RESUMO
African climate is generally considered to have evolved towards progressively drier conditions over the past few million years, with increased variability as glacial-interglacial change intensified worldwide. Palaeoclimate records derived mainly from northern Africa exhibit a 100,000-year (eccentricity) cycle overprinted on a pronounced 20,000-year (precession) beat, driven by orbital forcing of summer insolation, global ice volume and long-lived atmospheric greenhouse gases. Here we present a 1.3-million-year-long climate history from the Lake Malawi basin (10°-14° S in eastern Africa), which displays strong 100,000-year (eccentricity) cycles of temperature and rainfall following the Mid-Pleistocene Transition around 900,000 years ago. Interglacial periods were relatively warm and moist, while ice ages were cool and dry. The Malawi record shows limited evidence for precessional variability, which we attribute to the opposing effects of austral summer insolation and the temporal/spatial pattern of sea surface temperature in the Indian Ocean. The temperature history of the Malawi basin, at least for the past 500,000 years, strongly resembles past changes in atmospheric carbon dioxide and terrigenous dust flux in the tropical Pacific Ocean, but not in global ice volume. Climate in this sector of eastern Africa (unlike northern Africa) evolved from a predominantly arid environment with high-frequency variability to generally wetter conditions with more prolonged wet and dry intervals.
Assuntos
Clima , Chuva , África Oriental , Alcanos/análise , Atmosfera/química , Cálcio/análise , Dióxido de Carbono/análise , Clima Desértico , Poeira/análise , História Antiga , Gelo/análise , Oceano Índico , Lagos , Malaui , Folhas de Planta/química , Plantas , Estações do Ano , Temperatura , Ceras/químicaRESUMO
The measurement of protein turnover involves the product of the rates of protein synthesis and degradation. It is the dynamic balance between these two components that determines the measured net rate of protein synthesis. The data reported here show that brain cells from newborn animals incorporate arginine-(14)C into acid-insoluble protein at a rate 10-fold greater than the rate for brain cells obtained from 15-day old animals. This difference in incorporation occurred even though the rate of arginine accumulation and the resulting pool size of radioactive precursor were similar for both ages. The measurement of protein turnover in brain cell suspensions prepared from 1-day old animals was shown to be complex and to exhibit a cyclic phenomenon in regard to arginine-(14)C incorporation into and release from protein. The variation in half-life calculations (0.5-3.5 hr) due to this cyclic phenomenon is discussed. Although puromycin was added in an attempt to amplify the rate of degradation by preventing the synthesis of new protein, it was found that degradation was inhibited as well, suggesting a relationship between protein synthesis and degradation.
Assuntos
Encéfalo/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Arginina/metabolismo , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Isótopos de Carbono , Depressão Química , Meia-Vida , Técnicas In Vitro , Camundongos , Proteínas do Tecido Nervoso/biossíntese , Periodicidade , Puromicina/farmacologia , Solubilidade , Fatores de Tempo , Ácido Tricloroacético , Valina/metabolismoRESUMO
Discontinuous Ficoll-sucrose gradients were used to prepare subcellular fractions from mouse cerebral cortex at various stages of postnatal development. Representative samples of each subcellular fraction were obtained by sedimentation in an analytical ultracentrifuge and each fraction was examined quantitatively and qualitatively by electron microscopy. The amount of synaptosomal material was determined for each fraction on the basis of volume percentage, obtained from a series of contiguous micrographs, to circumvent any sampling error. This allowed an accurate appraisal of synaptosomal distribution during neural development and a direct comparison of the Ficoll-sucrose gradient fractions to the original crude mitochondrial preparations. The distribution of synaptosomal material was shown to be quantitatively altered during neural development, and maturation-dependent changes, at a qualitative level, were described. In addition, the relationship between neural maturation and the relative proportion and distribution of subcellular particles which contain processes tentatively identified as growth cones were characterized.
