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PubMed1977

Endogenous New World primate retrovirus: interspecies antigenic determinants shared with the major structural protein of type-D RNA viruses of Old World monkeys.

A reverse transcriptase-containing virus has recently been isolated from a squirrel monkey (Saimiri sciureus). Molecular hybridization studies demonstrate that the squirrel monkey retrovirus (SMRV) is endogenous to this New World primate, yet lacks detectable nucleotide sequence homology with cellular DNAs of representative Old World primates or with the genomes of previously isolated Old World primate retroviruses. The 35,000-dalton major structural protein (p35) of SMRV was purified and shown to possess antigenic determinants distinct from those of known retroviruses. While SMRV was found to lack antigenic determinants broadly shared among mammalian type-C viruses, immunologic crossreactivity was demonstrated between SMRV p35 and the major structural protein (p26) of Mason-Pfizer monkey virus, a prototype type-D retrovirus of Old World monkeys. These findings support the concept that SMRV and Mason-Pfizer monkey virus are evolutionarily related, and raise the possibility that a progenitor of type-D retroviruses became genetically associated with primates at a very early time in their evolution.

Animals↗
PubMed1996

Codon repeats in genes associated with human diseases: fewer repeats in the genes of nonhuman primates and nucleotide substitutions concentrated at the sites of reiteration.

Five human diseases are due to an excessive number of CAG repeats in the coding regions of five different genes. We have analyzed the repeat regions in four of these genes from nonhuman primates, which are not known to suffer from the diseases. These primates have CAG repeats at the same sites as in human alleles, and there is similar polymorphism of repeat number, but this number is smaller than in the human genes. In some of the genes, the segment of poly(CAG) has expanded in nonhuman primates, but the process has advanced further in the human lineage than in other primate lineages, thereby predisposing to diseases of CAG reiteration. Adjacent to stretches of homogeneous present-day codon repeats, previously existing codons of the same kind have undergone nucleotide substitutions with high frequency. Where these lead to amino acid substitutions, the effect will be to reduce the length of the original homopolymeric stretch in the protein.

Animals↗
PubMed1999

Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy.

The effects of normal aging on the primate brain are incompletely understood. Although both human and nonhuman primates demonstrate clear functional declines in selective attention, "executive" functions, and some components of declarative memory with aging, most studies have failed to demonstrate extensive neuronal atrophy or loss as a substrate for these degenerative changes in primates. In particular, extensive age-related neuronal loss in memory-related brain regions such as the hippocampus and entorhinal cortex has not been found. However, it is possible that neuronal loss or atrophy might occur in subcortical nuclei that modulate the activity of neocortical regions, thereby accounting for altered cognitive function with aging. In the present study, we describe, to our knowledge for the first time, a significant and extensive decline in the number and size of immunolabeled neurons in subcortical cholinergic basal forebrain regions of aged rhesus monkeys, the best animal model of human aging, by using stereological methods. Notably, the loss of subcortical cholinergic neuronal markers in aged monkeys was nearly completely reversed by human nerve growth factor gene delivery. These findings (i) identify reversible cellular atrophy as a potential mechanism contributing to age-related cognitive decline in primates, (ii) suggest, when considered with other studies, that subcortical brain regions exhibit greater vulnerability to the effects of aging than cortical regions, and (iii) indicate that neurotrophin gene transfer may be an effective means of preventing neuronal atrophy or degeneration in age-related neurodegenerative disorders.

Age Factors↗
PubMed2002

Subchronic administration of pyridostigmine or huperzine to primates: compared efficacy against soman toxicity.

