Embryotoxicity of a single dose of medroxyprogesterone acetate (MPA) and maternal serum MPA concentrations in cynomolgus monkey (Macaca fascicularis)

A single dose of MPA (Depo-Provera; Upjohn Co., Kalamazoo, Michigan) was administered intramuscularly to 12 time-mated pregnant cynomolgus monkeys on day 27 (+/- 2) of gestation at 25 mg/kg or at 100 mg/kg. Maternal blood samples were collected immediately prior to MPA injection and then at regular intervals until cesarean section at term (day 152 +/- 3). Infants in both dose groups had external genital abnormalities. Female infants in the low-dose groups had partial or complete labial fusion, prominent median raphe, and clitoral hypertrophy; at high doses (100 mg/kg), the female infants had complete labial fusion and a distinct penile urethra. MPA had an opposite effect on external genitalia of male infants. The penis was short and the scrotal swelling was absent or less conspicuous, and two males had hypospadias. The adrenal glands were significantly smaller (P less than 0.05) in infants of both sexes treated with 100 mg/kg. One of the infants treated with 25 mg/kg of MPA had a muscular ventricular septal defect. Serum concentrations of MPA were determined by radioimmunoassay in eight pregnant monkeys. In the 25 mg/kg group the patterns of MPA profiles in the serum were similar in all four animals. An initial peak occurred at 24-48 hr postinjection (2.7-9.6 ng/ml), followed by a slight decrease at 3 days postinjection (gestational day 30), and then a steady increase to maximum levels of 10-14 ng/ml occurring between gestational days 37 and 50. Serum levels gradually declined to concentrations below 5 ng/ml by midgestation in three of four monkeys. By comparison, both the patterns and magnitude of MPA concentration showed great interanimal variation in the 100 mg/kg group. MPA was present in cord blood at measurable concentrations in infants at both dose groups; the levels ranged from 0.6 to 8.3 ng/ml, corresponding to 40-72% of the maternal concentrations. These results demonstrate that a single injection of MPA during early pregnancy causes selective embryotoxicity in both male and female fetuses. Presence of high levels of MPA in maternal sera during the critical period of genital development can cause specific genital defects; however, the exact mechanism by which MPA causes these paradoxical genital abnormalities is unknown.     

Estradiol levels near the time of ovulation in the bonnet monkey (Macaca radiata)

Plasma estradiol-17beta and total progestins were determined to delineate the relationship between preovulatory estradiol-17beta peak and ovulation in the bonnel monkey (Macaca radiata). 6 monkeys were studied for 15 menstrual cycles. In subsequent cycles, serial laparotomy was performed in 5 of the 6 monkeys to correlate ovarian morphology to plasma estradiol-17beta. In 11 of the 15 cycles, estradiol-17beta peaks were 3- to 7-fold above baseline levels near the time of expected ovulation (Cycle Days 7-12). Plasma progestin rose significantly from follicular phase levels of .5 ng/ml to 2.6 ng/ml the day of the estradiol-17beta peak with peak levels of 4.5 ng/ml on the following day. Ovarian morphology in 4 of the 5 observed by laparotomy demonstrated ovulation within 48 hours following an estradiol-17beta peak of approximately 300 pb/ml.     

Serum insulin concentration and arginine tolerance test in the cynomolgus monkey (Macaca fascicularis)

The standard value of serum insulin was determined to be less than 75 microU/ml with ninety-eight female adult cynomolgus monkeys of wild origin. Then, fifteen apparently healthy laboratory-bred female cynomolgus monkeys aged 6-8 years were studied to know the usefulness of the arginine tolerance test (ATT) by measuring blood glucose, insulin and glucagon. Prior to ATT, all animals had been diagnosed as non-diabetic by the intravenous glucose tolerance test (IVGTT). Arginine hydrochloride was infused intravenously at a dose of 0.5 g/kg. BW under anesthesia. According to the standard value of insulin, fifteen animals were divided into two groups, that is, the low (n = 7) and the high (n = 8) value groups. In the low value group, glucose and insulin value did not change significantly after arginine infusion and their responses were similar to those in the control group (saline infused, n = 4). But glucagon markedly increased from 10 to 45 minutes post infusion. In the high value group, glucagon response was similar to that in the low value group, while glucose and insulin values significantly decreased. It is concluded that the pancreatic alpha-cell function (glucagon secretion) can be judged by the ATT in the cynomolgus monkey but the beta-cell function (insulin secretion) can not be diagnosed.     

