RESUMO
Lactobionic acid was first found in a Caucasian fermented milk product popularly known as "Caspian Sea yogurt" in Japan. The presence of lactobionic acid in the fermented milk was indicated by the results of both high-performance anion-exchange chromatographic analysis with pulsed amperometric detection and mass spectrometric analysis. Thereafter, the acid was purified from the yogurt and analyzed by nuclear magnetic resonance. A substantial amount of lactobionic acid was found to be accumulated in the upper layer of the yogurt, especially within 10 mm from the surface. A total of 45 mg of lactobionic acid per 100 g of the upper yogurt layer was collected after 4 d of fermentation. The annual intake of lactobionic acid in individuals consuming 100 g of the yogurt every day would be 0.5 to 1.0 g. A lactose-oxidizing bacterium was isolated from the fermented milk and was identified as Acetobacter orientalis. Washed A. orientalis cells oxidized monosaccharides such as d-glucose at considerable rates, although their activities for substrates such as lactose, maltose, and cellobiose were much lower. When A. orientalis cells were cultivated in cow's milk, they exhibited lactose-oxidizing activity, suggesting that this bacterium was the main organism involved in the production of lactobionic acid in the yogurt.
Assuntos
Acetobacter/metabolismo , Dissacarídeos/metabolismo , Microbiologia de Alimentos , Iogurte/microbiologia , Acetobacter/isolamento & purificação , Metabolismo dos Carboidratos , Dissacarídeos/análise , Japão , Oxirredução , Fatores de Tempo , Iogurte/análiseRESUMO
The 5-HT3 receptor blocking properties of YM060, YM114 (KAE-393), granisetron and ondansetron were examined in the vagus nerve and cerebral cortex of rats. 5-HT and 2-methyl-5-HT induced dose-dependent depolarizations of rat isolated vagus nerve with EC50 values of 2.53 (1.93-3.33) x 10(-6) and 4.03 (2.87-5.66) x 10(-6) M, respectively. YM060, YM114 and granisetron dose-dependently antagonized the depolarization of the rat vagus nerve induced by 5-HT, with decreases in the slope and maximal response at higher concentrations. Apparent pA2 values for these antagonists were 10.27 +/- 0.09, 10.12 +/- 0.16 and 9.44 +/- 0.40, respectively. Ondansetron produced a clear rightward shift of the concentration-response curve to 5-HT. The pA2 value was 8.63 (8.23-9.68). YM060 and YM114 at up to 10(-5) M produced no significant depression of the depolarizing responses to DMPP and GABA. YM060, YM114, granisetron and ondansetron displaced specific binding of [3H]GR65630 to rat cortical membranes with pKi values of 10.48 (10.41-10.57), 10.24 (10.18-10.28), 9.15 (9.02-9.28) and 8.70 (8.64-8.77), respectively. An excellent correlation (r = 0.97) was obtained between pA2 values in the vagus nerve and pKi values in the cerebral cortex. YM060, YM114, granisetron and ondansetron showed low affinities for 5-HT1A, 5-HT2 receptor, adrenergic alpha 1, alpha 2, dopamine D2, muscarinic M2, mu-opioid, benzodiazepine and histamine H1 receptors. These results support the possibility that the same type of 5-HT3 receptor occurs in rat vagus nerve and cerebral cortex.
Assuntos
Benzimidazóis/farmacologia , Córtex Cerebral/efeitos dos fármacos , Granisetron/farmacologia , Ondansetron/farmacologia , Antagonistas da Serotonina/farmacologia , Nervo Vago/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Eletrofisiologia , Cinética , Masculino , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
The binding characteristics of vasoactive intestinal peptide (VIP) in the liver membranes of the dog were examined using radioligand binding assay with 125I-VIP and unlabelled peptides and results were compared with those from the rat. The binding of VIP to canine liver membranes occurred in a reversible, saturable, specific and temperature-dependent manner. Guanine nucleotides dose-dependently inhibited VIP binding. The order of potency in competition experiments with unlabelled peptide was: VIP > pituitary adenylate cyclase activating peptide (PACAP)-27 > PACAP-38 >> peptide histidine isoleucine (PHI) = secretin in the dog, and PACAP-27 > PACAP-38 > VIP > PHI > secretin in the rat. PHI and secretin were about 5000 times less potent than VIP in the dog, but secretin was about 100 times less potent than VIP in the rat. The VIP binding sites in canine liver membranes have recognition sites for VIP which differ from those in rat liver membranes. As most of VIP in the portal vein was removed during its passage through the canine liver, the binding sites of canine liver may play a role in degradation of VIP.