Assuntos
Córtex Cerebral/citologia , Animais , Fracionamento Celular , Córtex Cerebral/crescimento & desenvolvimento , Camundongos , Microscopia Eletrônica , Sinaptossomos , UltracentrifugaçãoRESUMO
Partially purified interferon preparations, obtained from L-cell monolayers infected with Newcastle disease virus (NDV), were shown to inhibit protein synthesis in noninfected L cells. The incorporation of several amino acids-(14)C was equally sensitive to the pretreatment of the cells with the interferon preparation. Treatment of L-cell monolayers for 24 hr with 800 units of interferon resulted in a 50% decrease in amino acid incorporation. The degree of inhibition was found to be a function of the interferon concentration and the time of exposure of the cells to the partially purified preparations. No inhibitory effect was detected in medium obtained from noninfected cells and purified in an identical manner. The inhibitory effect was shown to be cell specific in that the partially purified interferon from L cells did not reduce amino acid incorporation in heterospecific cell lines. Heating the interferon preparations at 60 degrees C destroyed their antiviral activity and their ability to inhibit valine-(14)C incorporation in L cells.
Assuntos
Interferons/farmacologia , Células L , Biossíntese de Proteínas , Aminoácidos/metabolismo , Animais , Isótopos de Carbono , Embrião de Galinha , Cricetinae , Técnicas de Cultura , Depressão Química , Fibroblastos , Células HeLa , Temperatura Alta , Humanos , Rim , Lisina/metabolismo , Camundongos , Vírus da Doença de Newcastle , Valina/metabolismoRESUMO
The ability of glycopeptides, isolated from bovine cerebral cortex, to alter cell division was studied by cell-cycle analyses. The results showed that glycopeptides arrested baby hamster kidney (BHK)-21 cells and Chinese hamster ovary (CHO) cells in the G2 phase of the cell cycle. Upon removal of the growth inhibition from arrested BHK-21 cells, the mitotic index in colchicine-treated cultures increased from 5 to 40% within 6 h and the increase in mitotic activity was accompanied by a complete doubling of all arrested cells within this 6-h time period. Determination of DNA content in growth-arrested BHK-21 cells showed that growth-arrested cells contained about twice the DNA of control cell cultures. Although CHO cells treated in a like manner with growth inhibitor could not be arrested for the same length of time as BHK-21 cells (18 h vs. 72 h before initiation of escape) and to the same degree (60% of the cell population vs. 99% of BHK-21 cells), the escape kinetics of CHO cells did indicate a G2 arrest. Approximately 3.5 h after escape began, CHO cell numbers in treated cultures attained the cell numbers found in control cultures. This rapid growth phase occurring in less than 4 h indicated that the growth inhibitor induced a G2 arrest-point in CHO cells that was not lethal since the entire arrested cell population divided.
Assuntos
Córtex Cerebral/metabolismo , Glicopeptídeos/farmacologia , Inibidores do Crescimento , Interfase/efeitos dos fármacos , Animais , Bovinos , Células Cultivadas , Cricetinae , DNA/análise , Feminino , Glicopeptídeos/isolamento & purificação , Inibidores do Crescimento/isolamento & purificação , Rim , OvárioRESUMO
A map of the preservation pattern of siliceous microfossils was constructed from an examination of 125 piston and gravity cores of Quaternary sediments from throughout the eastern tropical Pacific. Preservation is enhanced where high surface water productivity supplies a high input rate of siliceous tests to the sea floor, except in a large area north of 5 degrees N, east of the East Pacific Rise. Here a high input rate of terrigenous silicates may adversely affect preservation of biogenic opal in the sea-floor sediments.
RESUMO
Seismic reflection profiles and the structure of sediments in box cores from Ontong-Java Plateau indicate large-scale land sliding and sediment flow processes, respectively. The topographic morphology of sliding and slumping is depth- dependent, suggesting control by dissolution processes.
RESUMO
Nuclei, isolated from mouse brain tissue at various stages of postnatal development and incubated under cell-free conditions, synthesized RNA molecules that were associated with polyadenylic acid [poly(A)]. The RNA synthesized by these nuclei was similar to the poly(A)-associated products described for intact eukaryotic cells. The brain nuclei synthesized a similar proportion of RNA-poly(A) in the presence either of Mg(2+) or of Mn(2+) with (NH(4))(2)So(4). The RNA from neonatal brain nuclei appeared to have a greater proportion of poly(A)-containing RNA than nuclear products obtained from more mature neural tissue.