Evaluation of the possible direct effects of gonadotrophin-releasing hormone analogues on the monkey (Macaca mulatta) testis

In Exp. 1, the effect of treatment with a GnRH agonist on basal concentrations of serum testosterone and peak values of serum testosterone after administration of hCG was determined. One group of adult male monkeys was treated with a low dose (5-10 micrograms/day) and a second group with a high dose (25 micrograms/day) of a GnRH agonist for 44 weeks. Basal and peak testosterone concentrations were both significantly reduced by GnRH agonist treatment in all groups compared to untreated control animals, but the % rise in serum testosterone above basal values in response to hCG administration was unchanged by agonist treatment. In Exp. 2, the GnRH agonist (100 or 400 ng) or a GnRH antagonist (4 micrograms) was infused into the testicular arteries of adult monkeys. The agonist did not alter testosterone concentrations in the testicular vein or testosterone and LH values in the femoral vein. In Exp. 3, testicular interstitial cells from monkeys were incubated with three concentrations (10(-9), 10(-7) and 10(-5)M) of the GnRH agonist or a GnRH antagonist with and without hCG. After 24 h, neither basal nor hCG-stimulated testosterone production was affected by the presence of the GnRH agonist or antagonist. The results from all 3 experiments clearly suggest that GnRH agonist treatment does not directly alter steroid production by the monkey testis.     

Inhibitory effects on steroid production from isolated adrenal cells of rhesus monkey (Macaca mulatta) of pro-opiomelanocorticotrophic peptides

Adrenal glands from Rhesus monkeys (Macaca mulatta) of 160 days gestation, newborn, 2 months-old infants or 6 months-old infants were excised and prepared, by a collagenase digestion, as a cell suspension. The cells were incubated with 10 pg/ml, 100 pg/ml or 1 ng/ml of a peptide of the ACTH/pro-opiomelanocortin 'family', 57K, 31K, 20K, alpha MSH, ovine-CLIP or gamma LPH either in the presence or absence of 166 pg/ml ACTH1-39. The production by cortisol and androstenedione was measured by radioimmunoassay. Using the steroid production by aliquots of the cell suspension with either no stimulating agent or ACTH1-39 alone as controls, the net influence of these different peptides on basal or ACTH1-39-stimulated production was observed. alpha MSH, ovine-CLIP and gamma LPH had no influence on either basal or stimulated cortisol or androstenedione production. Corticotrophic peptides of 57K, and 20K and pro-opiomelanocortin each had a steroidogenic activity alone, in all age groups. In the fetal and newborn monkeys' adrenal cells, peptides of 57K and 20K at 1 ng/ml had an inhibitory influence on ACTH1-39 stimulated cortisol and androstenedione production. The influence of the 20K peptide is partially inhibitory as the steroidogenic potential of this peptide is not additive with that of ACTH1-39. These results show that, as observed in other species, that the ACTH/pro-opiomelanocortin range of peptides are inhibitory to the action of ACTH1-39 in the developing adrenal.     

