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A number of chemicals have been classed as endocrine disrupting compounds due to their ability to mimic the actions of endogenous hormones in vivo and in vitro. The objective of this experiment was to determine the pathological changes and oestrogen receptor (ER) distribution in the cervix and uterus of prepubertal ovariectomised ewe lambs following exposure to a range of compounds with a predominantly oestrogenic effect. Lambs were exposed to diethylstilbestrol (0.175 mg/kg biweekly), bisphenol-A (3.5mg/kg biweekly) or octylphenol (3.5mg/kg biweekly) for 6 weeks. Following sacrifice, uterine and cervical tissue pathology was assessed. The endometrial and myometrial areas were quantified and the distribution of ERalpha and ERbeta assessed by immunohistochemistry. No differences were observed between control and octylphenol-exposed lambs in uterine gross pathology and histopathology. Uteri from bisphenol-A- and diethylstilbestrol-exposed lambs were heavier than both control and octylphenol-exposed lambs. In the bisphenol-A-exposed lambs, endometrial oedema accounted for a significant increase in the endometrial cross-sectional area over the other groups. Uteri from animals exposed to diethylstilbestrol showed variable pathology including oedema and cellular proliferation. Keratinisation of the cervical epithelium was observed in both bisphenol-A- and diethylstilbestrol-exposed lambs. Exposure to diethylstilbestrol and bisphenol-A was associated with a diffuse intracellular distribution of ERalpha and ERbeta in the uterine endometrium. This was in addition to the strong cytoplasmic staining of uterine epithelial cells and nuclear staining of specific sub-epithelial cells observed in all groups. We conclude that a 6-week exposure of lambs to bisphenol-A and diethylstilbestrol altered the uterocervical environment and has the potential to disrupt subsequent reproductive function. Pathological changes could not be detected in the uterus or cervix of lambs exposed to octylphenol.  相似文献   

3.
Recent reports have indicated a role of cell-to-cell interactions during gonadal development and functions. Numerous reports indicate that fetal hormonal disruption induces abnormalities in the developing reproductive system and, therefore, may interfere with reproductive functions later in adult life. Hence, this study investigated the effect of androgen deficiency during late prenatal periods on the gap junction-associated connexin 43 (Cx43) and the adherens junction-associated β-catenin expression in the fetal porcine gonads. Thus, pregnant gilts were injected with anti-androgen flutamide (for 7 d, 50 mg/kg BW per day) or corn oil (control groups) starting at 83 (GD90) or 101 (GD108) gestational day. On GD90 and GD108 the fetuses were excised and fetal gonads were obtained. To assess Cx43 and β-catenin expression real-time PCR and immunohistochemistry were performed. In fetal testes, Cx43 was localized between Leydig cells, whereas β-catenin was observed mainly within the seminiferous tubules. In fetal ovaries, Cx43 was detected between interstitial cells and between granulosa cells of forming follicles, whereas β-catenin was found within egg nests, in oocytes' membrane, and in granulosa cells of forming follicles. Immunohistochemistry showed decreased Cx43 and β-catenin expression in fetal gonads from flutamide-treated pigs compared with respective controls. However, the ovaries from animals treated with flutamide on GD108 showed increased Cx43 expression. The changes of Cx43 and β-catenin expression after prenatal flutamide treatment were confirmed at the mRNA level. These findings suggest that androgen deficiency during late gestation may lead to disturbed intercellular interactions in fetal porcine testes affecting testicular functions, as well as impaired follicular formation in fetal ovaries. Our results further signify the role of androgens in the regulation of cell-to-cell interactions within fetal porcine gonads.  相似文献   

4.
The present study was conducted to determine the effects of supplemental dietary l-carnitine at different levels on semen traits, reproductive parameters, and testicular histology in male Japanese quail breeders. Forty-five 5-wk-old male Japanese quail breeders were fed the same basal diet that was supplemented with 0 (control), 250, or 500 mg of l-carnitine/kg of diet. There were no significant effects of dietary l-carnitine supplementation at different levels on BW, feed intake, testes weight, fertility rate, hatchability rate of set and fertile eggs, and malonaldehyde production (μg/mL of semen) of male Japanese quail breeders. However, the supplementation of dietary l-carnitine at levels of 250 or 500 mg/kg to a basal diet significantly increased sperm viability and decreased multinucleated giant cells per testes in mature male Japanese quail breeders. Additional studies are required to explore the antioxidant role that l-carnitine has in Japanese quail breeders.  相似文献   

