Effects of a histamine type 2 receptor antagonist, BMY-26539-01, on equine gastric acid secretion.

A dose-response study was undertaken of the effects of a newly developed histamine type 2 receptor antagonist, BMY-26539-01, on gastric acid secretion in 4 fasted horses. Doses of 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, or placebo were administered in a randomly assigned treatment sequence. Hydrogen ion concentration and pH were variable during baseline measurements in all 4 animals; however, following BMY-26539-01 administration, mean pH increased and hydrogen ion concentration decreased in a dose-related pattern. At the 0.3 mg/kg and 0.5 mg/kg dose levels, pH remained elevated for > 4 h and > 8 h, respectively. No adverse effects were observed. A significant level of 0.01 was used for all statistical methods.     

Inhibition of glucose-induced insulin secretion by somatostatin in goats

Somatostatin inhibited glucose-induced insulin secretion in intact goats. The duration of the inhibition was short (10 minutes) which suggests that somatostatin was rapidly metabolised. The inhibitory effect of somatostatin was followed by a recovery period during which high levels of insulin were attained. These higher concentrations of insulin in the 30 to 60 minutes after somatostatin infusion, were accompanied by lowered free fatty acid and beta-hydroxybutyrate concentrations. It is suggested that the effects of somatostatin on these metabolites is brought about by modulation of insulin secretion and not by a direct effect of somatostatin on target tissues.     

Effect of photoperiod and temperature on prolactin secretion in ovariectomized gilts

Five ovariectomized (OVX) gilts were placed in each of two chambers at 20 C with a photoperiod of 12 h light and 12 h dark for 8 d (12L:12D). On d 1, blood samples were collected via jugular cannula every 30 min from 0830 to 1630. At 1630, 200 micrograms of thyrotropin releasing hormone (TRH) were injected iv and blood samples taken every 10 min for 1 h and every 30 min for the next 2 h. On d 2, samples were taken every 30 min from 0830 to 0930 and from 1530 to 1630. Temperature was changed to 10 C or 30 C on d 3. Samples were taken from 0830 to 1630 on d 3, 4 and 9. At 1630 on d 9, the TRH challenge was repeated. Mean basal serum concentrations of prolactin (PRL) were similar for all gilts and for all periods. However, serum PRL response (ng PRL X ml-1 X 150 min-1) to TRH increased (P less than .0001) after exposure to 30 C, while exposure to 10 C failed to alter PRL response. In Exp. 2, six ovariectomized gilts were assigned to each chamber. The protocol of Exp. 1 was followed through d 3, except temperature and photoperiod were changed to 10 C and 8L:16D or 30 C and 16L:8D. On d 34 the TRH challenge was repeated. Mean basal serum concentration of PRL was similar for all gilts and all periods. However, simultaneous increases in temperature and photoperiod increased (P less than .005) serum PRL response to TRH, whereas simultaneous decreases in temperature and photoperiod failed to alter PRL response to TRH.     

Effects of a histamine type-2 receptor antagonist (BMY-25368) on gastric secretion in horses.

The effects of a potent new histamine-2 (H2) receptor antagonist, BMY-25368, were studied on gastric acid secretion in 5 foals from which food was withheld. Doses of 0.02, 0.11, 0.22, and 1.10 mg/kg of body weight were administered IM in a randomly assigned treatment sequence. Following BMY-25368 administration, hydrogen ion concentration was decreased and mean pH was higher than baseline values in a dose-response pattern. At the 0.22 and 1.10 mg/kg doses, the high pH was sustained for greater than 4 hours. The BMY-25368 thus may be useful for treating gastric ulcer disease in horses.     