Effect of cerebrospinal fluid hyperosmolality on sweating in the heat-stressed patas monkey

Dehydration increases the osmolality of body fluids and decreases the rate of sweating during thermal stress. By localizing osmotic stimuli to central nervous system tissues, this study assessed the role of central stimulation on sweating in a heat-stressed nonhuman primate. Lenperone-tranquilized patas monkeys (Erythrocebus patas n = 5), exposed to 41 +/- 2 degrees C, were monitored for calf sweat rate, rectal and mean skin temperatures, oxygen consumption, and heart rate during infusions (255-413 microliters) of hypertonic artificial cerebrospinal fluid (ACSF) into the third cerebral ventricle. ACSF made hypertonic with NaCl to yield osmolalities of 800 and 1,000 mosmol/kgH2O significantly decreased sweat rate compared with control ACSF (285 mosmol/kgH2O), achieving maximal reductions during infusion of 37 and 53%, respectively. Rectal temperature significantly increased during the recovery period, reaching elevations of 0.69 and 0.72 degrees C, respectively, at 20 min postinfusion. In contrast, ACSF made hypertonic with sucrose (800 mosmol/kgH2O) failed to change sweat rate or rectal temperature during infusion in three animals. Thus, intracerebroventricular infusions of hypertonic ACSF mimicked dehydration-induced effects on thermoregulation. The reduction in heat loss during infusion appeared to depend on an elevation in cerebrospinal fluid [Na+] and not osmolality per se.     

Spontaneous diabetes mellitus in cynomolgus monkeys (Macaca fascicularis)

Glucose tolerance tests were performed with fourteen cynomolgus monkeys. They were divided into two groups with regard to the serum glucose level at the time of routine health-examination. Nine of them had normal glucose level (below 123 mg/dl, the normal group) and the other five monkeys exhibited hyperglycemia (the abnormal group). Fifty per cent glucose solution was administered into the saphenous vein at a dose of 4 ml/head. Blood samples were taken just before and 5, 10, 20, 30, 60 and 120 minutes after the glucose administration. K-value (K = 0.693/t 1/2 X 100) as the decreasing rate of serum glucose during from 5 to 60 minutes after the administration was calculated. Average K-value for eight monkeys of the normal group was 3.12 +/- 0.48. Both immunoreactive insulin level (IRI) and C-peptide immunoreactivity (CPR) increased just after the glucose administration and began to decrease 5 to 30 minutes after the administration in all the eight animals. Remaining one animal (No. 009) of the normal group showed 1.03 in K-value. For the abnormal group, K-value averaged 0.75 +/- 0.25. IRI was slightly higher in this group than in the 8 monkeys of the normal group. Furthermore, the abnormal group did not show any definite change of a certain trend in IRI and CPR. In conclusion, the former 8 monkeys were judged to be normal in the function of pancreatic beta-cells, and the latter 5 monkeys and No. 009 monkey were judged to be suffering from type II (noninsulin dependent) diabetes mellitus at different stages of the disease.     

Periovulatory time courses of plasma estradiol and progesterone in the Japanese monkey (Macaca fuscata)

Periovulatory time courses of plasma estradiol and progesterone were determined in 21 menstrual cycles of 20 Japanese monkeys. Both steroids were measured by radioimmunoassay. Ovulation was detected by serial laparoscopic observations of the ovaries. Three of the 21 cycles were anovulatory cycles. In the remaining 18 ovulatory cycles, a preovulatory estradiol peak occurred on day 12.2±1.4 (range 10–15) of the menstrual cycle. The estradiol concentration at the peak was 431±199 (range 210–930) pg/ml. The time interval between the estradiol peak and ovulation was within 48 hr; the shortest interval was 10–13 hr and the longest 32–48 hr. Although the progesterone levels began to increase slightly (0.6–1.4 ng/ml) before ovulation, they did not show a continuous increase but decreased once before ovulation. The increase in progesterone with development of the corpus luteum after ovulation was very gradual during the first 2 days after ovulation. Subsequently, in 13 of 18 ovulatory cycles the progesterone levels rose rapidly and reached a maximum, 4.0±1.2 (range 2.3–5.7) ng/ml, 4–8 days after ovulation. In 5 of the 18 cycles, the progesterone levels did not rise at all or did not exceed 2.0 ng/ml even if they showed more or less an increase. In the 5 cycles, the length of the luteal phase was 8.2±1.6 (range 6–10) days, which was significantly shorter than that of the former 13 cycles with 14.0±1.1 (range 13–16) days.     

