The effects of early lead exposure on the brains of adult rhesus monkeys: a volumetric MRI study.

Little is known about direct effects of exposure to lead on central nervous system development. We conducted volumetric MRI studies in three groups of 17-year-old rhesus monkeys: (1) a group exposed to lead throughout gestation (n = 3), (2) a group exposed to lead through breast milk from birth to weaning (n = 4), and (3) a group not exposed to lead (n = 8). All fifteen monkeys were treated essentially identically since birth with the exception of lead exposure. The three-dimensional MRI images were segmented on a computer workstation using pre-tested manual and semi-automated algorithms to generate brain volumes for white matter, gray matter, cerebrospinal fluid, and component brain structures. The three groups differed significantly in the adjusted (for total brain size) volumes of the right cerebral white matter and the lateral ventricles. A significant reduction was noted in right cerebral white matter in prenatally exposed monkeys as compared to controls (p = 0.045). A similar reduction was detected in the white matter of the contralateral hemisphere; however, this difference did not achieve statistical significance (p = 0.143). Prenatally exposed monkeys also had larger right (p = 0.027) and left (p = 0.040) lateral ventricles. Depending on the timing of exposure during development, lead may exhibit differential effects with resultant life-long alterations in brain architecture.     

铅对中枢神经系统功能及母体铅负荷对子代中枢神经系统发育的影响

采用猕猴作为实验对象进行了铅对中枢神经系统功能以及母体铅负荷对于代中枢神经系统发育的影响的实验研究。实验发现染铅组母猴脑铅和脑组织脂质过氧化物含量明显高于对照组（Ｐ＜０．０５），中枢神经递质５－ＨＴ含量降低。仔猴的观察指标改变与母猴相似。结果提示接触５～１５ｍｇ／ｋｇ剂量的醋酸铅可导致中枢神经细胞膜和功能的损害，并可发生中枢神经系统功能的改变。母体铅可经胎盘和乳汁传递至子代，长期铅接触可致子代脑发育不良。     

Inhibition of Glucose Catabolism in Rat, Hamster, Rhesus Monkey and Human Spermatozoa by α-Chlorohydrin

Spermatozoa from the cauda epididymidis of rats treated with RS -α-chlorohydrin (10 mg/kg/day p. o. × 7) had the same ATP content as control spermatozoa immediately after collection, but were unable to metabolize glucose in vitro and so their ATP content declined more rapidly than that of control spermatozoa.
The in vitro metabolism of glucose by spermatozoa from rat, hamster, rhesus monkey and human was inhibited by 80% or more after 15–30 min preincubation in the presence of RS-α-chlorohydrin concentrations of < 1, > 10, 5–10 and > 50 mM, respectively. Inhibition of glucose oxidation was correlated with a reduction in ATP concentration in the spermatozoa.
These data support the hypothesis that α-chlorohydrin acts as an antifer-tility agent by inhibition of sperm glycolysis but suggest that RS -α-chlorohydrin would not be an effective contraceptive in man. However, the glucose metabolism of human spermatozoa was significantly inhibited by < 10 mM of the S -enantiomer of α-chlorohydrin.     

Long-term effects of repeated methylamphetamine administration on monoamine neurons in the rhesus monkey brain

Previous studies indicate that the repeated administration of D-methylamphetamine (MA) produces a long-lasting depletion of dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) in various brain regions of a number of species. The objectives of the present study were: (1) to establish a short, subcutaneous injection regimen which would reliably produce the neuronal alterations; (2) to evaluate MA-induced NE depletions produced by this new regimen; and (3) to determine whether central MA-induced neuronal changes are reflected in changes in cerebrospinal fluid monoamine metabolite concentrations. It was observed that high doses of MA administered (s.c.) over a 2-week period to rhesus monkeys produced decreases in DA and 5-HT, but not NE levels, in various brain regions. The decrease in caudate DA levels was accompanied by a decrease in the number of DA uptake sites, a decrease in the level of homovanillic acid (HVA) and an increase in DA turnover. This decrease in brain DA was also accompanied by a decrease in the cerebrospinal fluid concentration of HVA.     

Effects of Long-Term Immunization Against the Beta-Subunit of Ovine Luteinizing Hormone on Circulating Immune Complex Formation and on Arterial Changes in Rhesus Monkeys*

ABSTRACT: A major safety issue of contraceptive methods based on long-term immunization is the possible effect of circulating immune complexes (CIC) on the arterial wall. We have measured CIC's in 24 monkeys, immunized against the β-subunit of ovine luteinizing hormone (oLHβ), emulsified with Freund's complete adjuvant, and in 7 nonimmunized controls by Raji assay, Clq assay, and an assay for rheumatoid factor. Eleven of the 24 immunized monkeys had CIC concentrations that were more than two standard deviations above the mean for controls in at least one of the assays. There was no correlation between antibody titer and CIC. Nine immunized and eight control animals on lowfat diets were killed to evaluate the effects of immunization on the artery wall. The cross-sectional intimal area was measured at several sites from projected microscopic images using a sonic digitizer. No statistically significant differences between test and control groups were found. However, when we compared the upper half of the distribution of test and control animals, we found that the mean intimal area of the thoracic aorta of immunized monkeys was twice that of controls and that that of the abdominal aorta was three times as large. These data indicate that long-term immunization against oLHβ induces CIC's in rhesus monkeys. Small increases in the intimal area were found in about half of the immunized animals. The results of this study suggest the need for a larger, more definitive study in which the diet is manipulated so that plasma lipids mimic those of human females in Western society.     

