Effects of PGF2alpha and PGF2alpha, 1-15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey.

The effects of prostaglandin (PG)F2alpha and PGF2alpha, 1-15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF2alpha, 1-15 lactone were significantly (P less than 0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P less than 0.008) lower by the second day after the initial treatment with either PGF2alpha or PGF2alpha, 1-15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P less than 0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF2alpha, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF2alpha, 1-15 lactone. These data indicate that PGF2alpha, 1-15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF2alpha, 1-15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF2alpha.     

Effects of PGF2α and PGF2α, 1–15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey

The effects of prostaglandin (PG)F_2α and PGF_2α, 1–15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF_2α, 1–15 lactone were significantly (P <0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P <0.008) lower by the second day after the initial treatment with either PGF_2α or PGF_2α, 1–15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P <0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF_2α, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF_2α, 1–15 lactone. These data indicate that PGF_2α, 1–15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF_2α, 1–15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF_2α.     

Early embryonal culture of the cynomolgus monkey (Macaca fascicularis)

Ovaries of ten female cynologus monkeys (Macaca fascicularis) were superstimulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). During this treatment, follicular development was monitored by ultrasonography. After three to four injections of PMSG, ovaries began to show an increase in their size. After seven to ten injections of PMSG and a hCG injection, a total of 183 oocytes (18.3±14.1/ animal, mean±SD) were recovered from these females by laparotomy. Five nulliparous females produced 24.2±18.2 oocytes per animal, and the remaining five parous females produced 12.5±5.46 oocytes per animal. In total, 133 (72.6%) of the 183 oocytes were classified morphologically as matured, and 130 of them were inseminated with cynomolgus monkey sperm for 18 hours in vitro. The second polar body was observed in 92 (71%) of the inseminated oocytes, and 54 (59%) of the 92 oocytes showed cleavage division at least once. When these oocytes were fertilized and cultured in serum-free media, they stopped their development at 4-cell stage. In contrast to this condition, about a half of fertilized oocytes in serum-free media were able to develop to morula stage 4 days after insemination by transferring them into serum-containing media after 2-cell stage.     

妊娠期妇女产次与龋病及牙周病发生关系的探究

目的探究妊娠期妇女龋病及牙周病发生情况和不同产次对妊娠期妇女龋病及牙周病发生的差异。方法以228名妊娠期妇女(其中初产妇140名,经产妇88名)和85名同龄未妊娠妇女(对照)为研究对象,检查其龋病及牙周病发生状况,并记录菌斑指数(PLI)、探诊深度(PD)、临床附着丧失(CAL)、牙石指数(CI)和龈沟出血指数(SBI),进行组间统计分析。结果 (1)初产组(47.86%)、经产组(67.05%)的患龋率均高于对照组(29.41%)(P0.05),且经产组的患龋率高于初产组(P0.05)。初产组、经产组和对照组的龋均分别为1.57、2.18和0.90。(2)PLI、CI、PD、CAL和SBI在初产组(0.60±0.06,1.92±0.54,4.38±1.20,0.21±0.05,2.51±1.14)和经产组(0.71±0.59,2.06±0.97,4.77±1.35,0.22±0.08,3.05±1.40)均高于对照组(0.52±0.28,1.26±0.39,2.80±0.78,0.18±0.11,2.06±1.17)(P0.05),且经产组的PD、SBI高于初产组(P0.05),而初产组和经产组间PLI、CI、CAL的差异无统计学意义(P0.05)。结论妊娠可能导致妇女患龋率、PLI、CI、PD、CAL和SBI的增加,且产次增加可能导致妇女患龋率、PD和SBI的增加。     

Serum cortisol levels affect the metabolic clearance rate of progesterone in female baboons.