Localized β-adrenergic receptor blockade does not affect sweating during exercise

The purpose of the current study was to determine the effect of a locally administered nonselective β-adrenergic antagonist on sweat gland function during exercise. Systemically administered propranolol has been reported to increase, decrease, or not alter sweat production during exercise. To eliminate the confounding systemic effects associated with orally administered propranolol, we used iontophoresis to deliver it to the eccrine sweat glands within a localized area on one forearm prior to exercise. This allowed for determination of the direct effect of β-adrenergic receptor blockade on sweating during exercise. Subjects (n = 14) reported to the laboratory (23 ± 1°C, 35 ± 3% relative humidity) after having refrained from exercise for ≥12 h. Propranolol (1% solution) was administered to a 5-cm(2) area of the flexor surface of one forearm via iontophoresis (1.5 mA) for 5 min. A saline solution was administered to the opposing arm via iontophoresis. Each subject then exercised on a motor-driven treadmill at 75% of their age-predicted maximal heart rate for 20 min, while sweat rate was measured simultaneously in both forearms. Immediately after cessation of exercise, the number of active sweat glands was measured by application of iodine-impregnated paper to each forearm. The sweat rate for the control and propranolol-treated forearm was 0.62 ± 41 and 0.60 ± 0.44 (SD) mg·cm(-2)·min(-1), respectively (P = 0.86). The density of active sweat glands for the control and propranolol-treated forearm was 130 ± 6 and 134 ± 5 (SD) glands/cm(2), respectively, (P = 0.33). End-exercise skin temperature was 32.9 ± 0.2 and 33.1 ± 0.3°C for the control and propranolol-treated forearm, respectively (P = 0.51). Results of the current study show that when propranolol is administered locally, thus eliminating the potential confounding systemic effects of the drug, it does not directly affect sweating during the initial stages of high-intensity exercise in young, healthy subjects.     

Thermogenic and psychogenic recruitment of human eccrine sweat glands: Variations between glabrous and non-glabrous skin surfaces

Human eccrine sweat-gland recruitment and secretion rates were investigated from the glabrous (volar) and non-glabrous hand surfaces during psychogenic (mental arithmetic) and thermogenic stimuli (mild hyperthermia). It was hypothesised that these treatments would activate glands from both skin surfaces, with the non-thermal stimulus increasing secretion rates primarily by recruiting more sweat glands. Ten healthy men participated in two seated, resting trials in temperate conditions (25–26 °C). Trials commenced under normothermic conditions during which the first psychogenic stress was applied. That was followed by passive heating (0.5 °C mean body temperature elevation) and thermal clamping, with a second cognitive challenge then applied. Sudomotor activity was evaluated from both hands, with colourimetry used to identify activated sweat glands, skin conductance to determine the onset of precursor sweating and ventilated sweat capsules to measure rates of discharged sweating. From glandular activation and sweat rate data, sweat-gland outputs were derived. These psychogenic and thermogenic stimuli activated sweat glands from both the glabrous and non-glabrous skin surfaces, with the former dominating at the glabrous skin and the latter at the non-glabrous surface. Indeed, those stimuli individually accounted for ~90% of the site-specific maximal number of activated sweat glands observed when both stimuli were simultaneously applied. During the normothermic psychological stimulation, sweating from the glabrous surface was elevated via a 185% increase in the number of activated glands within the first 60 s. The hypothetical mechanism for this response may involve the serial activation of additional eccrine sweat glands during the progressive evolution of psychogenic sweating.     

