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1.
J Neurosurg Sci ; 56(4): 363-71, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23111298

RESUMO

AIM: Cerebral vasospasm is a leading cause of death and disability following aneurysmal subarachnoid hemorrhage (SAH). Nitric oxide (NO) is a potent mediator of vasodilation, and citrulline is a known contributor to NO production. The leukocytosis inflammatory response can increase vasoconstrictive compounds that may also contribute to vasospasm. Dexamethasone is a glucocorticosteroid commonly administered after SAH, which may alter the production of leukocytes and citrulline. The goal of this project was to study the effects of dexamethasone on leukocytosis, citrulline, and angiographic vasospasm. METHODS: Experimental SAH was induced in 18 New Zealand white rabbits. Intravenous dexamethasone was administered to one group (N.=9) at 2 mg/kg/day. A placebo group (N.=9) was given a saline infusion with otherwise identical procedures. CSF citrulline, leukocytes, protein, and glucose, as well as plasma citrulline were measured at baseline and 3 days post-SAH in a blinded fashion. Basilar artery angiography was performed at baseline and repeated 3 days post-SAH. RESULTS: The change in CSF citrulline from day 0 to day 3 was significantly lower in the dexamethasone group compared to controls (P=0.002). The change in CSF white blood cells was also significantly lower (P=0.005). There was no significant change in plasma citrulline levels or angiographic vasospasm. CONCLUSION: Dexamethasone significantly decreases CSF citrulline and CSF leukocytosis after experimental SAH. It is possible this could lead to a relative vasoconstriction and vasodilation, respectively. These processes could cancel-out opposing effects of dexamethasone on cerebral vasospasm, partially contributing to the recognized, multifactorial, inconsistent effects of glucocorticoids on vasospasm.


Assuntos
Citrulina/líquido cefalorraquidiano , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Leucócitos/efeitos dos fármacos , Hemorragia Subaracnóidea/tratamento farmacológico , Vasoespasmo Intracraniano/tratamento farmacológico , Animais , Dexametasona/farmacologia , Modelos Animais de Doenças , Glucocorticoides/farmacologia , Óxido Nítrico/líquido cefalorraquidiano , Coelhos , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/líquido cefalorraquidiano , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/metabolismo
2.
Bone Marrow Transplant ; 47(1): 82-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21358691

RESUMO

Early lymphocyte recovery following auto-SCT for non-Hodgkin's lymphoma (NHL) has been reported to be associated with improved outcome. The significance of early lymphocyte recovery following a stem cell transplant in NHL subtype diffuse large B-cell lymphoma (DLBCL) in the rituximab era remains unclear. Patients who underwent an auto-SCT at our institution for DLBCL during the time period 1998-2008 (n=115) were included in the study. Patient characteristics were well-balanced in both rituximab naïve and rituximab-exposed groups. Prior rituximab therapy did not affect lymphocyte recovery on day 14 or day 28. Lymphocyte recovery on day 14 and day 28 and prior rituximab had no impact on survival after auto-SCT for DLBCL, despite early benefit. Other factors such as age, stage at presentation, number of salvage regimens, mobilization procedure, conditioning regimen, pre-transplant radiation therapy and pre-transplant disease status had no impact on survival. Our data showed that the survival benefit with early lymphocyte recovery and prior rituximab seen in previous reports may be lost with longer follow-up. Prior rituximab therapy does not appear to influence the lymphocyte count at days 14 and 28 following auto-SCT. Our findings suggest that future trials should consider manipulating the immune system as a post transplant intervention to improve long-term outcome.