Assuntos
Encéfalo/metabolismo , Núcleo Celular/metabolismo , Polinucleotídeos/biossíntese , RNA/biossíntese , Nucleotídeos de Adenina/biossíntese , Fatores Etários , Animais , Encéfalo/citologia , Sistema Livre de Células , Celulose , Cromatografia de Afinidade , Guanosina Trifosfato/metabolismo , Técnicas In Vitro , Magnésio , Manganês , Camundongos , RNA/isolamento & purificação , TrítioRESUMO
The effect of a single injection of phenylalanine (2 mg/g of body weight) on brain polyribosomes, which increases the number of inactive monoribosomes, persists for 2 to 3 hours. A single injection of seven large neutral amino acids after phenylalanine administration results in a reversal of the effect on brain polyribosomes with a resultant decrease in monoribosomes to near normal levels. The other common amino acids are apparently not limiting during hyperphenylalanemia, because an injection of these did not increase recovery.
Assuntos
Aminoácidos/farmacologia , Encéfalo/metabolismo , Fenilalanina/farmacologia , Ribossomos/metabolismo , Fenilalanina/sangueRESUMO
Profiles of grain sizes in five cores recovered from Lake Superior show that grain size increased with burial depth to the postglacial-glacial contact. The results reflect a substantial reduction in bottom-current velocity and the corresponding wind velocity from 9500 to 6500 years ago.
RESUMO
Anthropogenic climate change has the potential to alter many facets of Earth's freshwater resources, especially lacustrine ecosystems. The effects of anthropogenic changes in Lake Superior, which is Earth's largest freshwater lake by area, are not well documented (spatially or temporally) and predicted future states in response to climate change vary. Here we show that Lake Superior experienced a slow, steady increase in production throughout the Holocene using (paleo)productivity proxies in lacustrine sediments to reconstruct past changes in primary production. Furthermore, data from the last century indicate a rapid increase in primary production, which we attribute to increasing surface water temperatures and longer seasonal stratification related to longer ice-free periods in Lake Superior due to anthropogenic climate warming. These observations demonstrate that anthropogenic effects have become a prominent influence on one of Earth's largest, most pristine lacustrine ecosystems.
RESUMO
BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. One possible treatment is spinal manipulation therapy. One hypothesis is that mechanical dysfunction in certain vertebrae causes decreases spinal mobility. This could affect the sympathetic nerve supply to the blood vessels supplying the pelvic viscera, leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these vertebrae increases spinal mobility and may improve pelvic blood supply. Another hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal structures that share the same pelvic nerve pathways. The character of pain from musculoskeletal dysfunction can be very similar to gynaecological pain as it can present as cyclic pain altered by hormonal influences associated with menstruation. OBJECTIVES: To determine the safety and efficacy of spinal manipulative interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or other medical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1980 to April 2006), CINAHL (1982 to March 2006), AMED (1985 to April 2006), Biological Abstracts (1969 to March 2006), PsycINFO (1806 to April 2006), and SPORTDiscus (1830 to April 2006). Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Any randomised controlled trials (RCTs) including spinal manipulative interventions (for example chiropractic, osteopathy, or manipulative physiotherapy) versus each other, placebo, no treatment, or other medical treatment were considered. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an intrauterine device (IUD). DATA COLLECTION AND ANALYSIS: Four trials of high velocity, low amplitude manipulation (HVLA), and one of the Toftness manipulation technique were included. Quality assessment and data extraction were performed independently by two review authors. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis were reported as descriptive data and were also included for discussion. The outcome measures were pain relief or pain intensity (dichotomous, visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results from the four trials of high velocity, low amplitude manipulation suggest that the technique was no more effective than sham manipulation for the treatment of dysmenorrhoea, although it was possibly more effective than no treatment. Three of the smaller trials indicated a difference in favour of HVLA, however the one trial with an adequate sample size found no difference between HVLA and sham treatment. There was no difference in adverse effects experienced by participants in the HVLA or sham treatment. The Toftness technique was shown to be more effective than sham treatment by one small trial, but no strong conclusions could be made due to the small size of the trial and other methodological considerations. AUTHORS' CONCLUSIONS: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhoea. There is no greater risk of adverse effects with spinal manipulation than there is with sham manipulation.