Organophosphonate (OP) nerve agents, such as soman, are potent irreversible inhibitors of central and peripheral acetylcholinesterases (AChEs). Pre-treatment of OP poisoning relies on the subchronic administration of a reversible AChE inhibitor. In the present limited study, the protective effects against soman toxicity of such compounds, i.e., the current pre-treatment pyridostigmine and huperzine, a proposed pre-treatment, are compared in primates. This is the first time primates are used to study the potential of pre-treatment with hyperzine. Indeed, previous studies with huperzine used nonprimate models which are not the most appropriate for pre-treatment in humans. Each medication is given via a subcutaneous mini-osmotic pump for 6 days at a delivery rate providing about 20% inhibition of red cell AChE activity. In this trial with only four primates, huperzine selectively inhibits red cell AChE activity whereas pyridostigmine also inhibits plasma butyrylcholinesterase (BuChE). This latter may act as endogenous scavenger of OP compounds helping to confer additional protection against OPs. During intoxication, the cumulative dose of soman needed to produce convulsions and epileptic activity is 1.55-fold higher in the animals pre-treated with huperzine compared to those pre-treated with pyridostigmine. Thus, replacing PYR by HUP for a subchronic pre-treatment of primates gives them better tolerance to the epileptic effects of soman.

Alkaloids↗
PubMed1975

Proteoglycans in primate arteries. II. Synthesis and secretion of glycosaminoglycans by arterial smooth muscle cells in culture.

Glycosaminoglycan synthesis and secretion by primate arterial smooth muscle have been examined in cell culture. Mass cultures of diploid primate arterial smooth muscle cells were either double labeled with [35S]sulfate and [3H]acetate or single labeled with [3H]glucosamine for 24 h and glycosaminoglycans were extracted and isolated from the culture medium. Incorporation of labeled precursors into glycosaminoglycan was maximal during stationary phase of smooth muscle cell growth in culture and reduced, but not eliminated during logarithmic growth. The glycosaminoglycans synthesized and secreted into the culture medium were characterized by differential susceptibility to glycosaminoglycan-degradative enzymes and by cellulose acetate electrophoresis. Both assay procedures indicate that cultured primate arterial smooth muscle cells synthesize principally dermatan sulfate (60%-80% of total), chondroitin sulfate A and/or C (10%-20%of total) and little or no hyaluronic acid (0%-5% of total). This pattern of glycosaminoglycan formation differed significantly from that exhibited by isologous skin fibroblasts cultured under identical conditions. Dermal fibroblasts synthesize and secrete primarily hyaluronic acid (50%-60% of total) with lesser amounts of dermatan sulfate (10%-20% of total) and chondroitin sulfate A and/or C (10%-20% of total). These results indicate that differences exist in proteoglycan metabolism between these two connective tissue-producing cells in vitro, and suggest that the observed pattern of in vitro glycosaminoglycan synthesis by primate arterial smooth muscle cells may be characteristic for this cell type and not a general response to conditions of cell culture.

Animals↗
PubMed2003

Adeno-associated virus type 5: transduction efficiency and cell-type specificity in the primate retina.

Gene transfer using adeno-associated viruses (AAVs) has been effective for treating inherited retinal diseases in animal models. Further evaluation in primates must be performed prior to clinical application, however, because of the difference between the retina of the primate and those of other animals. Prior work has shown that AAV2 can transduce rod-photoreceptor and RPE cells in the non-human primate retina and that AAV5 is more efficient at transducing photoreceptor cells than AAV2 in the rodent retina. In this study, we evaluated the efficiency of AAV5 in the non-human primate retina after subretinal injections of the vector to distinct anatomic retinal regions (superior, inferior, nasal, macula, temporal). rAAV5 led to a rapid onset of transgene expression (within 2 weeks), with expression persisting up to 10 months. Postoperative electrophysiology studies showed that global retinal function was preserved following gene transfer. Quantitative analysis of gene transfer demonstrated a maximum transduction efficiency of 22% in the injected areas. Evaluation of cell types using confocal microscopy and cone-specific antibodies revealed that AAV5, expressing reporter genes from the cytomegalovirus (CMV) promoter/enhancer, preferentially transduced rods. No significant differences were found in the regional tropism of AAV5 among the five areas injected despite variation in retinal topography. Immunohistochemical studies revealed that the AAV5 receptor, PDGFR-A, is localized to the outer segments of rods but not cones providing a basis for the observed tropism. Our results support the utility of AAV5 for rod photoreceptor degeneration therapies.

Adenoviridae↗
PubMed1993

DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates.

