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1.
World J Urol ; 39(9): 3657-3663, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33758960

RESUMO

PURPOSE: To evaluate the learning curve of the simplified fluoroscopic biplanar (0-90º) puncture technique for percutaneous nephrolithotomy. METHODS: We prospectively evaluated patients with renal stones treated with percutaneous nephrolithotomy by a single institution's fellows employing the simplified bi-planar (0-90º) fluoroscopic puncture technique for renal access. The learning curve was assessed with the fluoroscopic screening time and the percutaneous renal puncture time. Data obtained were compared to a subset of patients operated by a senior surgeon. RESULTS: Eighty-nine patients were included in the study. Forty patients were operated by fellow-1, 39 by fellow-2, and 10 patients by the senior surgeon. Demographic data of all patients between groups were homogeneous, with no difference in gender (p = 0.432), age (p = 0.92), stone volume (p = 0.78), puncture laterality (p = 0.755), and body mass index (p = 0.365). The mean puncture time was 7.5, 4, and 3.1 min for fellow-1, fellow-2, and expert, respectively. The mean fluoroscopic screening time for the puncture was 10, 11, and 5.1 s for fellow-1, fellow-2, and the expert, respectively. Stone cases, both fellows needed to complete 10 procedures to match the senior surgeon in the mean puncture time (p = 0.046); meanwhile, the fluoroscopic screening time was equal even before to complete 10 procedures. CONCLUSION: This study suggests that with the simplified biplanar (0-90º) puncture technique, the fluoroscopic screening time used in the learning process is brief. A novice fellow could require to complete ten cases to flatten the learning curve treating complex stone cases, and a flat learning curve is seen since the beginning when treating simple renal stones.


Assuntos
Fluoroscopia/métodos , Cálculos Renais/cirurgia , Curva de Aprendizado , Nefrolitotomia Percutânea/métodos , Punções/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Genome ; 55(2): 105-17, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22272977

RESUMO

Great genome size (GS) variations described in desert-specialist octodontid rodents include diploid species ( Octomys mimax and Octodontomys gliroides ) and putative tetraploid species ( Tympanoctomys barrerae and Pipanacoctomys aureus ). Because of its high DNA content, elevated chromosome number, and gigas effect, the genome of T. barrerae is claimed to have resulted from tetraploidy. Alternatively, the origin of its GS has been attributed to the accumulation of repetitive sequences. To better characterize the extent and origin of these repetitive DNA, self-genomic in situ hybridization (self-GISH), whole-comparative genomic hybridization (W-CGH), and conventional GISH were conducted in mitotic and meiotic chromosomes. Self-GISH on T. barrerae mitotic plates together with comparative self-GISH (using its closest relatives) discriminate a pericentromeric and a telomeric DNA fraction. As most of the repetitive sequences are pericentromeric, it seems that the large GS of T. barrerae is not due to highly repeated sequences accumulated along chromosomes arms. W-CGH using red-labeled P. aureus DNA and green-labeled O. mimax DNA simultaneously on chromosomes of T. barrerae revealed a yellow-orange fluorescence over a repetitive fraction of the karyotype. However, distinctive red-only fluorescent signals were also detected at some centromeres and telomeres, indicating closer homology with the DNA sequences of P. aureus. Conventional GISH using an excess of blocking DNA from either P. aureus or O. mimax labeled only a fraction of the T. barrerae genome, indicating its double genome composition. These data point to a hybrid nature of the T. barrerae karyotype, suggesting a hybridization event in the origin of this species.


