Effect of ethynodiol diacetate and mestranol on serum folic acid and vitamin B12 levels and on tryptophan metabolism in baboons.

The effect of an oral contraceptive agent on serum folate and vitamin B12 levels and on some aspects of tryptophan metabolism in the baboon has been investigated. Folate levels were not affected by this treatment. Vitamin B12 levels were lowered during oral contraceptive treatment (P smaller than 0.1) and increased during a 30-day period of pyridoxine supplementation (P smaller than 0.01). Trends indicating deterioration of glucose tolerance and abnormal tryptophan metabolism were also observed. Definite conclusions concerning the effect of oral contraceptive agents on nutritive parameters could not be made. This is in keeping with the vast volume of literature published on the effects of oral contraceptive agents in humans and other species. It is concluded that perhaps, due to the biologically variable responses to oral contraceptive agents by individuals of any species, studies of serum levels of vitamins and other superficial biochemical parameters. Further, we conclude that the baboon could be a useful model for the study of endocrine influences on nutritive parameters, first because endocrine parameters resemble those of humans and second, because experimental protocols can be rigidly adhered to.

Education, outreach and the future of remote sensing in human health.

The human health community has been slow to adopt remote sensing technology for research, surveillance, or control activities. This chapter presents a brief history of the National Aeronautics and Space Administration's experiences in the use of remotely sensed data for health applications, and explores some of the obstacles, both real and perceived, that have slowed the transfer of this technology to the health community. These obstacles include the lack of awareness, which must be overcome through outreach and proper training in remote sensing, and inadequate spatial, spectral and temporal data resolutions, which are being addressed as new sensor systems are launched and currently overlooked (and underutilized) sensors are newly discovered by the health community. A basic training outline is presented, along with general considerations for selecting training candidates. The chapter concludes with a brief discussion of some current and future sensors that show promise for health applications.

Properties of optical data from activated partial thromboplastin time and prothrombin time assays.

Changes in characteristics of optical transmittance data from coagulation assays were examined as a function of concentration of coagulation proteins or anticoagulants. Transmittance data were collected for activated partial thromboplastin time (APTT) and prothrombin time (PT) assays from: 1) plasmas prepared by mixing normal plasmas with deficient plasmas to give varying levels of coagulation proteins; 2) plasmas containing added heparin; and 3) 200 specimen plasmas that were also assayed for fibrinogen, coagulation factors, and other components. Optical profiles were characterized using a set of parameters describing onset and completion of coagulation, magnitude of signal change, rate of coagulation and other properties. Results indicated that parameters other than those typically reported for APTT and PT are associated with individual deficiencies, but that diagnosis of specimen status on the basis of optical data is complex. These results suggest possibilities for expanded interpretation of PT/APTT optical data for clinical or research applications.

Controlled-release delivery systems for hormones. A review of their properties and current therapeutic use.

Biomedical engineering approaches used to develop controlled-release delivery systems for hormones are here reviewed regarding system design and therapeutic applications. The biomedical engineering approach uses a system of non-drug components to control the rate and duration of hormone delivery. The non-drug components vary from system to system, but generally include: a reservoir for the hormone; a barrier or regulator to contain the hormone within the reservoir and to control its release; an energy source to remove the hormone from the reservoir; and a pathway for egress of the hormone from the system. Controlled-release delivery systems for hormones discussed in this review include mechanical and osmotic pumps; intraocular, intravaginal and intrauterine platform devices; biodegradable and non-biodegradable subcutaneous implants; and small particulate systems including microcapsules, microspheres and liposomes. Examples of the therapeutic application of the various systems are given along with a discussion of design factors and pharmacological aspects relevant to their clinical use.

SP-I secretion by baboon embryos in vitro.

Baboon embryos cultured to postimplantation stages have been shown to secrete the placental protein SP-I into the culture medium in quantities of up to almost 5 micrograms/day, based on a rhesus monkey standard. Twelve embryos, for which spent media samples have been assayed, have been shown to secrete this protein, with measurable quantities usually being present on day four following attachment of the zonaless embryo to the culture dish. Secretion has continued for up to 14 days, with over 26 micrograms total SP-I secretion from one embryo. These observations further enhance the utility of the baboon embryo culture system as a model for studying early placental development in the primate.

The effects of oxytocin on fetal scalp temperature.

During a study of fetal temperature, it was found that there was a significantly higher temperature among infants whose mothers received oxytocin than among a comparable control group. These data indicate that normal-appearing oxytocin-induced contractions may reduce uterine blood flow and thereby raise the intrauterine fetal temperature.

Assessment of a remote sensing-based model for predicting malaria transmission risk in villages of Chiapas, Mexico.

