Long-term treatment effects of Pueraria mirifica phytoestrogens on parathyroid hormone and calcium levels in aged menopausal cynomolgus monkeys

To determine the effect of Pueraria mirifica (PM) on serum parathyroid hormone (PTH) and calcium levels on aged menopausal monkeys (Macaca fascicularis), subjects were treated with 10, 100, or 1,000 mg/day of PM. Blood samples were collected every 5 days for 30, 90, and 60 days during pre-treatment, treatment, and post-treatment periods, respectively. Sera were assayed for PTH, estradiol, and calcium levels. PM-1,000 had the strongest effect on the decrease in PTH (0.001相似文献   

Effect of Pueraria mirifica on the sexual skin coloration of aged menopausal cynomolgus monkeys

To investigate the estrogenic effect of Pueraria mirifica (PM), a Thai herbal plant that contains many phytoestrogens, sexual skin coloration was studied in cynomolgus monkeys. Aged menopausal monkeys were divided into three groups. Each group (n=3) was fed 10, 100, or 1,000 mg of PM daily. The treatment schedule was divided into three periods, a 30-day pre-treatment period, 90-day treatment period, and 60-day post-treatment period. The results show that the sexual skin exhibited reddish coloration within 24 h after PM-treatment and remained this way for the first half of the PM-feeding period. The changes in sexual skin coloration were not dose-dependent. The present results indicate that PM had estrogenic action by increasing reddish sexual skin coloration in aged menopausal monkeys.     

Assessment of urinary gonadotropin and steroid hormone profiles of female cynomolgus monkeys after treatment with Pueraria mirifica

This study investigated the changes in the urinary hormone levels of female monkeys (Macaca fascicularis) after single-dose and long-term treatments with Pueraria mirifica (PM). The monkeys were separated into 3 groups (n=3) and orally treated with 10, 100, or 1,000 mg of PM in each group. Two series of experiments were performed. In the first series of experiments, the monkeys were orally treated with a single dose of PM. The experimental schedule was divided into a one menstrual cycle pretreatment period and a two menstrual cycle post-treatment period. In the second series of experiments, the monkeys were orally treated daily with PM for 90 days. The experiment schedule was divided into a one menstrual cycle pretreatment period, a three menstrual cycle treatment period, and a two menstrual cycle post-treatment period. Urinary samples were collected daily and assayed for the FSH, LH, estradiol, and progesterone levels. The results showed that there were no changes in the FSH, LH, estradiol, and progesterone levels after treatment with a single dose of 10, 100, or 1,000 mg of PM or after daily treatment with 10 mg of PM for 90 days compared with the levels observed during the pretreatment period. Daily treatment with 100 mg and 1,000 mg of PM for 90 days only produced a clear reduction in the urinary FSH levels. This suggests that changes of urinary FSH levels can be considered an indicator for study of estrogenic effects on hormonal levels in female monkeys.     

Spontaneous vacuolar degeneration of the thyroid follicular epithelium in cynomolgus monkeys

Vacuolar degeneration of the thyroid follicular epithelium was observed in two untreated female cynomolgus monkeys assigned to control groups. In light microscopy, large vacuoles containing a homogenous substance occupied the basal region of the epithelium, and the nuclei had shifted toward the apical region. The vacuoles showed negative reactions to PAS and thyroglobulin. Electron microscopic observation revealed dilatation of the rough endoplasmic reticulum corresponding to the vacuoles. The plasma TSH, T3 and T4 levels determined for the samples kept frozen were within the normal ranges, suggesting that the thyroid function was kept intact.     

Fetal and neonatal goiter in cynomolgus monkeys following administration of the antithyroid drug thiamazole at high doses to dams during pregnancy