Assuntos
Dismenorreia/terapia , Manipulação da Coluna , Feminino , Humanos , Pelve/irrigação sanguínea , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
A novel glycopeptide inhibitor of cell division, isolated from bovine cerebral cortex cell surfaces, was shown to selectively protect nonmalignant cells from the cytoxic action of 5-bromo-2-deoxyuridine (5-BrdUrd). When mouse LM-22 cells (nonmalignant and devoid of gangliosides) were preincubated with GM1 ganglioside (3.0 micrograms/ml), the cell surface glycopeptide inhibitor effectively arrested cell division. In contrast to LM-22 cells, transformed mouse fibrosarcoma (No. 1316) cells were insensitive to the glycopeptide inhibitor whether or not they were preincubated with GM1 ganglioside. Mixed cultures of LM-22 cells preincubated with GM1 ganglioside and 1316 fibrosarcoma cells at an approximate ratio of 1:1 were established. Since LM-22 cells are resistant and 1316 fibrosarcoma cells are sensitive to 3.0 mM ouabain, the identity of surviving cells following BrdUrd treatment could easily be determined. Three hr after the establishment of the mixed cell population, 250 ng protein per ml of the purified bovine glycopeptide inhibitor was added to selectively arrest the mitosis of the LM-22 cells. After an additional 3 hr of incubation, 5-BrdUrd was added to a final concentration of 5.0 mM. Twelve hr later, cells were serially diluted and seeded into duplicate plates with and without 3.0 mM ouabain. LM-22 cells were effectively protected from the cytotoxic action of 5-BrdUrd (92 to 94% survival) while the majority of the 1316 fibrosarcoma cells were killed (21 to 30% survival). The selective protection of LM-22 cells was shown to be independent of differences in plating efficiency, cytotoxicity of 5-BrdUrd in the absence of the glycopeptide inhibitor, and the generation time of the two cell lines.
Assuntos
Membrana Celular/metabolismo , Gangliosídeo G(M1)/farmacologia , Gangliosídeos/farmacologia , Glicopeptídeos/metabolismo , Animais , Bromodesoxiuridina/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/análise , Córtex Cerebral/metabolismo , Fibrossarcoma , Glicopeptídeos/isolamento & purificação , CamundongosRESUMO
The decrease in the neural polyribosomes produced during hyperphenylalaninemia could not be restored to normal levels by the injection of other single neutral amino acids. All of the neutral amino acids that are transported with phenylalanine were found to produce an alteration of neural polyribosomes similar to that measured with phenylalanine. However, the injection of a balanced mixture of 6 or 7 neutral amino acids could restore the brain polyribosomes to normal states. Although this experimentally induced recovery did not lower brain phenylalanine concentrations, it did restore the acylation levels of methionyl-tRNA, and in particular, the methionyl-tRNA initiator species. This also led to a concomitant stimulation of the elongation rate of brain polypeptide synthesis. A natural recovery of brain polyribosomal levels (occurring 2 h after 1 mg/g phenylalanine is injected) did not appear to represent a real recovery of neural protein metabolism. Phenylalanine concentrations were increased in the brain, the acylation levels of methionyl-tRNA, alanyl-tRNA and the initiator methionyl-tRNA remained altered, and the rate of ribosome translocation was decreased 28%.
Assuntos
Encéfalo/efeitos dos fármacos , Proteínas do Tecido Nervoso/biossíntese , Fenilalanina/farmacologia , Polirribossomos/metabolismo , Aminoácidos/farmacologia , Animais , Encéfalo/metabolismo , Metionina/farmacologia , Camundongos , Elongação Traducional da Cadeia Peptídica/efeitos dos fármacos , Fenilalanina/antagonistas & inibidores , Fenilalanina/metabolismo , Aminoacil-RNA de Transferência/metabolismoRESUMO
The metabolism of neuroblastoma cell glycoproteins was examined using L-E13H]fucose. Incubation of monolayer cultures with [3H]fucose resulted in a rapid uptake of the radioactive precursor and its incorporation into acid-insoluble macromolecules. Less than 3% of the [3H]fucose that was isolated from neuroblastoma cells by trichloroacetic acid precipitation was associated with glycolipids. The metabolism of fucosylated macromolecules was studied in cells which were labelled to a steady state, and then reincubated under conditions which limited reutilization of the radioactive precursor (40 mM unlabelled fucose). During reincubation of the cells, we observed a rapid metabolism (27% by 2 h) of the prelabelled macromolecules which stabilized within a cell generation time to give an overall rate of turnover of 9%. This rapid loss of radioactivity from the cells was not due to exocytosis since less than 4% of the [3H]-fucose was lost into the media as macromolecules during a 5 h reincubation period. The presence of 40 mM fucose in the media did not affect cell growth until after 24 h of incubation or cellular protein synthesis until after 15 h of incubation. When the metabolism of neuroblastoma cell glycoproteins was measured in the presence of 1.8 - 10(-4) M cycloheximide, there appeared to be a less rapid decrease in cell-associated specific activity, and an increased reutilization of [3H]fucose. Although the major proportion of the radioactivity remained as e13H]fucose, extensive incubation of neuroblastoma cells with this radioactive precursor led to increased amounts of tritium associated with other cellular components; However, a rapid rate of glycoprotein metabolism could also be demonstrated with cells incubated with [14C]fucose. This eliminated the possibility that the above results were restricted to the tritiated precursor and merely a reflection of hydrogen-tritium exchange.
