RESUMO
Zimmermann-Laband syndrome is a very rare disorder characterized by gingival fibromatosis, abnormalities of soft cartilages of the nose and/or ears, hypoplastic or absent nails and terminal phalanges, joint hypermobility, hypatoslenomegaly, mild hirsutism and learning difficulties. Early presentation of Zimmermann-Laband syndrome in a newborn has rarely been described. This paper describes a newborn patient with Zimmermann-Laband syndrome.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Craniofaciais/diagnóstico , Fibromatose Gengival/diagnóstico , Deformidades Congênitas da Mão/diagnóstico , Cartilagem da Orelha/anormalidades , Feminino , Hirsutismo/patologia , Humanos , Recém-Nascido , Unhas Malformadas/patologia , Cartilagens Nasais/anormalidadesRESUMO
Immunosuppressant drugs are currently required by transplant recipients for the remainder of their lives, despite the many adverse effects associated with these therapies. Acute osteoporosis is one such effect, and a reproducible osteoporosis model has been established through the administration of the immunosuppressant drug FK506 in rats. The cause of this osteoporosis has been shown to be abnormal osteoclast proliferation, altering the process of bone remodeling. However, the reasons why FK506 induces osteoclast proliferation and whether this process is mediated by cytokine changes or an increase in bone resorption factors have been unclear. An investigation was therefore conducted focusing on the recent discoveries of osteoclast differentiation factor (ODF) and osteoclastogenesis inhibitory factor (OCIF). These factors led to elucidation of the osteoclast differentiation-maturation mechanism. An osteoporosis model was produced in rats utilizing intramuscular FK506 injection (1 mg/kg) for 28 consecutive days. Trabecular bone resorption was observed inferior to enchondral ossification in the FK506 group, and tartrate resistant acid phosphatase (TRAP) staining revealed a clear increase in osteoclasts at the site of enchondral ossification, relative to the control group. Real-time PCR and in situ hybridization (ISH) demonstrated minimal differences in OCIF expression between control and the treatment groups. However, Real-time PCR revealed clearly increased ODF expression in the treatment group. ODF expression was also shown to be increased in the treatment group using ISH. This was histologically consistent with a region of osteoclast proliferation inferior to enchondral ossification. The results of this study support the hypothesis that FK506-mediated osteoporosis occurs by action of the drug on osteoclasts, promoting expression of ODF messenger ribonucleic acid (mRNA) and thus prompting osteoclast differentiation and maturation.
Assuntos
Proteínas de Transporte/biossíntese , Glicoproteínas/biossíntese , Glicoproteínas de Membrana/biossíntese , Osteoclastos/efeitos dos fármacos , Osteoporose/metabolismo , Receptores Citoplasmáticos e Nucleares/biossíntese , Tacrolimo/farmacologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Imunossupressores/farmacologia , Masculino , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteoprotegerina , Ligante RANK , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose TumoralRESUMO
The role of phospholipids in the glucose-6-phosphatase system, including glucose-6-P phosphohydrolase and glucose-6-P translocase, was studied in rat liver microsomes by using phospholipases C and detergents. In the time course experiments on detergent exposure, the maximal activation of glucose-6-P phosphohydrolase varied according to the nature of the detergent used. On treatment of microsomes with phospholipase C of C. perfringens, the activity of glucose-6-P phosphohydrolase without detergent (i.e. without rupture of translocase activity) was gradually decreased with the progressive hydrolysis of phosphatidylcholine and phosphatidylethanolamine on the microsomal membrane, and was restored by incubation of these microsomes with egg yolk phospholipids. The extent of decrease in this phosphohydrolase activity in the detergent-exposed microsomes (with rupture of translocase activity) also varied depending on the detergent used (Triton X-114 or taurocholate). When 66% of the phosphatidylinositol on the membrane was hydrolyzed by phosphatidylinositol-specific phospholipase C of B. thuringiensis, the inhibition of glucose-6-P phosphohydrolase activity without detergent was very small. Although the inhibition of enzyme activity with detergent was apparently greater than that without detergent, the enzyme activity was stimulated by the breakdown of phosphatidylinositol when the enzyme activity was measured at lower concentration (0.5 mM) of substrate, glucose-6-P. The latency of mannose-6-P phosphohydrolase, a plausible index of microsomal integrity, remained above 70% after the hydrolysis of phosphatidylcholine, phosphatidylethanolamine, or phosphatidylinositol. The results show that the glucose-6-phosphatase system requires microsomal phospholipids for its integrity, suggesting that there exists a close relation between phosphatidylinositol and glucose-6-P translocase.