Studies on ovarian quiescence in the lactating bonnet monkey (Macaca radiata)

Lactating bonnet monkeys were used as a model to understand the mechanism of ovarian quiescence during lactation. The ovary of the bonnet monkey in the 3rd month of lactation responds well to exogenous pregnant mare serum gonadotropin stimulation with serum estrogen values reaching maximal levels by day 3 of the gonadotropin injection. The adminstration of ovine prolactin to such monkeys significantly inhibited the ovarian responsiveness to exogenous gonadotropin. The responsiveness of the pituitary of the lactating monkey (in the 3rd month of lactation) to luteinizing hormone releasing hormone injection was suppressed and supplementation with exogenous prolactin further accentuating this effect. The relative ability of chlorpromazine given intravenously/intramuscularly/intranasally to enhance endogenous prolactin levels was assessed. During the first 5 months of lactation when the basal prolactin levels were high, the luteinizing hormone levels were low. As the suckling stimulus reduces and prolactin levels fall, luteinizing hormone levels increase, the first post-parturient mensus occurring by 218 ± 4 days. This event was postponed by 3 months on increasing endogenous prolactin levels by administering chlorpromazine (250 μg/day by intranasal mode) over a 5 day period every month starting from the 3rd month of lactation.     

Function of human eccrine sweat glands during dynamic exercise and passive heat stress.

The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.     

DNA flow-cytometric analysis of testicular germ cell populations of the bonnet monkey (Macaca radiata) as a function of sexual maturity

Testicular germ cell populations of biopsies from 32 male bonnet monkeys in 5 different age groups were quantitated in a flow cytometer after labelling of germ cell DNA with the specific fluorochrome, 4,6-diamidino phenyl indole. The 5 quantifiable populations were spermatogonia (2C), preleptotene spermatocytes (S phase), primary spermatocytes (4C), round spermatids (1C) and elongate spermatids (HC). The seminiferous tubules of immature 3-4-year-old monkey had only Sertoli cells and spermatogonia (2C). At 5-6 years, germ cells in S-phase (9.5%), 4C (11.1%), 1C (41.8%) and HC (17.1%) stages of maturation appeared for the first time but at 7-8 years of age and beyond all cell types except HC decreased while 1C remained relatively constant. Histometric analysis correlated well with the flow-cytometric data. The decrease in cells of 2C, S-phase and 4C stages was associated with an increase in mitotic index, signifying acceleration in the kinetics of germ cell transformation into subsequent cell types. The total turnover in cell transformation (1C:2C) was significantly (P less than 0.01) increased at and beyond 7-8 years. Maximum transition from 2C to 4C occurred at 5-6 years (4C:2C ratio 0.8 at 5-6 years and 0.6 at 7-8 years). The ratio HC:1C (kinetics of cell transformation during spermiogenesis) attained near total efficiency only by 10 years of age (1.08 at 10-14 years; 0.9 at 18-20 years). Also, the cell associations within the seminiferous tubules of monkeys greater than or equal to 10 years of age were better defined than those of younger animals. The changes in germ cell ratios correlated well with alterations in testicular volume, sperm numbers in the ejaculate and surges of testosterone and increments in FSH in the serum, characteristic of development of sexual maturity. It is apparent from this study that DNA flow cytometry of testicular germ cell populations reveals subtle changes in spermatogenic status of bonnet monkeys with a high degree of sensitivity.     

Circulating blood volume of the Japanese monkey (Macaca fuscata) by means of the dye T-1824

The circulating blood volume has been measured in 65 healthy Japanese monkeys (Macaca fuscata) with the dye T-1824 (Evans blue). The values obtained were 83 ± 13 ml/kg in females, and 85 ± 12 ml/kg in females, almost the same as the figures reported in man.Sex difference of blood volume has been reported to be present in man, but from the data obtained here no significant difference was found in the Japanese monkey.In young monkeys aged from 1 to 5.5 years, the blood volume was 77 ± 5 ml/kg in males, and 78 ± 4 ml/kg in females. The blood volume of the monkey was found to increase with age; a significant difference was demonstrated between adult males and young males.     

Pilocarpine-induced sweat gland function in individuals with multiple sclerosis.