Assuntos
Glicoproteínas/metabolismo , Neuroblastoma/metabolismo , Linhagem Celular , Cicloeximida/farmacologia , Fucose/metabolismo , Glicoproteínas/biossíntese , CinéticaRESUMO
Cell proliferation is governed by the influence of both mitogens and inhibitors. Although cell contact has long been thought to play a fundamental role in cell cycling regulation, and negative regulators have long been suspected to exist, their isolation and purification has been complicated by a variety of technical difficulties. Nevertheless, over recent years an ever-expanding list of putative negative regulators have emerged. In many cases, their biological inhibitory activities are consistent with density-dependent growth inhibition. Most likely their interactions with mitogenic agents, at an intracellular level, are responsible for either mitotic arrest or continued cell cycling. A review of naturally occurring cell growth inhibitors is presented with an emphasis on those factors shown to be residents of the cell surface membrane. Particular attention is focused on a cell surface sialoglycopeptide, isolated from intact bovine cerebral cortex cells, which has been shown to inhibit the proliferation of an unusually wide range of target cells. The glycopeptide arrest cells obtained from diverse species, both fibroblasts and epithelial cells, and a broad variety of transformed cells. Signal transduction events and a limited spectrum of cells that are refractory to the sialoglycopeptide have provided insight into the molecular events mediated by this cell surface inhibitor.
Assuntos
Proteínas de Transporte , Divisão Celular/efeitos dos fármacos , Inibidores do Crescimento/toxicidade , Mitógenos/toxicidade , Animais , Bovinos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proteína 3 Ligante de Ácido Graxo , Proteínas de Ligação a Ácido Graxo , Substâncias de Crescimento/toxicidade , Humanos , Camundongos , Peptídeos/toxicidade , Sialoglicoproteínas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
A single intracerebroventricular injection of 100 ng of beta-endorphin altered the course of the central nervous system (CNS) infection of a temperature-sensitive mutant of vesicular stomatitis virus (VSV), tsG31-KS5. When mice were administered beta-endorphin and then 24 h later infected intracerebrally with tsG31-KS5 VSV, 70% of the animals died within 8 days of infection. In comparison, less than 10% of the animals had died after 21 days when infected with tsG31-KS5 VSV alone. When mice were injected with beta-endorphin and tsG31-KS5 VSV simultaneously, or with beta-endorphin 21 days after infection, the more aggressive clinical disease was not observed. Superficially, the more lethal disease induced by beta-endorphin appeared to be a result of a mild hypothermia caused by the neuropeptide. beta-Endorphin, however, did not influence the disease in nude (nu/nu) mice even though their core temperatures were reduced to an extent similar to that of BALB/c (+/+) mice, implicating the involvement of T lymphocytes in the alteration of the course of infection in normal mice.
Assuntos
Doenças do Sistema Nervoso Central/fisiopatologia , Viroses/fisiopatologia , beta-Endorfina/administração & dosagem , Animais , Doenças do Sistema Nervoso Central/tratamento farmacológico , Injeções Intraventriculares , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Vírus da Estomatite Vesicular Indiana , Viroses/tratamento farmacológicoRESUMO
Reconstitution of 3- to 4-week-old BALB/c nude (nu/nu) mice with 10(7) syngeneic splenocytes, 48 h before intracerebral inoculation with a temperature-sensitive (ts) mutant of VSV (tsG31 KS5), provided protection from the fatal consequences of clinical disease in 80-90% of the infected animals. Reconstitution of animals with 10(7) splenocytes, first depleted of natural killer (NK) cells with anti-asialo GM1 and complement, also afforded protection against the infectious disease. Depletion of T-lymphocytes with anti-thy-1.2 antibody and complement, however, provided little protection with approximately 40% of the animals succumbing to the virus infection within 30 days post-infection. A single intracerebroventricular injection with 14 pM of beta-endorphin, 24 h prior to viral infection, led to an increased fatality of mice previously reconstituted with T-lymphocytes but not in animals receiving only syngeneic NK cells. The increased fatality caused by the neuropeptide was antagonized by naloxone but not beta-endorphin-(1-27). Separation of splenocyte cell populations by buoyant density centrifugation demonstrated that small race lymphocytes, and not the large granular lymphocytes, were responsible for protection of nude mice from the central nervous system infection with ts-VSV. The beta-endorphin-responsive immune cells were shown to be a minor fraction of the small race T-lymphocyte population that bear the asialo-GM1 marker.