Assuntos
Evolução Biológica , Tamanho do Genoma/genética , Hibridização Genética , Sequências Repetitivas de Ácido Nucleico/genética , Roedores/genética , Animais , Hibridização Genômica Comparativa , Análise Citogenética , Hibridização In Situ , Especificidade da Espécie
3.
Neurosci Lett ; 491(1): 18-22, 2011 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-21215291

RESUMO

A spinal cord hemi-section with a homologous transplant of medullar tissue at the level of C5-C6 and preservation of the anterior spinal artery was used to evaluate the histological characteristics such as quantity and quality of axons, myelin index and blood vessels after quadriplegia recovery. Vascular changes after spinal injury results in severe endothelial damage, axonal edema, neuronal necrosis and demyelinization as well as cysts and infarction. Preservation of the anterior spinal artery has demonstrated clinical recuperation; therefore, in addition to the lesion we included a homologous transplant to visualize changes at a cellular level. Two groups of dogs (hemi-section and transplant) went through a traumatic spinal cord hemi-section of 50% at the level of C5-C6. The transplant group formed by animals which simultaneously had 4 mm of spinal cord removed and the equal amount substituted from a donor animal at the level of C5-C6 corresponding to the half right side; both preserving the anterior spinal artery. Histological evaluation of all groups took place at days 3 (acute) and 28 (chronic) post-operation. Changes of degeneration and axonal regeneration were found in the hemi-section and transplant groups at acute and chronic time, as well as same quadriplegia recovery at chronic time in the hemi-section and transplant groups which closely related to mechanisms which participate in regeneration and functional recuperation due to the preservation of the anterior spinal artery and presence of new blood vessels.


Assuntos
Regeneração Nervosa/fisiologia , Quadriplegia/cirurgia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/cirurgia , Medula Espinal/transplante , Animais , Modelos Animais de Doenças , Cães , Masculino , Quadriplegia/fisiopatologia , Medula Espinal/irrigação sanguínea , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Transplante de Tecidos/métodos
4.
Neurosci Lett ; 403(3): 233-8, 2006 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-16782274

RESUMO

Excitotoxic neuronal death occurs through the activation of NMDA and non-NMDA glutamatergic receptors in the CNS. Glutamate also induces strong activation of p38 and indeed, cell death can be prevented by inhibitors of the p38 pathway. Furthermore, intracellular signals generated by AMPA receptors activate the stress sensitive MAP kinases implicated in apoptotic neuronal death, such as JNK and p38. To investigate the relationship between these elements, we have used immunohistochemistry to analyze the expression of GluR2 in the cerebral cortex of postnatal rats (postnatal Day [PD] 8 and 14) after administering them with monosodium glutamate (MSG; 4 mg/g body weight on PD1, 3, 5, and 7). Similarly, the expression of REST, Fas-L and Bcl-2 mRNA transcripts in animals exposed to a p38 inhibitor, SB203580 (0.42 microg/g body weight, administered subcutaneously) was determined by reverse transcriptase-PCR. The enhanced GluR2-expression in the cerebral cortex at PD8 and the down regulation of this receptor at PD14 was correlated with neuronal damage induced by excitotoxicity. In addition, the enhanced expression of REST at PD8 and PD14 suggests that the induction of REST transcription contributes to glutamate-induced excitotoxic neurodegeneration, possibly by modulating GluR2 expression. Fas-L and Bcl-2 over expression at PD8 and their subsequent down regulation at PD14 also suggests that Fas-L could be the direct effector of apoptosis in the cerebral cortex. On the other hand, the presence of Bcl-2 at PD8 could attenuate certain survival signals in neurons under these neurotoxic conditions. Thus, a change in glutamate receptor composition, and enhanced Fas-L and Bcl-2 expression, coupled with activation of the p38/SAPK pathway appear to be events involved in the neuronal apoptosis induced under neurotoxic conditions.


Assuntos
Córtex Cerebral/metabolismo , Ácido Glutâmico/fisiologia , Neurônios/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Animais Recém-Nascidos , Morte Celular , Ativação Enzimática , Proteína Ligante Fas , Feminino , Ácido Glutâmico/toxicidade , Imuno-Histoquímica , Glicoproteínas de Membrana/biossíntese , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Wistar , Receptores de AMPA/biossíntese , Glutamato de Sódio/toxicidade , Fatores de Necrose Tumoral/biossíntese , Receptor fas/biossíntese
5.
J Natl Med Assoc ; 93(6): 201-7, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11446391

