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Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls.

Fetal substantia nigra (SN) cells were transplanted into the caudate nucleus (CN) of four vervet monkeys (Cercopithecus aethiops sabaeus) that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment appears to produce a syndrome similar to that observed in patients with idiopathic Parkinson's disease. Normal and parkinsonian behaviors were quantitated by trained observers 5 days/week. Twenty-eight behaviors based on previous factor analyses were individually scored and rated. Parkinsonian signs included freezing, head and limb tremor, difficulty in eating, delayed initiation of movement, poverty of movement, tremor that stopped with intention, decreased response to threats, and lying immobile in the cage. These signs were combined to give an overall rating of parkinsonism. A summary measure of 'normal' healthy behavior was also examined, including such behaviors as yawning, scratching, self-grooming, shifting, and eating. Overall ratings of parkinsonism increased and those of healthy behavior decreased after MPTP. In the 4 monkeys grafted with fetal SN cells into the CN, behavior returned to pre-treatment levels by the time of sacrifice (2, 5, or 7.5 months after grafting). Three control subjects were transplanted with either SN cells into an inappropriate brain site (cortex) or inappropriate, non-dopaminergic, cells (cerebellar) into the CN. Subjects were also compared with three control animals that did not receive MPTP but received cryopreserved or fresh SN and other cells into the CN. Only MPTP-treated subjects that received SN cells into the CN showed evidence of a reversal of the MPTP syndrome after transplantation. In addition, grafting in animals that were not MPTP-treated did not appear to affect behavior. This paper reports the specific behavioral effects of severe MPTP toxicity that were or were not reversed after transplantation and suggests that only fetal SN cells grafted into the CN may be able to reverse behavioral deficits in MPTP-treated monkeys.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Methylphenidate, apomorphine, THIP, and diazepam in monkeys: dopamine-GABA behavior related to psychoses and tardive dyskinesia.

In eight monkeys (Cercopithecus aethiops), previously treated with haloperidol for 4-14 months, we have examined the behavioral effect of: (1) methylphenidate vs apomorphine; (2) 4,5,6,7-tetrahydroisoxazolo-(5,4-c)-pyridin-3-ol(THIP, a GABA agonist) vs diazepam; and (3) THIP and diazepam in methylphenidate-induced behavior. Methylphenidate (0.5-5.0 mg/kg) and apomorphine (0.1-0.5 mg/kg) both increased locomotion, but otherwise exhibited different behavioral profiles. Methylphenidate induced repetitive movements of head, limbs, and trunk, and hallucinatory-like behavior, but not oral hyperkinesia (licking and gnawing), whereas apomorphine preferentially caused oral hyperkinesia. THIP produced a syndrome of bradykinesia, dystonia, ataxia, myoclonus, sedation, and decreased responsiveness, whereas diazepam produced only bradykinesia, ataxia, sedation, and decreased responsiveness, but not dystonia and myoclonus. Methylphenidate-induced locomotion and repetitive movements were reduced by THIP and diazepam, whereas hallucinatory-like behavior was markedly aggravated by THIP, but not by diazepam.

Animals↗

Dopamine, acetylcholine, and GABA effects in acute dystonia in primates.

Neurological side effects associated with neuroleptic drugs result from a complex interaction of multiple neurotransmitters. To clarify the etiology of neuroleptic-induced acute dystonic reactions, monkeys (Cercopithecus aethiops) were treated with haloperidol at doses sufficient to evoke dystonia, and the effects of agents that influenced dopaminergic, cholinergic, or GABAergic neurotransmitters were evaluated. Apomorphine, a dopamine (DA) agonist, and biperiden, an acetylcholine (ACh) antagonist, decreased acute dystonia, whereas alpha-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis, and physostigmine, an ACh agonist, agonist, increased the symptoms. Muscimol, a GABA agonist, increased the dystonias in a dose-dependent way, and GABA inhibition with picrotoxin also aggravated dystonia, complicated by systemic intoxication and seizures. The reciprocal interaction between DA and ACh influences is consistent with clinical findings and animal models of dyskinesias. Dystonia may also be modulated by GABAergic substrates, but the results suggest complex interactions among DA, ACh, and GABA neurotransmission. Symptoms involving the orofacial, limb, and trunk regions, and purposeless overactivity are discussed in comparison with acute and tardive neuroleptic-induced movement disorders.