Assuntos
Fígado/metabolismo , Receptores de Peptídeo Intestinal Vasoativo/análise , Animais , Ligação Competitiva , Membrana Celular/metabolismo , Cães , Nucleotídeos de Guanina/farmacologia , Radioisótopos do Iodo , Masculino , Neuropeptídeos/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Ratos Wistar , Secretina/metabolismo , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
In this study, we examined the distribution of intercellular adhesion molecule-1 (ICAM-1) in gastric adenomas and carcinomas immunohistochemically at the light and electron microscopic levels. ICAM-1 was expressed on tumour cells in 12 of 28 gastric carcinomas and in 3 of 11 adenomas but not on most normal gastric epithelial cells. ICAM-1 was localized on luminal sites of neoplastic glands in adenomas and in intestinal-type carcinomas, and rarely on the surface of tumour cells of diffuse carcinomas. Expression of ICAM-1 on the tumour cells was more frequent in intestinal-type than diffuse carcinomas (P < 0.005). At the ultrastructural level, ICAM-1 was present prominently on the apical membrane and weakly on the lateral surface of the tumour cells of the intestinal-type carcinoma and also localized on the perinuclear membrane and the membrane of the endoplasmic reticulum of cancer cells. There was no significant association between ICAM-1 expression and HLA antigen expression or the number of infiltrating lymphocyte subsets. These results may implicate the synthesis of ICAM-1 by gastric cancer cells, but the expression is infrequent and may not be sufficient for host immune surveillance of the tumour cell.
Assuntos
Adenocarcinoma/metabolismo , Adenoma/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Neoplasias Gástricas/metabolismo , Endotélio Vascular/metabolismo , Epitélio/metabolismo , Mucosa Gástrica/metabolismo , Antígenos HLA/metabolismo , Humanos , Imuno-Histoquímica , Linfócitos/citologia , Linfócitos/metabolismo , Microscopia Eletrônica , Células Estromais/metabolismoRESUMO
We investigated the effects of ramosetron (YM060, (-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1 H-benzimidazole monohydrochloride) on the short-circuit current (Isc) responses to 5-HT receptor agonists in the rat distal colon, and compared its potency to that of other 5-HT3 receptor antagonists. 5-Hydroxytryptamine (5-HT) concentration-dependently increased Isc. The Isc response to 5-HT was partially reduced by tetrodotoxin and ramosetron, and strongly inhibited by GR113808 ([[1-[(2-methyl-sulphonyl) amino]ethyl]-4-piperidin-yl]methyl 1-methyl-1 H-indole-3-carboxylate). 2-Methyl-5-HT and 5-methoxytryptamine also increased Isc. The former response was inhibited by ramosetron, and the latter was abolished by GR113808. Ramosetron, YM114 (KAE-393, (-)-(R)-5-[(1-indolinyl)carbonyl]-4,5,6,7-tetrahydro-1 H-benzimidazole monohydrochloride) and granisetron concentration-dependently antagonized the Isc responses to 2-methyl-5-HT with reduction in the maximal response at higher concentrations. Apparent pA2 values for these antagonists were 10.40, 10.37 and 8.99, respectively. Ondansetron produced clear rightward shifts of the concentration-response curves to 2-methyl-5-HT, with a pA2 value of 8.53. These results suggest that 5-HT increases Isc through the 5-HT3 and 5-HT4 receptors, and that ramosetron is a potent and selective 5-HT3 receptor antagonist in rat colonic mucosa.