A blind test of two remote sensing-based models for predicting adult populations of Anopheles albimanus in villages, an indicator of malaria transmission risk, was conducted in southern Chiapas, Mexico. One model was developed using a discriminant analysis approach, while the other was based on regression analysis. The models were developed in 1992 for an area around Tapachula, Chiapas, using Landsat Thematic Mapper (TM) satellite data and geographic information system functions. Using two remotely sensed landscape elements, the discriminant model was able to successfully distinguish between villages with high and low An. albimanus abundance with an overall accuracy of 90%. To test the predictive capability of the models, multitemporal TM data were used to generate a landscape map of the Huixtla area, northwest of Tapachula, where the models were used to predict risk for 40 villages. The resulting predictions were not disclosed until the end of the test. Independently, An. albimanus abundance data were collected in the 40 randomly selected villages for which the predictions had been made. These data were subsequently used to assess the models' accuracies. The discriminant model accurately predicted 79% of the high-abundance villages and 50% of the low-abundance villages, for an overall accuracy of 70%. The regression model correctly identified seven of the 10 villages with the highest mosquito abundance. This test demonstrated that remote sensing-based models generated for one area can be used successfully in another, comparable area.

Remote sensing as a landscape epidemiologic tool to identify villages at high risk for malaria transmission.

A landscape approach using remote sensing and geographic information system (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus abundance data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high and low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where 1) the landscape elements critical to vector survival are known and 2) these elements can be detected at remote sensing scales.

Demonstration of postovulatory sphincter action by the isthmus of the rabbit oviduct.

Doughnut-shaped, carbon-impregnated rubber microtransducers calibrated to measure changes in diameter are used to demonstrate the occurrence of a sphincter action in the isthmus of the rabbit oviduct following human chorionic gonadotropin (HCG)-induced ovulation. The postovulatory constricture of the isthmus is temporal and coincides with the period when ova are retained in the oviduct. The mean change in diameter of transducers positioned within the lumen of the isthmus in rabbits treated with HCG are significantly different from mean changes observed in nontreated control rabbits when tested at 8-hour intervals over a 104-hour period. The difference is due to a statistically significant decrease in transducer diameter which occurs between 16 and 56 hours post-HCG injection. Treatment with exogenous estrogen in combination with HCG enhances both the magnitude and duration of this constricture. Significant differences occur between 8 and 104 hours. Pretreatment with progesterone prior to HCG-induced ovulation completely blocks the constricture of the isthmus. Both oviducts exhibit identical responses following HCG-induced ovulation. Sphincter action is not confirmed to a small localized segment of the isthmus but occurs over a wide area.

A new long-acting injectable microcapsule system for the administration of progesterone.

A long-acting injectable microcapsule system for the controlled-release systemic administration of progesterone (P4) is described. The system consists of microcapsules made of the biodegradable polymer, d,l-polylactic acid, which contain crystalline P4. Following injection, P4 is released from the microcapsules by diffusion and biodegradation of the polymer matrix. The rate of P4 release from the prototype microcapsule system in vivo is 1.3 microgram of P4/day/mg of microcapsules, and the duration of release is 30 days. Vaginal estrous cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following a single injection of P4 microcapsules. The effects of continuous progesterone therapy on reproductive function in both rats and baboons are dose-dependent. The utility of the system as a once-a-month injectable contraceptive is established in the baboon model.

PIP: A longacting injectable microcapsule system for the controlled-release systemic administration of progesterone is described and photographed. The microcapsules are made of biodegradable polymer which contain crystalline progesterone. After injection, the progesterone is released over time from the microcapsules by diffusion and biodegradation of the polymer matrix. Rats and baboons were used to evaluate the in vivo rates of progesterone release from different capsule preparations. Results are graphed and tabulated. Tests showed that 50% of the progesterone is available for quick release while the other 50% remains to be released at a slower rate. Smaller microcapsules released the progesterone at a greater rate and a shorter duration. By using larger microcapules, it should be possible to extend the useful duration of the microcapsule system. Vaginal estrus cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following injection of the progesterone microcapsules. This method of delivery has the advantages that it obviates cyclic overdosing and underdosing and it can be delivered both locally and systemically.

Landscape surrounding human settlements and Anopheles albimanus (Diptera: Culicidae) abundance in Southern Chiapas, Mexico.

Landscape characteristics that may influence important components of the Anopheles albimanus Wiedemann life cycle, including potential breeding sites, suitable diurnal resting sites, and possible sources of blood meals, were analyzed at 14 villages in a malarious area of southern Mexico. An. albimanus adults were collected weekly in each village using UV-light traps between July 1991 and August 1992. Based on rainfall, the study was divided into 6 seasonal periods. Villages were considered to have high mosquito abundance when >5 mosquitoes per trap per night were collected during any 1 of the 6 seasonal periods. The extension and frequency of 11 land cover types surrounding villages were determined using aerial photographs and subsequently verified through field surveys. Elevation was the main landscape feature that separated villages with low and high mosquito abundance. All villages with high mosquito abundance were below 25 m. Transitional and mangrove land cover types were found only in the high mosquito abundance group. Flooded areas as potential breeding sites and potential adult resting sites in unmanaged pastures were significantly more frequent in areas surrounding villages with high mosquito abundance. No significant differences in density of cattle and horses were found among village groups. Overall, surrounding breeding sites located at low elevations in flooded unmanaged pastures seemed to be the most important determinants of An. albimanus adult abundance in the villages.