Acetylcholine↗

The pathogenesis of trypanosomiasis of the CNS. Studies on parasitological and neurohistological findings in trypanosoma rhodesiense infected vervet monkeys.

Parasitological examinations of the cerebrospinal fluid of 20 vervet monkeys (Cercopithecus aethiops), that had been infected with Trypanosoma rhodesiense, revealed that the CSF was regularly infested with trypanosomes in the early phase of the disease, at the earliest on the 13th day, in most of the animals in the 3rd or 4th week, after infection. Follow-up examinations of the CSF during the further course of the disease also regularly proved positive for trypanosomes. Histological studies in the animals that died at a mean of 65 days after infection (range 35 to 107 days) revealed encephalitis in the animal with the longest course of the disease. In all the other animals, meningitis alone was found. This was accompanied by a modified early encephalitic reaction, characterized by lympho-plasma-cellular infiltrates exclusively in the adventitial sheaths of those blood vessels passing into the brain from the leptomeninges affected by inflammatory infiltration. The early encephalitic reaction is interpreted as the morphological manifestation of an infestation of the perivascular spaces (Virchow-Robin spaces) with parasites. It indicates that CSF parasitosis in the early phase represents the point of departure for the encephalitis that develops in the late phase of the disease, and that the encephalitis presumably develops as a result of the migration of the trypanosomes out of the subarachnoid space into the perivascular spaces, and from there into the brain.

Animals↗

Cone synapses of a flat diffuse cone bipolar cell in the primate retina.

A Golgi-stained flat diffuse cone bipolar cell from a vervet monkey's retina (Cercopithecus aethiops), contacting six cones, was serially sectioned for electron microscopy (EM) to determine the types of synapses it made with the cone pedicles. All the synapses were basal (flat) contacts. Their distribution and ultrastructural type were similar at each pedicle. Approximately half the synapses were definable as triad-associated and the rest were elsewhere on the cone pedicle base. Their ultrastructure is the same regardless of those positions. About 25 synapses were made with each cone. Thus this type (DB2 of Boycott & Wässle, 1991) of flat diffuse cone bipolar cell is in contact with six cones through about 150 synapses. At the eccentricity studied each cone pedicle probably makes 90-100 basal synapses with between three and four DB2 bipolar cells. This is between two and three times the number that are made with all the types of invaginating bipolar cells. A brief review of cone photoreceptor synapses with bipolar cells shows that, for those so far examined in the primate retina, the dichotomy into two types of bipolar cell invaginating (ribbon-related), with axons ending in the b-layer of the inner plexiform layer (IPL) (hence presumptive On-bipolars) and flat (basal synapses), with axons ending in the a-layer of the inner plexiform layer (hence presumptive Off-bipolars) is the rule. But other vertebrate retinae, including that of the cat, also have bipolar cells which vary from this pattern.

Animals↗

Isolation and characterization of simian immunodeficiency virus from African white-crowned mangabey monkeys (Cercocebus torquatus lunulatus).

Forty-eight of 236 sera from seven species of African non-human primates in Kenya, including those of white-crowned mangabey monkeys (Cercocebus torquatus lunulatus) had antibodies to simian immunodeficiency viruses (SIVs). Isolates of simian lentivirus were obtained from seropositive white-crowned mangabey monkeys which are indigenous in West Africa. This virus, designated as SIVWCM, appeared morphologically similar to HIV by electron microscopy, showed Mg(2+)-dependent reverse transcriptase activity, and induced cytopathic effects in human CD4-positive cells. Western blotting analysis revealed that env products of SIVWCM cross-reacted with those of SIVAGM more strongly than with those of HIV-1 and SIVMAC, and clear hybridization bands were detected with an SIVAGM probe. For comparison of the virus sequence with those of other primate lentiviruses, part of the pol gene and the long terminal repeats (LTRs) were amplified and cloned. Sequencing showed that SIVWCM isolates were closely related to SIVAGM isolates. This study suggested that SIVAGM from the Cercopithecus genus and SIVWCM from the Cercocebus genus may be members of an SIV group that is genetically distinct from the SIV from a sooty mangabey monkey (SIVSMM) of the genus Cercocebus, to which the white-crowned mangabey monkey also belongs.

Animals↗

Early cytoplasmic vacuolization of African green monkey kidney cells by SV40.