Assuntos
Linfócitos/imunologia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Recuperação de Função Fisiológica/imunologia , Transplante de Células-Tronco , Adulto , Fatores Etários , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Fatores de Tempo , Transplante Autólogo
3.
Indian J Med Res ; 129(5): 587-92, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19675389

RESUMO

BACKGROUND & OBJECTIVE: This study was carried out to determine the effects of reactive oxygen species in the balance between the pro-oxidant and antioxidant levels in experimental peripheral constriction injury induced by silver wire looping of sciatic nerve of rats. METHODS: Rats were divided into experimental group 1 (silver wire ligated) and group 2 (control, sham operated). Functional and behavioural activities were assessed by a modified Basso Beattie Bresnahan (BBB) locomotory rating scale. Mechanical pain intensity was measured with Randall and Selitto apparatus. Foot positioning, toe spread, paw withdrawal threshold and paw withdrawal latency were carried out on days 1, 3, 7, 14, 21 and 28 in rats with chronic pain. Oxidative stress markers such as malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were measured along with antioxidants such as glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) on day 30 after constriction in sciatic nerve, spinal cord, dorsal root ganglion, dorsal root and ventral root. RESULTS: Significant (P<0.05) increase in MDA, AOPP, SOD and GPx and decrease in the GSH and catalase activities in sciatic nerve, spinal cord, dorsal root ganglion, dorsal root and ventral root were observed in experimental group rats compared to control group. There was no recovery in foot positioning and toe spread. Reduced paw withdrawal threshold and paw withdrawal latency was observed in ligated rats compared to control rats. INTERPRETATION & CONCLUSION: Foot positioning, toe spread, paw withdrawal threshold and paw withdrawal latency with no recovery until day 30 confirmed locomotory deficits, hyperalgesia and neuronal impairment. Oxidative stress evidenced by increased MDA, AOPP and decreased GSH and catalase support the generation of reactive oxygen species in constriction model. The present experimental model for chronic pain induced by silver wire spirally coiled around sciatic nerve may be useful for future studies.


Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Nervo Isquiático/lesões , Análise de Variância , Animais , Constrição , Locomoção/fisiologia , Malondialdeído/metabolismo , Sistema Nervoso/metabolismo , Medição da Dor , Ratos
4.
J Med Chem ; 44(3): 390-403, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11462979

RESUMO

Twelve analogues of 1N,14N-bisethylhomospermine (BE-4-4-4) with restricted conformations were synthesized in the search for cancer chemotherapeutic agents with higher cytotoxic activities and lower systemic toxicities than BE-4-4-4. The central butane segment of BE-4-4-4 was replaced with a 1,2-substituted cyclopropane ring, a 1,2-substituted cyclobutane ring, and a 2-butene residue. In each case, the cis/trans-isomeric pair was synthesized. Cis-monounsaturation(s) was also introduced at the outer butane segment(s) of BE-4-4-4. The two possible cis-dienes and a cis-triene formally derived from the tetraazaeicosane skeleton of BE-4-4-4 were also prepared. Four cultured human prostate cancer cell lines (LnCap, DU145, DuPro, and PC-3) were treated with the new tetramines to examine their effects on cell growth with a MTT assay. One representative cell line (DuPro) was selected to further study the cellular uptake of the novel tetramines, their effects on intracellular polyamine pools, and their cytotoxicity. All tetramines entered the cells, reduced cellular putrescine and spermidine pools while exerting only a small effect on the spermine pool, inhibited cell growth, and killed 2-3 logs of cells after 6 days of treatment at 10 microM. Four new tetramines, the two cyclopropyl isomers, the trans-cyclobutyl isomer, and the (5Z)-tetraazaeicosene, were more cytotoxic than their saturated counterpart (BE-4-4-4). Their cytotoxicity, however, could not be correlated either with their cellular uptake or with their ability to deplete intracellular polyamine pools. We attribute their cytotoxicity to their specific molecular structures. The cytotoxicity was markedly reduced when the central butane segment was deprived of its rotational freedom by replacing it with a double bond. Introduction of a triple bond or a benzene-1,2-dimethyl residue at the central segment of the polyamine chain, led to complete loss of biological activity. The conformationally restricted alicyclic derivatives were not only more cytotoxic than was the freely rotating BE-4-4-4 by several orders of magnitude but also had much lower systemic toxicities than the latter. Thus, we obtained new tetramines with a wider therapeutic window than BE-4-4-4.