Assuntos
Glucose-6-Fosfatase/metabolismo , Lipídeos de Membrana/fisiologia , Microssomos Hepáticos/enzimologia , Fosfolipases/farmacologia , Fosfolipídeos/farmacologia , Fosfolipídeos/fisiologia , Fosfolipases Tipo C/farmacologia , Animais , Antiporters , Membranas Intracelulares/análise , Cinética , Masculino , Proteínas de Transporte de Monossacarídeos , Fosfotransferases/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Through kinetic analysis, the relationships between the glucose-6-phosphatase system and constituent phospholipids were studied in rat liver microsomes. When phosphoglycerides such as phosphatidylcholine and phosphatidylethanolamine on the microsomal membrane were hydrolyzed by phospholipase C of C. perfringens, the activities of glucose-6-P phosphohydrolase and glucose-6-P:glucose phosphotransferase both decreased with or without subsequent exposure to taurocholate. In these cases, the Michaelis constants (Km) for glucose-6-P were increased, concomitant with the decrease in the maximal velocities (Vmax) for glucose-6-P hydrolysis. On exposure to taurocholate, the apparent Km for glucose of phosphotransferase was decreased. When phosphatidylinositol was hydrolyzed by phosphatidylinositol-specific phospholipase C of B. thuringiensis, the activities of phosphohydrolase and phosphotransferase were both decreased on exposure to taurocholate. In this case, the value of Vmax of phosphohydrolase was decreased and that of Km for glucose-6-P was slightly decreased, while the apparent Km for glucose of phosphotransferase was increased. Without exposure to detergent, the activities of phosphohydrolase and phosphotransferase both decreased at glucose-6-P concentrations higher than 10 mM. However, at a concentration lower than 1 mM, the activity of phosphohydrolase became higher than that of the control, and Vmax and Km for glucose-6-P were decreased. A similar tendency was also observed in microsomes where membranous phosphatidylinositol was hydrolyzed, when they were treated with DIDS (an anion-transport inhibitor). From these results, it is concluded that the activity of glucose-6-phosphatase is greatly influenced by changes of the phospholipids on the microsomal membrane, and the activity of glucose-6-P translocase is stimulated by the breakdown of phosphatidylinositol.
Assuntos
Glucose-6-Fosfatase/metabolismo , Lipídeos de Membrana/fisiologia , Microssomos Hepáticos/enzimologia , Fosfolipases/farmacologia , Fosfolipídeos/fisiologia , Fosfolipases Tipo C/farmacologia , Animais , Antiporters , Clostridium perfringens/enzimologia , Membranas Intracelulares/fisiologia , Cinética , Masculino , Proteínas de Transporte de Monossacarídeos , Fosfatidilinositóis , Fosfotransferases/metabolismo , Ratos , Ratos Endogâmicos , Especificidade por Substrato , Fosfolipases Tipo C/metabolismoRESUMO
Coxiella burnetii, the Q fever agent, is an obligate intracellular bacterium and survival in phagolysosomes is an important virulence factor. The present study was performed to determine the relationship between its pathogenicity and genes related to its survival in macrophages, i.e. macrophage infectivity potentiator and Q fever agent regulatory sensor-like protein. The sequence similarity was more than 99% among Japanese, European and American strains, and no relationship was found between pathogenicity in guinea pigs and these genes.