As early as 3--4 hours after infection with SV40 at a high input multiplicity, African green monkey (Cercopithecus aethiops) kidney (AGMK) cells developed cytoplasmic vacuolization. At 10--20 hours after infection, the vacuolization reached its maximal level, then disappeared and SV40 specific cytopathic change followed. This vacuolization developed before the synthesis of the specific T and V antigens. This early cytoplasmic vacuolization (ECV) was prevented by preincubating the virus with specific antiserum, or by heating the virus with MgCl2. The ECV could be induced by UV-irradiated SV40. Addition of metabolic inhibitors had no effect on the induction of the ECV. These results suggest that the capacity to induce the ECV resides in a structural component(s) of SV40 virion and the vacuolization is not associated with the replication of SV40.

Animals↗

The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary.

Fluorescence in situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescence in situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata and Cercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines.

Animals↗

Allelic diversity at the primate Mhc-G locus: exon 3 bears stop codons in all Cercopithecinae sequences.

Twenty-seven major histocompatibility complex (Mhc)-G exon 2, exon 3, and exon 2 and 3 allelic sequences were obtained together with 12 different intron 2 sequences. Homo sapiens, Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus, Macaca fascicularis, Macaca mulatta, and Cercopithecus aethiops individuals were studied. Polymorphism does not follow the classical pattern of three hypervariable regions per domain and is found in all species studied; exon 3 (equivalent to the alpha 2 protein domain) shows stop codons in the Cercopithecinae group but not in the Pongidae and human groups. Dendrograms show that cotton top tamarin (Saguinus oedipus) Mhc-G sequences are closer to Homo sapiens and Pongidae than to Cercopithecinae, probably due to the stop codons existing at exon 3 of the latter. There is a clear trans-species evolution of allelism in Cercopithecinae and also in exon 2 of all the other apes studied, but a generation of allelism within each species may be present on exon 3 sequences. This discrepancy may be due to the preferential use of exon 2 over exon 3 at the mRNA splicing level within each species in order to obtain the appropriate functional G product. Mhc-G intron 2 shows conserved motifs in all species studied, particularly a 23 base pair deletion between positions 161 and 183 which is locus specific, and some of the invariant residues, important for peptide presentation, conserved in classical class I molecules from fish and reptiles to humans were not found in Mhc-G alleles; the intron 2 dendrogram also shows a particular pattern of allelism within each species. In summary, Mhc-G has substantial differences from other classical class I genes: polymorphism patterns, tissue distribution, gene structure, splicing variability, and probably an allelism variability within each species at exon 3. The G proteins may also be different. This indicates that the Mhc-G function may not be peptide presentation to the clonotypic T-cell receptor.

Alleles↗

The distribution of serum high density lipoprotein subfractions in non-human primates.

The ultracentrifugal flotation patterns in 1.2 g/ml solvent and ultracentrifugal gradient distribution of high density lipoproteins (HDL) from the primates--human, apes and monkeys--were determined, with emphasis on the gorilla species of apes and rhesus monkeys. Diets for non-human primates were commercial chow, which is low in cholesterol. Molecular weights and protein, cholesterol, phospholipid and triglyceride compositions of various density fractions were determined on human, gorilla and rhesus HDL. The HDL2/HDL3 ratio was determined from the two peaks observed upon flotation in high salt in the analytical ultracentrifuge. The HDL2 of all three species of apes--gorillas (Gorilla gorilla), chimpanzees (Pan troglodytes) and orangutans (Pongo pygmaeus)--was always greater than HDL3, while that of all six species of Old World monkeys--Rhesus (Macaca mulatta), sooty mangabeys (Cercocebus atys), cynomolgus (Macaca fascicularis), stumptails, (Macaca arctoides) patas (Erythrocebus patas) and African greens (Cercopithecus aethiops)--was less. In addition, the HDL3 concentration in five gorillas was about 15 mg/dl as cholesterol while the HDL2 concentration was 92 mg/dl, much lower and higher, respectively, than humans. HDL2 of gorillas was similar in density and molecular weight to that of humans. The distribution of densities in gorilla HDL was predominantly in HDL2, while rhesus HDL usually, but not always, was unimodal, having a density distribution similar in heterogeneity to human HDL3, but somewhat less dense (peaking at 1.109 vs. 1.129 g/ml). The molecular weight of rhesus HDL was about the same as human HDL3 in all three density subfractions and at the peak density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of dietary fiber on lipids and aortic composition of vervet monkeys.