RESUMO

Human milk provides newborns with several physiologically important proteins not found in cow's milk, including bile salt-stimulated lipase (BSSL) that compensates for the reduced lipolytic capability of the newborn intestine. We analyzed the milk of two ethnically distinct groups of women in northern Nigeria and Nepal. The milk of the Nepalese women (n = 36) contained slightly more BSSL activity (mean, 38.8 units/mL) than that of Fulani (n = 48; mean, 30.3 units/mL) and Kanuri (n = 90; mean 27.6 units/mL) women in Nigeria. There was also a weak positive correlation between the BSSL content of the milk and the body mass index (BMI) of the lactating women. The BSSL activity declined with the length of lactation for both well-nourished and undernourished women. The presence of a heat-stable inhibitor of BSSL in cow's milk was also demonstrated. This finding, along with the decrease in BSSL activity postgestation, could be of significance to populations such as the Fulani of the western Sahel who supplement the diets of their infants with unpasteurized cow's milk.


Assuntos
Etnicidade , Leite Humano/enzimologia , Esterol Esterase/análise , Animais , Índice de Massa Corporal , Aleitamento Materno , Bovinos , Estudos Transversais , Inibidores Enzimáticos/análise , Feminino , Humanos , Leite/química , Nepal/etnologia , Nigéria/etnologia
6.
Biol Neonate ; 79(2): 122-30, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11223654

RESUMO

Gasping is an important mechanism for survival that appears to be developmentally modulated by the glutamate-nitric oxide (NO) pathway. However, the temporal characteristics of NO brain tissue levels during gasping are unknown. We hypothesized that during anoxia-induced gasping, the gasping frequency would be closely correlated with caudal brainstem tissue NO concentrations in developing rats. Brainstem and cortical tissue NO levels were measured during anoxia using a voltammetric electrode in adult rats and 5-day-old pups during control conditions and following pretreatment with the NMDA receptor antagonist MK-801 (1 mg/kg) or the neuronal NO synthase inhibitor 7-nitro-indazole (7-NI; 100 mg/kg). In young animals, NO tissue levels followed a triphasic trajectory coincident with gasp frequency which was markedly altered by MK-801 and 7-NI, albeit with preservation of gasp frequency-NO tissue level relationships. In adult rats, 40-fold higher NO tissue levels occurred and followed a monophasic trajectory coincident with gasp patterning. In the cortex, monophasic increases in NO levels occurred at all ages. We conclude that anoxia-induced gasping neurogenesis is modulated via NMDA-NO mechanisms in the developing rat. We postulate that higher NO brainstem concentrations may favor early autoresuscitation, but limit anoxic tolerance.


Assuntos
Envelhecimento/metabolismo , Animais Recém-Nascidos/metabolismo , Tronco Encefálico/metabolismo , Hipóxia/complicações , Hipóxia/metabolismo , Óxido Nítrico/metabolismo , Transtornos Respiratórios/fisiopatologia , Respiração , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Maleato de Dizocilpina/farmacologia , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Indazóis/farmacologia , Neocórtex/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Transtornos Respiratórios/etiologia
8.
J Appl Physiol (1985) ; 86(5): 1478-82, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10233107

RESUMO

Short-term potentiation of ventilation (VSTP) may be observed in healthy subjects on sudden termination of an hypoxic stimulus. We hypothesized that the level of hypoxia preceding normoxia would modify the duration and magnitude of the ensuing ventilatory decay. Ten healthy adults were studied on two different occasions, during which they were randomly exposed to isocapnic 6 or 10% O2 for 60 s and then switched to an isocapnic normoxic gas mixture. Both hypoxic gases induced significant ventilatory responses, and mean peak minute ventilation before the isocapnic normoxic switch was higher in 6% O2 (P < 0.001). The fast time constant of the two-exponential equation representing the best fit for ventilatory decay was unaffected by the magnitude of the hypoxic stimulus. However, the slow time constant, which is considered to represent VSTP, was markedly prolonged in 6% compared with 10% O2 [106.7 +/- 11.3 vs. 38. 2 +/- 6.1 (SD) s, respectively; P < 0.0001]. This result indicates that VSTP is stimulus dependent. We conclude that the magnitude of hypoxia preceding a normoxic transient modifies VSTP characteristics. We speculate that the interdependence function of ventilatory stimulus and short-term potentiation is crucial for preservation of system stability during transitions from high to low ventilatory drives.