To evaluate morphologic alterations in the thyroid gland in the second generation in cynomolgus monkeys, pregnant dams were exposed to high doses of thiamazole. In Experiment A, dams received thiamazole intragastrically via a nasogastric catheter from gestation day (GD) 50 to GD 150 or on the day before delivery. Initially, the dose level was 20 mg/kg/day (10 mg/kg twice daily); however, the dose level was subsequently decreased to 5 mg/kg/day (2.5 mg/kg twice daily), since deteriorated general conditions were observed in two dams. Six out of seven neonates died on the day of birth. The cause of neonatal death was tracheal compression and suffocation from goiter. The transplacental exposure to thiamazole affected the fetal thyroid glands and induced goiter in all neonates. The surviving neonate was necropsied 767 days after discontinuation of thiamazole exposure and showed reversibility of the induced changes. In Experiment B, dams were intragastrically administered thiamazole at 5 mg/kg/day (2.5 mg/kg twice daily) for treatment periods from GDs 51 to 70, 71 to 90, 91 to 110, 111 to 130 and 131 to 150. All fetuses showed enlarged thyroid glands but were viable. Histopathologically, hypertrophy and/or hyperplastic appearance of the follicular epithelium of the thyroid gland was observed at the end of each treatment period. The most active appearance of the follicular epithelium, consisting of crowded pedunculated structure, was demonstrated at end of the treatment period from GD 131 to 150. This is the first report on the morphology of fetal and neonatal goiter in the cynomolgus monkey.     

The Incidence of Lymphoplasmacytic Gastritis in the Fundus and Antrum of Cynomolgus Monkey ( Macaca fascicularis ) Stomachs

Lymphoplasmacytic gastritis is a concern for toxicological pathologists reading preclinical, non-human primate toxicity studies because subtle gastric changes which could be treatment-related may be masked and gastritis lesions may be confused with treatment-related effects and thus a gastric finding may be incorrectly assigned as a treatment-related lesion. This paper discusses the incidence of lymphoplasmacytic gastritis in cynomolgus monkeys at a contract research organization. The incidence of lymphoplasmacytic gastritis in the fundus and antrum of control cynomolgus monkeys on 18 non-gastric compound studies, was scored. The average fundus score ranged from 0.3 to 1.5 and the average antral score ranged from 0.9 to 3.5 in the cynomolgus monkey stomachs examined. The number of affected control animals in a study ranged from 0 to 5 control animals. No correlation between the route of vehicle administration and the severity or incidence of the lesions was noted. The percentage incidence of affected animals ranged from 0 to 100%. An increased incidence lymphoplasmatic gastritis from 2000 to 2004 was noted. The implications of lymphoplasmacytic gastritis in cynomolgus monkeys used for acute toxicity studies are discussed.     

Goblet cell hyperplasia and muscular layer thickening in the small intestine of a cynomolgus monkey

We report here the interesting case of a 5-year-old male cynomolgus monkey with goblet cell hyperplasia and thickening of the muscular layer throughout the small intestine without exhibiting any clinical symptoms. Necropsy examination showed diffuse thickening of the intestinal wall from the jejunum to the ileum, with an appearance likened to a rubber tube. Histopathologically, marked thickening was observed in both the mucosal and muscular layers in the jejunum and ileum, and slight thickening was observed in the duodenum. Goblet cell hyperplasia with extension of the circular folds and villi was prominently observed. The mucosal surface was covered with a thick mucus layer containing desquamated mucosal epithelial cells, and both the inner and outer muscular layers were markedly thickened due to smooth muscle hypertrophy. Neither macroscopic nor histopathological examination identified any causative factors, such as infection, enteritis and intestinal stenosis, or obstruction that may have caused development of this lesion. Given these observations, this case may simply be considered of spontaneous goblet cell hyperplasia and muscular layer thickening in the small intestine of a cynomolgus monkey.     

催情助孕液对小鼠雌、孕激素水平及其受体mRNA表达的影响

分别以0.1、0.2、0.4 mL/d剂量的催情助孕液给21日龄小鼠灌服7d后,检测体质量、脏器指数、血清雌激素和孕激素水平、子宫组织中雌激素和孕激素受体基因mRNA的表达情况,并与腹腔注射雌二醇4d的小鼠进行比较.结果显示与对照组和雌二醇注射组比较,0.2 mL的催情助孕液能显著促进小鼠子宫发育,并增强雌激素水平及其受体基因表达,而对孕激素水平及其受体基因表达无显著影响.结果表明,催情助孕液对动物生殖发育与促进发情具有较好的效果.     