A semipurified, cholesterol-free diet containing 40% carbohydrate can produce aortic sudanophilia or aortic atherosclerosis in vervet monkeys (Cercopithecus aethiops pygerethrus) depending on the particular carbohydrate fed. Four groups of vervet monkeys (three males and three females per group) were fed semipurified diets containing lactose. Two of the groups were also fed 15% cellulose (C) or 15% cellulose plus 0.1% cholesterol (CC); the two other groups were fed 15% pectin (P) or 15% pectin plus 0.1% cholesterol (PC). The average serum total cholesterol and low density lipoprotein cholesterol levels over the entire feeding period (mg/dl +/- SEM) were, for C, 156 +/- 14 and 95 +/- 5; for P, 173 +/- 15 and 112 +/- 8; for CC, 187 +/- 27 and 122 +/- 21; and for PC, 155 +/- 11 and 108 +/- 7. Cholesterol levels at autopsy (mg/dl +/- SEM) were, for C, 103 +/- 6; for P, 108 +/- 16; for CC, 92 +/- 9; and for PC, 106 +/- 7. Aortic sudanophilia (percentage of area) was, for C, 5.9 +/- 2.7; for P, 13.5 +/- 9.4; for CC, 5.3 +/- 2.1; and for PC, 21.6 +/- 10.3. Dietary pectin led to more severe sudanophilia (increased by 129% in the absence of cholesterol and by 308% in its presence) than did cellulose. Analysis of aortic glycosaminoglycans (GAG) revealed that dermatan sulfate levels fell in both cholesterol-fed groups, and chondroitin sulfate fell in aortas of group CC. Heparan sulfate levels were unaffected by cholesterol feeding. Hexuronic acid, galactosamine and hexosamine levels were elevated in the pectin-fed monkeys, but levels were unaffected by dietary cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Activation of metastatic potential in African green monkey kidney cell lines by prolonged in vitro culture.

Studies on the tumorigenicity of Vero kidney cells of Cercopithecus aethiops monkey origin were extended to various passage levels of BSC-1 aneuploid cells and to low passage CV-1 diploid cells (derived also from C. aethiops monkey kidney). It was found that BSC-1 cells -- like Vero cells -- showed increased tumorigenicity with increasing passage level in antithymocyte globulin (ATG) treated newborn rats and in nude mice. Cells passaged over 250 times in cultures formed invasive adenocarcinomas in newborn rats. Their malignant tumor growth was further demonstrated around the 500 passage level when tumor metastases were detected in the lungs of four of the 14 inoculated rats. Vero cells induced such lung metastases in rats already at passage 227. CV-1 diploid cells at low passage level produced small nodules of epithelioid cells in newborn rats at 6th day after inoculation that had disappeared by the 21st day, and caused no local invasion nor lung metastasis. In vitro tumorigenicity tests on BSC-1 and CV-1 cells, using chick embryo skin, human muscle and colony formation in agarose, confirmed the animal test results. The results of this study indicate that BSC-1 and Vero cell lines at low and high passage levels may prove to be useful tools to study the molecular basis of malignancy.

Adenocarcinoma↗

Distribution, population density, and status of sympatric cercopithecids in the Campo-Ma'an area, Southwestern Cameroon.