Assuntos
Proteínas de Bactérias/genética , Coxiella burnetii/patogenicidade , Genes Bacterianos , Imunofilinas , Proteínas de Membrana/genética , Peptidilprolil Isomerase , Sequência de Bases , Coxiella burnetii/genética , DNA Bacteriano/química , Dados de Sequência MolecularRESUMO
Borrelia afzelii, B. japonica, and 'B. tanukii' isolated from various sources and geographical origins in Japan were characterized by restriction fragment length polymorphism (RFLP) analysis and sequencing analysis of the outer surface protein C (OspC) amplicon. B. afzelii and 'B. tanukii' generated variable RFLP patterns and differences in ospC gene sequence were confirmed. In contrast, 26 isolates of B. japonica generated one OspC RFLP type, and sequence similarity between B. japonica ranged from 96.4 to 99.7%. These finding suggests that B. japonica is unique in comparison with other members of B. burgdorferi sensu lato species with respect to homogeneity of the ospC gene.
Assuntos
Antígenos de Bactérias , Proteínas da Membrana Bacteriana Externa/genética , Borrelia/genética , DNA Bacteriano/genética , Animais , Genes Bacterianos/genética , Japão , Muridae/microbiologia , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Carrapatos/microbiologiaRESUMO
A lignin-related cone extract of pine (Pinus parviflora Sieb et Zucc) (FrVI) or a synthetic lignin (DHP-FA) (175 micrograms/0.1 ml 0.9% NaCl solution) was injected intravenously to SHN mice bearing spontaneous mammary tumours three cycles each with consecutive 3 days of treatment and 4 days of interruption. Activities of both thymidylate synthetase (TS) and thymidine kinase (TK), i.e., DNA synthesizing enzymes in de novo and salvage pathways of pyrimidine metabolism, respectively, were apparently decreased in mammary tumours of FrVI-treated mice compared to those of the control mice bearing tumours without treatment. While the percent change of mammary tumour size during the experiment differed little among groups, both FrVI and DHP-FA prevented tumours from ulceration. Furthermore, the development and growth of preneoplastic mammary hyperplastic alveolar nodules were decreased by the treatments of both agents. They showed no toxicity. All results suggest that these lignin-related compounds, especially FrVI, may be useful as chemopreventive agents, with some improvement of administration method, and/or for employment in combination with any other agents.
Assuntos
Lignina/farmacologia , Neoplasias Mamárias Animais/enzimologia , Extratos Vegetais/farmacologia , Timidina Quinase/antagonistas & inibidores , Timidilato Sintase/antagonistas & inibidores , Animais , Divisão Celular , Feminino , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/patologia , Camundongos , Lesões Pré-Cancerosas/enzimologiaRESUMO
The effects of lombricine extracted and purified from earthworm (Lumbricus terrestris) skin on the growth of palpable sizes (approximately 5 mm) of spontaneous mammary tumours were studied in SHN mice. In Experiment 1, daily subcutaneous injections of lombricine (0.3 mg/0.05 ml olive oil) inhibited markedly the growth of tumours associated with the retardation of the growth of preneoplastic mammary hyperplastic alveolar nodules. In 1H-NMR spectra, the experimental mice had lower serum levels of lactic acid and glucose than the control. On the other hand, urine of the former group contained higher levels of allantoin, creatine and creatinine than that of the latter. In Experiment 2, lombricine given as diet at the concentration of 120 mg/kg also inhibited the growth of tumours, though to a lesser degree than the injection. The treatment had little effect on 1H-NMR spectra of either serum or urine and normal and preneoplastic mammary gland growth. All results indicate that the inhibition by lombricine of the growth of mammary tumours is at least partly due to the maintenance of homeostasis of the body including the regulation of the excess uptake of glucose as a source of energy and nutrition.
Assuntos
Neoplasias Mamárias Animais/tratamento farmacológico , Serina/análogos & derivados , Animais , Peso Corporal , Endometriose/tratamento farmacológico , Feminino , Neoplasias Mamárias Animais/patologia , Camundongos , Oligoquetos/análise , Lesões Pré-Cancerosas/patologia , Serina/uso terapêuticoRESUMO
It is known that hyperplastic alveolar nodule (HAN) is a representative preneoplastic state in mammary glands of mice. We examined the effect of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) on HAN formation in a high mammary tumour strain of SHN virgin mice. Oral administration of UFT for 5 months beginning at one month of age significantly reduced the number of HAN and DNA-synthesizing enzyme activities in the mammary glands. These results indicate that long-term administration of low dose UFT reduces the de novo and salvage synthesis of DNA and suppresses preneoplastic HAN.