Assuntos
Antineoplásicos/síntese química , Espermina/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Neoplasias da Próstata , Espermina/análogos & derivados , Espermina/química , Espermina/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
5.
J Med Chem ; 44(3): 404-17, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11462980

RESUMO

From the results of our previous physicochemical studies of polyamine-nucleic acid interactions, we concluded that polyamine analogues in cisoidal conformation are capable of wrapping around the major groove of the double helix, of displacing natural polyamines from their nucleic acid binding sites, and of inhibiting cell division. On the basis of this hypothesis, nine unsaturated pentamines, formally derived from the cytotoxic pentamine 3,8,13,18,23-pentaazapentacosane (BE-4-4-4-4), were prepared in an attempt to increase antineoplastic activity. Cis-double bonds were introduced in all possible sites in the saturated pentaazapentacosane structure of BE-4-4-4-4 to yield two pentacosenes, four pentacosadienes, two pentacosatrienes, and one pentacosatetraene. Cis-double bonds should also provide good targets for mixed-function oxidases that might eliminate the accumulation of unsaturated pentamines in serum, thereby reducing systemic toxicity in animals. We determined the ability of these new pentamines to inhibit growth in four cultured human prostate cancer cell lines (LnCap, DU145, PC-3, and DuPro) using a MTT assay. LnCap and DU145 cells were very sensitive, PC-3 cells were relatively resistant, and DuPro cells were intermediate in sensitivity to most of these synthetic pentamines. In all cell lines, pentamines that had unsaturation(s) at the end of the chain showed the highest cell growth inhibitory effects. The cellular uptake, effects on cellular polyamine levels, and cytotoxicity of these pentamines on one representative prostate cancer cell line (DuPro) were further examined with a colony-forming efficiency (CFE) assay. The pentamines with unsaturation(s) at the end of the chain were once again the most cytotoxic among both the saturated (BE-4-4-4-4) and unsaturated analogues. Appreciable amounts of all pentamines entered DuPro cells and depleted cellular polyamine pools by day 6 of treatment. For most pentamines, however, cell growth inhibitory and cytotoxic effects could not be directly correlated either with their cellular uptake or with their ability to deplete cellular polyamine pools. The position of the double bonds in the aliphatic backbone seems to be the most important determinant of cytotoxicity. For some pentamines, however, depletion of cellular polyamines may add to their efficacy.


Assuntos
Antineoplásicos/síntese química , Espermina/análogos & derivados , Espermina/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Neoplasias da Próstata , Espermina/química , Espermina/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
6.
Indian Heart J ; 53(4): 508-10, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11759947

RESUMO

Acute reversible left ventricular dysfunction due to myocardial stunning is a known phenomenon during acute myocardial infarction, coronary angiography, coronary angioplasty or after coronary artery bypass surgery. We report a rare case of acute reversible dysfunction of the myocardium as a complication of general anesthesia in a patient with normal coronary arteries. This is a potentially fatal complication unless recognized early and treated aggressively.


Assuntos
Anestesia Geral/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/terapia , Doença Aguda , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia , Disfunção Ventricular Esquerda/diagnóstico por imagem
7.
Antimicrob Agents Chemother ; 44(10): 2891-4, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10991882

RESUMO

Cryptosporidium parvum infection of T-cell receptor alpha (TCR-alpha)-deficient mice results in a persistent infection. In this study, treatment with a polyamine analogue (SL-11047) prevented C. parvum infection in suckling TCR-alpha-deficient mice and cleared an existing infection in older mice. Treatment with putrescine, while capable of preventing infection, did not clear C. parvum from previously infected mice. These findings provide further evidence that polyamine metabolic pathways are targets for new anticryptosporidial chemotherapeutic agents.