This investigation tested the hypothesis that cholinergic sweat function of individuals with multiple sclerosis (MS) (MS-Con; n = 10) is diminished relative to matched healthy control subjects (Con; n = 10). In addition, cholinergic sweat function was determined before and after 15 wk of aerobic training in a subgroup of individuals with MS (MS-Ex; n = 7). Cholinergic sweating responses were assessed via pilocarpine iontophoresis on ventral forearm skin. A collection disk placed over the stimulated area collected sweat for 15 min. Sweat rate (SR) was calculated by dividing sweat collector volume by collection area and time. Iodine-treated paper was applied to the stimulated area to measure number of activated sweat glands (ASG). Sweat gland output (SGO) was calculated by dividing SR by density of glands under the collector. Sweat gland function was determined in MS-Ex to test the hypothesis that exercise training would increase sweating responses. No differences in ASG were observed between MS-Con and Con. SR and SGO in MS-Con [0.18 mg.cm(-2).min(-1) (SD 0.08); 1.74 microg.gland(-1).min(-1) (SD 0.79), respectively] were significantly lower (P < or = 0.05) than in Con [0.27 mg.cm(-2).min(-1) (SD 0.10); 2.43 microg.gland(-1).min(-1) (SD 0.69)]. Aerobic exercise training significantly (P < or = 0.05) increased peak aerobic capacity in MS-Ex [1.86 (SD 0.75) vs. 2.10 (SD 0.67) l/min] with no changes in ASG, SR, and SGO. Sweat gland function in individuals with MS is impaired relative to healthy controls. Fifteen weeks of aerobic training did not increase stimulated sweating responses in individuals with MS. Diminished peripheral sweating responses may be a consequence of impairments in autonomic control of sudomotor function.     

Successful artificial insemination for indoor breeding in the Japanese monkey (Macaca fuscata) and the cynomolgus monkey (Macaca fascicularis)

Methods of artificial insemination (AI) for indoor breeding in the Japanese monkey and the Cynomolgus monkey were investigated. For the Japanese monkey AI was carried out in six females during the winter mating season and in six females during the summer non-mating season. During the mating season, semen was inseminated near ovulation time in natural menstrual cycles. In the mating season study, three females inseminated at the uterine cavity became pregnant. Three inseminated at the cervical canal failed to become pregnant. For the non-mating season study, ovulation was induced artificially by PMSG and hCG and AI was carried out near the induced ovulation time. In the non-mating season, no animals became pregnant. Of four Cynomolgus monkeys used, pregnancy occurred in two animals inseminated near ovulation time in natural menstrual cycles. AI occurred at the uterine cavity in one and cervical canal in the other. In both species ovulation was verified by laparoscopy. Semen was collected by penile electro-stimulation then diluted to 2.5 to 5.0×10⁷/ml with Whitten's medium. Diluted semen of 0.2l was inseminated at the uterine cavity or cervical canal. Our results indicate the usefulness of vaginal AI as a method of artificial indoor breeding.     

Effect of physical training on peripheral sweat production

The purpose of this study was to determine the in vivo secretory activity of sweat glands from sedentary and trained subjects. Peripheral sweat production was determined using pilocarpine iontophoresis in 40 volunteers (10 sedentary men, 10 endurance-trained men, 10 sedentary women, 10 endurance-trained women). Peripheral sweat rate was significantly (P less than 0.05) greater in trained men [6.9 +/- 0.6 (SE) g.m2.min-1] and women (6.1 +/- 0.7) compared with sedentary men (3.1 +/- 0.5) and women (2.5 +/- 0.4). Furthermore, peripheral sweat rate was significantly correlated (r = 0.73) with maximal O2 uptake. The above two findings would suggest that physical training improves the secretory activity of the human sweat gland. Such a result supports previous findings that have suggested that the potentiation in sweating seen after training is achieved via a peripheral mechanism. In addition, several gender-related differences were found in the sudorific response of men and women. Specifically, women have a significantly greater sweat gland density, whereas men have a greater sweat production per gland.     

Measurment of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins.

