rhBNP治疗射血分数保留急性心力衰竭的临床研究

目的:探讨重组人脑利钠肽(rh BNP)对急性射血分数保留心力衰竭的临床治疗作用。方法:选择2008年6月至2014年6月间我院收治的20例急性射血分数保留心力衰竭患者为研究对象,其中10例予以硝普钠静脉注射48小时,10例予以rh BNP静脉注射48小时。48小时后,评估和比较两组患者心力衰竭的临床改善情况;72小时后,复查和比较两组患者血浆NT-pro BNP的下降值。结果:硝普钠组患者呼吸困难缓解积分(1.4±1.35)明显低于rh BNP组(3.5±0.71),rh BNP组呼吸困难缓解时间(3.68±1.69 h)显著短于硝普钠组(21.50±18.43 h),血浆NT-pro BNP浓度下降值(864.60±585.92 pg/ml)明显高于硝普钠组(423.30±284.06 pg/ml)。结论:rh BNP治疗急性射血分数保留心力衰竭的临床疗效优于硝普钠。     

Oestrogenic effects of ICI 182,780, a putative anti-oestrogen,on the secretion of oxytocin and prostaglandin F2α during oestrous cycle in the intact ewe

The effect of ICI 182,780, oestrogen antagonist, on the concentrations of oxytocin and uterine PGF_2α was investigated in intact Border Leicester Merino cross ewes during the late oestrous cycle. Twelve cyclic ewes (n=6 per group) were randomly assigned to receive, at 6 h intervals, intra-muscular injection of either peanut oil or ICI 182,780 (1.5 mg kg⁻¹ day⁻¹) in oil for 2 days, starting at 1900 h on day 13 until 1300 h on day 15 post-oestrus. Hourly blood samples were collected via a jugular catheter from 0800 h on day 14 for 37 h and then daily over days 16, 17 and 18 post-oestrus. Peripheral plasma concentrations of oxytocin, the metabolite of prostaglandin F_2α, 15-keto-13,14-dihydro-prostaglandin F_2α, (PGFM) and progesterone were measured by radioimmunoassay. All ewes treated with ICI 182,780 exhibited functional luteal regression as indicated by a marked reduction in plasma progesterone concentrations to less than 1000 pg/ml over the period of 18–36 h during sampling period on days 14 and 15 of the oestrous cycle. In five of six vehicle-treated ewes, progesterone concentrations declined between day 16 and day 18 post-oestrus. In the remaining control ewe, progesterone concentrations reach less than 1000 pg/ml within 36 h of the commencement of the sampling period. During the frequent sampling period, the number of oxytocin pulses in the ICI 182,780 treated ewes was significantly higher compared to control ewes (2.7±0.3 vs. 0.8±0.3). The mean amplitude of oxytocin pulses observed was also greater (70.4±19.5 pg/ml) in ewes treated with ICI 182,780, but was not significantly different from control ewes (33.5±12.9 pg/ml). Oxytocin pulses may however have occurred following the initial two ICI 182,780 injections but before commencing blood sampling. The oxytocin pulses were detected at a mean of 3.2±0.2 h following each injection with ICI 182,780 during blood sampling. In the ICI 182,780-treated ewes, the pulsatile pattern of plasma PGFM in jugular blood samples over the 37 h sampling period on days 14 and 15 post-oestrus had a higher amplitude (512.9±158.9 vs. 121.7±78.7 pg/ml) and pulse area (618.1±183.3 vs. 151.5±102.9 (pg/ml)τ) compared to the vehicle-treated ewes (P<0.05) respectively. The average number of PGFM pulses observed per ewe was 3.0±0.7 in the ICI 182,780-treated group and was significantly (P<0.02) higher than the number of pulses (0.5±0.3) observed in ewes treated with vehicle alone. The PGFM pulses were detected at 4.2±0.6 h following each injection with ICI 182,780 during blood sampling. The percentage of PGFM pulses that occurred coincidently with a significant elevation of oxytocin concentrations was 44.4% in ICI 182,780-treated compared to 66.6% in control ewes. We conclude that administration of oestrogen antagonist ICI 182,780 accelerated development of the luteolytic mechanism by enhancing pulsatile secretion of oxytocin and PGFM which suggests that ICI 182,780 acts as an agonist for oxytocin and prostaglandin F_2α release in intact ewes when administered at 1.5 mg/kg/day over Day 13 to 15 post-oestrus.     