以放射配基法比较四种培养细胞LDL受体活性

低密度脂蛋白(LDL)受体在脂代谢调控及动脉粥样硬化中起关键作用。笔者建立的放射配基测定法实用、可靠、精密度高,以此比较了人胚肺成纤维细胞,人胚皮肤成纤维细胞,恒河猴胚肾上皮细胞和猴内皮细胞的 LDL 受体活性,可作为研究 LDL受体活性及影响因素的重要手段。     

Studies on the accessibility of prolactin and growth hormone to brain: effect of opiate agonists on hormone levels in serial, simultaneous plasma and cerebrospinal fluid samples in the rhesus monkey

The accessibility of prolactin and growth hormone to the cerebrospinal fluid (CSF) was investigated in rhesus monkeys fitted with reservoirs connected to catheters placed in the fourth ventricle. Simultaneous blood and CSF samples were collected after opiate agonists. There was a brisk, marked rise in plasma prolactin following i.v. morphine sulphate which was followed by a slower, lesser rise in CSF prolactin. After i.v.d-Ala²,MePhe⁴,Met-O-(ol)-enkephalin (DAMME, FK 33–824, Sandoz) two animals responded similarly but the third showed a much smaller plasma and absent CSF response. Growth hormone showed inconsistent plasma patterns after morphine but a late rise following DAMME; however, CSF growth hormone did not change. Infusion of exogenous human prolactin produced plasma and CSF prolactin levels of similar magnitude and time-course as following opiate agonists. Infusions of larger amounts of purified human growth hormone greatly elevated plasma levels but only led to modest increases in CSF growth hormone. It is concluded that prolactin has relatively ready access to CSF, especially in comparison to growth hormone. The possible significance and mechanisms are discussed.     

Indirect immunofluorescence, serum neutralization, and viremia responses of rhesus monkeys (Macaca mulatta) to Machupo virus

Although indirect immunofluorescent antibody tests (IFAT) have been developed for several arenaviruses, none has been applied to the rhesus monkey model for Bolivian hemorrhagic fever (caused by the arenavirus Machupo). We infected eight rhesus monkeys with Machupo virus and bled them weekly for determination of viremia and for serum antibody detection by IFAT and serum neutralization (SN) testing. Viremia peaked day 14 post-inoculation (PI), when two of eight animals had low IFAT titers. At day 21 PI, the six surviving monkeys had elevated IFAT titers and diminished viremias. SN titers were not observed until 28 days PI, when three of four survivors had low titers. Results of the IFAT were available more rapidly than the SN, and detected increased serum antibody titers earlier than the SN. Acetone fixation did not completely inactivate BHF antigen spot slides.     

Primate spinothalamic pathways: II. The cells of origin of the dorsolateral and ventral spinothalamic pathways

The cells of origin of the dorsolateral (DSTT) and the ventral (VSTT) spinothalamic tracts were studied in 11 monkeys. The spinothalamic tract cells were retrogradely labeled by horseradish peroxidase (HRP) injected in the thalamus. All animals also received a midthoracic spinal cord lesion on the side ipsilateral to the thalamic injections. The distribution of labeled cells found in these animals throughout the cervical segments was similar to animals with no spinal cord lesions. Five animals had ventral quadrant lesions to demonstrate the cells of origin of the DSTT. In macaques with complete ventral quadrant lesions, more than 80% of the HRP label in the contralateral L4-L7 segments was located in lamina I, while in squirrel monkeys, the label in the contralateral lower lumbar region was distributed between laminae I-III and IV-VI. Few labeled cells were found in laminae VII-X. Six animals received dorsolateral funiculus lesions to demonstrate the cells of origin of the VSTT. In animals with adequate lesions, 84-99% of the contralateral HRP label in L4-L7 was located in laminae IV-X. Macaques had a larger percentage of labeled cells located in lamina I than squirrel monkeys. The results indicate the existence of two spinothalamic pathways in the primate. The DSTT was calculated to compose about one fourth of the total spinothalamic population.     

The effect of heterologous gonadotropins on the fecundity of rhesus monkeys

Ovarian stimulation with heterologous gonadotropins over a period of a single month did not depress the fecundity or fecundability of 50 rhesus monkeys as compared to 60 untreated monkeys in a timed breeding colony. The birth rates, seasonality of births, interbirth intervals, and waiting time to the next pregnancy were not significantly different before treatment, after treatment, or among the untreated. The stillbirth rate was not increased after treatment.