Since interactions between progesterone (P₄), Cortisol (F), cortisone (E) and corticosteroid binding globulin (CBG) may influence the metabolic clearance rates (MCR) of these steroids, the effect of altering circulating F concentrations on clearance of the steroids was determined. MCR of P₄, F and E were determined by the iv constant infusion method in 6 pregnant and 6 nonpregnant baboons (Papio papio). Serum F concentrations were altered by iv infusion of 5 mg F/90 min or im injection of betamethasone (3 mg bi-daily for 2 days). Mean MCR-P₄ (1/d/kg ± SE) was greater (P < 0.01) in pregnant (92.8 ± 8.5) than in nonpregnant (53.9 ± 4.4) animals while mean MCR-F was similar in both groups ($\text{10.8 ± 1.2}\text{vs}\text{13.0 ± 1.5}$, respectively). Mean MCR-E was also similar in pregnant (30.8 ± 4.9) and nonpregnant (34.1 ± 4.5) baboons. Mean serum F concentrations (/gmg/100 ml ± SE) in 4 nonpregnant (42.0 ± 8.6) and 4 pregnant (52.2 ± 10.0) baboons were increased (P < 0.05) 60% by F administration but MCR-P₄, -F and -E were unaltered. Betamethasone treatment reduced (P < 0.05) serum F 75% in both groups. In nonpregnant baboons, betamethasone treatment reduced (P < 0.01) MCR-P₄ (37.3 ± 3.9), MCR-F (7.4 ± 1.6) and MCR-E (18.5 ± 3.7). Betamethasone treatment of pregnant animals reduced (P < 0.01) MCR-P₄ (56.5 ± 7.4), MCR-F (6.3 ± 0.8) and MCR-E (14.6 ± 2.6). Infusion of F into betamethasone-treated animals increased serum F levels and increased MCR-P4, -F and -E. It is concluded that variations in serum F levels affect the clearance of F, E and P₄ presumably because of the mutual interactions of these steroids with CBG.     

Studies on the metabolism of free fatty acids of the plasma in non-pregnant female and pregnant rats.

In non-pregnant female and pregnant rats the concentration (0.41 mumoles/ml and 0.49 mumoles/ml), the turnover time (0.6 min and 0.8 min), and the irreversible disposal rate (8 mumoles/min and 7 mumoles/min) of plasma free fatty acids (FFA) were determined. The results indicate that there are no major differences in the metabolism of the plasma FFA between non-pregnant female and pregnant rats.     

Maternal liver docosahexaenoic acid (DHA) stores are increased via higher serum unesterified DHA uptake in pregnant long Evans rats

Maternal docosahexaenoic acid (DHA, 22:6n-3) supplies the developing fetus during pregnancy; however, the mechanisms are unclear. We utilized pregnant rats to determine rates of DHA accretion, tissue unesterified DHA uptake and whole-body DHA synthesis-secretion. Female rats maintained on a DHA-free, 2% α-linolenic acid diet were either:1) sacrificed at 56 days for baseline measures, 2) mated and sacrificed at 14–18 days of pregnancy or 3) or sacrificed at 14–18 days as age-matched virgin controls. Maternal brain, adipose, liver and whole body fatty acid concentrations was determined for balance analysis, and kinetic modeling was used to determine brain and liver plasma unesterified DHA uptake and whole-body DHA synthesis-secretion rates. Total liver DHA was significantly higher in pregnant (95±5 μmol) versus non-pregnant (49±5) rats with no differences in whole-body DHA synthesis-secretion rates. However, liver uptake of plasma unesterified DHA was 3.8-fold higher in pregnant animals compared to non-pregnant controls, and periuterine adipose DHA was lower in pregnant (0.89±0.09 μmol/g) versus non-pregnant (1.26±0.06) rats. In conclusion, higher liver DHA accretion during pregnancy appears to be driven by higher unesterified DHA uptake, potentially via DHA mobilization from periuterine adipose for delivery to the fetus during the brain growth spurt.     

Serum reference levels of selenium,zinc and copper in healthy pregnant women at a prenatal screening program in southeastern mediterranean region of Turkey

ProjectThe aim of the study was to investigate the serum reference range for Selenium (Se), Zinc (Zn) and Copper (Cu) levels in women of 10–14 (group I) and 16–20 (group II) weeks of gestation and compare them with those in non-pregnant healthy women and healthy men.ProcedureThis cross-sectional study was performed in 351 pregnant women [group I (n: 177) and group II (n: 174)], 30 non-pregnant women and 30 men as controls. The levels of Se, Zn and Cu levels were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction.ResultsIn the 10–14 weeks of gestation Se, Zn and Cu serum levels were 44.85±9.23, 81.30±31.94 and 132.33±38.24 ug/dl, in 16–20 weeks of gestation were 47.18±10.92, 74.25±22.47 and 164.86±39.69 ug/dl, in non-pregnant women were 55.38±8.81, 121.41±29.22 and 104.75±39.14 ug/dl also in men 72.24±9.28, 134.85±15.95 and 78.29±20.90 ug/dl, respectively.ConclusionA significant low level of serum Se, Zn and a high level of Cu in the pregnant women in the 10–14 and 16–20 weeks of gestation were detected when compared with that of non-pregnant women and men.     