Evidence that 19-hydroxyandrostenedione is secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system in man

Plasma 19-hydroxyandrostenedione (19-OH-A-dione) concentrations in man were evaluated using a specific and sensitive radioimmunoassay. Plasma 19-OH-A-dione concentrations (mean ± SE) in normal subjects are 151 ± 14 pg/ml (n=13) in males and 141 ± 9 pg/ml (n=14) in females. Plasma 19-OH-A-dione (mean ± SE) rises significantly during ACTH stimulation (116 ± 25 pg/ml vs 288 ± 38 pg/ml; P<0.01; n=5), declines significantly during dexamethasone suppression (180 ± 30 pg/ml vs 36 ± 14 pg/ml; P<0.01; n=4) and rises significantly during angiotensin II infusion (89 ± 10 pg/ml vs 159 ± 27 pg/ml; P<0.05; n=5). Plasma 19-OH-A-dione in the adrenal vein is much higher than that in the inferior vena cava (2076–3076 pg/ml vs 115–184 pg/ml; n=2). These results demonstrate that 19-OH-A-dione is directly secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system.     

Involvement of serum vascular endothelial growth factor family members in the development of obesity in mice and humans

Adipose tissue is highly vascularized implying that angiogenesis takes place in its expansion. The aim of this study was to compare the concentrations of members of the vascular endothelial growth factor (VEGF) family in obesity. Serum concentrations of VEGFs were analyzed in 15 lean (BMI 20.3±2.5 kg/m²) and 24 obese (BMI 47.6±5.9 kg/m²) volunteers. Obese patients showed significantly increased circulating VEGF-A (150±104 vs. 296±160 pg/ml; P<.05), VEGF-B (2788±1038 vs. 4609±2202 arbitrary units; P<.05) and VEGF-C (13 453±5750 vs. 17 635±5117 pg/ml; P<.05) concentrations. Interestingly, levels of VEGF-D were reduced in obese individuals (538±301 vs. 270±122 pg/ml; P<.01). In addition, VEGF-A significantly decreased after weight loss following Roux-en-Y gastric bypass (BMI from 46.0±8.0 to 28.9±4.2 kg/m² P<.0001 vs. initial) from 345±229 to 290±216 pg/ml (P<.01). Moreover, in order to corroborate the human findings VEGF-A levels were analyzed during the expansion of adipose tissue in two dynamic models of murine obesity. Serum VEGF-A was significantly increased after 12 weeks on a high-fat diet (43.3±9.0 vs. 29.7±9.1 pg/ml; P<.01) or in ob/ob mice (52.2±18.0 vs. 29.2±7.7 pg/ml; P<.01) and was normalized after leptin replacement in the latter (32.4±14.0 pg/ml; P<.01 vs. untreated ob/ob). Our data indicates the involvement of these factors in the expansion of adipose tissue that takes place in obesity in relation to the need for increased vascularization, suggesting that manipulation of the VEGF system may represent a potential target for the pharmacological treatment of obesity.     