Assuntos
Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Tegafur/uso terapêutico , Uracila/uso terapêutico , Animais , Feminino , Crescimento/efeitos dos fármacos , Hiperplasia/tratamento farmacológico , Hiperplasia/enzimologia , Glândulas Mamárias Animais/enzimologia , Neoplasias Mamárias Animais/enzimologia , Camundongos , Camundongos Endogâmicos , Lesões Pré-Cancerosas/enzimologia , Tegafur/administração & dosagem , Timidina Quinase/metabolismo , Timidilato Sintase/metabolismoRESUMO
The purpose of this study was to demonstrate immunohistochemically the localization and distribution of human beta-defensin-2 (HBD-2), a peptide with antimicrobial activity, in oral carcinoma tissues. Tissue samples were embedded in paraffin, and HBD-2 was immunostained by the streptavidin-biotin coupled peroxidase method. Cancer cells in the cornified region of well differentiated squamous cell carcinomas were stained intensely. Stained cancer cells detected by anti-HBD-2 antibody were scattered among the cells of the non-cornified region.
Assuntos
Carcinoma de Células Escamosas/química , Neoplasias Bucais/química , Proteínas de Neoplasias/análise , Peptídeos/análise , beta-Defensinas , Diferenciação Celular , Humanos , Técnicas ImunoenzimáticasRESUMO
The purpose of this study was to demonstrate the immunohistochemical localization and distribution of human alpha- and beta-defensins, peptides with antimicrobial activity, in oral mucoepidermoid carcinoma tissue. Tissue samples were embedded in paraffin and alpha- and beta-defensins were immunostained by the streptavidin-biotin coupled peroxidase method. Cancer cells that constituted the ducts, as well as neutrophils, were positively immunostained with the anti-alpha-defensin antibody (HNPs). On the other hand, epidermoid cells and intermediate cells were intensely stained with the anti-beta-defensin-2 (HBD-2) antibody. Mucous-secreting cells were clearly not immunostained with the anti-HBD-2 antibody. The epithelial hyperplasia region adjacent to the tumor tissues was also positively immunostained with the anti-HBD-2 antibody.
Assuntos
Carcinoma Mucoepidermoide/metabolismo , Neoplasias Bucais/metabolismo , alfa-Defensinas/metabolismo , beta-Defensinas/metabolismo , Carcinoma Mucoepidermoide/imunologia , Humanos , Imuno-Histoquímica , Neoplasias Bucais/imunologia , Inclusão em Parafina , Coloração e Rotulagem/métodos , alfa-Defensinas/imunologia , beta-Defensinas/imunologiaRESUMO
Danazol is an isoxazol derivative of the synthetic steroid, 17 alpha-ethinyltestosterone (ethisterone). Intragastric administration of danazol (10 mg/100 g body weight) markedly reduced plasma levels of luteinizing hormone and testosterone, and the number of S-phase cells labelled with bromodeoxyuridine (BrdU) in the submaxillary glands which were androgen-dependent in adult male rats. These results demonstrated that danazol might show a potency as antiandrogenic and/or antigonadotrophic agent.
Assuntos
Antagonistas de Androgênios/farmacologia , Replicação do DNA/efeitos dos fármacos , Danazol/farmacologia , Glândula Submandibular/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Ratos , Ratos Endogâmicos , Glândula Submandibular/metabolismo , Testosterona/sangueRESUMO
Thymidine kinase (TK) is a key enzyme in the pyrimidine salvage pathway. High TK activity and the existence of cytosolic isozyme have consistently been observed in rapidly proliferating tissues. Oestrogen treatment induces the moderate increase of activities of mitochondrial TK and the fetal type TK isozyme in immature rat uterus. These results indicate that oestrogen induces the increase of uterine DNA synthesis in both cytosol and mitochondria in immature rats.