DNA, or genetic, inoculation mimics aspects of attenuated vaccines in that synthesis of specific foreign proteins is accomplished in the host. These proteins can be processed and presented on the relevant major histocompatibility complex (MHC) antigens and ultimately become the subject of immune surveillance. Very recently, we have described the use of the new technology to generate immune responses in mice against the human immunodeficiency virus type 1 (HIV-1) envelope using a gp160 DNA construct. Further analysis of this technology specifically in regard to HIV vaccine design is clearly important. In this report, we describe the analysis of additional HIV constructs as immunogens in both mice and report the use of this genetic immunization technology in nonhuman primates. In these studies, successful seroconversion occurs in more than 70% of the mice following the second immunization with 100 micrograms of construct DNA; three and four immunizations result in routinely 100% seroconversion of the mice. Furthermore, the same strategy has successfully seroconverted primates following their second inoculation, resulting in the generation of both antiviral and neutralizing antibodies in this animal species. These studies are the first report of which we are aware that demonstrate successful immunization of nonhuman primates through genetic vaccination technology and the first to describe genetic immunization of primates against HIV antigens. This technology has relevance for the development of safe and efficacious immunization strategies against HIV because it provides for relevant antigen production in vivo without the use of infectious agents.

AIDS Vaccines↗
PubMedDate not supplied

Calcium-binding protein-containing neuronal populations in mammalian visual cortex: a comparative study in whales, insectivores, bats, rodents, and primates.

This study is focused on comparative analysis of gamma-aminobutyric acid-positive (GABAergic) neuronal populations in primary visual cortex of totally aquatic toothed whales and select terrestrial mammals with different evolutionary histories and various ecological adaptations. The distribution of neuronal populations containing the calcium-binding proteins calbindin and parvalbumin, which are recognized markers for the GABAergic neurons in cerebral cortex, is compared in five species of toothed whales and in representatives (one species each) of insectivores, bats, rodents, and primates. Computerized image analysis has shown that overall quantitative characteristics of GABAergic cortical neurons in toothed whales are similar to those in other mammalian orders. Thus, GABA-positive neurons represent 26% of the total population of cortical neurons in the visual cortex of whales. Some 97% of GABA-positive cells contain calcium-binding proteins, which is numerically similar to these parameters found in primates and other mammals. On the other hand, the typology and laminar distribution of calcium-binding protein-containing neurons in the primary visual cortex of five whale species (Delphinapterus leucas, Globicephala melaena, Phocoena phocoena, Stenella coeruleoalba, and Tursiops truncatus) differ significantly from those of primates (Macaca mulatta) and rodents (Rattus rattus) and are similar to those found in insectivorous bats (Eptesicus fuscus) and hedgehogs (Erinaceus europaeus). In whales, bats, and hedgehogs a significant concentration of calbindin-positive, vertically oriented bipolar and bitufted neurons was found in layers I, II, and IIIc/V with their axons arranged in a three-dimensional network. In primates and rodents they are distributed evenly across all cortical layers and are predominantly multipolar or bitufted neurons found in all cortical layers with their axons oriented along the vertical axis of the cortical plate. The parvalbumin-positive neurons in all mammalian species, including toothed whales, are represented by variously sized multipolar non-pyramidal cells. As opposed to all other mammalian species, the major concentrations of parvalbumin-positive neurons in whales are found in layers IIIc/V and VI, whereas in other cortical layers there are only scattered parvalbumin-positive neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Low CA1 spine synapse density is further reduced by castration in male non-human primates.

The hippocampus plays a major role in learning and memory and its morphology and function are readily affected by gonadal hormones in female non-human primates. We sought to determine whether the gonads also affect pyramidal cell spine synapse density in the CA1 hippocampal area of male primates. Unbiased electron microscopic stereological calculations were performed to determine the volumetric density of pyramidal cell spine synapses and semiquantitative analyses on the surface density of glial fibrillary acidic protein-containing glia processes and the diameter of pyramidal cell apical dendrites in the CA1 area of intact and orchidectomized (1 month) St Kitts vervet monkeys (Chlorocebus aethiops sabaeus). The volumetric density (number of spine synapse/ micro m(3)) of spine synapses was significantly lower (40%) in the gonadectomized animals than in control monkeys; conversely, the density of glia processes was significantly higher (15%) and the diameter of dendritic shafts located in this area was also larger (30%) in the orchidectomized animals than in the controls. Strikingly, when compared to female values, intact male primates had lower spine synapse densities than either intact or ovariectomized females. Since the primate hippocampus is very similar to that of a human's, the present observations suggest that physiological levels of circulating androgen hormones are necessary to support normal spine synapse density in the CA1 stratum radiatum of human male hippocampus.