Effects of systemic and intrafollicular injections of LH,prostaglandins, and indomethacin on the luteinization of rabbit Graafian follicles

The possibility that initiation of luteinization in ovarian follicles by luteinizing hormone (LH) is mediated by prostaglandins (PG's) was investigated in rabbits. Estrous rabbits, given an ovulatory dose of LH (50 μg) intravenously, were administered indomethacin (IM), an inhibitor of PG biosynthesis, by various routes. Progesterone levels in the serum and in the induced corpora lutea (CL) were subsequently measured by radioimmunoassay. Continued daily subcutaneous injections of IM from 2 days before through 2 days after LH treatment reduced the corpus luteal level, measured at 72 hours post-LH, of PGF from 208 ± 43 to 98 ± 20 pg/CL (P < 0.025) and that of PGE from 272 ± 31 to 115 ± 9 pg/CL (P < 0.005). At the same time, progesterone levels were 72 ± 12 and 93 ± 10 ng/CL (P > 0.05) in the oil-treated and IM-treated rabbits, respectively. Serum progesterone continued to rise in a linear fashion during the period from 24 to 72 hours following LH treatment, whether IM was injected or not. Intrafollicular treatment with LH (100 ng/follicle) raised the progesterone content in the treated follicles 72 hours later from 1.1 ± 0.5 to 50.1 ± 13.5 ng. (P < 0.01). This progesterone content reached 21.5 ± 15.8 ng (P < 0.05) in follicles similarly treated with PGE₂ (5 μg/follicle), but remained meagre at lower doses of PGE₂ (100 ng/follicle and 2 ng/follicle). Serum progesterone increased from 0.5 ± 0.1 to 1.2 ± 0.1 ng/ml (P < 0.005) within 72 hours in rabbits treated intrafollicularly with LH, but remained unaltered in those similarly treated with PGE₂ (P > 0.1). Intrafollicular injections with PGF_2α failed to induce changes in either level of progesterone. It is concluded that prostaglandins probably do not mediate the luteinizing action of LH in rabbit Graafian follicles, although some degree of luteinization can be induced by high levels of exogenous PGE₂.     

Luteinizing hormone,total estrogens and progesterone secretion during lactation and after weaning in sows

Two experiments were conducted to determine changes in serum concentrations of LH, total free estrogens and progesterone before and after weaning in sows. Blood was collected either via indwelling anterior vena cava cannula or by venipuncture and serum hormones were measured by radioimmunoassay. In Exp. I, blood was collected at 15-min intervals for 4 hr on day 7 and day 21 postpartum from three sows on each day. In addition, individual samples were collected from 10 sows on days 4 and 14 postpartum and from 11 sows on days 1, 3 and 5 after weaning (day 23 postpartum). Serum LH ranged from .2 to .8 ng/ml during lactation and averaged 1.1 ± .7, 1.1 ± .7 and 2.7 ± .7 on days 1, 3 and 5 after weaning, respectively. Progesterone was low (< 1 ng/ml) during lactation and averaged 1.9 ± .3, .6 ± .3 and 1.2 ± .3 on days 1, 3 and 5 after weaning. Estrogens were variable during lactation, averaged 121 ± 36 pg/ml on day 1 after weaning and decreased thereafter. Estrus began on day 3 after weaning in 1 sow and on day 5 in the remaining 10 sows.In Exp. II, blood was collected from seven sows at 12 to 24 hr intervals from 2 days before until 5 days after weaning (day 26 postpartum). Mean serum LH was .7 ± .1 ng/ml during 48 hr before weaning and remained unchanged after weaning until day 3 when LH increased to 6.1 ± .8 ng/ml. Serum LH concentrations then declined to 1.3 ± .8 and .9 ± .8 ng/ml on days 4 and 5 after weaning. Total estrogens averaged 31 ± 4 pg/ml during 48 hr prior to weaning and 32 ± 4, 43 ± 17, 28 ± 1, 30 ± 2, 16 ± 2 and 18 ± 2 on days 0 to 5 after weaning. Progesterone increased from 1.0 ± .3 ng/ml 24 hr before weaning to 3.0 ± .3 at weaning and then remained low (< 1 ng/ml) until after ovulation when progesterone increased. Estrus began on day 4 after weaning in all seven sows.Results from these two experiments indicate that in sows: (1) LH is suppressed during early lactation (day 7), gradually increases during late lactation (day 21) and then reaches peak concentrations after weaning near the onset of estrus, (2) estrogens increase between weaning and estrus and decline thereafter, and (3) progesterone rises transiently at weaning and then increases after estrus and ovulation.     