Assuntos
Hipóxia/fisiopatologia , Mecânica Respiratória/fisiologia , Adulto , Algoritmos , Dióxido de Carbono/metabolismo , Feminino , Humanos , Masculino , Consumo de Oxigênio , Testes de Função Respiratória
9.
J Med Chem ; 41(20): 3879-87, 1998 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-9748363

RESUMO

Derivatives of the sesquiterpene 8-deoxyhemigossylic acid (2, 3-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthoic acid) were synthesized that contained altered alkyl groups in the 4-position and contained alkyl or aralkyl groups in the 7-position. These substituted dihydroxynaphthoic acids are selective inhibitors of human lactate dehydrogenase-H (LDH-H) and LDH-M and of lactate dehydrogenase from the malarial parasite Plasmodium falciparum (pLDH). All inhibitors are competitive with the binding of NADH. Selectivity for LDH-H, LDH-M, or pLDH is strongly dependent upon the groups that are in the 4- and 7-positions of the dihydroxynaphthoic acid backbone. Dissociation constants as low as 50 nM were observed, with selectivity as high as 400-fold.


Assuntos
Inibidores Enzimáticos/síntese química , L-Lactato Desidrogenase/antagonistas & inibidores , Plasmodium falciparum/enzimologia , Sesquiterpenos/síntese química , Animais , Inibidores Enzimáticos/metabolismo , Humanos , Cinética , Ácido Láctico/metabolismo , NAD/metabolismo , Oxirredução , Ácido Pirúvico/metabolismo , Sesquiterpenos/metabolismo
10.
Respir Physiol ; 112(3): 283-90, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9749951

RESUMO

Protein kinase C (PKC) activation in the nucleus tractus solitarii (NTS) is critical for mounting an appropriate hypoxic ventilatory response (HVR). Furthermore, hypoxia elicits translocation of both Ca2+-dependent and Ca2+-independent PKC isoforms in the NTS. However, the relative functional contribution of such PKC isoforms in mediating HVR is unclear. To study these issues, chronically instrumented adult Sprague-Dawley rats underwent hypoxic challenges (10% O2 balance in N2) following dorsocaudal brainstem microinjections of the selective Ca2+-dependent PKC inhibitor Gö 6976 (10 mmol in 1 microl). Compared with vehicle, Gö 6976 did not modify normoxic ventilation but maximally attenuated HVR by 38.4 +/- 6.7% (n = 9; P < 0.01), with similar contributions from tidal volume and respiratory frequency. In seven additional animals, when the non Ca2+-selective PKC blocker BIM I was concurrently microinjected with Gö 6976, further reductions in peak ventilatory responses to hypoxia occurred (P < 0.04). When BIM V, the inactive analog, was microinjected with Gö 6976, the magnitude of HVR attenuation was unchanged (n = 6; Gö 6976 vs. Gö 6976 + BIM V: P = NS). We conclude that in the dorsocaudal brainstem, PKC-mediated components of HVR involve activation of both Ca2+-dependent and Ca2+-independent PKC isoforms.