5.
In spite of widespread application of flutamide in the endocrine therapies of young and adult patients, the side effects of this antiandrogen on spermatogenesis and germ‐cell morphology remain unclear. This study evaluates the short‐term androgen blockage effect induced by the administration of flutamide to the testes of pubertal (30‐day old) and adult (65‐ and 135‐day old) guinea pigs, with an emphasis on ultrastructural alterations of main cell types. The testes removed after 10 days of treatment with either a non‐steroidal antiandrogen, flutamide (10 mg/kg of body weight) or a pharmacological vehicle alone were processed for histological, quantitative and ultrastructural analysis. In pubertal animals, flutamide androgenic blockage induces spermatogonial differentiation and accelerates testes maturation, causing degeneration and detachment of primary spermatocytes and round spermatids, which are subsequently found in great quantities in the epididymis caput. In post‐pubertal and adult guinea pigs, in addition to causing germ‐cell degeneration, especially in primary spermatocytes, and leading to the premature detachment of spherical spermatids, the antiandrogen treatment increased the relative volume of Leydig cells. In addition, ultrastructural evaluation indicated that irrespective of age antiandrogen treatment causes an increase in frequency of organelles involved with steroid hormone synthesis in the Leydig cells and a dramatic accumulation of myelin figures in their cytoplasm and, to a larger degree, in Sertoli cells. In conclusion, the transient exposition of the guinea pigs to flutamide, at all postnatal ages causes some degenerative lesions including severe premature detachment of spermatids and accumulation of myelin bodies in Leydig and Sertoli cells, compromising, at least temporarily, the spermatogenesis.  相似文献   

6.
The pharmacokinetic properties of marbofoxacin, a third generation fluoroquinolone, were investigated in 12 healthy adult cats after single subcutaneous (SC) administration of 2 mg/kg BW (Part I, n=8 cats) and 4 mg/kg BW (Part II, n=4 cats). In each part of the study blood and urine samples were collected before treatment and thereafter for 5 days. The plasma and urine concentrations of marbofloxacin were determined by HPLC with UV detection. Pharmacokinetic calculations were performed for each treated animal using an open one-compartment-model with first-order elimination after SC dosing. Marbofloxacin in plasma (means): Maximum concentrations (Cmax) of about 1.2 and 3.0 microg/ml were measured 2.3 and 4 hours (tmax) after dosing of 2 and 4 mg/kg BW, respectively. Elimination from the body was low with a total clearance (Cl/F) of approximately 0.1 l/h/kg for both dosages. The half-life (t 1/2) for this process was calculated with 8-10 hours. AUC increased almost proportional when doubling the dose, i.e., 19.77 +/- 6.25 microg * h/ml (2 mg/kg BW) and 51.26 +/- 11.83 microg * h/ml (4 mg/kg BW). Plasma kinetics measured were in accordance with data from literature. Marbofloxacin in urine (means): Maximum drug concentrations were detected 4 and 8 hours after dosing with 70 microg/ml (2 mg/kg BW) and 160 microg/ml (4 mg/kg BW), respectively. Inhibitory effects of the urinary matrix on the antimicrobial activity of the drug were taken into account when performing PK/PD calculations. However, a concentration-dependent bactericidal activity (Cmax/MIC > 8-10) which is claimed for fluoroquinolones was sufficiently met with focus on Escherichia (E.) coli (MIC90 0.5 microg/ml). In the same matrix a threshold value of 1.0 microg/ml was undercut 82 and 116 hours after SC dosing, respectively. Hence, a time-dependent bacteria killing kinetic (T > MIC) which may be of relevance for some Gram-positive germs like Staphylococcus spp. (MIC90 1.0 microg/ml) should be covered, too.  相似文献   