Assuntos
Antiprotozoários/uso terapêutico , Criptosporidiose/tratamento farmacológico , Cryptosporidium parvum , Genes Codificadores da Cadeia alfa de Receptores de Linfócitos T/genética , Espermina/análogos & derivados , Animais , Ceco/parasitologia , Ceco/patologia , Criptosporidiose/parasitologia , Criptosporidiose/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Putrescina/farmacologia , Espermina/uso terapêutico
8.
Clin Pediatr (Phila) ; 38(2): 87-92, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10047941

RESUMO

The pulse oximetry saturation values and the average percentage of time that normal newborns spend at different saturation ranges in the first 6 hours of life were determined in a cross-sectional study. Pulse oximetry saturation values were measured for a single 20-minute period in 101 normal term newborns between 20 minutes and 6 hours of age. The 25th percentile saturation values in the first postnatal hour (range 91%-100%) were lower than those from the second postnatal hour (range 96%-100%) onward. There was no significant difference between the 50th percentile (range 96%-100%) and the 75th percentile (range 97%-100%) saturation values in all postnatal hours. The babies spent a majority of time with saturations > or = 96% in all postnatal hours. A newborn more than 20 minutes old who does not achieve a pulse oximetry saturation value of 96% over several minutes of observation may need evaluation or continuous monitoring.


Assuntos
Oximetria , Estudos Transversais , Humanos , Recém-Nascido
9.
J Med Chem ; 41(24): 4723-32, 1998 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-9822543

RESUMO

Eight analogues of 1N,12N-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1, 2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained (three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). 1N,12N-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the 4N, 9N-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1, 2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.


Assuntos
Antineoplásicos/síntese química , Espermina/análogos & derivados , Espermina/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Espermina/química , Espermina/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
10.
Neuroscience ; 64(1): 193-208, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7708205

RESUMO

Glutamate is considered to be a major excitatory neurotransmitter in the central nervous system. The presence of glutamate-like immunoreactive neurons in the rodent locus coeruleus has been reported previously. In this study we used both immunohistochemical and electrophysiological techniques to answer two major questions: (1) Is there any glutamate-like immunoreactivity in the catecholaminergic coeruleospinal system of the cat? (2) What is the physiological role, if any, of glutamate in descending locus coeruleus control of spinal motoneurons? Following injections of rhodamine-labeled latex microspheres or Fast Blue into the seventh lumbar segment of the spinal cord of the cat, retrogradely labeled cells were found throughout the rostrocaudal extent of the dorsolateral pontine tegmentum. They were primarily observed in the nucleus locus coeruleus and the Kolliker-Fuse nucleus. Some labeled cells were also present in the nucleus subcoeruleus and, to a lesser extent, in the parabrachial nuclei. Data from immunohistochemical studies indicate that 86% of all dorsolateral pontine tegmentum neurons that project to the spinal cord contain glutamate-like immunoreactivity, and 77% co-contain both glutamate- and tyrosine hydroxylase-like immunoreactivity. Electrical stimulation (four pulses of 500 microseconds duration at 500 Hz; intensity = 50-200 microA) of the locus coeruleus, in decerebrate cats, consistently induced lumbar motoneuron discharges recordable ipsilaterally as ventral root responses. These motoneuronal responses were reversibly antagonized following chemical inactivation of noradrenergic locus coeruleus neurons by local infusion of the alpha 2-adrenergic agonist clonidine, suggesting the locus coeruleus neurons to be the main source of evoked ventral root responses. Additionally, the evoked ventral root responses were reversibly reduced by 34.20 +/- 4.45% (mean +/- S.E.M.) upon intraspinal injections of the non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into the ventral horn of seventh lumbar spinal cord segment (three to four injections, 20 nmol in 0.2 microliter of 0.1 M Tris-buffered saline for each injection). Similar volumes of vehicle injections had no significant effect on the locus coeruleus-evoked ventral root responses. These ventral root responses were also partially blocked (62.30 +/- 11.76%) by intravenous administration of the alpha 1-adrenergic receptor antagonist prazosin (20 micrograms/kg). In the light of several anatomical reports of noradrenergic and glutamatergic terminals in close contact with spinal motoneurons, our present findings suggest that the locus coeruleus-evoked ventral root response probably involves the synaptic release of both norepinephrine and glutamate onto lumbar motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Locus Cerúleo/fisiologia , Neurônios Motores/fisiologia , Neurônios/fisiologia , Medula Espinal/fisiologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Gatos , Clonidina/farmacologia , Relação Dose-Resposta a Droga , Ácido Glutâmico , Locus Cerúleo/ultraestrutura , Região Lombossacral , Nervo Fibular/fisiologia , Prazosina/farmacologia
11.
Microsc Res Tech ; 29(3): 219-25, 1994 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-7849326