Immobilization with a single dose of ketamine hydrochloride and a combination of xylazine hydrochloride-ketamine hydrochloride and antagonism by yohimbine hydrochloride in the Japanese monkey (Macaca fuscata)

Forty-nine free-ranging Japanese monkeys (Macaca fuscata) were immobilized with 4.3–15.6 mg/kg (mean±S.D.=10.0±2.5 mg/kg) of ketamine hydrochloride (HCl), and 27 Japanese monkeys kept in enclosures were immobilized with a combination of 0.8–1.4 mg/kg (1.0±0.2 mg/kg) of xylazine HCl and 4.0–7.1 mg/kg (5.0±0.6 mg/kg) of ketamine HCl. In the xylazine HCl-ketamine HCl combination, good myorelaxation was induced. The mean induction times for the single dosage of ketamine HCl and the xylazine HCl-ketamine HCl combination were 2.8±1.5 min and 6.9±4.4 min, respectively. The mean immobilization times with the single dosage of ketamine HCl and the xylazine HCl-ketamine HCl combination were 39.3±16.5 min and 58.8±34.2 min, respectively. A half dose of ketamine HCl in combination with xylazine HCl could also immobilize Japanese monkeys successfully. Administrations of 0.5 mg/kg i.v. and 1.0 mg/kg i.m. of yohimbine HCl as an antagonist to xylazine HCl at 30 min after the induction reduced the immobilization time to 31.4±0.5 min and 49.0±22.1 min, respectively. Yohimbine HCl appears to be an effective antagonist to combination anesthesia by xylazine HCl-ketamine HCl in the Japanese monkey.     

High plasma adenosine levels in overweight/obese pregnant women

We aim to investigate whether overweight/obese pregnant women have elevated plasma levels of adenosine associated with increased consumption of high-calorie food. Sixty women were included. They were divided into lean (n = 23 and n = 12) or overweight/obese (n = 7 and n = 18) non-pregnant and pregnant women, respectively. Clinical records and maternal blood samples were collected after informed consent. A self-reported dietary questionnaire was also completed. Plasma adenosine levels were determined with high-performance liquid chromatography. Biochemical parameters, including glucose, total protein, and lipid profile, were determined using standard colorimetric assays. Adenosine levels were higher in pregnant women than in non-pregnant women (18.7 ± 1.6 vs 10.8 ± 1.3 nM/μg protein, respectively, p < 0.0001). Overweight/obese pregnant women (21.9 ± 2.5 nM/μg protein) exhibited higher adenosine levels than lean pregnant (14.5 ± 1.0 nM/μg protein, p = 0.04) or non-pregnant women (11.7 ± 1.5 nM/μg protein, p = 0.0005). Also, pregnant women with elevated weight gain exhibited higher (26.2 ± 3.7 nM/μg protein) adenosine levels than those with adequate weight gain (14.9 ± 1.4 nM/μg protein, p = 0.03). These differences were not statistically significant compared with those of pregnant women with reduced weight gain (17.4 ± 2.1 nM/μg protein, p = 0.053). Body mass index and adenosine only in pregnant women were positively correlated (r = 0.39, p = 0.02). While, polyunsaturated fatty acid (PUFA) consumption was negatively correlated with plasma adenosine levels only in non-pregnant women (r = ?0.33, p = 0.03). Pregnancy is associated with high plasma adenosine levels, which are further elevated in pregnant women who are overweight/obese. High PUFA intake might reduce plasma adenosine levels in non-pregnant women.     

CLEARANCE RATE OF EXOGENOUS 3H-THYMIDINE FROM THE PLASMA OF PREGNANT RHESUS MONKEYS

The plasma clearance rate of ³H-TdR was determined by thin-layer chromatography of samples from pregnant rhesus monkeys who had received a single intravenous injection of ³H-TdR. At 10 min after the injection the circulating levels of ³H-TdR had fallen to less than 0.2% of the initial theoretical distribution of the label. In general the plasma clearance rate can be described by a ‘double exponential’curve with half-lives of 1 min and 20 min. Thus, ³H-TdR disappears from the circulation of the pregnant monkey more rapidly than it does from the bloodstream of rodents, which correlates with previously detected interspecies differences in autoradiographic labeling of neurons. This means (1) that higher doses of ³H-TdR must be used for autoradiographic labeling of monkey tissues and (2) that the monkey may be useful for studying cell kinetics because it has a short pulse labeling of the DNA.     