Assuntos
Estradiol/farmacologia , Isoenzimas/análise , Mitocôndrias/efeitos dos fármacos , Timidina Quinase/análise , Útero/efeitos dos fármacos , Animais , Cromatografia DEAE-Celulose , Citosol/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Nucleotídeos de Desoxicitosina/farmacologia , Feminino , Mitocôndrias/enzimologia , Ratos , Ratos Endogâmicos , Nucleotídeos de Timina/farmacologia , Útero/enzimologiaRESUMO
Buserelin, a potent LH-RH agonist, has been used for the treatment of hormonal disorders such as precocious puberty, endometriosis, cystic mastitis and prostatic carcinoma. Prolonged treatment with buserelin has been known to induce a refractory phase of pituitary desensitization. In the present study, we found that two-week treatment with buserelin strongly suppressed the activities of thymidylate synthetase and thymidine kinase, and markedly reduced the appearance of BrdU-immunoreactive (S-phase) cells in both prostate glands and uteri in male and female adult rats, respectively.
Assuntos
Busserrelina/farmacologia , DNA/biossíntese , Próstata/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Estro/fisiologia , Feminino , Imuno-Histoquímica , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/metabolismo , Ratos , Ratos Sprague-Dawley , Testosterona/sangue , Útero/metabolismoRESUMO
A rare case of mature teratoma in both the mediastinum and the intrapulmonary system is presented. A 30-year-old male was admitted to our hospital due to tumor masses in the mediastinum and the left lung. We performed mediastinal tumor resection and left upper partial lobectomy. Neither tumor communicated with each other. Pathological findings revealed teratoma in the mediastinal lymph node and the intrapulmonary system including no malignant cells in either tumor. In this case, because metastasis and perforation were negative, we proposed that both tumors occurred at the same time in the early embryo.
Assuntos
Neoplasias Pulmonares/etiologia , Neoplasias do Mediastino/etiologia , Neoplasias Primárias Múltiplas , Teratoma/etiologia , Adulto , Humanos , Neoplasias Pulmonares/patologia , Masculino , Neoplasias do Mediastino/patologia , Teratoma/patologiaRESUMO
The relationships between the convulsions induced by the local anesthetic procaine and monoamines in the spinal cord were investigated in rats. The levels of dopamine (DA) and serotonin (5-HT) in the spinal cord were time-dependently increased after procaine (170 mg/kg, i.p.), which induced clonic convulsions, but the level of norepinephrine (NE) was unchanged. The rats that died during convulsions had a marked increase in DA. Phenobarbital (25 mg/kg, s.c.) produced both depletion of DA and elevation of 5-HT in the spinal cord and completely protected rats against convulsions. A 5-HT precursor, 5-hydroxytryptophan (5-HTP; 20-80 mg/kg, i.p.), suppressed the convulsions in a dose-dependent manner as shown by a decrease in the incidence and a prolongation of the latency, but a DA precursor, 3,4-dihydroxyphenylalanine (L-DOPA; 20-80 mg/kg, i.p.), markedly shortened the latency. Furthermore, the effect of L-DOPA on the convulsions was inhibited by the combination of 5-HTP. alpha-Methyl-p-tyrosine (20-80 mg/kg, i.p.) or DL-p-chlorophenylalanine (20-80 mg/kg, i.p.), an inhibitor of NE and DA or 5-HT biosynthesis, had a slight effect on the convulsions. These results suggest that procaine causes significant elevations of rat spinal DA and 5-HT in the convulsive process and suggest that dopaminergic and serotonergic neurons may be associated with procaine-induced convulsions.