腹主动脉下段球囊临时阻断术时钙蛋白T水平的变化及临床意义

目的:探讨腹主动脉下段球囊临时阻断术时钙蛋白T(TnT)水平的变化及临床意义。方法:回顾性分析2015年5月至2016年12月我院收治的58例难治性盆腔类手术患者的临床资料,包括骨盆骨折11例、凶险性前置胎盘并发胎盘植入22例、骶骨肿瘤切除术12例、盆腔肿瘤切除术13例。以上全部操作均给予腹主动脉下段球囊临时阻断术。分别于术前、球囊阻断时、术后的血液样本对钙蛋白T(TnT)进行检测。手术时间2~5 h,平均3.6 h。结果:术前,所有患者血清TnT水平为(90±5)pg/m L。阻断时,血清TnT升高至(109±3)pg/m L,与术前比较差异有统计学意义(p0.05)。解除阻断后1小时,TnT升高至(113±2)pg/m L;解除阻断后2小时TnT较阻断时升高至(115±3)pg/m L,较阻断前明显升高,差异有统计学意义(p0.05)。解除阻断后6小时,TnT较阻断时下降(95±5)pg/ml,较阻断后2 h明显下降并恢复至正常值,差异有统计学意义(p0.05)。结论:腹主动脉下段球囊临时阻断术不可避免引起心肌细胞不同程度的缺血再灌注损伤,但是此类损伤不大,为一过性、可代偿的损害。     

The influence of prolactin (PRL) on progesterone secretion by porcine luteal cells in vitro

Porcine luteal cells were obtained from corpora lutea on the 5th, 13th and 17th days of the estrous cycle. The cells were suspended at a concentration of 5 × 10⁴ cells/ml in Eagle's medium with 2% human serum albumin. These cells were incubated with or without 0.01, 0.1, 1 or 10 μg/ml porcine prolactin. The amount of progesterone in cultures was estimated by a radio-immunological method after 30 min, 3 h and 6 h of culturing.Luteal cells obtained on the 5th day of the estrous cycle and incubated without prolactin secreted 71.24 ± 21.91 ng progesterone/ml of medium, whereas under the influence of prolactin at 0.01, 0.1, 1 and 10 μg/ml, 39.06 ± 13.33, 44.31 ± 12.69, 44.88 ± 16.85 and 51.62 ± 15.01 ng progesterone/ml (P<0.01) were secreted. Luteal cells from the 13th day of the estrous cycle incubated without prolactin secreted on average 70.72 ± 9.21 ng progesterone/ml of medium, whereas under the influence of different prolactin doses 50.75 ± 8.52, 46.54 ± 7.13, 43.30 ± 6.78 and 41.68 ± 7.21 ng progesterone/ml (P<0.01) were secreted.Prolactin did not change progesterone secretion by luteal cells obtained on the 17th day of the estrous cycle. An influence of the incubation time on progesterone secretion by these cells was observed: after 30 min of incubation the cells secreted 8.83 ± 2.95 ng/ml, after 3 h 8.12 ± 2.57 ng/ml and after 6 h 6.86 ± 1.91 ng/ml, irrespective of the amount of PRL added.The results suggest that prolactin plays a role in the luteolysis of the corpus luteum.     