Ability of deglycosylated human chorionic gonadotropin (dghCG) to block luteal function and establishment of pregnancy in bonnet monkeys (Macaca radiata).

The ability of deglycosylated hCG (dghCG) prepared by deglycosylation of a clinical hCG (3000 IU/mg) preparation, to block luteal function during regular cycles as well as luteal rescue in simulated and mated cycles of female bonnet monkeys (M. radiata) has been evaluated. The cycle length (C:28 vs E:24 days) and the total progesterone produced during the luteal phase was significantly reduced (by 45%, P < .05) by injecting 450 micrograms of dghCG/day (in split doses) on days 18, 19, and 20 of cycle. At the doses tested the dghCG used did not exhibit any agonistic activity in the female monkey. In a second experiment injection of 200 micrograms of dghCG/day on days 18-20 of cycle blocked the normal response of the luteal tissue to exogenous hCG (10 micrograms of a 12,000 IU/mg preparation) injected on day 23 of cycle. In a third experiment no pregnancies occurred when a group of 5 animals were injected dghCG (450 micrograms dghCG/day) on days 18-21 of their mated cycle. Animals chosen for this study were proven fertile regularly cycling monkeys and these were cohabited with males between days 9 and 14 of cycle. Each of the monkeys was exposed to 3 consecutive treatment cycles. During post-treatment phase 2 out of 3 monkeys exposed to males became pregnant. The study clearly demonstrates that it is possible to block normal luteal function as well as luteal rescue of the female monkey by using dghCG in the right dose and mode.     

The use of radioreceptor assay for the detection of pregnancy in the mare

Jugular blood samples were collected between 42-45 days from the last breeding for measurement of pregnant mare serum gonadotropin (PMSG) and progesterone in 46 pregnant mares. A radioreceptor assay (RRA) was developed to measure human chorionic gonadotropin (hCG) and subsequently modified to measure PMSG. Highly purified hCG was iodinated using a lactoperoxidase enzymatic procedure and served as the labeled antigen for both the hCG and PMSG RRA. Standard curves were generated using purified hCG or PMSG. Bovine corpora lutea served as the receptor source. The assay was conducted at 37 degrees C for one hour with a total elapsed time from preparation of the luteal cell homogenate until final results were calculated of 2.5 hours. Twelve of the 46 mares failed to maintain their pregnancy, returned to estrus and reovulated after 45 days post-breeding (non-foaling mares). Thirty-four of the 46 mares delivered foals following a gestation of normal length. Mean concentrations of PMSG in the foaling mares was higher than in non-foaling mares. A concentration of 6.9 I.U. of PMSG/ml was used as the lowest concentration necessary for the confirmation of pregnancy. Five of the mares delivering foals had low concentrations of PMSG and were called non-pregnant. Thus, the incidence of false negatives by RRA was 14.7%. All of the non-foaling mares were correctly diagnosed non-pregnant for an error rate (false positive) of 0.0. Mare Immunological Pregnancy (MIP) tests on the 12 non-foaling mares indicated three false positives - an error rate of 25%. Of the 34 foaling mares, the MIP test indicated 8 inconclusive or false negatives, an error rate of 23.5%. At day 42-45, there was no significant difference in progesterone concentrations (determined by RIA) between foaling and non-foaling mares. RRA is a quick, accurate and quantitative method for measuring PMSG in the mare and can be used to diagnose pregnancy at 42-45 days post-ovulation. Plasma progesterone concentrations at this time were not associated with subsequent pregnancy maintenance as were plasma PMSG concentrations.     

Pharmacokinetics of ketoprofen enantiomers in monkeys following single and multiple oral administration

Pharmacokinetic studies are reported after single oral administration of 3 mg/kg of stereochemically pure (S)-ketoprofen [(S)-KP] and (R)-ketoprofen [(R)-KP] to three male Cynomolgus monkeys and after repeated administration for 6 months of 3, 15 and 75 mg/kg/day of (S)-KP to both male and female monkeys. A high-performance liquid chromatographic (HPLC) analysis was performed without derivatization of the samples, using a chiral column. The pharmacokinetic parameters for (S)-KP after administration of (S)-KP and for (R)-KP after administration of (R)-KP were, respectively, elimination half-life 2.32 ± 0.36 and 1.64 ± 0.40 h; oral clearance 3.50 ± 0.66 and 7.50 ± 3.20 ml/min/kg; apparent volume of distribution 0.74 ± 0.24 and 1.16 ± 0.76 liter/kg; mean residence time 1.79 ± 0.77 and 1.41 ± 0.65 h; area under the concentration/time curve 14.16 ± 2.93 and 7.31 ± 2.98 μg·h/ml. Forty-nine percent unidirectional bioinversion of (R)-KP to (S)-KP was observed in this species and the pharmacokinetic parameters for the (S)-KP resulting from this inversion were also calculated. In the study of 6-month repeated administration of (S)-KP, linear pharmacokinetic behavior and no evidence of drug accumulation were observed at the three dose levels. © 1994 Wiley-Liss, Inc.     