Animals↗
PubMed2002

Functional studies of subcutaneous ovarian transplants in non-human primates: steroidogenesis, endometrial development, ovulation, menstrual patterns and gamete morphology.

BACKGROUND: The study objective was to determine if ovarian function would be restored following fresh and cryopreserved extrapelvic autologous ovarian transplantation and if vascular endothelial growth factor (VEGF) administration would augment the success rate. METHODS: Sixteen regularly cycling female cynomolgus monkeys underwent bilateral oophorectomy and were randomly assigned to one of three treatment groups: (i) sham transplant group (n = 5) underwent transplantation of pieces of adipose tissue; (ii) fresh autologous ovarian transplantation without VEGF administration (n = 6) and (iii) fresh autologous ovarian transplantation with 1 microg of VEGF (n = 5) administered at the transplantation site daily for 14 days after transplantation. The ovarian tissue from the sham transplanted group was cryopreserved. This material was later thawed and transplanted in four out of five of the sham operated group. RESULTS: Five out of six (83%) of the primates in our transplantation group without VEGF had functioning ovarian transplants while two of five (40%) primates in our transplantation group with VEGF administration had functioning ovarian transplants. The cryopreserved group had two of four primates (50%) with functioning transplants. Ovarian stimulation yielded multiple follicles and one metaphase II oocyte from the fresh and one metaphase II oocyte from the cryopreserved group. CONCLUSIONS: The success of ovarian transplantation in these non-human primates with menstrual cycles bodes well for the development of ovarian transplantation protocols for women at risk of ovarian failure.

Animals↗
PubMed2005

Relationship between urinary estrogen levels before conception and sex ratio at birth in a primate, the gray mouse lemur.

BACKGROUND: In primates, including humans, bias of sex ratio at birth has been reported to depend on maternal condition at conception. In a Malagasy primate, the gray mouse lemur, male-biased sex ratio at birth occurred in captive parous females. The male bias was previously demonstrated to be pre-conceptual and independent of the female's nutritional state. It was hypothesized to be related to changes in hormonal state at ovulation. METHODS AND RESULTS: The relationship between urinary estradiol (E2) levels during the follicular phase until estrus and litter production (number and sex of newborns) was assessed in 91 females mated under controlled conditions. Changes in E2 levels prior to ovulation followed the typical primate pattern characterized by a gradual rise during the 10 days preceding the sharp increase at estrus. A clear decline in E2 levels occurred with ageing. Direction of the sex ratio bias was unrelated to E2 levels at ovulation time but was significantly dependent on E2 levels during the follicular phase. Reduced E2 levels prior to estrus led to male-biased litters. CONCLUSION: This study suggests that hormonal stimulation during the follicular phase plays a role in shifting sex ratio at conception through changes in the local environment of the ova. This hypothesis deserves testing by assessing estrogen levels throughout the follicular phase in other primate species including humans.

Age Factors↗
PubMedDate not supplied

Trace level determination of doxylamine in nonhuman primate plasma and urine by GC/NPD and HPLC.

Bendectin contains doxylamine succinate and is used for the treatment of nausea and vomiting in pregnant women. Trace level analytical chemical procedures for analysis of doxylamine in primate urine and plasma were required before toxicological tests with the drug in three species of nonhuman primates could be performed. A gas chromatographic procedure using a nitrogen phosphorus detector was developed to quantitate doxylamine in primate plasma at levels as low as 100 ppb. A high-pressure liquid chromatographic procedure was also developed to assay the drug in primate urine at levels as low as 250 ppb. Data from stability studies with the drug in plasma at -5 degrees and -20 degrees C, and recovery of the drug from Bendectin tablets, plasma, and urine are also presented.