Inhibition of lacteal leukocyte phagocytosis by colostrum, nonlactating secretion, and mastitic milk

The Fc receptors on leukocytes obtained from normal milk, colostrum, nonlactating gland secretion, and mastitic milk were detected by rosette formation, using sensitized erythrocytes. The percentage of leukocytes bearing Fc receptors from normal milk was significantly (P less than 0.01) greater than that from other secretions. Fc receptors were found primarily on polymorphonuclear leukocytes from normal milk, mastitic milk, and colostrum. However, in nonlactating gland secretion obtained 6 weeks after milking was completed, Fc receptors were predominantly on macrophages. The low percentage of leukocytes bearing Fc receptors obtained from colostrum, nonlactating gland secretion obtained 7 days after milking was completed, and mastitic milk was associated with the presence of a blocking factor in these secretions, which specifically attached to Fc receptors. These secretions significantly (P less than 0.01) blocked the Fc receptors on leukocytes from normal milk and on other cells bearing FC receptors. The presence of Fc receptors on leukocytes obtained from normal milk was related to a high percentage of phagocytizing leukocytes through Fc receptors and a large number of phagocytized bacteria (phagocytic activities). In contrast, the low percentage of leukocytes bearing Fc receptors from colostrum, from nonlactating gland secretion (7 days after milking), and from mastitic milk was associated with depressed phagocytic activities. Preincubation of leukocytes from normal milk with whey from colostrum, nonlactating gland secretion (7 days after milking), and mastitic milk significantly (P less than 0.01) inhibited phagocytosis. This effect was associated with the blocking of Fc receptors by these secretions. Possible mechanisms for and implications of these findings are discussed.     

Endogenous opioid modulation of luteinizing hormone and prolactin secretion in postpartum ewes and cows

A possible role for endogenous opioid peptides (EOP) in the control of luteinizing hormone (LH) and prolactin (PRL) secretion was studied by injecting the opioid antagonist, naloxone (NAL), into postpartum ewes and cows. Twelve ewes that lambed during the fall breeding season and nursed their lambs were injected iv with NAL (1.0 mg/kg) on d 10, 14, 18, 22 and 26 postpartum. Blood samples were collected at 15-min intervals from 2 h before to 2 h after NAL, and serum concentrations of LH and PRL were quantified. Following treatment on d 10, suckling lambs were removed from 6 of the 12 ewes, creating non-suckled (NS) and suckled (S) treatment groups for subsequent study on d 14 through 26. On d 10, NAL treatment increased LH (P less than .01) but concentrations of PRL were not affected. When averaged across d 14 to 26, post-NAL concentrations of LH were greater (P less than .001) than pre-NAL concentrations (6.5 +/- .7 vs 1.9 +/- .4 ng/ml). In contrast, concentrations of PRL in the post-NAL period were lower (P less than .001) than pre-NAL concentrations (129 +/- 15 vs 89 +/- 10 ng/ml). Compared with S ewes over d 14 to 26, those in the NS group had similar pre-NAL concentrations of LH, tendencies for higher (P less than .10) post-NAL concentrations of LH, lower (P less than .001) mean serum concentrations of PRL (pre- and post-NAL) and similar pre-NAL vs post-NAL differences in serum PRL. Six suckled beef cows on d 24 to 35 were injected iv with either saline or NAL (.5 mg/kg) in a replicated crossover design. Injections of NAL increased serum concentrations of LH (P less than .05), when averaged over all 12 injections in the six cows, but serum PRL was not changed. However, three of six cows did not respond to NAL with increases in serum LH. These non-responding cows were similar to the responding cows in their pre-injection concentrations of LH and PRL, but they tended (P = .10) to have higher serum concentrations of cortisol than responding cows.     

Effect of intraluteal injection of endothelin type A receptor antagonist on PGF2alpha-induced luteolysis in the cow

Endothelin-1 (ET-1) is a luteolytic mediator in the bovine corpus luteum (CL), and its action appears to be via endothelin type A receptor (ETR-A). Thus, the aim of the present study was to determine the effect of ETR-A antagonist on PGF2alpha-induced luteolysis in the cow. Cows on days 10-12 of the estrous cycle were subjected to five intraluteal injections of the ETR-A antagonist LU 135252 in saline or only saline at -0.5, 2, 4, 6, and 8 h after PGF2alpha administration (=0 h). Serial luteal biopsies were conducted to determine the expression of mRNA in the luteal tissue. There were no significant differences in the decrease in plasma progesterone (P) concentrations and the mRNA expressions of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase/Delta5, Delta4-isomerase between the ETR-A antagonist-treated group and the control group. However, the start of the decline in CL volume and blood flow area surrounding the CL was delayed for almost two days in the ETR-A antagonist-treated group compared to the control group. The mRNA expression of preproET-1 and endothelin type B receptor increased in both groups, while the ETR-A mRNA remained unchanged. In addition, caspase-3 mRNA expression increased significantly at 24 h in the control group only and its level was higher than that of the ETR-A antagonist-treated group. Thus, the present study suggests that ET-1 regulates structural luteolysis via ETR-A by controlling blood vessel contraction in the CL of the cow.     