Plasma FSH concentrations in seasonally anoestrous ewes induced to ovulate with repeated injections or continuous infusion of GnRH

Plasma FSH concentrations were monitored in 34 seasonally anoestrous ewes in which ovulation was induced by the administration of low doses of GnRH, given as either a series of i.v. injections (75, 125, 250 or 500 ng/2 h) or as a continuous i.v. infusion (125 or 250 ng/h). Fifteen of the animals had been pretreated with progesterone for 14 days. Before the start of GnRH treatment, mean FSH concentrations did not differ between progesterone-pretreated and non-pretreated ewes (23 ± 3.0 and 20 ± 2.0 ng/ml, respectively). In a significant (P < 0.01) proportion of animals mean FSH concentrations were elevated for the first 2 h of GnRH treatment, but thereafter they declined progressively and were significantly (P < 0.001) lower than pretreatment levels over the second 12 h of GnRH treatment. These changes in FSH concentrations were not related to dose of GnRH, the mode of administration or to progesterone priming. These results demonstrate that the pattern of FSH secretion associated with GnRH-induced ovulation in the seasonally anoestrous ewe is similar to that observed from the time of luteal regression in the naturally cycling ewe. In addition, although pretreatment with progesterone has a marked effect on subsequent luteal function, this is not mediated through changes in plasma FSH concentrations.     

Gonadal development and steroid hormone profile of wild caught grey mullet (Mugil cephalus)

The grey mullet Mugil cephalus is one of the popular and fast growing fishes being cultured in tropical and subtropical regions. In the present study, histological observation of gonadal development and corresponding changes in sex steroid levels from different maturity stages of wild caught male and female were studied. In female, testosterone and 17β-estradiol increased with the advancement of maturation and reached peak (17β-estradiol, 323 ± 13 pg/ml; testosterone, 938 ± 7.87 pg/ml) in mature stage, whereas the level of progesterone was maximum (488 ± 4.9 pg/ml) during ripe stage. Vitellogenin level in serum showed a similar trend as 17β-estradiol. In case of male, the testosterone level in serum increased gradually with advancement of maturation and was maximum (1820 ± 40.25 pg/ml) during ripe stage, whereas significant decrease in 17β-estradiol and progesterone was noticed with advancement of maturation. The fundamental information from this investigation would be useful for developing protocol for accelerating maturation and spawning under captive condition.     

A non-chromatographic radioimmunoassay of prugesterone in serum

Convenient methodology based on separation of progesterone from alcoholic neutral steroids by means of a sulfation-procedure has been developed for the radioimmunoassay (RIA) of progesterone in male and female serum. When coordinated with our previously published nonchromatographic procedure for the RIA of estrone and estradiol in serum, all 3 seteroids can be determined in the same specimen. Validation of the procedure was based on: 1. Agreement between results obtained using TLC and sultation to fractionate progesterone (r=0.98; b=0.86), 2. accurate recovery of different quantities of progesterone added to serum, 3. independence of the concentration of progesterone and volume of serum used for assay, 4. low procedural blanks (3.6 ± 1.3 pg), 5. low intraassay (9.7 – 10.3%) and interassay (11.0 – 11.6%) variability and 6. correspondence of observed values for progesterone in male serum (108 ± 20 pg/ml) and in female serum (follicular, 285 ± 149 pg/ml; luteal, 3.46±1.45 ng/ml) with those reported previously by others.     

Evidence from a dual action of converting enzyme inhibitor on blood pressure in normal man

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 meq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4±3.2 mm fall in blood pressure (p<0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day, abolished the blood pressure response (2.5±0.9 mm Hg, p>0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8±1.1 vs. 10.0±3.1 mm Hg, p>0.5). CEI increased plasma renin on both diets (1.7±0.5 to 3.5±0.8 and 2.8±0.6 to 12.5±3.1 ng/ml/hr respectively both p<0.05). Aldosterone did not change (high Na⁺) or fell (low Na⁺). Inhibition of prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.     