Changing responsiveness of luteal cells of the marmoset monkey (Callithrix jacchus) to luteotrophic and luteolytic agents during normal and conception cycles

Dispersed marmoset luteal cells were incubated for 2 h and progesterone production measured after exposure to hCG, cloprostenol, dibutyryl cAMP, PGF-2 alpha, PGF-2, adrenaline or melatonin. The cells were studied on Days 6, 14 and 20 after ovulation in conception and non-conception cycles. Luteal cells from Day 14 non-pregnant marmosets were compared with human luteal cells taken in the mid-luteal phase. All the treatments stimulated progesterone production including cloprostenol, which is luteolytic when administered to the marmoset in vivo, but the degree of response varied with the stage of the cycle or pregnancy and between marmoset and human luteal cells. In the marmoset, overall analysis of the effect of the treatments showed that, on Day 6 after ovulation, there was no significant effect of any of the treatments in cells from pregnant or non-pregnant animals. In contrast, luteal cells from non-pregnant animals on Day 14 showed a significant response to the treatments (F (8,41) = 2.79, P less than 0.0145) whereas cells from pregnant Day-14 animals were responsive; in cells from pregnant animals, the control production of progesterone was high and already equivalent to the levels stimulated by the treatments. By Day 20, cells from pregnant animals produced lower control concentrations of progesterone than did those on Day 14 and there was a significant overall effect of the treatments (F (8,33) = 3.78, P less than 0.003). These results show that the marmoset CL gains responsiveness to treatment between Days 6 and 14 after ovulation in the non-pregnant cycle. In pregnancy, on Day 14, 2 days after attachment of the embryo, the high control concentrations of progesterone and absence of response to treatment suggest that an embryo message may have affected the CL, providing an endogenous stimulus.     

Carbonic anhydrase and acid base balance in relation to thermal stress in buffaloes (Bubalus bubalis)

The blood samples from fifteen normal lactating buffaloes were taken from December 15th 1978 to 31st August, 1979. Depending upon the climatic conditions, the whole period of study was divided into four seasons. The mean values of carbonic anhydrase (moles CO₂/l/sec×10^?5) were 3.08±0.26, 4.94±0.44, 5.23±0.35, 6.44±0.32 in pregnant and 4.87±0.27, 4.53±0.41, 4.74±0.45, 6.36±0.40 in non-pregnant animals during winter, spring, hot and dry and hot and humid seasons. Mean values of pO₂ (mm Hg) were 31.26±1.41, 31.92±0.61, 35.90±0.59, 33.80 ±0.67 in pregnant and 31.89±0.44, 31.53±0.54, 35.52±0.69, 31.65±0.95 in non-pregnant buffaloes during winter, spring, hot and dry and hot and humid periods, respectively. There were highly significant (P< 0.01) differences between seasons with respect to pO₂, pCO₂, actual HCO₃ and heamoglobin. However, PCV changed significantly (P<0.01) with the physiological status of the animal. Different correlation of biochemical parameters with climatic elements were discussed. Thus, the shifts in the levels of carbonic anhydrase, HCO₃ and heamoglobin may prove to be a better tool/index for thermal stress in buffaloes.     

Evaluation of progesterone and 20-oxo-progestagens in the plasma of Asian (Elephas maximus) and African (Loxodonta africana) elephants