A study on species composition, distribution, and population density of cercopithecids in the Campo-Ma'an area, Southwestern Cameroon, was undertaken from December 1997 until August 2000. A total of 665.5 km of line transects was used for the census. Thirteen diurnal primate species including five endangered species (Gorilla g. gorilla, Pan troglodytes, Mandrillus sphinx, Colobus satanas, Cercocebus torquatus) were recorded in the Campo Forest, the greatest part of which is a logging concession. Cercopithecus nictitans (1.43 groups/km2), C. cephus (1.13 groups/km2), C. pogonias (0.81 groups/km2), and C. torquatus (0.51 groups/km2) occurred at medium frequencies compared to figures from other Central African study sites. Mandrill densities estimated (0.27 groups/km2) show that the area is very important for the conservation of this rare species. Guenon densities found inside areas with a high level of human activities did not differ significantly from densities estimated in areas with a lower level of human activities. C. torquatus densities were significantly higher in the areas with a low level of human disturbance and encounter rates with Lophocebus albigena also indicate a preference of less disturbed areas. Mangabeys are thus likely to be adversely affected by human activities in the area. In the Ma'an Forest, which has not been logged yet, ten species were confirmed. The population densities of two guenons (C. nictitans and C. cephus) were estimated to be twice as high in the unlogged forest area as compared to the logged forest of Campo. Other species are rarer in the Ma'an Forest than in the Campo Forest. Although mangabeys are adversely affected by human activities, the results still indicate that selective logging may be compatible with the conservation of cercopithecids, if a reduced damage logging concept and antipoaching measures are implemented. Increased hunting activities following logging operations will definitely have a negative longterm impact on primate populations in the Campo-Ma'an area if no further, more effective conservation measures will regulate wildlife use in future.

Animals↗

"Rodent-like" and "primate-like" types of astroglial architecture in the adult cerebral cortex of mammals: a comparative study.

Previous observations disclosed that astroglia with interlaminar processes were present in the cerebral cortex of adult New and Old World monkeys, but not in the rat, and scarcely in the prosimian Microcebus murinus. The present report is a more systematic and comprehensive comparative analysis of the occurrence of such processes in the cerebral cortex of several mammalian species. Brain samples were obtained from adult individuals from the following orders: Carnivora (canine), Rodentia (rat and mouse), Marsupialia (Macropus eugenii), Artiodactyl (bovine and ovine), Scandentia (Tupaia glis), Chiroptera (Cynopteris horsfieldii and C. brachyotis), and Primate: Prosimian (Eulemur fulvus), non-human primate species (Cebus apella, Saimiri boliviensis, Callithrix, Macaca mulatta, Papio hamadryas, Macaca fascicularis, Cercopithecus campbelli and C. ascanius) and from a human autopsy. Tissues were processed for immunocytochemistry using several antibodies directed against glial fibrillary acidic protein (GFAP), with or without additional procedures aimed at the retrieval of antigens and enhancement of their immunocytochemical expression. The cerebral cortex of non-primate species had an almost exclusive layout of stellate astrocytes, with only the occasional presence of long GFAP-IR processes in the dog that barely crossed the extent of lamina I, which in this species had comparatively increased thickness. Species of Insectivora and Chiroptera showed presence of astrocytes with long processes limited to the ventral basal cortex. Interlaminar GFAP-IR processes were absent in Eulemur fulvus, at variance with their limited presence and large within- and inter-individual variability as reported previously in Microcebus murinus. In New World monkeys such processes were absent in Callithrix samples, at variance with Cebus apella and Saimirí boliviensis. Overall, the expression of GFAP-IR interlaminar processes followed a progressive pattern: bulk of non-primate species (lack of interlaminar processes)--Chiroptera and Insectivora (processes restricted to allocortex) < strepsirhini < haplorhini (platirrhini < catarrhini). This trend is suggestive of the emergence of new evolutionary traits in the organization of the cerebral cortex, namely, the emergence of GFAP-IR long, interlaminar processes in the primate brain. Interlaminar processes may participate in a spatially restricted astroglial role, as compared to the one provided by the astroglial syncytium. It is proposed that the widely accepted concept of an exclusively astroglial syncytium is probably linked with a specific laboratory animal species ("rodent-type" or, rather, "general mammalian-type" model) that misrepresents the astroglial architecture present in the cerebral cortex of most anthropoid adult primates ("primate-type" model), including man.

Aged↗

Effects of lesions to area V6A in monkeys.

In order to assess the role played by area V6A in visuomotor control, two adult green monkeys ( Cercopithecus aethiops) were subjected to small, bilateral lesions in the anterior bank of the parieto-occipital sulcus. Before and after the lesions, monkeys were tested for naturally designed reaching, grasping and picking-up pieces of food from various positions on a plate and from a differently oriented narrow slit. All movements were recorded with closed circuit TV and analysed offline on a single-photogram basis for defective reaching and wrist orientation. V6A lesions provoked parietal weakness, reluctance to move, and specific deficits in reaching, wrist orientation and grasping. Recovery from the observed deficits was rapid, even after a second, contralateral lesion was given, creating a bilateral lesion. Thus, together with previous anatomical and electrophysiological data, these results directly support the hypothesis that area V6A is part of the network involved in the control of reaching movements and wrist orientation.