Assuntos
Tronco Encefálico/fisiologia , Cálcio/fisiologia , Hipóxia/fisiopatologia , Proteína Quinase C/fisiologia , Mecânica Respiratória/fisiologia , Animais , Gasometria , Carbazóis/farmacologia , Inibidores Enzimáticos/farmacologia , Hemodinâmica/efeitos dos fármacos , Indóis/farmacologia , Masculino , Proteína Quinase C/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley
11.
Am J Physiol ; 275(2): R604-11, 1998 08.
Artigo em Inglês | MEDLINE | ID: mdl-9688699

RESUMO

Platelet-activating factor receptor (PAFR) activation is associated with increases in neuronal excitability. We hypothesized that PAF may play a role in cardiorespiratory control. Ventilatory responses to microinjection of a long-acting PAF analog (mc-PAF, 1 microg in 1 microl) within the dorsocaudal brain stem were measured in unrestrained adult rats. mc-PAF elicited significant minute ventilation (VE) enhancements that were primarily due to tidal volume increases and were accompanied by respiratory alkalosis, heart rate increase, and reduction of arterial blood pressure. Such cardiovascular and respiratory effects did not occur after administration of either vehicle or the inactive analog lyso-PAF. The effect was blocked when animals were coadministered the presynaptic PAFR antagonist BN-52021 or recombinant PAF acetyl hydrolase. To determine the relative contribution of PAF to hypercapnic and hypoxic ventilation, microinjections were performed in additional animals with either vehicle (CO, 1 microl) or with 5 microg in 1 microl of BN-52021. Hypercapnic challenges with 5% CO2 were unaffected by BN-52021. In contrast, although 10% O2 breathing increased VE from 120.4 +/- 7.5 to 204.6 +/- 11.4 ml/min in CO, after BN-52021, VE increased only from 118.7 +/- 6.9 to 137.3 +/- 8. 9 ml/min (CO vs. BN-52021, P < 0.001). We conclude that PAFR activation in the dorsocaudal brain stem exerts significant cardioventilatory effects during normoxia and appears to play an important modulatory role in the VE response to hypoxia in conscious rats.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Tronco Encefálico/fisiologia , Diterpenos , Frequência Cardíaca/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Respiração/efeitos dos fármacos , 1-Alquil-2-acetilglicerofosfocolina Esterase , Animais , Pressão Sanguínea/fisiologia , Tronco Encefálico/efeitos dos fármacos , Dióxido de Carbono/sangue , Preparações de Ação Retardada , Ginkgolídeos , Frequência Cardíaca/fisiologia , Lactonas/farmacologia , Masculino , Microinjeções , Oxigênio/sangue , Pressão Parcial , Fosfolipases A/metabolismo , Fator de Ativação de Plaquetas/administração & dosagem , Fator de Ativação de Plaquetas/análogos & derivados , Fator de Ativação de Plaquetas/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Respiração/fisiologia , Volume de Ventilação Pulmonar/efeitos dos fármacos
12.
Am J Dermatopathol ; 20(3): 242-5, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9650695

RESUMO

It is widely accepted that a histopathologic differentiation between localized scleroderma (LS) and systemic scleroderma (SS) is not always possible. With the objective of identifying differentiating histopathological features between them, 32 cases of LS and 19 cases of SS were reviewed. Histological features such as the distribution, composition, and density of the inflammatory cell infiltrate, thickness of the dermis, alterations of dermal collagen, and the presence of calcification were evaluated in each case. On the basis of our observations, LS and SS can be differentiated usually by the distribution and density of the inflammatory infiltrate and by the involvement of the papillary dermis. Inflammatory changes are more prominent in LS than in SS. Sclerosis of the papillary dermis is frequently seen in LS but is absent in SS.


Assuntos
Esclerodermia Localizada/patologia , Escleroderma Sistêmico/patologia , Adolescente , Adulto , Idoso , Biópsia , Calcinose/metabolismo , Criança , Colágeno/metabolismo , Diagnóstico Diferencial , Feminino , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Esclerodermia Localizada/metabolismo , Escleroderma Sistêmico/metabolismo , Pele/química , Pele/patologia
13.
J Appl Physiol (1985) ; 84(6): 1982-90, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9609793