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone

OBJECTIVE: The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. DESIGN: The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. PROCEDURE: Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. RESULTS: Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. CONCLUSIONS: Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.     

Expression of the cannabinoid receptor type 1 in the pituitary of rabbits and its role in the control of LH secretion

The aim of this study was to elucidate the possible direct regulatory role of the endocannabinoids in the modulation of LH secretion in rabbits, a reflex ovulator species. The cannabinoid receptor type 1 (CB1) was characterized by RT-PCR techniques in the anterior pituitary of intact and ovariectomized does treated with GnRH and primed with estrogen and CB1 antagonist, rimonabant. Cannabinoid receptor type 1 immune reaction was evidenced by immunohistochemistry in the cytoplasm of approximately 10% of the pituitary cells with a density of 8.5 ± 1.9 (per 0.01 mm²), both periodic acid–Schiff positive (30%) and negative (70%). All CB1-immunoreactive cells were also immune reactive for estrogen receptor type 1. Ovariectomy, either alone or combined with estrogen priming, did not modify the relative abundances of pituitary CB1 mRNA, but decreased (P < 0.01) the expression of estrogen receptor type 1 mRNA. Treatment with CB1 antagonist (rimonabant) inhibited (P < 0.01) LH secretory capacity by the pituitary after GnRH injection, and estrogen priming had no effect. The present findings indicate that the endocannabinoid system is a potential candidate for the regulation of the hypothalamic-pituitary-ovarian axis in reflex ovulatory species.     

Relationship of growth hormone, prolactin and thyrotropin secretion to individual and progeny performance of Hereford bulls

Six Hereford bulls from a line selected with an index of body weight and muscling score were compared with six bulls from a control line to determine if increased growth in the selected line was associated with changes in plasma levels of growth hormone (GH), prolactin (PRL) and (or) thyrotropin (TSH). The predictive value of sire hormone data for growth rate of progeny was also evaluated. Bulls of the index line were heavier at birth (P less than .02) and had higher postweaning daily gains (P less than .01) than bulls of the control line. Blood samples were collected from bulls (ages 2 and 3 yr) at 15-min intervals for 8 h. Overall plasma GH concentrations were higher (P less than .03) in the index bulls than those in the control line. All characteristics of PRL secretion examined tended to be higher in the index bulls, but only mean overall and baseline differences approached significance (P less than .10). There were no significant differences in measures of TSH secretion between lines. Sire differences in hormone characteristics accounted for significant amounts of variation in birth weight and postweaning gain of progeny, but not in gain to weaning. Also, when considered jointly, hormone characteristics generally added significantly to predictions that used sire growth rate alone. The results suggest that serum hormone characteristics in parents may provide additional predictors of growth rates of progeny.     

A comparative study of ovine placental lactogen and prolactin secretion patterns in genetically dissimilar fetal co-twins