Animals↗
PubMed1996

Development of in-vitro-fertilized primate embryos into blastocysts in a chemically defined, protein-free culture medium.

The formulation of chemically defined culture media that support primate embryo development would facilitate studies on primate preimplantation embryogenesis. The specific aims of this study were (i) to evaluate the development of the macaque embryos in a simple, chemically defined, protein-free medium developed for a rodent embryo model, and (ii) to determine if a two-step progressive culture system could enhance blastocyst development and zona escape. In experiment 1, in-vitro-fertilized pronucleate-stage embryos (n = 81) from nine monkeys were randomly allocated to one of three treatments: (a) hamster embryo culture medium-6 (HECM-6; chemically defined, protein-free medium), (b) CMRL-BCS medium (modified CMRL-1066 medium containing 20% bovine calf serum; BCS), and (c) a two-step culture procedure (HECM-6 through to the 8- to 12-cell stage, and CMRL-BCS medium beyond that stage). Optimal development was attained equally (P > or = 0.05) with embryos cultured in CMRL-BCS medium or the two-step procedure (48 and 61%), but not to the blastocysts respectively). HECM-6 alone supported development to the morula stage (72%) equally as well as CMRL-BCS medium (80%) or the two-step procedure (69%), but not to the blastocyst stage (22 versus 48 and 61% respectively). Hatching of the blastocysts was essentially limited to the serum-containing media (CMRL-BCS medium, 31%; two-step procedure, 44%). In experiment 2, in-vitro-fertilized pronucleate-stage embryos (n = 87) from nine monkeys were randomly placed in each of four two-step treatments: (a) HECM-6 through to the 8- to 12-cell stage and CMRL-BCS medium beyond that stage, (b) HECM-6 through the 8- to 12-cell stage and HECM-6-BCS beyond that stage, (c) HECM-6 through to the morula stage and CMRL-BCS medium beyond that stage, and (d) HECM-6 through to the morula stage and HECM-6-BCS beyond that stage. Greater (P < or = 0.05) percentages of embryos developed into blastocysts, expanded blastocysts and hatched blastocysts when switched at the 8- to 12-cell versus the morula stage in the second step medium. When transferred into BCS-containing medium at either the 8- to 12-cell or morula stage, embryos underwent blastulation and expansion equally well in CMRL-BCS medium versus HECM-6-BCS. However, when embryos were switched to the second step medium at the 8- to 12-cell stage, hatched blastocysts were obtained more (P < or = 0.05) frequently in CMRL-BCS medium (50.9%) than in HECM-6-BCS (37%). This work is the first to produce in-vitro-fertilized primate blastocysts cultured from the pronucleate stage in chemically defined, protein-free medium, and demonstrates that while primate embryos can form morulae in such a medium, their requirements for blastocoel formation and zona escape appear to be more demanding, and may be acquired as early as the 8-cell stage.

Animals↗
PubMed2000

Effects of dietary oltipraz and ethoxyquin on aflatoxin B1 biotransformation in non-human primates.

Following aflatoxin B1 (AFB) exposure, rats readily develop liver tumors. However, treatment of rats with a variety of compounds, including the synthetic dithiolthione oltipraz and the antioxidant ethoxyquin, protects these rodents from AFB-induced hepatocarcinogenesis. Several epidemiological studies strongly suggest that AFB is also a causative agent of liver cancer in humans. However, relatively little is known about the efficacy of cancer chemoprevention in human and non-human primates. To this end, we examined the effects of chemopreventive agents on AFB metabolism in non-human primates. Hepatic aflatoxin B1 metabolism profiles of macaque (Macaca nemestrina) and marmoset (Callithrix jacchus) monkeys were determined and compared to humans. Quantitatively, the oxidative metabolism of this mycotoxin was similar in the three primate species. In contrast to macaques, both humans and marmosets lacked AFB-glutathione conjugating activity. It was concluded that marmosets resembled human AFB metabolism more closely than the macaques, and therefore, marmoset monkeys were chosen for this study. Eleven adult male marmosets were randomly assigned to three groups. Animals received the synthetic dithiolthione oltipraz, the antioxidant ethoxyquin, or vehicle only. In addition, two single doses of AFB were also administered orally before and after animals were treated with aforementioned compounds. Both oltipraz and ethoxyquin induced aflatoxin B1-glutathione conjugating activity in the livers of some but not all marmosets. In addition, 10 microM oltipraz inhibited cytochrome P450-mediated activation of AFB to the ultimate carcinogenic metabolite, aflatoxin B1-8,9-epoxide, in vitro, up to 51%. Furthermore, animals treated in vivo with oltipraz, but not ethoxyquin, exhibited a significant reduction (53% average) in AFB-DNA adduct formation relative to the control animals (p < 0.05). Together, our data suggest that chemoprevention is also effective in primates; however, most likely to a lesser degree than in rodents.