RESUMO

This study aimed to determine the role of protein kinase C (PKC) in signal transduction mechanisms underlying ventilatory regulation in the nucleus tractus solitarii (NTS). Microinjection of phorbol 12-myristate 13-acetate into the commissural NTS of nine chronically instrumented, unrestrained rats elicited significant cardiorespiratory enhancements that lasted for at least 4 h, whereas administration of vehicle (n = 15) or the inactive phorbol ester 4alpha-phorbol 12,13-didecanoate (n = 7) did not elicit minute ventilation (VE) changes. Peak hypoxic VE responses (10% O2-balance N2) were measured in 19 additional animals after NTS microinjection of bisindolylmaleimide (BIM) I, a selective PKC inhibitor (n = 12), BIM V (inactive analog; n = 7), or vehicle (Con; n = 19). In Con, VE increased from 139 +/- 9 to 285 +/- 26 ml/min in room air and hypoxia, respectively, and similar responses occurred after BIM V. BIM I did not affect room air VE but markedly attenuated hypoxia-induced VE increases (128 +/- 12 to 167 +/- 18 ml/min; P < 0. 02 vs. Con and BIM V). When BIM I was microinjected into the cerebellum (n = 4), cortex (n = 4), or spinal cord (n = 4), VE responses were similar to Con. Western blots of subcellular fractions of dorsocaudal brain stem lysates revealed translocation of PKCalpha, beta, gamma, delta, epsilon, and iota isoenzymes during acute hypoxia, and enhanced overall PKC activity was confirmed in the particulate fraction of dorsocaudal brain stem lysates harvested after acute hypoxia. These studies suggest that, in the adult rat, PKC activation in the NTS mediates essential components of the acute hypoxic ventilatory response.


Assuntos
Hipóxia/fisiopatologia , Isoenzimas/fisiologia , Proteína Quinase C/fisiologia , Mecânica Respiratória/fisiologia , Núcleo Solitário/fisiologia , Animais , Gasometria , Western Blotting , Hemodinâmica/efeitos dos fármacos , Hipóxia/enzimologia , Masculino , Microinjeções , Ésteres de Forbol/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
15.
J Appl Physiol (1985) ; 84(3): 853-61, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9480943

RESUMO

N-methyl-D-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (VE) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (VT) decreased while frequency increased, resulting in a modest reduction in VE. Inspiratory time (TI) decreased, whereas expiratory time remained unchanged. The VE responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (VT/TI) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas VT was unaffected. Sodium cyanide doses associated with significant VE increases were 5 and 50 microg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reduced VE during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.


Assuntos
Células Quimiorreceptoras/fisiologia , Neurônios Aferentes/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Gasometria , Corpo Carotídeo/fisiologia , Células Quimiorreceptoras/efeitos dos fármacos , Denervação , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Hipercapnia/fisiopatologia , Masculino , Degeneração Neural/fisiopatologia , Neurônios Aferentes/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Mecânica Respiratória/efeitos dos fármacos , Mecânica Respiratória/fisiologia
16.
Biol Neonate ; 73(4): 264-74, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9551193

RESUMO

Gasping is an important mechanism for survival. Nitric oxide (NO) plays an excitatory role in brainstem regions mediating respiratory responses to hypoxia. We hypothesized that neural structures mediating anoxia-induced gasping would display NO dependency. Two- to 15-day-old rat pups underwent anoxic exposures with 100% N2 in a plethysmograph following administration of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) blocker, L-arginine (L-Arg), a NO precursor, or normal saline. In general, gasp latencies were significantly shorter after L-Arg, and were prolonged with L-NAME. Furthermore, NOS inhibition prolonged gasping duration and reduced gasping frequency at all postnatal ages, although this effect was particularly increased with advancing postnatal age. NADPH-diaphorase staining and Western blots of protein lysates from the lateral tegmental field, the putative neural center underlying gasp generation, revealed progressively increased neuronal NOS abundance with animal maturation. We conclude that anoxia-induced gasping neurogenesis is modulated by NO mechanisms in neonatal pups. We postulate that higher NO brainstem concentrations may favor early autoresuscitation but be detrimental to overall survival during prolonged asphyxia.