The corpus luteum of African elephants produces high amounts of 5α-reduced progesterone metabolites (5α-pregnane-3,20-dione and 5-α-pregnane-3α-ol-20-one), whereas progesterone itself is quantitatively less important, and plasma levels of progesterone during the estrous cycle in elephants are considerably lower than those of other mammals. The objective of this study was to compare the concentration of progesterone in plasma of Asian and African elephants as determined by specific progesterone assays with those of total immunoreactive progestagens containing a 20-oxo-group (20-oxo-P). These metabolites were determined by an enzyme immunoassay using an antibody against 5-α-pregnane-3β-ol-20-one, 3HS:BSA. Plasma of non-pregnant Asian (n = 4) and African (n = 4) elephants was collected at weekly intervals for periods of 8–15 months and at random intervals during pregnancy in one Asian elephant. High-performance liquid chromatography separation of plasma samples of both species demonstrated that in the 20-oxo-P assay, 5α-pregnane-3,20-dione makes up ˜60% of the total immunoreactive material. The progesterone and 20-oxo-P values during the estrous cycle showed a parallel pattern and were significantly correlated (P < 0.001; Asian: r = 0.80; y = 3.76 × –0.10; African: r = 0.75; y = 2.66 × –0.08). Progesterone and 20-oxo-P values in Asian and African elephants were <0.15 ng/ml during the follicular phase (weeks –4 to 0) of the estrous cycle; progesterone values during the luteal phase (weeks 2–9) were 0.60 ± 0.03 and 0.53 ± 0.03 ng/ml, and the 20-oxo-P values were 2.19 ± 0.16 and 1.48 ± 0.12 ng/ml, respectively. The 20-oxo-P values of the pregnant animal, although slightly higher, were comparable to those of non-pregnant elephants during the luteal phase. Total immunoreactive 20-oxo-P values are about three times higher than those of progesterone during the luteal phase, and 5α-pregnane-3,20-dione is the major immunoreactive 20-oxo-P in the plasma of Asian and African elephants. Zoo Biol 16:403–413, 1997. © 1997 Wiley-Liss, Inc.     

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.     

Metoclopramide,a dopamine antagonist,stimulates aldosterone secretion in rhesus monkeys but not in dogs or rabbits

This study was designed to investigate the role of dopamine in the control of aldosterone secretion in three frequently used laboratory animals. Five New Zealand rabbits, five mongrel dogs and five rhesus monkeys received metoclopramide (MCP) (200 μg/kg iv) and blood samples were collected at 0,5,15,30 and 45 minutes after drug administration. MCP had no effect on plasma aldosterone concentrations at any sampling time in the rabbits or dogs. However, MCP produced a rapid and marked increase in plasma aldosterone from 6.5±0.6 ng/dl to 18.1±2.8 ng/dl at 5 min. and a maximum level of 40.5±4.4 ng/dl at 10 min. after drug administration in the monkeys. MCP had no significant effect on plasma cortisol or plasma renin activity levels in the three species. Prolactin rose in the monkeys from 8.6±1.2 ng/ml to a maximum of 123.5±8.5 ng/ml at 15 min. after MCP. Administration of MCP resulted in a rise in plasma 18-hydroxycorticosterone in the monkeys from 12.5±1.4 ng/dl to a maximum concentration of 50.0±5.1 ng/dl 15 min. after drug administration. Plasma corticosterone, 11-deoxycorticosterone, and 18-hydroxydeoxycorticosterone were not altered by MCP. Although unlikely, it is possible that ketamine may have accounted for some of the changes in plasma aldosterone and 18-hydroxycorticosterone observed after metoclopramide in the monkeys. The findings suggest that dopamine modulates aldosterone biosynthesis in the monkey probably by regulating glomerulosa 18-hydroxylase activity.     

Disposition of methadone in the ovine maternal-fetal unit

The distribution of methadone between mother and fetus after a single dose and at steady state was determined using the chronic pregnant ewe preparation. Chronic indwelling catheters were placed in the maternal aorta and vena cava, umbilical vein and fetal aorta. Following a single i.v. dose (0.5 mg/kg) to the mother, methadone was rapidly distributed to the fetus, with peak concentration in the umbilical vein occurring within two min. An umbilical venous-arterial gradient existed for 10–15 min after drug administration, indicating uptake of methadone by fetal tissues. Methadone concentration in the fetus was 2–5 times lower than those in the mother even in the post-distribution phase. The terminal half-life of methadone in 4 animals was 57±7.6 (S.E.) min in the mother, and 58.5±10.0 (S.E.) min in the fetus. When methadone was infused at a constant rate to the mother (0.01 mg/kg/min), steady state was achieved in both mother and fetus by 4–5 hrs. In 5 animals, maternal steady state was found to be 203±18.8 (S.E.) ng/ml, and fetal steady state was found to be 29.7±2.9 (S.E.) ng/ml. These studies show that methadone is rapidly distributed to the fetus, but fetal concentration remain lower than maternal concentration at all times.