Assuntos
Benzimidazóis/farmacologia , Colo/efeitos dos fármacos , Colo/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/fisiologia , Antagonistas da Serotonina/farmacologia , Animais , Interações Medicamentosas , Eletrofisiologia , Hexametônio/farmacologia , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Serotonina/análogos & derivados , Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Tetrodotoxina/farmacologiaRESUMO
We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a newly synthesized 5-HT(3) receptor agonist, on defecation in normal and constipated ferrets, and evaluated it as an agent against constipation. YM-31636 facilitated defecation without inducing diarrhea or emetic episodes. This effect occurred within 1 h after oral administration, mostly within 30 min, whereas sodium picosulfate, a widely used laxative, tended to increase the frequency of defecation for several hours with much lower peak incidence than that of YM-31636, and induced diarrhea. UK14304 (brimonidine), an alpha2 receptor agonist, and morphine reduced the frequency of defecation and YM-31636 restored it. These effects of YM-31636 were antagonized by ramosetron, a 5-HT(3) receptor antagonist. These results suggest that YM-31636 could be promising in the treatment of constipation. Because of an early and reliable onset of action compared with sodium picosulfate, YM-31636 could make it easier to control the time of defecation.
Assuntos
Constipação Intestinal/fisiopatologia , Defecação/efeitos dos fármacos , Pirróis/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Tiazóis/farmacologia , Animais , Citratos , Relação Dose-Resposta a Droga , Fezes , Furões , Masculino , Náusea/induzido quimicamente , Compostos Organometálicos , Picolinas/farmacologia , Pirróis/efeitos adversos , Agonistas do Receptor de Serotonina/efeitos adversos , Tiazóis/efeitos adversos , Fatores de Tempo , Vômito/induzido quimicamente , Água/metabolismoRESUMO
We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastrointestinal functions including visceral pain reflex in rats. Injection of YM-31636 increased the number of fecal pellets. This effect was completely inhibited by ramosetron, a 5-HT3 receptor antagonist. YM-31636 also increased the intracolonic pressure measured in both conscious and anesthetized rats. In isolated distal colon, YM-31636 increased the short-circuit current response. This effect was abolished by ramosetron. Both the maximal response and the potency of YM-31636 were weaker than those of other 5-HT3 receptor agonists. In two visceral pain reflex models, YM-31636 neither changed the magnitude of pressor response to colonic distension in anesthetized rats nor affected the visceromotor threshold to colorectal distension in conscious rats. In conclusion, YM-31636 facilitated defecation without increasing visceral pain. Consequently, 5-HT3 receptor agonists like YM-31636 would be promising in the treatment of chronic constipation.
Assuntos
Colo/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Pirróis/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Tiazóis/farmacologia , Dor Abdominal , Animais , Benzimidazóis/farmacologia , Colo/inervação , Defecação/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Masculino , Pressão , Ratos , Ratos Wistar , Reflexo Abdominal/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Água/metabolismoRESUMO
We investigated the in vitro pharmacological profile of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate). In cloned human 5-HT3A receptors, YM-31636 had a pKi value of 9.67 vs. ramosetron and pKi values for other 5-HT3 receptor agonists were less than 7. YM-31636 showed very low affinities for other receptors. YM-31636 induced contraction of isolated guinea pig distal colon. The intrinsic activity was approximately 0.90 compared with 5-hydroxytryptamine's (5-HT) 1.0, and the potency was 26 times greater than that of 5-HT. YM-31636 increased short-circuit current (Isc) in the isolated guinea pig distal colon. In this case, the relative intrinsic activity was approximately 0.19. In isolated guinea pig right atrium, YM-31636 induced tachycardia with the relative intrinsic activity of approximately 0.23. All these effects of YM-31636 were antagonized by ramosetron, a selective 5-HT3 receptor antagonist. These results suggest that YM-31636 is a potent and selective 5-HT3 receptor agonist, preferentially acting on the contraction of the colon.