Simultaneous fetal and maternal ovine placental lactogen (oPL) and prolactin (oPRL) measurements were determined from blood samples collected from six mixed breed (MB; gestation = 141.5 +/- .7 d) pregnancies and single Rambouillet (n = 2; Ra gestation = 148 and 149 d) and Finnish Landrace (n = 2; Finn gestation = 141 and 143 d) pregnancies for the purpose of examining a possible relationship between fetal-maternal oPL and oPRL levels in the prepartal period. The MB pregnancies were produced by embryo transfer and consisted of genetically different fetuses co-existing in a common uterine environment. Despite the apparent prematurity of Ra co-twins in MB pregnancies, similar oPL and oPRL patterns during the final 14 d of gestation were observed for both Ra and Finn co-twins. Fetal oPL levels decreased at parturition (range 23 to 90 ng/ml) to approximately 60% of values recorded 8 d prepartum (range 100 to 150 ng/ml) in both fetal siblings. Increases in fetal oPRL concentrations, first observed at approximately 4 d prepartum in all fetuses, reached peak concentrations (40 to 60 ng/ml) at term. Results of this study suggest a similarity in regulation of fetal oPL and oPRL secretion, despite genetic differences for gestation period, in fetuses in the M.B. pregnancy.     

Characterization of muscarinic receptor subtype mediating contraction and relaxation in equine coronary artery in vitro

In coronary arterial rings isolated from horses, 10-^-8-10^-6 mol/l acetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment with I,-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower concentrations of Ach 10-¹⁴-10-⁸ mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced contractions in the coronary rings without endothelium were competitively inhibited by each muscarinic subtype selective antagonist in the following order of potency: 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > pirenzepine ≥ parafluoro-hexahydrosiladiphenidol (pFHHSiD) > methoctramine. ACh-induced relaxation in the rings with endothelium was inhibited by LNAG or MB, and by each selective antagonist in the following order of potency: 4-DAMP < pFHHSiD ≥ pirenzepine ≥ methoctramine. These results suggest that the ACh-induced contraction and relaxation in equine coronary arteries are mediated mainly by an M₃-receptor located on the smooth muscle cells and endothelial cells, respectively, and that the stimulation of the M₃-receptor on the endothelial cells liberates nitric oxide.     

Reciprocal cross effects on growth hormone and prolactin secretion in cattle: influence of genotype and maternal environment

The influence of prenatal maternal and reciprocal cross effects on growth and growth hormone (GH) and prolactin (PRL) secretion in calves was investigated through the use of embryo transfer. Eight full-sib pairs of Angus-Red Poll reciprocal cross calves whose gestational development occurred in cows of either the Angus or Red Poll breeds were used in the study. The calves were nonsurgically transferred to recipient cows of each breed 8 d post-estrus. Three to five days after birth the calves were removed from their gestational dams and thereafter raised on milk replacer. The male calves were castrated at birth. At an average age of 61 d, blood samples were collected at 15-min intervals for an 8-h period via indwelling jugular cannula. The concentrations of GH and PRL were quantitated by radioimmunoassay. The temporal concentrations were analyzed and estimates of the secretory patterns determined. Sex influenced mean and basal GH concentrations and amplitude of GH peaks (P less than .1). Difference between reciprocal crosses (Angus X Red Poll vs Red Poll X Angus) was significant for basal PRL concentration. Birth weight and 150-d weight were significantly affected by recipient breed and reciprocal cross was significant for 150-d weight, birth to 150-d average daily gain, and mean concentration and number of GH peaks. The interaction of recipient breed and sex was significant for 150-d weight and mean GH concentration. These data add secretion of GH and PRL to those traits influenced by prenatal maternal environment.     

Inhibition of porcine circovirus type 1 and type 2 production in PK-15 cells by small interfering RNAs targeting the Rep gene

Porcine circovirus type 1 (PCV1) and type 2 (PCV2) are two genotypes of porcine circovirus. Both of them are presumed to be widespread in the swine population. Currently, there is no specific treatment for their infections. RNA interference (RNAi) is a sequence-specific RNA degradation mechanism mediated by small interfering RNA (siRNA), which represents a possible therapeutic application for the treatment of viral infections. In this study, three siRNA expression plasmids (pS-RepA, pS-RepB and pS-RepC) were generated to target three different coding regions of the Rep protein (Rep) of PCV. These siRNAs were used to inhibit PCV production in a porcine kidney cell line, PK-15 cells. Our results revealed that Rep gene expression was inhibited by pS-RepA, pS-RepB and pS-RepC to different degrees. Moreover, our study also showed that the production of PCV1 and PCV2 was reduced by these siRNAs. pS-RepC, which targets the middle region of Rep gene, proved to be the most efficient siRNA for inhibition of Rep expression and viral production. Taken together, our data suggest that RNAi could be investigated as a potential treatment for PCV infection.     