In vivo evaluation of cholesterol as a matrix for the controlled-release of progesterone.

Twelve adult, female baboons were used to test the rate and duration of progesterone (P4) release from cholesterol (C) pellets implanted subcutaneously. Four different preparations were tested (3 baboons per group). Each group was treated with pellets containing a different sized distribution and P4-cholesterol ratio (P4:C). Group 1 = 0.25--0.5 mm, 59% P4:41% C; Group 2 = 0.25--0.5 mm, 65% P4:35% C; Group 3 = 0.5 -1.0 mm, 59% P4:41% C; and Group 4 = 0.5 -1.0 mm, 65% P4:35% C. All baboons received the identical quantity of P4 (500 mg). Following treatment, blood samples were obtained at selected intervals, and the levels of progesterone were determined by radioimmunoassay. Serum-progesterone clearance curves were parallel for each experimental group. The rate of release of progesterone calculated from the serum clearance curves for groups 1--4 were: 42; 55; 29; and 38 mg P4/week. The mean duration of release for experimental groups 1--4 were 12, 9, 17, and 13 weeks respectively. The continuous progesterone treatment inhibited normal baboon ovarian function during the period of progesterone release.

Demonstration of an early abortifacient effect of norethisterone (NET) in the primate (baboon).

A long-acting injectable contraceptive which provides continuous controlled release of norethisterone (NET) for three months following a single intramuscular injection was tested for antifertility effects in baboons using a low dose of microcapsules (total NET dose 2.5 mg; daily dose approximately 0.03 mg/day) which has no effect on ovarian function or ovulation. The continuous administration of NET during the cycle of conception had no effect on ovulation, fertilization or implantation as evidenced by the occurrence of nine pregnancies following 23 test matings. Pregnancy was diagnosed by the measurement of baboon chorionic gonadotropin hormone and the maintenance of elevated serum progesterone levels past the normal time of menstruation. Six of the nine pregnancies, however, ended in abortion between days 27 and 35 of pregnancy. The remaining three pregnancies continued to term and normal, healthy babies were delivered. Five control baboons included in this study became pregnant and all delivered normal, healthy infants. The results of this study demonstrate that early abortion should be considered as a mechanism of antifertility action of NET when administered continuously in low doses. These findings are contrary to the generally accepted explanation that low-dose synthetic progestins exert their contraceptive effect by inhibiting sperm transport and/or preventing implantation.

The abortifacient effect of synthetic androstane derivatives in the baboon.

Synthetic androstane derivatives have been tested for their ability to induce abortion during early pregnancy in primates. Two compounds were studied following intramuscular (IM) and oral treatment in fourteen baboons. A five-day treatment regimen was started at approximately day 20 of pregnancy in 12 baboons, with treatment delayed until after day 40 in two baboons. All seven baboons treated IM with either compound aborted following intramuscular treatment, although three required a second treatment series beginning on approximately day 40 of pregnancy. Two of five baboons treated orally aborted following the single treatment series initiated around day 20 of pregnancy. The two baboons treated only after day 40 continued to term and delivered healthy infants. These compounds are therefore effective at terminating pregnancy when given around the time of the missed menstrual period. Further studies are necessary to determine optimal dose and treatment schedule.

A 4-year summary of the nonsurgical recovery of baboon embryos: A report on 498 eggs.

A nonsurgical embryo recovery procedure, developed to allow the economical acquisition of cleavage stage baboon embryos, has been successfully used for 4 years. With this technique, 498 eggs have been recovered from 979 uterine flushes (50.9%) on 71 baboons. Of 467 eggs recovered from mated baboons, 290 (62.1%) were fertilized. Papio anubis females provided a higher percentage of fertilized eggs (75.3%) than did Papio hamadryas (47.8%) or Papio cynocephalus (44.3%) females following exposure to males during estrus, although sexual preference may be responsible for the reduced fertilization rate in the P. cynocephalus females. Recovery rates from individual baboons ranged from 0% (n = 11) to between 66% and 93% for ten baboons from each of which 12-33 eggs have been recovered. Fertilized eggs were at the two-cell (n = 23) to blastocyst (n = 53) stage at recovery 1-6 days postdeturgescence (PD) of the sex skin, with morulae (n = 84) being the most frequent cell stage recovered (30%). The optimum time for performing the procedure was the third day PD, when 113 (40%) embryos were recovered. The abilities of baboons to become pregnant and to provide fertilized embryos were significantly related (P < 0.005), allowing the embryo recovery technique to be used as a screening procedure for evaluating baboon fertility.