7.
The present study investigated the effects of long-term administration of Pueraria mirifica (PM) at non-toxic doses on the ovarian function and fertility of adult female mice based on evaluation of hematological and biochemical parameters. Female mice were divided into 4 groups (36 mice/group). Groups 1-3 were orally treated with a dose of 0 (PM-0), 10 (PM-10) or 100 mg/kg BW/day PM (PM-100), and group 4 was subcutaneously injected with 200 mug/kg BW/day of synthetic estrogen diethylstilbestrol (DES). The treatment schedule was separated into treatment and post-treatment periods. The duration of each period was 8 weeks. The PM-10 mice exhibited regular estrous cycles, while the PM-100 and DES treatments induced prolonged estrous cycles. Although no changes were observed in the uterus and ovary weights of the mice after the PM-100 and DES treatments, hyperplasia of the uterine endothelium and a decrease in the number of growing ovarian follicles were detected. The changes in the ovarian histologies of the PM-100 and DES mice were related to reductions in the levels of LH and FSH, which subsequently caused a decrease in mating efficiency. Once the PM mice were able to copulate, they were capable of successfully becoming pregnant and mothering offspring. No abnormalities were observed in the external morphologies and reproductive organ weights of the 50-day-old offspring. In conclusion, our results suggest that long-term exposure to 100 mg/kg BW of PM has adverse effects on the mating efficiency and reproduction of adult female mice and that administration of 10 mg/kg BW of PM does not induce any changes in the hypothalamic-pituitary-ovarian-uterine axis.  相似文献   

8.
Evidence is mounting that the foetal and neonatal period of reproductive tract development is highly sensitive to hormonal disruption induced by various endocrine active compounds. Thus, we asked whether androgen withdrawal caused by prenatal (GD20, GD80) or neonatal (PD2) exposure to an anti-androgen flutamide alters Cx43 gene expression and may induce delayed effects on morphology and function of adult pig testes. Flutamide was given in five doses (50 mg/kg bw). Our histological analysis and TUNEL staining revealed varying degrees of seminiferous tubules abnormalities in all experimental pigs. Testes of pigs exposed to flutamide in utero exhibited moderate alterations of the spermatogenic process, whereas those of exposed neonatally were severely impaired. The most striking effects were spermatogenic arrest, germ cell detachment and a statistically significant increase in the frequency of germ cell apoptosis (p<0.01). Moreover, all pigs exposed to flutamide displayed Leydig cell hyperplasia. Because the network of cell-cell communication provided by gap junction channels plays an essential role in the regulation and maintenance of spermatogenesis, the physiological significance of Cx43-based gap junctions with regards to the gonadal impairment was evaluated by analysis of its expression using immunohistochemical, Western blot and qRT-PCR approaches. Significantly, lower Cx43 expression was found when flutamide was administered neonatally, which has coincided with severe disruption of spermatogenesis. Our data suggest that neonatal exposure to flutamide induces long-term effects on the spermatogenic capacity of the pig testis through alterations of Cx43-mediated intercellular communication and permanent alteration of both Sertoli and Leydig cell functions.  相似文献   

9.
The median effective dosage (ED50) for induction of anesthesia with propofol was determined by using the up-and-down method in 31 unpremedicated cats, in 30 cats premedicated with butorphanol, 0.4 mg/kg body weight (BW), and acepromazine, 0.1 mg/kg BW, intramuscularly, and in 30 cats premedicated with morphine, 0.2 mg/kg BW, and acepromazine, 0.1 mg/kg BW, intramuscularly. The dose required for a satisfactory anesthetic induction in 50% of unpremedicated cats (ED50) was 7.22 mg/kg BW and of premedicated cats was 5.00 mg/kg BW. The reduction in dose was statistically significant in both premedicated groups compared with no premedication. There was no significant difference in ED50 between premedication regimes. Cyanosis was the most common adverse effect observed in all groups following anesthetic induction with propofol.  相似文献   