Reproductive characteristics of Japanese monkeys on Shimokita Peninsula,Japan, the northernmost habitat of wild primates in the world

The Shimokita Peninsula in Aomori Prefecture, Japan, which is inhabited by Japanese monkeys (Macaca fuscata), is the northernmost habitat for wild primates in the world. This study was the first to determine the conception dates of specific individuals and estimate the pregnancy rate of wild populations in this region. The pregnancy rate of animals aged 5 years or more at delivery was estimated to be 40.9% (27/66). Conception dates of each fetus were also estimated using a regression line of Pig-tail monkeys (Macaca nemestrina), which are taxonomically related to Japanese monkeys and have a similar physique. The conception dates were distributed across 90 days between September 24th and December 23rd, with a mean conception date of November 4th (SD=22.3 days, n=53). Using these findings, the mean birth date was estimated as April 25th, more than two weeks earlier than the mean birth date in previous research determined using direct observations carried out over the past 20 years ago. Global warming due to climate change is thought to be one of the main causes of this difference.     

The influence of dietary selenium levels on blood levels of selenium and glutathione peroxidase activity in the horse

Twenty mature geldings, averaging 535 kg, were used to determine the influence of dietary selenium (Se) on the blood levels of Se and Se-dependent glutathione peroxidase (SeGSH-Px) activity in the horse. Horses were randomly assigned within breed to four treatments consisting of five horses each and fed a basal diet containing .06 ppm of naturally occurring Se. Diets were supplemented with .05, .10 and .20 ppm Se, as sodium selenite. Blood was drawn for 2 wk before, and for 12 wk following, the inclusion of supplement Se in the diets. Whole blood and plasma Se concentrations and plasma SeGSH-Px activities were determined from all blood samples. Selenium concentrations in plasma and whole blood increased linearly from wk 1 to wk 5 and 6, respectively, in Se-supplemented horses. After these times, no significant changes in Se concentration were observed in Se-supplemented or in unsupplemented horses throughout the remainder of the 12-wk trial. Plasma Se reached plateaus of .10 to .11, .12 to .14, and .13 to .14 micrograms/ml in horses supplemented with .05, .10 and .20 ppm Se, respectively. Whole blood Se reached plateaus of .16 to .18, .19 to .21, and .17 to .18 micrograms/ml in horses supplemented with .05, .10 and .20 ppm Se, respectively. Plasma SeGSH-Px activity was not significantly affected by dietary treatment. Therefore, this enzyme was not a good indicator of dietary Se in these mature horses.     

The influence of exercise on serum enzyme levels in the horse.

A group of clinically normal horses was subjected to controlled strenuous exercise. Elevated serum concentrations of lactic dehydrogenase, aldolase and creatine kinase were observed after exercise but no significant change in serum glutamic-oxalacetic transaminase was noted. These changes were reduced by repeated exposure to exercise suggesting that measurement of serum enzyme elevations, particularly creatine kinase, might be a useful index of fitness in the horse. Administration of prednisolone prior to exercise also reduced these changes. Since the serum enzyme concentrations had returned to normal within 72 hours of exercise, and since the cytoplasmic enzyme glutamic oxalacetic transaminase was not released from the tissues this supported the hypothesis that efflux of intracellular enzymes into the circulation was due to a temporary selective change in cell membrane permeability rather than to tissue necrosis.     

The effect of chorionic gonadotropin administration on testosterone levels in the blood of boars with sexual function disorders]

Thirty-three boars with sexual dysfunctions and twenty-six boars clinically sound as to their reproductive capacity were evaluated for the testosterone levels in the blood plasma before i.v. administration of 500 i.u. of chorionic gonadotropin and two hours after the administration. A group of animals with reproduction disorders comprised boars with an impaired quality of ejaculate and low fertility ability (18 boars) and with sexual dysfunctions (15 boars). No statistically significant difference in the basal concentration of testosterone in the blood was found in the boars with the studied sexual dysfunctions, as compared with the boars with no sexual dysfunctions. Administration of chorionic gonadotropin increased significantly the plasma testosterone levels in both groups. If the effect of chorionic gonadotropin on the studied level of this hormone was compared in boars with sexual dysfunctions and in boars without any disorders, no significant differences were proved. It has been inferred from the above findings that there are no significant disorders of androgen supply and incretion reserve of the gonads in the boars with sexual dysfunctions.     

