentos , Gastrinas/sangre , Humanos , Enfermedades Renales/sangre , Neoplasias Pancreáticas/diagnóstico , Polipéptido Pancreático/sangre , Radioinmunoensayo , Nervio Vago/fisiología , Péptido Intestinal Vasoactivo/sangre , Vipoma/diagnóstico , Síndrome de Zollinger-Ellison/diagnóstico

RESUMEN

An experiment involving 48 white leghorn layers fed 0, 10 and 100 p.p.m. of toxaphene has been conducted. Except for a slight decrease in egg production, no adverse effects on various performance parameters including fertility, hatchability and survival of progeny were observed. A significant increase (P less than .05) in average 7-day weights of progeny was noted.

Asunto(s)

Pollos/fisiología , Insecticidas/toxicidad , Toxafeno/toxicidad , Animales , Peso Corporal , Huevos , Femenino , Fertilidad , Oviposición