10.
We investigated whether the limited access to androgens during late prenatal period alters expression of steroidogenic enzymes involved in androgen production: 3β‐hydroxysteroid dehydrogenase/Δ5‐Δ4 isomerase (3β‐HSD), cytochrome P450 17α‐hydroxylase/17,20‐lyase (CYP17) and 17β‐hydroxysteroid dehydrogenase type 1 (17β‐HSD1) or type 3 (17β‐HSD3) in the foetal porcine gonads. Pregnant gilts were injected with anti‐androgen flutamide (for seven days, 50 mg/day/kg bw) or corn oil (control) starting at 83 (GD90) or 101 (GD108) gestational day. To assess 3β‐HSD, CYP17 and 17β‐HSD1 or 17β‐HSD3 expression, real‐time PCR and immunohistochemistry were performed. In testes from flutamide‐treated foetuses, increased 3β‐HSD and CYP17 mRNA expression was observed in the GD90 group, while decreased 3β‐HSD and 17β‐HSD3 mRNA expression and increased CYP17 mRNA expression were found in the GD108 group. CYP17 and 17β‐HSD3 were localized in Leydig cells. Following flutamide administration, the intensity of CYP17 immunostaining was higher in both treated groups, while 17β‐HSD3 intensity was lower in the GD108 group. In ovaries from flutamide‐treated foetuses in the GD90 group, mRNA level for 3β‐HSD was elevated, but it was diminished for CYP17 and 17β‐HSD1. In the GD108 group, flutamide treatment led to lower mRNA level for 3β‐HSD but higher for CYP17. 3β‐HSD was found in granulosa cells, while CYP17 was localized within egg nests and oocytes of forming follicles. Following flutamide treatment, the intensity of 3β‐HSD and CYP17 immunostaining was higher in the GD90 and GD108 groups, respectively. Immunohistochemical staining for 3β‐HSD was restricted to the ovary. Concluding, diminished androgen action in the porcine foetal gonads during late gestation induces changes in steroidogenic enzymes expression, which may led to changes in gonadal function. However, it seems that androgens exert diverse biological effects depending on the gestational period.  相似文献   

11.
33 ferrets (Mustela putorius furo, 11 females, 22 males, ASA I-II) were neutered in a combination anaesthesia with medetomidine, midazolam and ketamine. The animals were randomized into 3 groups. All animals received 20 microg/kg BW medetomidine and 0.5 mg/kg BW midazolam. The three groups differed regarding dosis and way of application of ketamine (IM10 = 10 mg/kg BW intramuscularly; IM07 = 7 mg/kg BW intramuscularly; SC10 = 10 mg/kg BW subcutaneously). After 30 minutes anaesthesia was partially antagonised with 100 microg/kg BW atipamezole i.m.. Sedation, muscle relaxation, analgesia, and overall anaesthetic impression were compared by a scoring protocol. Reactions to painful stimuli of clamping the spermatic cord or the ovarial ligament including the A. ovarica were judged, too. All animals lost their righting reflex and could be placed in dorsal recumbency. Induction and recovery time were significantly the shortest in study group IM10 with 1.73 +/- 0.3 and 9.73 +/- 4.6 min respectively. Recovery was significantly prolonged in group SC10 with 30.27 +/- 15.6 min. The MMK-anaesthesia with 10 mg/kg ketamine i.m. is very useful for neutering ferrets. Respiratory depression and bradycardia typically for medetomidine were seen in all three combinations, but quickly reversed after partial antagonisation. Induction and intubation, followed by inhalation anaesthesia, were possible with all three regimes.  相似文献   