A sensitive and specific double antibody radio-immunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The anti-serum was raised to LDL (d 1.030-1.040 g/ml) and the LDL(2) (d 1.020-1.050 g/ml) was labeled with (125)I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02-0.5 micro g of LDL(2), had an inter-assay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an "average American diet," a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet. The control monkeys (n = 13) had a serum cholesterol of 146 +/- 28 mg/dl and an apoB of 50 +/- 18 mg/dl. In the monkeys maintained on the atherogenic diets the serum apoB was elevated: 103 +/- 28 mg/dl (American), 102 +/- 35 mg/dl (peanut oil), and 312 +/- 88 mg/dl (coconut oil). The values for serum total cholesterol were 333 +/- 65 mg/dl (American), 606 +/- 212 mg/dl (peanut oil), and 864 +/- 233 mg/dl (coconut oil) and were elevated relative to controls (P < 0.001). For each of the diets, total serum cholesterol correlated with serum apoB (P < 0.001). The slopes of the regression lines of serum apoB vs. cholesterol for the monkeys on the PMC, American, and coconut oil diets were similar (m = 0.531, 0.401, and 0.359, respectively), but differed from that of monkeys on the peanut oil diet (m = 0.121). The immunoreactivities of rhesus and human LDL were compared using specific antisera raised against these antigens. In homologous assay systems, monkey and human LDL exhibited unique immunological determinants. The same results were obtained with the delipidated preparations of the two LDLs using antisera raised against either monkey or human apoB. Crossover studies using a heterologous tracer with each anti-serum resulted in the selection of a specific population of antibodies directed against antigenic sites shared by these two LDL species.     

Functional and morphological changes in the eccrine sweat gland with heat acclimation

Three adult male patas monkeys (11-15 kg) were heat acclimated by continuous exposure to an ambient temperature of 33 +/- 1 degree C at 13% relative humidity for 9 mo. During the last month, they were also exposed to 45 degrees C at 10% relative humidity for 4 h/day and 5 days/wk. Before and after 3 wk of acclimation, the animals were given a heat-tolerance test in which rectal (Tre) and mean skin (Tsk) temperatures, heart rate, and sweat rate (msw) were monitored during a 90-min exposure to 45 degrees C heat with 24% relative humidity under lenperone (1.0-1.4 mg/kg im) tranquilization. Maximal in vivo msw was also determined in response to subcutaneous injections (1 and 10% solutions) of methacholine (MCh). Before and after 9 wk and 9 mo of acclimation, sweat glands were dissected from biopsy specimens of the lateral calf, cannulated, and stimulated in vitro with MCh. Morphological measurements of isolated tubules were compared with maximal secretory rates produced by MCh stimulation. Three weeks of acclimation 1) reduced Tre and Tsk and increased msw during the heat tolerance test and 2) significantly increased maximal msw in response to MCh stimulation. Acclimation also increased (P less than 0.05) sweat gland size, as measured by tubular length and tubular volume. Maximal in vitro msw produced by MCh stimulation and msw per unit length of secretory coil also increased significantly. We conclude that heat acclimation increases the size of eccrine sweat glands and that these larger glands produce more sweat. They are also more efficient because they produce more sweat per unit length of secretory coil.     

Fetotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for rhesus macaques (Macaca mulatta)

The fetotoxic and teratogenic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for rhesus macaques (Macaca mulatta) was tested through oral administration to monkeys early in pregnancy. A single or divided dose, 1 μg of TCDD/kg of body weight, was followed by abortion in 13 of 16 pregnant monkeys treated between days 20 and 40 of gestation. One of four aborted at 0.2 μg/kg, and two of two at 5 μg/kg. None of the mothers given 0.2 μg/kg showed signs of toxicity. Eight of the monkeys aborting at 1 μg/kg showed clinical toxicity 44 to 111 days after aborting, and three died. Both given 5 μg/kg became toxic soon after abortion and died. No malformations except for two minor palatal abnormalities of questionable significance were found in the six fetuses that were not aborted at doses of 0.2 and 1.0 μg/kg. These results indicate (1) that TCDD is fetotoxic at doses that frequently have delayed toxicity to the mother, but that conclusions about teratogenicity cannot be drawn, and (2) that pregnant rhesus females are more sensitive to the toxic effects of TCDD than any species tested but the guinea pig.