Assuntos
Colo/efeitos dos fármacos , Pirróis/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/análogos & derivados , Tiazóis/farmacologia , Acetilcolina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Antraquinonas/farmacologia , Função Atrial , Biguanidas/metabolismo , Biguanidas/farmacologia , Ligação Competitiva , Colo/fisiologia , Dinoprostona/farmacologia , Relação Dose-Resposta a Droga , Cobaias , Átrios do Coração/efeitos dos fármacos , Humanos , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Receptores 5-HT3 de Serotonina , Serotonina/metabolismo , Serotonina/farmacologia , Agonistas do Receptor de Serotonina/metabolismoRESUMO
The role of 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptors in the regulation of gut motility in the ferret was investigated. The selective 5-HT3 receptor antagonist ramosetron (1 - 10 microg/kg s.c.) prolonged the interval of gastric antral migrating motor complex, but had only slight effect on small intestinal and colonic motility in unfed animals. The selective 5-HT4 receptor antagonist SB 204070 did not affect motility throughout gut in unfed animals. Neither ramosetron nor SB 204070 affected the motility throughout gut in fed animals. In conclusion, neither 5-HT3 nor 5-HT4 receptors tonically regulate ferret gut motility except that 5-HT3 receptors have a key role in the occurrence of migrating motor complex specifically in the stomach. The role of 5-HT3 and 5-HT4 receptor system in the regulation of gut motility in ferrets is similar to that in other mammalian species studied, including humans. This similarity suggests that the ferret is a suitable model animal to study gut motor functions in humans.
Assuntos
Furões/fisiologia , Motilidade Gastrointestinal/fisiologia , Receptores de Serotonina/fisiologia , Animais , Benzimidazóis/farmacologia , Dioxanos/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Masculino , Piperidinas/farmacologia , Receptores 5-HT3 de Serotonina , Receptores 5-HT4 de Serotonina , Antagonistas da Serotonina/farmacologiaRESUMO
Three limonoid glycosides were isolated from Citrus unshiu peels, and their structures were determined based on MS and NMR spectroscopic data as nomilinic acid 17-O-beta-D-glucopyranoside (1), methyl nomilinate 17-O-beta-D-glucopyranoside (2), and obacunone 17-O-beta-D-glucopyranoside (3). In particular, the location of the sugar moiety was clearly determined by the B/E constant linked scan FABMS method. No limonoid glycosides obtained here were found to have antitumor activity in NCI-H292 and EL-4 cell lines.
Assuntos
Citrus/química , Glicosídeos/química , Glicosídeos/isolamento & purificação , Animais , Sequência de Carboidratos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Dados de Sequência Molecular , Células Tumorais CultivadasRESUMO
New polyisoprenepolyols (hypsiziprenol AA and BA) were isolated from an edible mushroom (Hypsizigus marmoreus). These polyols occur as a mixture of homologous polyisoprene derivatives with 40-70 carbon atoms. Analyses by FAB/MS in the positive and negative ion modes are complementary with each other in that the former provides information on the number of hydroxy groups present while the latter specifies the isoprenoid sequence, and thus become a powerful tool for analyzing the structures of polyisoprenepolyols. No polyisoprenepolyols obtained here were found to have antitumor activity on NCI-H292 and EL-4 cell lines.
Assuntos
Agaricales/química , Álcoois Graxos/química , Terpenos/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Álcoois Graxos/farmacologia , Humanos , Indicadores e Reagentes , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Paladar , Terpenos/farmacologia , Células Tumorais CultivadasRESUMO
L-2,5-Dihydrophenylalanine (DHPA), a phenylalanine analogue, induced apoptosis in human promyelocytic leukemia cells (HL-60). This apoptosis was demonstrated by morphological changes of the cells, such as fragmentation of nuclei and chromatin condensation, and by some evidence found in biochemical analysis, such as DNA ladder and activation of caspase 3. The DHPA-induced apoptosis was prevented by a pan-caspase inhibitor, Z-VAD-fmk, and a cysteine protease inhibitor, E-64d, which inhibits calpains and cathepsin B and L. A calpain inhibitor, Z-LL-H, did not affect this apoptosis. A cathepsin B specific inhibitor, CA074-Me, prevented only chromatin condensation. However, E-64d and a cathepsin L specific inhibitor, Z-FY(t-Bu)-dmk, protected the cells from both chromatin condensation and oligonucleosomal DNA fragmentation. As proceeding to the apoptotic process, the activities of both cathepsin B and L increased gradually. These results indicated that DHPA was an inducer of cathepsin-dependent apoptosis in HL-60 cells.