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The objective of these studies was to evaluate the effects of dietary restriction and Se on maternal and fetal metabolic hormones. In Exp. 1, pregnant ewe lambs (n = 32; BW = 45.6 +/- 2.3 kg) were allotted randomly to 1 of 4 treatments. Diets contained (DM basis) either no added Se (control), or supranutritional Se added as high-Se wheat at 3.0 mg/kg (Se-wheat), or sodium selenate at 3 (Se3) and 15 (Se15) mg/kg of Se. Diets (DM basis) were similar in CP (15.5%) and ME (2.68 Mcal/kg). Treatments were initiated at 50 +/- 5 d of gestation. The control, Se-wheat, Se3, and Se15 treatments provided 2.5, 75, 75, and 375 microg/kg of BW of Se, respectively. Ewe jugular blood samples were collected at 50, 64, 78, 92, 106, 120, and 134 d of gestation. Fetal serum samples were collected at necropsy on d 134. In Exp. 2, pregnant ewe lambs (n = 36; BW 53.8 +/- 1.3 kg) were allotted randomly to treatments in a 2 x 2 factorial arrangement. Factors were nutrition (control, 100% of requirements vs. restricted nutrition, 60% of control) and dietary Se (adequate Se, 6 microg/kg of BW vs. high Se, 80 microg/kg of BW). Selenium treatments were initiated 21 d before breeding, and nutritional treatments were initiated on d 64 of gestation. Diets were 16% CP and 2.12 Mcal/kg of ME (DM basis). Blood samples were collected from the ewes at 62, 76, 90, 104, 118, 132, and 135 d of gestation. Fetal blood was collected at necropsy on d 135. In Exp.1, dietary Se source and concentration had no effect (P > 0.17) on maternal and fetal serum IGF-I, triiodothyronine (T(3)), or thyroxine (T(4)) concentrations. Selenium supplementation increased (P = 0.06) the T(4):T(3) ratio vs. controls. In Exp. 2, dietary Se had no impact (P > 0.33) on main effect means for maternal and fetal serum IGF-I, T(3), or T(4) concentrations from d 62 to 132; however, at d 135, high-Se ewes had lower (P = 0.01) serum T(4) concentrations than adequate-Se ewes. A nutrition by Se interaction (P = 0.06) was detected for the T(4):T(3) ratios; ewes fed restricted and adequate-Se diets had greater (P = 0.10) T(4):T(3) ratios compared with the other treatments. Nutrient-restricted ewes had lower (P < 0.05) serum IGF-I, T(3), and T(4) concentrations. Fetal serum IGF-I concentrations were lower (P = 0.01) in restricted-vs. control-fed ewes; however, fetal T(3) and T(4) concentrations were unaffected (P > 0.13) by dietary Se or maternal plane of nutrition. These data indicate that dietary Se may alter maternal T(4):T(3) ratios. In addition, nutrient restriction during gestation reduces maternal IGF-I, T(3), and T(4) and fetal IGF-I concentrations.  相似文献   

14.
1. Two experiments were carried out to investigate responses in performance and bone compositional and structural characteristics in broilers fed diets containing 4 concentrations of vitamin D3 (5, 20, 125 and 250 microg cholecalciferol/kg) at different concentrations of calcium, available phosphorus and vitamin A. 2. In experiment 1, body weight and tibia breaking strength were maximised at 14d with 250 microg vitamin D3/kg, tibia ash was maximised with 125 microg vitamin D3/kg. A high incidence of tibial dyschondroplasia (TD) was decreased to very low levels with 125 microg vitamin D/kg. 3. At 42d, performance and bone characteristics showed no response to vitamin D3 concentrations above 20 microg/kg. 4. Dietary vitamin A within the range 2-4 to 4.5 mg retinol/kg did not show any interaction with vitamin D3 status at either age. 5. In experiment 2, responses to vitamin D3 were strongly influenced by dietary calcium/available phosphorus. With 13 g calcium and 5 g available phosphorus/kg, performance and bone characteristics responded to vitamin D3 concentrations up to 125 microg/kg but more was needed at less optimal concentrations of calcium and available phosphorus. TD incidence was minimised with 250 microg/kg. 6. This study shows that high dietary concentrations of vitamin D3 can prevent TD. It is concluded that the vitamin D3 requirement of broilers up to 14 d of age at optimal dietary calcium and available phosphorus concentrations may be in the range 35 to 50 microg/kg for cortical bone quality and up to 250 microg/kg for prevention of TD. The vitamin D3 requirement for cortical bone quality after 14 d is not higher than 20 microg/kg. These requirements are much higher than earlier estimates and may be related to higher calcium requirements of modern broiler genotypes. Current regulations limiting maximum vitamin D3 concentrations in broiler starter diets may need to be reviewed.  相似文献   