Salivary progesterone for the assessment of the ovarian function in the capuchin monkey (Cebus apella)

Salivary and plasma progesterone were measured in normally cycling (n=10) and castrated (n=4) femaleCebus monkeys (Cebus apella). During the follicular phase, progesterone levels in saliva ranged between 0.05 and 1.40 ng/ml and in the luteal phase they increased to between 0.22 and 4.70 ng/ml. These values represented on average 6.5 and 3.2% of those values measured in plasma, for the follicular and luteal phases, respectively. The regression analysis of the steroid concentrations in both fluids showed a highly significant correlation (r=0.8985,n=180,P<0.0001). Ovariectomized monkeys had consistently low salivary (0.37±0.02 ng/ml) and plasma (4.70±0.25 ng/ml) progesterone, showing a low, but significnat, correlation coefficient (r=0.2592,n=58,P=0.047). The ratio of plasma/salivary progesterone was significantly higher in the luteal phase (31.09±1.65) than in the follicular phase (23.06±2.26) and in castrated monkeys (16.00±1.38). The free fraction of progesterone constituted 5.3±0.2% of the total plasma progesterone during the follicular phase and 3.3±0.1% during the luteal phase. Ovariectomized monkeys showed a significantly higher percentage of free progesterone in plasma (7.7±0.1%). In contrast, free progesterone made up 64.4 and 70.9% of the total salivary progesterone for the follicular and luteal phases, respectively. The proportion of free progesterone in castrated animals was within the range observed in cycling animals. We suggest that the levels of progesterone in the saliva of capuchin monkey follow a pattern similar to that for plasma progesterone, reflecting the free steroid fraction. Thus, the measurement of such steroid in saliva may offer a valuable alternative to plasma determinations for the assessment of the ovarian function inCebus and probably other New World monkey species.     

Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: A randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice

Inadequate intake of the recommended five-a-day fruit and vegetable portions might contribute to increased cardiovascular disease risk. We assessed the effects of dietary intake of a blackcurrant juice drink, rich in vitamin C and polyphenols, on oxidative stress and vascular function. This was a double-blind, placebo-controlled, parallel group study of 66 healthy adults who habitually consume <2 portions of fruit and vegetables per day. Participants were randomly allocated to consume 250 ml of placebo (flavored water) or low or high blackcurrant juice drink four times a day for 6 weeks. Flow-mediated dilation (FMD) and plasma concentrations of F₂-isoprostanes and vitamin C were measured. In the high blackcurrant juice drink group FMD increased significantly (5.8±3.1 to 6.9±3.1%, P=0.022) compared with the placebo group (6.0±2.2 to 5.1±2.4%). Plasma vitamin C concentration increased significantly in the low (38.6±17.6 to 49.4±21.0 µmol/L, P<0.001) and high (34.6±20.4 to 73.8±23.3 µmol/L, P<0.001) blackcurrant juice drink groups compared with the placebo group (38.1±21.0 to 29.0±17.6 µmol/L). F₂-isoprostane concentrations were significantly lower in the high blackcurrant juice drink group (225±64 pg/ml) compared with the low blackcurrant juice drink (257±69 pg/ml, P=0.002) and placebo group (254±59 pg/ml, P=0.003). At follow-up, changes in plasma vitamin C correlated significantly with changes in FMD (r=0.308, P=0.044). Consumption of blackcurrant juice drink high in vitamin C and polyphenols can decrease oxidative stress and improve vascular health in individuals with habitually low dietary fruit and vegetable intake.     