The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses

A study of the effects of intravenous administration of either 150 mg or 250 mg of furosemide to standardbred mares pre-treated with other drugs was undertaken to determine whether a unique pattern of drug elimination into urine and from plasma for each compound occurred. Furosemide significantly reduced the plasma concentrations of codeine compared to control 2-6 h after furosemide administration. In contrast, the plasma concentrations of theophylline, phenylbutazone, pentazocine, guaifenesin and flunixin were not markedly altered by furosemide. In the case of acepromazine, clenbuterol and fentanyl, the data generated were insufficient to state with certainty whether or not furosemide affected the plasma concentrations of these three drugs. A significant reduction was noted in the urinary concentrations of guaifenesin, acepromazine, clenbuterol, phenylbutazone, flunixin, fentanyl and pentazocine within 1-4 h of furosemide administration. The urinary concentrations of theophylline remained reduced as long as 8 h after furosemide injection. Furosemide administration to horses pre-treated with codeine resulted in depression of urinary morphine concentrations 2-4 h and 9-12 h after furosemide injection. A lower furosemide dose (150 mg) produced changes in drug urinary excretion and plasma elimination equivalent to the higher dose (250 mg). It is evident that furosemide affects the urinary and plasma concentrations of other co-administered drugs but not in a predictable fashion, which limits the extrapolation of these results to as yet untested drugs.     

The influence of various feedstuffs containing fat and protein on the digestibility of crude nutrients in young calves

Digestibility trials were carried out with calves, aged 3, 5, 7, 9, and 11 weeks, which were fed with feedstuffs of various energy and protein levels (various amounts of dried skim milk supplement with 146, 219, 323 g per day of the milk replacer Laktin) plus concentrate and hay. The purpose of the experiment was to find out what effect the amount of milk replacer varying daily had on the digestibility of the nutrients. The experiments confirm that the amount of milk replacer has a great influence on the digestibility of the crude fat. The amount of digestible crude fat consumed with the feed considerably influcenced the digestibility of the energy, it had little influence on the digestibility of the other nutrients, however. With increasing age the calves received more plant protein sources with a lower biologic value. Thus the digestibility of the protein in the complete ration was diminished as well. This shows that the digestibility was influenced by the protein quality, not, however, by the amount of crude protein. The digestibility of the dry matter andthe organic matter as well as of the N-free extractives in the feed ration diminished according to the changed composition with the increasing age of the animals; in constrast to this the digestibility of the crude fibres increased gradually.     

The effect of progesterone alone or in combination with estradiol on follicular dynamics, gonadotropin profiles, and estrus in beef cows following calf isolation and restricted suckling

The effects of calf isolation and restricted suckling on LH pulse characteristics and interval to first ovulation (postpartum interval) were studied in 52 multiparous beef cows, with or without exogenous progesterone. At 30 d postpartum, cows were randomly allocated to one of four treatments (n = 13/treatment): 1) Ad lib, ad libitum access of cows to calves; 2) CI/RS, calf isolation/restricted suckling, where suckling was restricted to once daily; 3) CI/RS+P4, same as CI/RS but cows received an intravaginal progesterone-releasing device at calf isolation for 6 d; or 4) CI/RS+P4+E2, as CI/RS+P4 but the intravaginal progesterone-releasing device had a 10-mg estradiol capsule attached. Daily ovarian scanning and twice-daily blood sampling were performed from d 25 postpartum until the day of second ovulation. A random sample of cows from each treatment (n = 31 in total) were blood-sampled at 15-min intervals for 10 h on d 29, 32, 35, and 38. Ovulatory response to treatment was regarded as ovulation of either the dominant follicle growing at d 30 or the subsequent DF. There was a treatment x day effect (P = .09) on LH pulse frequency, but neither progesterone (CI/ RS+P4) nor progesterone and estradiol (CI/RS+P4+E2) treatment suppressed the calf isolation/restricted suckling-induced increase in LH pulse frequency. The estradiol capsule (CI/RS+P4+E2) delivered sufficient estradiol to delay new follicle wave emergence (treatment x stage; P < .001) and the associated preemergence increase in concentrations of FSH (treatment, P < .05) in cows treated at the postselection stage of follicle wave development, prolonging dominance of the dominant follicle present at treatment initiation (P < .001). The number of cows that ovulated in response to treatment was greater (P < .001) in cows with calf isolation/restricted suckling than in cows suckled ad libitum. Hence, cows assigned to the Ad lib treatment had a longer postpartum interval (P < .001) than cows of the other treatments. Exogenous progesterone treatment increased the frequency of cows exhibiting clinical signs of estrus at first ovulation (P < .001) and reduced the frequency of short estrous cycles (P < .001). We conclude that, in beef cows with calves, a 6-d progesterone treatment does not suppress the calf isolation/restricted suckling-induced increase in LH pulse frequency. Hence, on progesterone withdrawal, the LH pulse frequency is sufficient to stimulate first ovulation, accompanied by overt estrous expression and elimination of a short estrous cycle in most cows.     