Assuntos
Monoaminas Biogênicas/fisiologia , Procaína/toxicidade , Convulsões/induzido quimicamente , Medula Espinal/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Masculino , Fenobarbital/farmacologia , Ratos , Ratos EndogâmicosRESUMO
Reaction products of calf thymus DNA with (1R,2S,3S)-3-methylcyclohexanediamineplatinum (abbreviated as Pt(RSS-dach)Cl2) were investigated by enzymatic degradation of the platinated DNA and subsequent HPLC analysis. Five platinated adducts involving d(GpG), d(ApG) and (dG)2 residues were identified by HPLC after complete digestion using deoxyribonuclease I, nuclease P1, and alkaline phosphatase. The adducts with d(GpG) and d(ApG) consisted of two geometrical isomers, because Pt(RSS-dach)Cl2 lacks a C2 symmetry element. The d(GpG) and d(ApG) adducts were intrastrand compounds crosslinked between the N7 atoms of the adjacent purine bases. The two d(GpG) adducts were most abundant and comprised more than 65% of all the platinated adducts. The relative ratio of the two d(GpG) isomers was 3:2 for reaction with DNA, whereas the ratio was 1:1 for reaction with a single stranded oligonucleotide. The detailed structure of the two d(GpG) adducts is also described based on NMR spectroscopic data.
Assuntos
Cisplatino/análogos & derivados , Adutos de DNA/isolamento & purificação , DNA/química , Compostos Organoplatínicos/química , Fosfatase Alcalina/química , Animais , Cromatografia Líquida de Alta Pressão , Cisplatino/química , DNA/metabolismo , Adutos de DNA/química , Desoxirribonuclease I/química , Espectroscopia de Ressonância Magnética , Endonucleases Específicas para DNA e RNA de Cadeia Simples/química , Estereoisomerismo , Timo/metabolismoRESUMO
The effects of a local anaesthetic, tolycaine, on brain monoamine levels were investigated during the convulsive process in rats. The influence of central monoamine modifications on tolycaine-induced convulsions was also examined. Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of noradrenaline and 5-hydroxytryptamine levels in all brain regions in the convulsive state from the levels in the non-convulsive state. Their levels returned to normal during the postconvulsive state. Dopamine levels were depleted in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the convulsive process and increased in the cerebellum. Pretreatment with alpha-methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine-induced convulsions, as shown by a decrease in the incidence; L-3,4-dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)-disulfide, which increase brain catecholamine, intensified the convulsions, as shown by shortening of the latency and increase in the mortality. Antagonists of beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and pimozide, markedly suppressed the convulsions, but an antagonist of alpha-adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5-hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the convulsions, and DL-p-chlorophenylalanine, which depletes brain 5-hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor, methysergide and methiothepin, suppressed the convulsions. These results suggest that brain noradrenaline and 5-hydroxytryptamine are major regulators in the tolycaine-induced convulsive process and that central catecholaminergic neurones act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic neurones act suppressively.
Assuntos
Anestésicos Locais/toxicidade , Benzoatos/toxicidade , Monoaminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Convulsões/induzido quimicamente , Adrenérgicos/farmacologia , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Dopaminérgicos/farmacologia , Interações Medicamentosas , Masculino , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Serotonina/metabolismo , Serotoninérgicos/farmacologiaRESUMO
The effects of local anesthetics (procaine and lidocaine) on the gamma-aminobutyric acid (GABA) and L-glutamic acid (Glu) levels in rat spinal cord were studied during the convulsive process. The present study also investigated the influence of central GABA manipulations on the local anesthetic-induced convulsions. An increase in spinal GABA levels was observed at the preconvulsive and convulsive states after administration of procaine (170 mg/kg, i.p.) or lidocaine (120 mg/kg, i.p.), which induced clonic convulsions; in the depressive state, GABA levels returned to normal; in all states, Glu levels were unchanged. Semicarbazide (25-100 mg/kg, i.p.), a glutamic acid decarboxylase inhibitor, produced a decrease in spinal GABA content and strongly enhanced both local anesthetic-induced convulsions as shown by a shortening of the latency and an increase in the mortality. Aminooxyacetic acid (AOAA; 10-40 mg-kg, i.p.), a GABA transaminase inhibitor, dose-dependently increased spinal GABA content and markedly suppressed procaine-induced convulsions. However, lidocaine-induced convulsions were enhanced by AOAA. These results suggest that the spinal GABA neuron may respond to the convulsions induced by local anesthetics. Furthermore, there is a clear relationship between spinal GABA content and procaine-induced, but not lidocaine-induced, convulsions.