Animals↗

Retinogeniculate projections following early cerebral hemispherectomy in the vervet monkey.

The effects of early, unilateral cerebral hemispherectomy on retinogeniculate projections were studied in the vervet monkey (Cercopithecus aethiops sabeus). Hemispherectomy eliminates all geniculocortical pathways and thus removes cortical factors involved in the survival of retinogeniculate projections. Complete removal of the left cerebral cortex was performed in two monkeys at 6 months and 8 months of age. After a post-surgical survival period of 50 months (SHG3) and 45 months (SHG4), both animals and a normal adult monkey received intraocular injections of [3H]proline (5 mCi) in the left eye and WGA-HRP (100 microliters, 5%) in the right eye. The dorsal lateral geniculate nucleuseuron (LGNd) ipsilateral to the hemispherectomy was on average 73% smaller than the contralateral LGNd. The magno- and parvocellular layers ipsilateral to the cortical ablation in both hemispherectomized subjects received a layered, eye-specific pattern of retinal input. This suggests that retinogeniculate projections could be sustained in the absence of geniculate relay cells.

Animals↗

Efferent synaptic connections of dopaminergic neurons grafted into the caudate nucleus of experimentally induced parkinsonian monkeys are different from those of control animals.

This study investigated the question of whether grafted dopamine cells in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys form synapses and, if they do, whether their postsynaptic targets were the same as those in control monkeys or in previous studies in rats. Electron-microscopic single immunostaining was performed for tyrosine hydroxylase on vibratome sections prepared from the head of the caudate nucleus of controls and MPTP-treated African green monkeys (Cercopithecus aethiops sabaeus) that received a graft. Furthermore, correlated light- and electron-microscopic double immunostaining was carried out for tyrosine hydroxylase and calbindin in the same brain area of MPTP-treated plus grafted animals. In control monkeys, the majority (97%) of dopamine boutons terminate on spines that were also synaptic targets of immunonegative boutons forming asymmetric synaptic contacts: synaptic triads. In MPTP-treated, grafted animals, the majority of transplanted dopamine cells terminate on dendritic shafts (67%) and somata (32%), and only a few (1.33%) form axospine synapses. The results of the double immunostaining experiments indicated that these newly formed axosomatic and axodendritic synapses are associated with calbindin-immunoreactive, medium-sized, spiny striatonigral projection neurons. These observations indicate that: (1) dopamine from transplanted embryonic tissue acts via synaptic contacts on host neurons; (2) the primary synaptic targets of transplanted dopamine cells are not spines but dendrites and somata of host neurons; (3) these target neurons are the same as in control animals; and (4) comparing these observations with results of control and grafted rats, there are major species differences between rats and monkeys in the dopamine innervation of both control and transplanted animals.

Animals↗

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from lubricating oil.

OBJECTIVES: Percutaneous penetration of polycyclic aromatic hydrocarbons (PAHs) is affected by various factors connected to exposure conditions. The nature of the matrix, such as that of oil, can strongly affect their percutaneous penetration. Risk assessment should consider these effects. We examined the effect of matrix on percutaneous penetration of PAHs, particularly that of lubricating oil. METHODS: The test apparatus consisted of an in vitro static diffusion cell system using full-thickness monkey (Cercopithecus aetiops) skin as the membrane and saline solution with gentamycin sulfate and 4% bovine serum albumin as receptor fluid. Chemical analysis of PAHs in the samples obtained from cells was carried out by inverse-phase HPCL, and the results were read by spectrofluorimetry. RESULTS: Comparing the penetration of 13 PAHs from a lubricating oil and from acetone solution with artificial sweat resulted in a significantly slower passage from the oil matrix for acenaphthene, anthracene, phenanthrene, fluoranthene, naphthalene, pyrene, fluorene (Mann-Whitney U test, P < 0.05). No significant differences in the passage were found for chrysene because, in the test with oil, its concentration was very often below the detection limit. For benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene it was possible to demonstrate a passage through the skin only when compounds were applied in acetone solution with artificial sweat. CONCLUSIONS: The results of the study suggest the necessity of dermal penetration data relevant for risk assessment, obtained under experimental conditions similar to the real exposure conditions.

Acetone↗