RESUMO

This paper reviews the anatomical evidence for the presence of glutamate (GLU) in noradrenergic neurons of the nucleus locus coeruleus (LC) and adjacent nuclei in the dorsolateral pontine tegmentum (DLPT) that project to the spinal cord, cerebellum, or cerebral cortex. Additionally, the evidence for the existence of methionine-enkephalin (ENK) in noradrenergic neurons of the DLPT that project to the spinal cord of the cat is reviewed. In these studies, we have combined the retrograde transport of either Fast Blue (FB), rhodamine labeled latex microspheres (MS), or rhodamine labeled dextran and indirect immunofluorescence histochemistry to determine whether the neurons that contain tyrosine hydroxylase (TH) and project to these terminal fields also contain GLU or ENK. The neurons of the cat that project to the spinal cord, cerebellum, and neocortex were observed in the nucleus LC and Kölliker-Fuse (KF) nucleus. They were also present, to a lesser extent, in the nucleus subcoeruleus (SC) and nuclei parabrachialis medialis (PBM) and lateralis (PBL). In the rat the majority of the neurons that project to the neocortex and hippocampus were located in the nucleus LC. Our data revealed a major proportion of these neurons to be immunostained for both GLU and TH (cat, rat), or ENK and TH (cat). Functional implications of such colocalized neurochemicals within individual LC projection neurons are discussed.


Assuntos
Encefalina Metionina/análise , Ácido Glutâmico/análise , Locus Cerúleo/química , Neurônios/química , Norepinefrina/análise , Animais , Gatos , Imunofluorescência , Locus Cerúleo/enzimologia , Locus Cerúleo/ultraestrutura , Microesferas , Neurônios/enzimologia , Neurônios/ultraestrutura , Ponte/química , Ponte/ultraestrutura , Ratos , Rodaminas , Tirosina 3-Mono-Oxigenase/análise
12.
Eur J Pharmacol ; 259(1): 7-13, 1994 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-7957596

RESUMO

Lithium has been extensively used as an antidepressant in the treatment of manic depressive disorders requiring chronic administration. Here, we report a study of the effect of long-term lithium treatment on the activities of membrane adenosine triphosphatases (ATPases) in certain postural muscles of rat. Specifically, Ca(2+)-ATPase, Na+,K(+)-ATPase and Mg(2+)-ATPase activities were measured in the soleus, extensor digitorum longus and plantaris muscles following 6 weeks of treatment with LiCl. Increases were observed in the Na+,K(+)-ATPase activity whereas the Mg(2+)-ATPase activity decreased with prolonged LiCl treatment. The most pronounced effect was a highly significant (P < 0.001) increase in the mitochondrial Ca(2+)-ATPase and Na+,K(+)-ATPase activity to almost 50-100% above the control. The increases in the mitochondrial Ca(2+)-ATPase activity of extensor digitorum longus and plantaris were 70% and 100%, respectively. The corresponding increases in the Na+,K(+)-ATPase activity were 127%, 99% and 87% for soleus, extensor digitorum longus and plantaris, respectively. Irrespective of the differences in the fiber pattern and physiological function, all three muscles responded in a similar way to Li+. The changes in the membrane ATPases reflect a deranged ATP turnover, thus affecting the overall energy state of the animal. Based on these results, we hypothesize that Li+ produces its effects by interfering with cation transport processes. Since Li+ affects the neural excitability of the cell it is suggested that the stimulation of the ATPases may be important in the psychotropic properties of the ion.