15.
In this study, flutamide, an androgen receptor antagonist, was used as a tool to better understand the role of androgen receptor signaling and androgen signaling disruption during fetal and neonatal periods on porcine Leydig cell development and function. Flutamide, 50 mg kg(-1) d(-1) was administered into pregnant gilts during gestational days 20 to 28 and days 80 to 88 and into male piglets on postnatal days 2 to 10 (PD2). Leydig cells of flutamide-exposed boars, especially those of PD2 males, displayed morphologic alterations, increased size, and occupied increased area (P < 0.001) of the testes when compared with the control. Despite this, testosterone concentrations were reduced significantly in comparison with those of controls (P < 0.05, P < 0.001). Reduced testosterone production in response to flutamide exposure appeared to be related to changes in testosterone metabolism, as shown by increased aromatase mRNA (P < 0.05, P < 0.01), protein expression (P < 0.01, P < 0.001), and elevated estradiol concentrations (P < 0.001). Moreover, impaired Leydig cell responsiveness to LH was indicated by the decreased expression of LH receptor (P < 0.05, P < 0.001). No significant effect of flutamide was found on LH and FSH concentrations. Taken together, our data indicate that flutamide when administered during prenatal or neonatal period have a long-term effect on Leydig cell structure and function, leading to androgen-estrogen imbalance. Leydig cell failure was most evident in adult boars neonatally exposed to flutamide, suggesting that androgen action during neonatal development is of pivotal importance for the differentiation and function of porcine adult Leydig cell population.  相似文献   

16.
It has been reported that Calbindin-D9k (CaBP-9k) is rapidly and strongly induced by environmental estrogenic compounds, possibly through estrogen receptors (ERalpha) in the uterus of mammals. CaBP-9k can be evaluated as an early gene marker for assaying estrogenic effects of putative environmental chemicals in the rat uterus. This study was undertaken to investigate CaBP-9k mRNA and protein expression in the postnatal rat uterus following maternal exposure to 17beta-estradiol (E2) and bisphenol A (BPA) during the neonatal period. Treatment with a high dose of BPA (600 mg/kg body weight (BW) per day) resulted in a 3-fold increase in CaBP-9k mRNA expression for 3 days, while a single dose of E2 (40 microg/kg BW per day) induced 2-fold increase of this gene in the maternal uterus. In an agreement with maternal CaBP-9k mRNA, postnatal CaBP-9k mRNA in the uterus increased 4-fold when treated with BPA (600 mg/kg BW per day). In addition, treatment with increasing concentrations of BPA resulted in significant increases in CaBP-9k protein in the maternal rat uterus. It is of interest that increasing doses of BPA induced a significant ERalpha mRNA increase in the postnatal uterus. Furthermore, immunohistochemistry revealed that treatment with BPA induced CaBP-9k protein in the maternal uterus. We demonstrated that maternal exposure to BPA during late pregnancy induced CaBP-9k mRNA and protein in maternal and postnatal rat uteri. These results suggest that rapid absorption and distribution of environmental estrogenic compounds occurs in maternal and neonatal rat uteri and these chemicals can easily pass though the placenta during pregnancy to affect postnatal reproductive functions.  相似文献   

17.
This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.  相似文献   

18.
The present study was conducted to determine whether corticosteroids influence the inductive effect of growth hormone (GH) on plasma concentrations of insulin-like growth factor I (IGF-I). The first experiment was designed to determine the effects of corticosterone alone on basal concentrations of IGF-I. Rats were treated daily for 4 d with 0, 50, 100, 250, or 500 mg of corticosterone/kg of BW. There was a close positive relationship between the dose of steroid injected and plasma concentrations of corticosterone and a close negative relationship between plasma corticosterone and growth. Plasma concentrations of IGF-I showed a positive relationship to dose and plasma concentrations of corticosterone and a negative relationship to growth rate. In the second experiment, rats were treated daily for 21 d with either porcine growth hormone (10 mg of pGH/kg of BW), pGH plus corticosteroid, or vehicle. The dose of steroid administered was increased every 3 d until the mean weight gain of the group was zero. Animals treated with pGH alone gained significantly more weight than controls. This growth response was not impaired significantly by corticosterone acetate at doses up to 500 mg/kg of BW. The more potent corticosteroid, cortisone, arrested the growth of pGH-treated rats at a dose of 80 mg/kg of BW, however. Plasma concentrations of IGF-I were increased by pGH treatment (57%) and increased further by concurrent cortisone treatment (212%). In summary, corticosteroids increase plasma concentrations of IGF-I and enhance the inductive effect of pGH on this hormone despite their catabolic actions.  相似文献   