Assuntos
Apoptose/efeitos dos fármacos , Catepsinas/fisiologia , Fenilalanina/análogos & derivados , Fenilalanina/farmacologia , Calpaína/antagonistas & inibidores , Caspase 3 , Inibidores de Caspase , Caspases/metabolismo , Catepsinas/metabolismo , Divisão Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Cromatina/efeitos dos fármacos , Cicloexenos , Inibidores de Cisteína Proteinase/farmacologia , Fragmentação do DNA , Corantes Fluorescentes , Células HL-60 , Humanos , Nucleossomos/efeitos dos fármacos , Nucleossomos/metabolismo , Fenilalanina/antagonistas & inibidores , Inibidores de Proteases/farmacologiaRESUMO
To investigate the hydrolysis of glucosyl esters by beta-glucosidase, p-hydroxybenzoyl beta-D-glucose (pHBG) was chemically synthesized. The hydrolytic activity of some beta-glucosidases for pHBG was compared to that for p-nitrophenyl beta-glucoside (pNPG). The Clavibacter michiganense and Flavobacterium johnsonae enzymes could hydrolyze pHBG and steviol glycosides which are natural glucosyl esters. The commercial beta-glucosidase originating from Caldocellum saccharolyticum also hydrolyzes pHBG despite having no activity for steviol glycosides. The beta-glucosidase from Aspergillus niger cleaved the glucosyl ester linkage much more weakly than the glucosidic linkage. The pH-activity profile for the hydrolysis of pHBG was similar to that of pNPG by the C. saccharolyticum beta-glucosidase. The similar profiles for these substrates suggested that the active site for the glucosyl ester chemically resembles that for glucoside with respect to catalysis. Kinetic analysis of the C. saccharolyticum beta-glucosidase for mixed substrates of pHBG and pNPG showed that the hydrolysis of pHBG competed with that of pNPG. This result indicated that there is only one active site for both the glucosyl ester and glucoside. Mass spectroscopic analysis of the hydrolysates of pHBG in H218O suggested that beta-glucosidase hydrolyzes glucosyl esters between the anomeric carbon of glucose and the carbonyl oxygen, not between the carbonyl carbon and the carbonyl oxygen.
RESUMO
To clarify the immunological function of 'M' (microfold or membranous) cells in the large intestine, we examined the expression of intercellular adhesion molecule-1 (ICAM-1) and HLA-class II antigens immunohistochemically in M cells and follicle-associated epithelia (FAE) covering isolated lymphoid follicles of the human colon in comparison with their expression in Peyer's patches of the small intestine. In Peyer's patches of the small intestine, ICAM-1 was not expressed on the epithelial cells covering the lymphoid follicles, but their cell surfaces were stained positively for HLA-DR. In contrast, colonic M cells expressed ICAM-1 on their cell surfaces but were negative for HLA class II antigens. By immunoelectron microscopy, ICAM-1 was seen to be distributed on the surface of microfolds, on the membranes of apical vesicles and on part of the basolateral plasma membranes of M cells, but was not expressed on adjacent FAE. These findings imply that the M cells in the colon and in Peyer's patches have different immunological roles. In addition, identification of ICAM-1 expression on the colonic M cells should help elucidate the pathogenesis of some inflammatory colonic diseases which appear to start in the lymphoid follicles of the colonic mucosa.
Assuntos
Colo/citologia , Colo/imunologia , Antígenos HLA-DR/análise , Molécula 1 de Adesão Intercelular/análise , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nódulos Linfáticos Agregados/imunologiaRESUMO
The antagonism of histamine H2-receptor by SWR-104SA (1'-bromo-N-[3-[3-(1-piperidinylmethyl) phenoxy] propyl]-spiro [1,3-dioxolane-2,9'-pentacyclo-[4.3.0.0.(2,5)0.(3,8) 0.(4,7)]nonane]-4'-carboxamide monooxalate) was estimated using the isolated guinea-pig atrium and gastric acid secretion in rats. The concentration-response curves for the positive chronotropic effect of histamine on the atrium were displaced to the right in parallel without change in the maximum response by SWR-104SA and roxatidine acetate hydrochloride (roxatidine). The pA2 values of SWA-104SA and roxatidine acetate hydrochloride were 7.27 and 7.38, respectively. The slopes of the regression line of log (DR-1) against log SWR-104SA and roxatidine concentration were 1.00 and 0.92, respectively. There was no significant difference between the two compounds with respect to the histamine H2-receptor antagonism and/or binding manner in vitro. In the rat gastric fistula model stimulated by histamine, however, antisecretory potency of SWR-104SA was 3 times less than that of roxatidine. SWR-104SA given p.o. prevented the formation of gastric lesion induced by HCl-ethanol and indomethacin dose-dependently, roxatidine also prevented its formation by HCl-ethanol, but failed to prevent that by indomethacine. These antiulcer activities of SWR-104SA were shown at the lesser doses of antisecretory activity. On the other hand, roxatidine did not prevent the ulcer formation at the same dose level of antisecretory activity. These results indicate that the antiulcer effect of SWR-104SA is not caused by the antisecretory action alone. In addition, the mucosal protective activity of SWR-104SA for HCl-ethanol induced gastric lesion was independent of endogenous prostaglandins. Moreover SWR-104SA had inhibitory effects on indomethacin-induced gastric hypermotility in rats. These actions may partly explain the gastric protection of this compound and additional mechanisms such as mucosal blood flow could be involved in the antiulcer efficacy. Consequently, it appears that SWR-104SA is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.