Role of interleukin-23 circulating levels increase in resected colorectal cancer before and after chemotherapy: preliminary data and future perspectives

Expression of IL‐23, a heterodimeric cytokine involved in the induction of Th17 cells, is increased in human tumors. Although the endogenous IL‐23 expression has been reported to promote tumor development and growth, the studies using local and systemic administration of IL‐23 have shown that its application at the excessive amount induces antitumor immune responses. IL‐23 is, today, considered the key driver of intestinal inflammation and its role in inflammatory responses is tissue‐specific. The aim of this study was to investigate the role of circulating levels of IL‐23 in patients with resected colorectal cancer (CRC) before and after chemotherapy, respect to healthy controls. Twenty‐five patients were enrolled between June 2007 and January 2009, and followed through 2010. All patients underwent chemotherapy, mostly FOLFOX4. Twenty‐sex and age‐matched healthy donors were recruited as controls. IL‐23 serum concentrations, measured by a quantitative enzyme immunoassay technique, were significantly higher in patients with resected CRC (26.02 ± 28.63 pg/ml versus 7.1 ± 6.4 pg/ml, P < 0.001) and after chemotherapy respect to controls (21.74 ± 23.82 pg/ml versus 7.17 ± 6.43 pg/ml, P < 0.001). An increase was documented also before chemotherapy (26.02 ± 28.63 pg/ml versus 21.74 ± 23.82 pg/ml, P = 0.7) but not statistically significant. This work investigated, for the first time, the role of IL‐23 in CRC resection and chemotherapy, showing no correlation with the severity of disease, tumor removal, and chemotherapeutic treatment. However, other works are needed to better clarify if IL‐23 could be considered a key‐molecule in human CRC and a target for tumor treatment. J. Cell. Physiol. 226: 3032–3034, 2011. © 2011 Wiley‐Liss, Inc.     

Secretion patterns of oxytocin and PGF2alpha-metabolite in response to cervical dilatation in cyclic mares

We conducted the present study to establish a standardized method for cervical stimulation without affecting the endometrium, and to investigate the effect on estrous cycle pattern and concentrations of progesterone, oxytocin and PGF2alpha-metabolite of cervical dilatation in the mare. Six healthy Haflinger mares underwent three different treatments (control, insertion, dilatation) on Days 5 and 7 of the cycles in different orders according to a Latin square design. During dilatation, the balloon of the catheter was inflated stepwise every 30s with warm physiological saline to a maximum of 50 ml. At this stage the size of the balloon was 4.5 cm in diameter and 6 cm length. Estrous cycle length was significantly shortened by dilatation when compared to controls (control: 22.8+/-1.7, insertion: 21.8+/-2.5, dilatation: 20.0+/-1.3 days; P<0.05). Concentrations of progesterone at Days 10, 12 and 14 after ovulation were significantly lower in dilatation cycles. Calculation of the area under the curve (AUC) for progesterone secretion from Day 7 to Day 12 also revealed a significant decrease in progesterone secretion in the dilatation group (dilatation: 34.1+/-7.3, insertion: 35.6+/-7.8, control: 39.1+/-5.9 ng/ml; P<0.05). Cervical insertion and dilatation caused a rapid and pronounced increase in plasma concentrations of oxytocin from basal levels (1.0-6.1 pg/ml) to maximum peaks (insertion: 125.5 pg/ml and dilatation: 305.2 pg/ml). The AUC for oxytocin was significantly higher after insertion (Day 5: 858.4+/-469.9; Day 7: 411.9+/-213 pg/ml/h) and dilatation (Day 5: 1697+/-1725; Day 7: 1078.5+/-764 pg/ml/h) when compared to controls (Day 5: 186+/-98; Day 7: 156+/-23.5 pg/ml/h; P<0.05). Manipulations did not cause considerable changes in plasma PGF2alpha-metabolite concentrations. Because cervical dilatation up to a diameter of 4.5 cm did not cause any immediate PGF2alpha release, the luteolytic pathway is unlikely to be responsible for shortening the length of diestrus and the estrous cycle. The present data suggest an involvement of oxytocin in the shortening of the luteal phase in response to cervical manipulation.     