Assuntos
Encefalopatias/imunologia , Gangliosídeo G(M1) , Linfócitos T/efeitos dos fármacos , Vírus da Estomatite Vesicular Indiana , Viroses/imunologia , beta-Endorfina/farmacologia , Animais , Glicoesfingolipídeos/análise , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Linfócitos T/fisiologiaRESUMO
A single intracerebroventricular (i.c.v.) injection of 14 pmol of beta-endorphin into 6-7-week-old BALB/c (+/+) donor mice, 24 h prior to isolation of their T lymphocytes for use for reconstitution of athymic BALB/c (nu/nu) nude mice, altered the immuno-protective effect of adoptive transfer against an intracerebral (i.c.) infection with a temperature-sensitive mutant of vesicular stomatitis virus (tsG31 KS5 VSV). Simultaneous injection of beta-endorphin and naloxone into donor animals negated the opiate effects on splenic lymphocytes. T lymphocytes, isolated from beta-endorphin-treated donors, and then depleted with anti-asialo GM1 antiserum and complement failed to demonstrate the detrimental effects of beta-endorphin.
Assuntos
Linfócitos T/transplante , beta-Endorfina/farmacologia , Animais , Gangliosídeo G(M1)/imunologia , Injeções Intraventriculares , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Naloxona/farmacologia , Linfócitos T/imunologia , beta-Endorfina/administração & dosagemRESUMO
A 100 plaque forming unit (pfu) dose of a temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV), tsG31 KS5, engendered a slowly progressive paralytic central nervous system (CNS) disease that killed all BALB/c nude mice within 28 days. Reconstitution of nude mice with 10(7) syngeneic splenocytes 24 h before intracerebral inoculation with tsG31 KS5 VSV, however, protected 92% of the animals from death. When these reconstituted animals were injected intracerebroventricularly with 14 pmol of beta-endorphin 24 h after reconstitution with splenocytes and 24 h before inoculation with tsG31 KS5 VSV, only 72% of the animals survived. Furthermore, whereas 40% of the afflicted reconstituted nude mice given intracerebroventricular injections of sterile water were able to recover from the symptoms of disease, those surviving animals which received beta-endorphin were unable to do so. A single intravenous injection of 14 pmol beta-endorphin, or repeated postinfection administration of 28 pmol of beta-endorphin intravenously into nude mice reconstituted with syngeneic splenocytes, which were pretreated with beta-endorphin, did not alter the course of CNS disease induced by tsG31 KS5 VSV. The effect induced by intracerebroventricular injection of beta-endorphin was antagonized by naloxone, but not by the neuropeptide fragment beta-endorphin-(1-27). A simultaneous intracerebroventricular injection of reconstituted nude mice with 1220 pmol of naloxone and 14 pmol of beta-endorphin resulted in a 89% survival rate, and 33% of the afflicted animals were able to overcome the symptoms of the disease induced by tsG31 KS5 VSV. Intracerebroventricular injection of reconstituted nude mice with 330 pmol of beta-endorphin-(1-27) and 14 pmol of beta-endorphin resulted in a 72% survival rate and the surviving animals were unable to improve appreciably the clinical status of their disease. Injection of reconstituted nude mice with either 1220 pmol of naloxone or 330 pmol of beta-endorphin-(1-27) alone did not alter the course of the CNS disease in any way. A single intracerebroventricular injection of 29 pmol of another psychoactive peptide, [Des-Tyr]-endorphin, 24 h after reconstitution of nude mice with splenocytes and 24 h prior to infection with virus, resulted in 74% survival; and 39% of the afflicted animals were able to recover from the clinical symptoms.