Aflatoxin B1↗
PubMed2003

Growth differentiation factor-9 is expressed by the primate follicle throughout the periovulatory interval.

Expression of growth differentiation factor 9 (GDF-9), an apparent regulator of follicular development, reportedly differs between compartments of the rodent (oocytes) and human (oocytes and granulosa cells) ovary. To further characterize GDF-9 expression and action in the primate periovulatory follicle, adult female rhesus monkeys received recombinant human gonadotropins to promote multiple follicular development. Whole ovaries or follicular aspirates were obtained before and at various times after administration of an ovulatory dose of hCG; time points for tissue collection spanned the 40-h periovulatory interval. GDF-9 mRNA was detected by reverse transcription polymerase chain reaction assay in each oocyte and every granulosa cell sample examined, but granulosa cell GDF-9 mRNA levels did not change across the periovulatory interval. GDF-9 was also detected in follicular fluid using Western blotting; GDF-9 protein concentration in follicular fluid did not change across the periovulatory interval. Immunocytochemical staining for GDF-9 indicated that oocytes of both small and large antral follicles were positive for GDF-9. GDF-9 immunoreactivity was also present in cumulus granulosa cells and mural granulosa cells near the cumulus stalk. When granulosa cells from preovulatory follicles were exposed to recombinant GDF-9 in culture, GDF-9 increased vascular endothelial growth factor levels in culture medium. These data demonstrate that the cells of the primate periovulatory follicle both produce and respond to GDF-9. However, GDF-9 expression and action differ between rodent and primate follicles, suggesting a possible regulatory role for GDF-9 that is unique to the primate follicle.

Animals↗
PubMed1997

Localization of steroidogenic enzymes in macaque luteal tissue during the menstrual cycle and simulated early pregnancy: immunohistochemical evidence supporting the two-cell model for estrogen production in the primate corpus luteum.

It is hypothesized that the two-cell model for estrogen production by the ovarian follicle is preserved in the primate corpus luteum, but there is little direct evidence to support this theory. To determine the sites of androgen and estrogen synthesis within the primate corpus luteum and to ascertain whether changes in steroid hormone levels are related to steroidogenic enzyme expression, the enzymes converting progesterone to androgen (cytochrome P450 17alpha-hydroxylase/17,20 lyase; P450(c17)) and then to estrogen (aromatase; P450(arom)), as well as P450 side-chain cleavage (P450(scc)) and 3beta-hydroxysteroid dehydrogenase (3beta HSD), were detected by immunohistochemistry in macaque luteal tissue throughout the menstrual cycle and simulated early pregnancy. Corpora lutea were collected from rhesus monkeys in the early (Days 2-4 post-LH surge), mid (Days 6-8), mid-late (Days 10-12), and late (Days 14-15) luteal phase and after 1, 3, 6, or 9 days of hCG treatment that began on Day 9 of the luteal phase. Specific cytoplasmic staining for P450(c17), P450(arom), P450(scc), and 3beta HSD was present in luteal cells, but not in the microvasculature, within all luteal tissues examined. P450(c17)-stained luteal cells were located along the vascular tracts and around the periphery of the corpus luteum. Intensely stained luteal cells were associated with blood vessels entering from the outer surface of the corpus luteum, but not with blood vessels returning from the connective tissue centrum. In contrast, P450(arom)-stained luteal cells were distributed throughout the luteal parenchyma. P450(c17) staining intensity was similar at all stages of the luteal phase; however, the number and intensity of P450(arom)-stained cells decreased by late luteal phase. In simulated early pregnancy, cells stained for P450(c17) were present near blood vessels, with some positive cells scattered throughout the corpus luteum. P450(arom) immunostaining was heterogeneous within the corpus luteum; many intensely stained cells were interspersed among others that were only lightly stained. Overall, cellular staining for P450(c17) and P450(arom) remained intense through 9 days of simulated early pregnancy. In contrast, P450(scc) and 3beta HSD immunoreactivity were not located in distinct luteal compartments. These results are consistent with a two-cell model for steroid hormone production in the primate corpus luteum, whereby paraluteal (theca-luteal) cells produce androgen substrate that is converted to estrogens by true (granulosa-) luteal cells. The divergence in enzyme detection as the luteal phase progresses, with P450(c17) labeling high and P450(arom) staining having decreased, suggests a shift in the function of the corpus luteum as it ages. Enzyme localization during chorionic gonadotropin exposure simulating early pregnancy demonstrates the continued capacity of the primate corpus luteum to produce steroid hormones.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Cysteine conjugate beta-lyase-dependent biotransformation of the cysteine S-conjugates of the sevoflurane degradation product compound A in human, nonhuman primate, and rat kidney cytosol and mitochondria.