Steroidogenic capabilities of the early mouse embryo

Preimplantation embryos from ICR albino mice were used to determine progesterone and estradiol-17β production during incubation in BMOC-2. Following culture of 40 embryos/culture at either the morula, early blastocyst or late blastocyst stages, progesterone and estradiol-17β contents were 192±27 and 82±22 pg, 289±50 and 147±46 pg and 157±28 and 88±23 pg, respectively, for incubated samples and 306±68 and 89±40 pg, 404±63 and 125±44 pg, and 241±54 and 86±39 pg, respectively for control samples. Although, there were significant stage of development and treatments effects (P<0.05) for progesterone, production of this steroid was not evident. These data suggest that the early preimplantation mouse embryo does not produce progesterone or estradiol-17β in a defined culture system.     

Effect of progestins on serum hormones,semen production,and agonistic behavior in the gerenuk (Litocranius walleri walleri)

The use of progestins to suppress endogenous testosterone production to reduce agonistic behavior and prevent semen production was studied in gerenuk. Five male gerenuk (20 months to 3 years of age), housed as a bachelor group, were treated with 3 monthly injections of medroxyprogesterone acetate (MPA; 2.5–20 mg/kg), followed by a melengestrol acetate implant (MGA; 0.3 g/kg) for 2 months. Blood samples collected monthly were assayed for serum testosterone and cortisol using enzyme‐linked immunoassays. Quantitative behavioral data were collected for 30 min 3/week starting 1 month before treatment. Body weight, testes volume, and semen traits were measured before treatment, after MPA treatment, and after MGA treatment. Results showed lower (P<0.05) mean serum testosterone concentrations after MPA (4.34 pg/ml) and MGA (5.02 pg/ml) treatment compared to pre‐treatment values (65.9 pg/ml) in four of five gerenuk. The remaining sub‐adult gerenuk had low testosterone initially (4.9 pg/ml) that did not decrease further with treatment (1.4 and 7.8 pg/ml for MPA and MGA, respectively). Mean serum cortisol concentrations decreased markedly after treatment with MPA (6.0±3.7 ng/ml) and MGA (0.8±0.3 ng/ml). Cortisol concentrations were regained rapidly post‐treatment (42.8±4.8 ng/ml) and were not significantly different from the pre‐treatment value (60.6±12.6 ng/ml; P>0.05). The mean incidence of combined aggressive/dominant behaviors (horning, sparring, supplanting, threat) was not different before and after treatment. Body weight, total numbers of spermatozoa produced per ejaculate, percent motility, and percent normal spermatozoa declined maximally 8 months after treatment. Mean testes volume decreased (P<0.05) after MGA treatment (10.53 cm³vs. 11.96 cm³ pre‐treatment). Elevated hepatic enzymes and bile acids were seen in three of five animals after progestin treatment and anorexia was noted in two males after MGA implant removal, however two of three males had elevated liver enzymes before progestin treatment began. Results show that reducing serum testosterone concentration does not seem to modify agonistic behavior in bachelor gerenuk groups. Zoo Biol 26:245–257, 2007. © 2007 Wiley‐Liss, Inc.     

Hypercalcemia in association with a Leydig cell tumor in the rat: A model for tumor-induced hypercalcemia in man

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 ± 0.3 m mg/dl to 12.5 ± 0.4 mg/dl at day 10 and 16.4 ± 1.3 mg/dl (p<0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 ± 0.17 mg/d to 3.52 ± 0.72 mg/d (Day 12, p<0.01). Serum phosphate decreased from a baseline of 7.5 ± 0.3 mg/dl to 5.5 ± 0.6 mg/dl at day 13 (p<0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p<0.01). Calcitonin increased from 59 ± 2 pg/ml to 88 ± 9 pg/ml (p<0.01). The plasma prostaglandin E metabolite, 13, 14-dihydro-15-keto-PGE₂ increased from 407 ± 103 pg/dl to 647 ± 62 pg/ml (p<0.05) and the active Vit D compound 1, 25(OH)₂D increased from 94.8 ± 5.2 pg/ml to 162.3 ± 11.8 pg/ml (p<0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 ± 3 nmol/d to 172 ± 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.