GnRH antagonist inhibition of gonadotropin and steroid secretion in boars in vivo and steroid production in vitro

The hormone GnRH has a stimulatory effect on gonadotropin synthesis and secretion. The objective of the first study was to evaluate concentrations of FSH and LH in plasma of boars after successive treatment with SB75, a GnRH antagonist. Thirteen boars greater than 1 yr of age (eight White Composite [WC] and five Meishan [MS]) were injected once daily with SB75 (10 microg/kg of body weight) for 4 d. Plasma concentrations of LH and testosterone (T) decreased after 1 h from the first dose of SB75. After 12 h of treatment, LH gradually returned to pretreatment concentrations, but T remained suppressed (< 2 ng/mL) until after the last injection of SB75. There was a modest, but significant, reduction in FSH during treatment with SB75. The prolonged inhibitory effect of SB75 on suppression of plasma T concentrations, in the presence of pretreatment concentrations of LH, implied direct effects of SB75 at the testis. In the second experiment, testicular tissue from adult boars was incubated in the presence of three doses of human chorionic gonadotropin (hCG; 0, .5, and 5 IU) with SB75 (250 ng/mL) or with Deslorelin, a GnRH agonist (500 ng/mL). Samples of media were collected every hour for 3 h, and concentrations of T and estrone (E1) were determined by RIA. Concentrations of T and E1 increased with time in response to treatment with hCG. Co-treatment with SB75 decreased media concentrations of T (P < .01) and E1 (P < .03) compared to controls (77.9 vs 85.7 +/- 2.0 and 4.7 vs 5.3 +/- .2 ng/g). In contrast, treatment with Deslorelin had no effect on the amount of T (P > .50) or E1 (P > .26) released with all dosages of hCG. These results indicate that a GnRH antagonist has a direct effect on the testis, decreasing amounts of T and E1 released from the Leydig cells; however, treatment with a GnRH agonist had no direct effect on release of these gonadal steroids. Thus, it remains unresolved whether the site of action of GnRH antagonist on testicular steroidogenesis is through a testicular GnRH receptor or through some other mechanism.     

亚抑菌质量浓度的桂皮醛对金黄色葡萄球菌毒力因子的抑制作用

通过吸光度测量、免疫印迹等方法,在体外检测亚抑菌质量浓度的桂皮醛作用下金黄色葡萄球菌毒力因子产量的变化。结果显示,16~128 mg/L桂皮醛对金黄色葡萄球菌的多种毒力因子有抑制作用,且呈质量浓度依赖性。各剂量的桂皮醛作用后,α溶血素、肠毒素A、B和聚集因子的产量显著低于对照组(P0.05),而凝固酶的产量只在桂皮醛为64 mg/L和128 mg/L时才有降低(P0.05)。     

Effects of intracerebroventricular corticotropin-releasing hormone and intravenous morphine on cortisol, prolactin and growth hormone secretion in sheep.

It has previously been demonstrated that naloxone and morphine modify the adrenocortical and pituitary responses of sheep to stress. Since CRH acts within the brain to co-ordinate the stress response, the present experiment was conducted to determine whether morphine has similar effects in sheep given oCRH centrally. Plasma concentrations of cortisol, prolactin and growth hormone were measured in blood samples collected at 10 min intervals from sheep (N = 5) over a 3-hr period. Intravenous injections of saline vehicle or morphine sulphate (0.4 mg/kg) were given after 40 min and intracerebroventricular injections of oCRH (0, 5 or 20 micrograms) were administered after 60 min. Sustained, dose-related, increases in cortisol were induced by oCRH and, in agreement with findings in stressed sheep, these responses were reduced by pretreatment with morphine. Prolactin levels appeared to increase after morphine but oCRH, on its own, did not increase prolactin secretion in this study. There was no change in growth hormone concentrations after oCRH whereas morphine transiently stimulated release.