BACKGROUND: 2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (compound A) is a fluorinated alkene formed by the degradation of sevoflurane in the anesthesia circuit. Compound A is toxic to the kidneys in rats and undergoes glutathione-dependent metabolism in vivo. Several nephrotoxic halogenated alkenes also undergo cysteine conjugate beta-lyase-dependent biotransformation. These experiments were designed to test the hypothesis that cysteine S-conjugates of compound A undergo beta-lyase-dependent biotransformation. METHODS: S-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine 4, S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-L-cysteine 5, and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine 11 were incubated with rat, human, and nonhuman primate (cynomolgus, rhesus, and marmoset) kidney cytosol and mitochondria. beta-Lyase activity was determined by measuring pyruvate formation. RESULTS: Compound A-derived conjugates 4 and 5 as well as conjugate 11, a positive control, were substrates for cytosolic and mitochondrial beta-lyase from human, nonhuman primate, and rat kidney. For all substrates, beta-lyase activity was highest in the rat and lowest in the human and was higher in cytosol than in mitochondria. Conjugate 11 was a much better substrate than conjugates 4 or 5. The biotransformation of conjugates 4, 5, and 11 was inhibited by the beta-lyase inhibitor (aminooxy)acetic acid and was stimulated by the amino group acceptor 2-keto-4-methylthiolbutyric acid, indicating a role for beta-lyase. CONCLUSIONS: These data confirm the presence of beta-lyase activity in human and rat kidney and show that activity is also present in kidney tissue from nonhuman primates. The data also show that compound A-derived conjugates 4 and 5 undergo beta-lyase-catalyzed biotransformation. beta-Lyase activity in rat and nonhuman primate kidney tissue was 8 to 30 times and one- to three times, respectively, higher than in human kidney tissue.

Anesthetics, Inhalation↗
PubMed2001

Enhancing fMRI contrast in awake-behaving primates using intravascular magnetite dextran nanopartieles.

Functional MRI in awake-behaving primates is an emerging tool for bridging the gap between human fMRI and neurophysiology information from nonhuman primates. We report the use of magnetite dextran nanoparticles (Feridex) as a blood-pool agent to enhance fMRI contrast-to-noise (CNR) in primate FMRI. The intravascular half-life of the magnetite dextran was long compared to lanthanide chelates (T(1/2) = 198 min) with shortened T(2) relaxation observed in blood and cerebral cortex. Greater than 3-fold enhancement in the percentage MR signal change was observed using nanoparticles (13%) compared with conventional BOLD fMRI (4%). The calculated regional cerebral blood volume in macaque primary visual cortex increased 32% with photic stimulation. The increased CNR allows greater flexibility in the design of awake-behaving primate fMRI studies with the potential for improvements in resolution and significantly shortened imaging times.

Animals↗