Assuntos
Dioxolanos/farmacologia , Ácido Gástrico/metabolismo , Antagonistas dos Receptores H2 da Histamina/farmacologia , Compostos de Espiro/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Etanol , Motilidade Gastrointestinal/efeitos dos fármacos , Cobaias , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Ácido Clorídrico , Indometacina , Masculino , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamenteRESUMO
A 51-year-old woman, who had both aortitis syndrome (Takayasu arteritis) and IgA nephropathy, presented with hypertension, fever, a high erythrocyte sedimentation rate, high C-reactive protein and serum IgG levels, proteinuria, and renal dysfunction. Renal arteriography showed stenosis and poststenotic dilatation at the origin of the right renal artery, as well as tortuosity of the left renal artery branches and marked atrophy of the left kidney. Renal biopsy showed IgA nephropathy with deposits of IgA, C3, and fibrinogen in the glomeruli and arteriolosclerosis. The present patient had human leukocyte antigen (HLA)-B 52, which is reported to be related to the aortitis syndrome, as well as HLA-DR 4, which is possibly related to IgA nephropathy, suggesting that HLA status may be involved in the pathogenesis of both diseases.
Assuntos
Síndromes do Arco Aórtico/imunologia , Glomerulonefrite por IGA/imunologia , Antígenos HLA/imunologia , Adulto , Síndromes do Arco Aórtico/complicações , Síndromes do Arco Aórtico/diagnóstico por imagem , Síndromes do Arco Aórtico/patologia , Feminino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico por imagem , Glomerulonefrite por IGA/patologia , Humanos , RadiografiaRESUMO
BACKGROUND: The withdrawal response elicited by a nociceptive stimulus, i.e., evoked pain measure, is commonly used as an efficacy endpoint in neuropathic pain animal models. It, however, has several limitations, which highlight the importance of examining spontaneous pain. The present study describes an automated method for measuring spontaneous pain behaviour in a rat model of neuropathic pain caused by chronic constriction injury (CCI) of sciatic nerve. METHODS: After CCI surgery, a small magnet was implanted into the operated limb. The rat was placed in a test chamber that was surrounded by wire coil. Limb movements, including lifting/guarding, flinching/shaking, licking and walking in the operated limb, caused changes in the electromagnetic field, including a change in voltage and transformed into a signal via an amplifier. RESULTS: CCI rats consistently showed more frequent limb movement than sham rats. There was no significant correlation between the frequency of spontaneous pain behaviour and the evoked pain symptoms. Treatment with duloxetine (30 mg/kg p.o.) and amitriptyline (30 and 100 mg/kg p.o.) significantly reduced this frequency. Pregabalin at 30 mg/kg p.o. tended to reduce the frequency, and diclofenac up to 10 mg/kg p.o. had no effect. CONCLUSION: A non-subjective automated method for measuring spontaneous pain behaviour in an animal model of neuropathic pain was established. It is expected that the current system will greatly enhance the analysis of spontaneous pain-related behaviour, which is a predominant symptom in patients with neuropathic pain. The current system may also be valuable in the screening of potential analgesic treatments.