Assuntos
Hipóxia/fisiopatologia , Óxido Nítrico/fisiologia , Respiração , Animais , Arginina/farmacologia , Inibidores Enzimáticos/farmacologia , Histocitoquímica , Immunoblotting , NADPH Desidrogenase/análise , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos
17.
J Appl Physiol (1985) ; 84(2): 641-8, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9475876

RESUMO

Although protein kinase C (PKC) is an essential component of multiple neurally mediated events, its role in respiratory control remains undefined. The ventilatory effects of a systemically active PKC inhibitor (Ro-32-0432; 100 mg/kg i.p.) were assessed by whole body plethysmography during normoxia, hypoxia (10% O2), and hyperoxia (100% O2) in unrestrained Sprague-Dawley rats. A sustained expiratory time increase occurred within 8-10 min of injection in room air[mean 44.8 +/- 5.2 (SE) % ], was similar to expiratory time prolongations after Ro-32-0432 administration during 100% O2 (45.5 +/- 8.1%; not significant), and was associated with mild minute ventilation (VE) decreases. Hypercapnic ventilatory responses (5% CO2) remained unchanged after Ro-32-0432. During 10% O2, VE increased from 122.6 +/- 15.6 to 195.7 +/- 10.1 ml/min in vehicle-treated rats (P < 0.001). In contrast, marked attenuation of VE hypoxic responses occurred after Ro-32-0432 [86.2 +/- 6.2 ml/min in room air to 104.1 +/- 7.1 ml/min in 10% O2; pre- vs. post-Ro32-0432, P < 0.001 (analysis of variance)]. Overall, PKC activity was reduced and increases with hypoxia were abolished in the particulate subcellular fraction of brain tissue after Ro-32-0432 treatment, indicating that this compound readily crosses the blood-brain barrier. We conclude that systemic PKC inhibition elicits significant centrally mediated expiratory prolongations and ventilatory reductions as well as blunted ventilatory responses to hypoxia but not to hypercapnia. We postulate that PKC plays an important role in signal transduction pathways within brain regions underlying respiratory control.


Assuntos
Pressão Sanguínea , Frequência Cardíaca , Hipercapnia/fisiopatologia , Hipóxia/fisiopatologia , Proteína Quinase C/antagonistas & inibidores , Ventilação Pulmonar/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipercapnia/enzimologia , Hipóxia/enzimologia , Indóis/farmacologia , Masculino , Neocórtex/efeitos dos fármacos , Neocórtex/enzimologia , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley
18.
Respir Physiol ; 114(3): 213-25, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9926986

RESUMO

Platelet activating factor (PAF) has recently emerged as an important modulator of neuronal excitability by enhancing synaptic glutamate release. Since PAF receptors (PAFR) are ubiquitously distributed in the brain, we hypothesized that PAF may play a role in respiratory control. To examine this issue, hypoxic (10% O2 for 15 min, n = 14) and hypercapnic (5% CO2 for 30 min, n = 6) challenges were performed in chronically-instrumented, unrestrained adult rats following administration of the pre-synaptic PAFR antagonist BN52021 (i.p. 20 mg/kg in 0.5 ml) or vehicle (Veh). In normoxia, BN52021 elicited VT decreases and corresponding f increases such that minute ventilation (VE) was unaffected. During hypercapnia, peak VE increased similarly after both treatments (103+/-18% in BN52021 vs. 94+/-19% in Veh, p-NS). In contrast, significant reductions in the peak hypoxic VE response occurred after BN52021 (42+/-10% vs. 104+/-18% in Veh, P<0.002). BN52021 increased normoxic arterial blood pressure and decreased heart rate. However, hypoxia-induced chronotropic responses were attenuated and depressor responses were enhanced by BN52021. We further examined protein kinase C (PKC) translocation patterns during acute hypoxia after systemic BN52021 administration. Activation of PKC beta and delta was blocked by BN52021, PKC gamma was attenuated, with no effects on PKC alpha, epsilon, theta, iota, mu, and zeta. We conclude that systemic administration of a PAFR antagonist attenuates cardioventilatory recruitment to hypoxia and selectively attenuates activation of PKC in the rat brainstem. We speculate that enhanced regional PAF production and release during hypoxic conditions may contribute important excitatory inputs and signal transduction pathways within neuronal structures underlying cardiovascular and respiratory control.