Assuntos
Adenosina Trifosfatases/metabolismo , Cloreto de Lítio/farmacologia , Músculos/enzimologia , Animais , ATPase de Ca(2+) e Mg(2+)/metabolismo , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Membrana Celular/enzimologia , Masculino , Mitocôndrias Musculares/enzimologia , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo
13.
Arch Ital Biol ; 132(2): 61-72, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7519004

RESUMO

The present study utilizes a combined retrograde transport of Fast Blue (or rhodamine-labeled latex microspheres) and simultaneous immunofluorescence technique to demonstrate directly the coexistence of serotonin and methionine enkephalin in bulbospinal neurons of the cat. The bulbospinal neurons that immunostained for both serotonin and enkephalin were observed, without any distinct somatotopic organization, in the nuclei raphe pallidus, obscurus and magnus. They were also observed in the nucleus reticularis magnocellularis and the ventrolateral medulla (cell group B1/3). Among the bulbospinal neurons encountered within individual 5-HT-rich medullary nuclei, high proportions of these neurons co-containing serotonin and methionine enkephalin were evidenced in the nucleus raphe obscurus (64%) and nucleus raphe pallidus (56%), less so in cell group B1/3 (41%), nucleus raphe magnus (39%), and the nucleus reticularis magnocellularis (29%). Physiological significance of such a morphological substrate is discussed.


Assuntos
Encefalina Metionina/análise , Neurônios Motores/química , Núcleos da Rafe/fisiologia , Serotonina/análise , Medula Espinal/citologia , Amidinas , Animais , Transporte Axonal , Biomarcadores , Mapeamento Encefálico , Tronco Encefálico/química , Tronco Encefálico/citologia , Gatos , Vias Eferentes , Feminino , Imunofluorescência , Masculino , Microesferas , Núcleos da Rafe/citologia , Rodaminas , Medula Espinal/química
14.
Talanta ; 41(2): 237-41, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18965914

RESUMO

A simple and sensitive spectrophotometric method for the determination of cerium(IV) in an aqueous medium is reported. The metal ion formed a 1:1 orange-red coloured complex with 2,4-dihydroxy benzophenone benzoic hydrazone (DHBPBH) at pH 10.0 showing an absorption maximum at 400 nm. The molar absorptivity and Sandell's sensitivity of the method are found to be 2.0 x 10(4)1/mol/cm and 0.007 mug/cm(2), respectively. Beer's law is obeyed in the range 0.7-7.0 mug/ml. Titanium, vanadium and molybdenum do not interfere. The extent of interferences by other ions is presented. The method is applied for the determination of cerium in simulated rock samples.

15.
Brain Res Bull ; 35(5-6): 423-32, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7859099

RESUMO

This article reviews evidence for a direct noradrenergic projection from the dorsolateral pontine tegmentum (DLPT) to spinal motoneurons. The existence of this direct pathway was first inferred by the observation that antidromically evoked responses occur in single cells in the locus coeruleus (LC), a region within the DLPT, following electrical stimulation of the ventral horn of the lumbar spinal cord of the cat. We subsequently confirmed that there is a direct noradrenergic pathway from the LC and adjacent regions of the DLPT to the lumbar ventral horn using anatomical studies that combined retrograde tracing with immunohistochemical identification of neurotransmitters. These anatomical studies further revealed that many of the noradrenergic neurons in the LC and adjacent regions of the DLPT of the cat that send projections to the spinal cord ventral horn also contain colocalized glutamate (Glu) or enkephalin (ENK). Recent studies from our laboratory suggest that Glu and ENK may function as cotransmitters with norepinephrine (NE) in the descending pathway from the DLPT. Electrical stimulation of the LC evokes a depolarizing response in spinal motoneurons that is only partially blocked by alpha 1 adrenergic antagonists. In addition, NE mimicks only the slowly developing and not the fast component of LC-evoked depolarization. Furthermore, the depolarization evoked by LC stimulation is accompanied by a decrease in membrane resistance, whereas that evoked by NE is accompanied by an increased resistance. That Glu may be a second neurotransmitter involved in LC excitation of motoneurons is supported by our observation that the excitatory response evoked in spinal cord ventral roots by electrical stimulation of the LC is attenuated by a non-N-methyl-D-aspartate glutamatergic antagonist. ENK may participate as a cotransmitter with NE to mediate LC effects on lumbar monosynaptic reflex (MSR) amplitude. Electrical stimulation of the LC has a biphasic effect on MSR amplitude, facilitation followed by inhibition. Adrenergic antagonists block only the facilitator effect of LC stimulation on MSR amplitude, whereas the ENK antagonist naloxone reverses the inhibition. The chemical heterogeneity of the cat DLPT system and the differential responses of motoneurons to the individual cotransmitters help to explain the diversity of postsynaptic potentials that occur following LC stimuli.