异地育肥对大别山黄牛部分激素水平的影响

为了测定异地育肥对大别山黄牛血清中激素水平的动态影响，选择30头经临床检查健康大别山黄牛，特进行0（到达牛场时）、14、28和42d时血清激素水平测定。经颈静脉无菌采血，分离血清，测定生长激素（GH）、胰岛素（INS）、三碘甲腺原氨酸（T3）、甲状腺素（T4）和皮质醇（COR）水平。记录试验牛平均体质量（Aw），平均日增重高（ADG），平均日采食精、粗料量（ADFI），平均日饮水量（ADWI）和发病牛头数。结果表明：14d时，牛开始增重，42d时，平均日增重高于28d和14d时（P〈0．05或P〈0．01）；平均日采食精、粗料量在42d时高于14、28d时（P〈0．01或P〈0．05）。GH、INS、T3和T4激素水平在0d时最低，在14d时最高。INS水平在14d时极显著高于28d和42d时（P％0．01）。COR水平，在0d时最高（P％0．01），14、28和42d时差异不显著。在整个试验期内，均有试验牛发病。通过激素水平动态变化发现大别山黄牛进场14d内处于应激状态之中，进而能明显影响牛体生长性能。     

The influence of exogenous pituitary growth hormone on the ovulatory response to PMSG and hCG and the LH response to estradiol benzoate in prepubertal gilts

Two experiments were performed to examine the influence of exogenous growth hormone on the reproductive axis in gilts. Experiment one employed 26 Yorkshire × Landrace prepubertal gilts, which were selected at 150 d and 86.5 ± 1.5 kg bodyweight (BW) and assigned equally to two treatments. Gilts received injections of either porcine growth hormone at 90 μg/kg BW, or vehicle buffer, from 150 to 159 d. At 154 d gilts received 500 IU PMSG, followed 96 hr later by 250 IU hCG. Gilts were slaughtered at 163 days and their ovaries recovered to determine ovulatory status. In each treatment, gilts failed to show any ovarian response to PMSG/hCG. All remaining control gilts ovulated and their ovaries appeared morphologically normal. In gilts receiving exogenous growth hormone, fewer ovaries (4/11, P<.01) appeared morphologically normal. The ovaries of all other growth hormone injected gilts had very large (12–25 mm) non-luteinized follicles. In experiment two, 20 prepubertal Yorkshire × Landrace gilts were selected at 138 days and 85 kg BW. These gilts received injections of growth hormone at 90 μg/kg BW (n=9) or vehicle (n=11) from 138 to 147 days. At 143 days, all gilts were given an injection of estradiol benzoate (EB) at 15 μg/kg BW. Blood samples were taken at the time of EB injection, at 24 and 36 hr and then at 6 hr intervals until 78 hr. All samples were assayed for serum LH concentrations. The EB induced LH peak height was lower (P<.04) in gilts receiving exogenous growth hormone than in controls. The results presented indicate that the daily injection of growth hormone at 90 μg/kg BW reduced the estradiol-induced release of LH in addition to reducing the number of corpora lutea in gonadotrophin stimulated gilts.     

The influence of feeding conditions on urine pH and plasma bicarbonate levels in healthy sheep

In healthy sheep the reaction of the urine has generally been accepted to be on the alkaline side (Bentinck-Smith 1963). Thus Healy et al. (1928) only found 2 of 40 healthy sheep with an acid urine. Bentinck-Smith reported that nursing animals in contrast to adults will produce an acid urine. However, the influence of feeding on urine pH and plasma bicarbonate levels in sheep does not seem to have been systematically investigated. During recent years it has often been observed in this laboratory that healthy animals, examined as a matter of routine, may produce an acid urine. Based on these observations healthy sheep under different feeding conditions were examined in order to elucidate the influence of the diet on the pH of the urine and the plasma bicarbonate content. Since an excessive lactic acid production and increased fat metabolism may also influence the acid-base balance, the lactic acid concentration of rumen fluid was determined, and the urine was tested for ketone bodies.