Assuntos
Diterpenos , Hipóxia/fisiopatologia , Lactonas/farmacologia , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Ventilação Pulmonar/efeitos dos fármacos , Receptores de Superfície Celular , Receptores Acoplados a Proteínas G , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Ginkgolídeos , Masculino , Oxigênio/metabolismo , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Volume de Ventilação Pulmonar/efeitos dos fármacos
19.
Pediatr Res ; 42(6): 872-7, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9396572

RESUMO

After anoxia-induced apnea, gasping remains the last operative mechanism for survival. In developing rats, the gasping response to anoxia exhibits triphasic characteristics. Because anoxia is associated with enhanced release of glutamate, we hypothesized that N-methyl-D-aspartate (NMDA) glutamate receptors may underlie components of the gasping response. Rat pups aged 2 d (n = 50), 5 d (n = 43), 10 d (n = 42), and 15 d (n = 45) underwent anoxic challenges with 100% N2 in a whole body plethysmograph, 30 min after intraperitoneal administration of MK801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate; dizocilpine] (3 mg/kg), a noncompetitive NMDA glutamate receptor channel antagonist, or normal saline. In control pups, after primary apnea onset, a triphasic gasping pattern was apparent at all postnatal ages and included two distinct types of gasps (I and II). In 2- and 5-d MK801-treated animals, phase 1 and type I gasps were absent, leading to marked prolongations of the gasp latency and phase 2, the latter displaying type II gasps only. In addition, phase 3 duration was also prolonged with increased type II gasp frequencies. In contrast, in some 10-d-old (40%) and in all 15-d-old MK801-treated pups, although overall gasping duration was prolonged, the triphasic gasping pattern seen in matched controls was also present. We conclude that NMDA glutamate receptors mediate particular phasic components of the gasping response during early postnatal life but not at later stages of development. We speculate that developmental changes occur in both function and expression of NMDA and other neurotransmitters within brainstem regions underlying the neural substrate for gasp generation.


Assuntos
Apneia/fisiopatologia , Hipóxia Encefálica/fisiopatologia , Receptores de N-Metil-D-Aspartato/fisiologia , Mecânica Respiratória/fisiologia , Análise de Variância , Animais , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ratos , Ratos Sprague-Dawley , Mecânica Respiratória/efeitos dos fármacos
20.
Neurosci Lett ; 232(3): 175-8, 1997 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-9310308

RESUMO

Nitric oxide (NO) is a novel neurotransmitter with important cardiorespiratory functions. To determine the functional topography of NO in a brainstem preparation, extracellular and intrinsic optical signal recordings were simultaneously acquired from a 300 microm coronal brainstem slice at the level of the obex. During control conditions, spontaneous spike activity in the nucleus tractus solitarius (NTS) was 6.2 +/- 1.4 Hz. When the competitive NOS inhibitor, L-NAME, was applied to the bath (1 mM), spike activity either ceased or was markedly reduced in frequency (1.2 +/- 0.7 Hz; n = 7; P < 0.01). The decrease in activity was reversed when the NOS substrate L-arginine (L-Arg) was added to the bath (9.4 +/- 1.8 Hz; P < 0.04). Concurrent intrinsic optical signal imaging of the slice preparation consistently revealed coincident decreases in activity within the NTS with L-NAME (deltaT/T: -2.4 +/- 0.9%; P < 0.02), and increases with L-Arg (+2.1 +/- 0.8%; P < 0.04). Such changes were absent in other regions such as the hypoglossal nuclei or area postrema. We conclude that in this brainstem region, NO modulation of neuronal activity is primarily circumscribed to the NTS.


Assuntos
Neurônios/efeitos dos fármacos , Óxido Nítrico/farmacologia , Núcleo Solitário/efeitos dos fármacos , Animais , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Wistar
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