Assuntos
Locus Cerúleo/fisiologia , Neurônios Motores/fisiologia , Neurotransmissores/fisiologia , Ponte/fisiologia , Animais , Gatos , Locus Cerúleo/citologia , Vias Neurais/citologia , Vias Neurais/fisiologia , Ponte/citologia
16.
Brain Res Bull ; 35(5-6): 485-91, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7859106

RESUMO

The effects of intrahippocampally injected beta-amyloid protein (beta-AP) on glutamate- (Glu) and tyrosine hydroxylase (TH)-like immunoreactivities in the neurons of the locus coeruleus (LC) were studied in rats. A synthetic peptide or the vehicle alone was injected into the hippocampus as controls. All injections were made once a week (two or three injections; 3 nmol in 2 microliters of distilled water). Fluorescent microspheres (either alone or with one of the peptides) were also injected into the hippocampus to identify coeruleo-hippocampal neurons. The results revealed cell loss in the hippocampus at the site near beta-AP or control peptide deposition. Furthermore, in beta-AP/microsphere injected animals, only 22.4% and 49.6% of hippocampal projection neurons contained Glu and TH, respectively, compared to 88.4% and 85.3% in the animals that received control peptide with microspheres. Our results suggest that beta-AP has an effect on noradrenergic cells whose axons project to the hippocampus. These effects may contribute to the TH cell loss in the LC of Alzheimer's brains.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/fisiologia , Locus Cerúleo/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Peptídeos beta-Amiloides/administração & dosagem , Animais , Hipocampo/efeitos dos fármacos , Imuno-Histoquímica , Injeções , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/enzimologia , Masculino , Vias Neurais/citologia , Vias Neurais/fisiologia , Ratos , Ratos Sprague-Dawley
17.
Brain Res Bull ; 35(5-6): 505-12, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7859108

RESUMO

This study distinguished three types of immunolabeled neurons in nucleus locus coeruleus (LC) of the rat and mouse: cells single labeled either for tyrosine hydroxylase-like immunoreactivity (TH-LI) or glutamate (Glu)-LI, and those double labeled for both antigens. Although the double labeled neurons tend to be located in the middle and ventral thirds of the rat LC nucleus, throughout its rostrocaudal extent, such feature was not apparent in the mouse. Quantitatively a majority of neurons cocontaining TH- and Glu-LI were commonly observed in the rat (62%) and mouse (77%) LC. Additional studies utilizing the combined retrograde and immunohistochemical labeling revealed that such a high incidence of coexistence of the TH- and Glu-LI was also represented by coeruleocortical neurons in the rat (69% and 75% of all ipsilateral and contralateral projection cells, respectively). A possible role of coeruleocortical neurons involvement in Glu- and norepinephrine-mediated target neuron dysfunction is discussed.