19.
A series of experiments were conducted to investigate the elimination of swainsonine in the milk of lactating ruminants following a single dose oral exposure to swainsonine (locoweed; Oxytropis sericea) and to assess subsequent subclinical effects on the mothers and their nursing young. In a preliminary experiment, lactating ewes were gavaged with locoweed providing 0.8 mg swainsonine/kg BW (n = 4; BW = 75.8 +/- 3.6 kg; lactation = d 45) and lactating cows were offered up to 2.0 mg swainsonine/kg BW free choice (n = 16; BW = 389.6 +/- 20.9 kg; lactation = d 90). Serum and milk were collected at h 0 (before treatment), 3, 6, 12, and 24 for ewes, and h 0 (before treatment), 6, 12, 18, and 24 for cows. Swainsonine was highest (P < 0.05) by h 6 in the serum and milk of ewes. Consumption of at least 0.61 mg swainsonine/kg BW induced consistent (> 0.025 microg/mL) appearance of swainsonine in cow serum and milk. In response to the results obtained in the preliminary experiment, a subsequent experiment utilizing lactating ewes (n = 13; BW = 74.8 +/- 6.4 kg; lactation = d 30) and cows (n = 13; BW = 460.8 +/- 51.9 kg; lactation = d 90) was conducted. Each lactating ruminant was gavaged with a locoweed extract to provide 0 (control), 0.2, or 0.8 mg swainsonine/kg BW and individually penned with her nursing young. Serum and milk from the mothers and serum from the nursing young were collected at h 0 (before treatment), 3, 6, 9, 12, 24 and 48 (an additional sample was obtained at h 72 for ewes and lambs). Serum and milk swainsonine was higher (P < 0.05) in the 0.8 mg treated groups and maximal (P < 0.05) concentrations occurred from h 3 to 6 for ewes and h 6 to 12 h for cows (P < 0.05). Rises in alkaline phosphatase activity indicated subclinical toxicity in the treated ewes (P < 0.05). Following a single dose oral exposure to 0.2 and 0.8 mg swainsonine/kg BW provided by a locoweed extract, swainsonine was detected in the serum and milk of lactating ewes and cows, and rises in serum alkaline phosphatase activity were observed in the ewes. Neither swainsonine nor changes in alkaline phosphatase activity was detected in the serum of the lambs and calves nursing the ewes and cows dosed with swainsonine.  相似文献   

20.
The present study investigated the doseeffect relationship of graded levels of lipoic acid supplementation on growth performance and small intestinal development in a weaned rat model.Seventy-two weaned Sprague-Dawley rats,were fed semipurified diets(n=12),either unsupplemented(group Ⅰ)or supplemented with 12.5,25,125,or 250 mg/kg body weight(BW)fipoic acid(groups Ⅲ,Ⅳ,Ⅴ,and Ⅵ),with 200 mg/kg BW aureomycin as the antibiotic control(group Ⅱ).The experiment lasted 21 days.Growth performance was not significantly different (P>0.05)between rats under the antibiotc control (group Ⅰ)and rats fed low levels(12.5 and 25 mg/kg BW)of lipoic acid(groups Ⅳ and Ⅳ).In contrast,high level(125 and 250 mg/kg BW)lipoic acid supplementation(groups Ⅴ and Ⅵ)(P<0.05)reduced weight gain,feed consumption,and feed efficiency.In addition,high levels(125 and 250 mg/kg BW)of lipoic acid significantly(P<0.05)reduced the villus height/crypt depth ratio,as well as the numbers of lactobacillus.total aerobes.and total anerobes in the gastrointestinal tract compared with the other treatments,which meant that high levels of lipoic acid impaired intestinal morphology and disordered the balance of intestinal microbiology.Furthermore,the results showed that high leveIs of lipoic acid supplementation(P<0.05)elevated interferonγ and intefleukin-2,but dramatically(P<0.05)depressed interleukin-4 and interleukin-10 compared with the low levels of lipoic acid supplementation and the control group,which indicated that high levels of lipoic acid would induce bias of Th1/Th2 lymphocytes.Taken together,the results indicate that lipoic acid supplementation can't improve growth performance and intestinal development of normal animals,especially,high levels(≥125 mg/kg BW)of lipoic acid supplementation restrained growth performance and intestinal development,in association with unbalance of certain cytokines.  相似文献   

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