Assuntos
Ácido Glutâmico/metabolismo , Locus Cerúleo/metabolismo , Neurônios/metabolismo , Norepinefrina/fisiologia , Animais , Imunofluorescência , Imuno-Histoquímica , Locus Cerúleo/citologia , Masculino , Camundongos , Camundongos Mutantes Neurológicos , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismo
18.
Neurosci Lett ; 164(1-2): 117-20, 1993 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-7908727

RESUMO

The lateral reticular nucleus (LRN) and afferents to the cerebellum are known to contain glutamate-like immunoreactive (Glu-LI) neurons and axons, respectively. However, such a direct link between the Glu-LI LRN neurons and the cerebellar vermal cortex has not been identified. In this study we have combined the retrograde transport of rhodamine labeled latex microspheres and immunofluorescence histochemistry to determine the locations of Glu-LI neurons of the kitten reticulocerebellar system. Following microsphere injections into the cerebellar vermis (lobules V-VII), retrogradely labeled neurons were encountered throughout the rostrocaudal extent of the LRN. More than 60% (n = 3 kittens) of these retrogradely labeled neurons were immunostained for Glu-like immunoreactivity. Our observations of the Glu-like immunoreactivity in a majority of the reticulocerebellar neurons suggest that Glu in these neurons may participate in LRN's control of target neuron activities in the cerebellar vermis of kittens.


Assuntos
Núcleos Cerebelares/metabolismo , Glutamatos/metabolismo , Neurônios/metabolismo , Formação Reticular/metabolismo , Animais , Gatos , Núcleos Cerebelares/citologia , Feminino , Imunofluorescência , Ácido Glutâmico , Imuno-Histoquímica , Masculino , Microesferas , Vias Neurais/citologia , Vias Neurais/metabolismo , Formação Reticular/citologia
19.
Talanta ; 39(10): 1383-5, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18965545

RESUMO

A sensitive spectrophotometric method is developed for the determination of manganese in aqueous medium. The metal ion forms a yellowish brown coloured complex with resacetophenone oxime (RPO) in ammonium chloride and ammonium hydroxide buffer of pH 10.5. The 1:1 complex shows maximum absorbance at 380 nm with a Beer's law range of 0.09-1.7 ppm. The molar absorptivity and the Sandell sensitivity are found as 2.5 x 10(4) l.mole(-1).cm(-1) and 0.002 mug/cm(2), respectively. The stability constant of the complex calculated by Job's method is 7.5 x 10(5). The interfering effects of various cations and anions are studied. The present method is applied to the determination of manganese in some steel and alloy samples.

20.
Mol Cell Biochem ; 111(1-2): 109-15, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1588932

RESUMO

Exhaustive endurance exercise in adult female albino rats (C-Ex) increased the generation of free radicals (R.) in the myocardium, probably through enhanced oxidative mechanisms. Free radical mediated lipid peroxidation measured in the form of tissue MDA content also increased in C-Ex animals, suggesting the exercise-induced oxidative stress in these animals. Dietary supplementation of Vit E, for a period of 60 days significantly increased Vit E incorporation into the serum and myocardium, more so in the myocardium. Vit E supplementation to exercising animals completely abolished the radical production. The protection of Vit E against oxidative stress appears to be not mediated through the improvement of antioxidant mechanisms by enzymes like SOD, catalase and Se-GSH Px. However the non Se-GSH Px, the enzyme involved in the reduction of endoperoxides increased significantly in control and Vit E fed animals in response to exercise. The protection of Vit E against exercise-induced oxidative stress was correlated with its multivarious activities like a) scavenger of free radicals; b) inhibition of lipoxygenases; and c) reduction of peroxides in association with lipoxygenases. These studies indicate that dietary supplementation of Vit E protects the animals from the possible oxidative damages of endurance exercise.


Assuntos
Radicais Livres/metabolismo , Coração/fisiologia , Oxigênio/metabolismo , Esforço Físico/fisiologia , Estresse Fisiológico/fisiopatologia , Vitamina E/farmacologia , Animais , Peso Corporal , Feminino , Alimentos Fortificados , Peroxidação de Lipídeos/fisiologia , Miocárdio/metabolismo , Tamanho do Órgão , Ratos , Ratos Endogâmicos , Estresse Fisiológico/metabolismo , Superóxido Dismutase/metabolismo , Vitamina E/metabolismo , Xantina Oxidase/metabolismo
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