Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54
Filtrar
Más filtros

Medicinas Complementárias
Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
J Physiol Pharmacol ; 64(1): 65-75, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23568973

RESUMEN

We examined the effect of egualen, a stable azulene derivative, against gastric damage induced by ischemia/reperfusion (I/R), gastric bleeding induced by double antiplatelet therapy with aspirin (ASA) plus clopidogrel, and small intestinal damage generated by loxoprofen, and investigated the possible mechanisms involved in its protective action. Male C57BL/6 mice or SD rats were used under urethane anesthesia (gastric lesions) or in a conscious (intestinal lesions) state. I/R-induced gastric injury was produced in mice by clamping the celiac artery for 30 min, followed by reperfusion for 60 min. Gastric bleeding was induced in rats by luminal perfusion with 25 mM ASA+50 mM HCl for 2 hours in the presence of clopidogrel (30 mg/kg). To produce small intestinal lesions the rats were given loxoprofen (60 mg/kg) p.o. and killed 24 hours later. Egualen was given i.d. 60 min before I/R or ASA perfusion, while given p.o. twice 30 min before and 6 hours after loxoprofen. Egualen significantly prevented the I/R-induced gastric damage, and the effect was equivalent to that of seratrodast (TXA2 antagonist). This agent also significantly suppressed gastric bleeding induced by ASA plus clopidogrel, similar to PGE2. Likewise, egualen significantly prevented loxoprofen-induced damage in the small intestine, accompanied by an increase in the secretion of mucus and suppression of bacterial invasion as well as iNOS expression. These results suggest that egualen has a prophylactic effect against various lesions in the gastrointestinal mucosa, probably through its characteristic pharmacological properties, such as TXA2 antagonistic action, local mucosal protection, and stimulation of mucus secretion.


Asunto(s)
Azulenos/farmacología , Hemorragia Gastrointestinal/tratamiento farmacológico , Tracto Gastrointestinal/irrigación sanguínea , Fenilpropionatos/toxicidad , Daño por Reperfusión/tratamiento farmacológico , Sesquiterpenos/farmacología , Animales , Aspirina/toxicidad , Benzoquinonas/toxicidad , Clopidogrel , Mucosa Gástrica/irrigación sanguínea , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/metabolismo , Hemorragia Gastrointestinal/patología , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/patología , Ácidos Heptanoicos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Moco/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Úlcera Péptica/prevención & control , Peroxidasa/metabolismo , Inhibidores de Agregación Plaquetaria/toxicidad , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/patología , Ticlopidina/análogos & derivados , Ticlopidina/toxicidad
2.
Diabetes Obes Metab ; 12(3): 224-33, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20151999

RESUMEN

AIM: Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and voglibose, an alpha-glucosidase inhibitor, have different but complementary mechanisms of action on glucagon-like peptide-1 (GLP-1) regulation and glucose-lowering effects. The present study evaluated the chronic effects of combination treatment with alogliptin and voglibose in prediabetic db/db mice. METHODS: Alogliptin (0.03%) and voglibose (0.001%) alone or in combination were administered in the diet to prediabetic db/db mice. RESULTS: After 3 weeks, voglibose treatment increased GLP-1 secretion (voglibose alone, 1.6-fold; alogliptin plus voglibose, 1.5-fold), while it decreased plasma glucose-dependent insulinotropic polypeptide (GIP) (voglibose alone, -30%; alogliptin plus voglibose, -29%). Alogliptin, voglibose and combination treatment decreased plasma DPP-4 activity by 72, 15 and additively by 80%, respectively, and increased plasma active GLP-1 levels by 4.5-, 1.8- and synergistically by 9.1-fold respectively. Combination treatment increased plasma insulin by 3.6-fold (alogliptin alone, 1.3-fold; voglibose alone, 1.8-fold), decreased plasma glucagon by 30% (alogliptin alone, 11%; voglibose alone, 8%), and prevented the development of diabetes, much more effectively than either agent alone. After 4 weeks, alogliptin, voglibose and combination treatment increased pancreatic insulin content by 1.6-, 3.4- and synergistically by 8.5-fold respectively. Furthermore, combination treatment resulted in an increased expression of insulin, pancreatic and duodenal homeobox 1 (PDX1) and glucose transporter 2 (GLUT2), and maintenance of normal beta/alpha-cell distribution in the pancreatic islet. CONCLUSIONS: Chronic treatment with alogliptin in combination with voglibose concurrently increased active GLP-1 circulation, increased insulin secretion, decreased glucagon secretion, prevented the onset of the disease, and preserved pancreatic beta-cells and islet structure in prediabetic db/db mice.


Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Hipoglucemiantes/administración & dosificación , Inositol/análogos & derivados , Células Secretoras de Insulina/efectos de los fármacos , Piperidinas/administración & dosificación , Estado Prediabético/tratamiento farmacológico , Uracilo/análogos & derivados , Animales , Quimioterapia Combinada/métodos , Inositol/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas de Unión al ARN , Factores de Transcripción/efectos de los fármacos , Uracilo/administración & dosificación
4.
J Dent Res ; 84(6): 515-20, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15914587

RESUMEN

The application of implant therapy is still limited, because of various risk factors and the long healing time required for bone-titanium integration. This study explores the potential for osseointegration engineering with dental pulp cells (DPCs) by testing a hypothesis that DPCs generate mineralized tissue on titanium. DPCs extracted from rat incisors positive for CD44, alkaline phosphatase activity, and mineralizing capability were cultured on polystyrene and on machined and dual-acid-etched (DAE) titanium. Tissue cultured on titanium with a Ca/P ratio of 1.4 exhibited plate-like morphology, while that on the polystyrene exhibited fibrous and punctate structures. Tissues cultured on titanium were harder than those on polystyrene, 1.5 times on the machined and 3 times on the DAE. Collagen I, osteopontin, and osteocalcin genes were up-regulated on titanium, especially the DAE surface. In conclusion, DPCs showing some characteristics of the previously identified dental pulp stem cells can generate mineralized tissue on titanium via the osteoblastic phenotype, which can be enhanced by titanium surface roughness.


Asunto(s)
Calcificación Fisiológica/fisiología , Pulpa Dental/citología , Titanio , Grabado Ácido Dental , Animales , Fenómenos Biomecánicos , Calcio/análisis , Colágeno Tipo I/análisis , Medios de Cultivo , Pulpa Dental/fisiología , Dureza , Masculino , Biología Molecular , Osteocalcina/análisis , Osteopontina , Fosfoproteínas/análisis , Fósforo/análisis , Poliestirenos/química , Ratas , Ratas Sprague-Dawley , Sialoglicoproteínas/análisis , Propiedades de Superficie , Técnicas de Cultivo de Tejidos , Titanio/química
5.
Diabetes Obes Metab ; 6(5): 384-90, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15287932

RESUMEN

AIM: This study was designed to examine the therapeutic effect of acarbose on serum triglyceride (TG), free fatty acid (FFA), very low-density lipoprotein (VLDL) and chylomicron (CM) in the meal tolerance test (MTT) before and after acarbose treatment in type 2 diabetes mellitus (DM2). METHODS: Effects of acarbose on postprandial lipid metabolism were examined in DM2 patients. The subjects with normotriglyceridaemia (TG > or = 1.7 mmol/l, n = 60) were divided to three groups (A, B and C), and DM2 patients with hypertriglyceridaemia (TG > 1.7 mmol/l, n = 20) were designated group D. Group A was a control, and group B was designed to examine the one-dose effect of acarbose (100 mg) on lipid levels in MTT using the balanced food of 400 kcal. In groups C and D, acarbose 300 mg/day was administered for 8 weeks, and MTT with the one-dose acarbose administration was performed. We determined the levels of fasting and postprandial levels of glucose, insulin, FFA and TG-rich lipoproteins such as CM and VLDL. RESULTS: Acarbose treatment lowered plasma glucose levels and insulin secretion. In comparison among study groups A, B and C, acarbose significantly lowered serum TG levels in postprandial state. In group D, after the 8-week acarbose administration, fasting or postprandial FFA, TG and VLDL levels were also lowered. Interestingly, postprandial increase in CM was suppressed by acarbose administration in group B, C or D. CONCLUSIONS: Acarbose lowers postprandial TG and CM levels in DM2 with either normotriglyceridaemia or hypertriglyceridaemia. Improvement of insulin resistance with acarbose may also reduce fasting TG levels in DM2 with hypertriglyceridaemia. Acarbose is a beneficial therapeutic agent to reduce TG levels in DM2 patients, thereby leading to suppression of cardiovascular events.


Asunto(s)
Acarbosa/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Glicósido Hidrolasas , Estudios de Casos y Controles , VLDL-Colesterol/sangre , Quilomicrones/sangre , Diabetes Mellitus Tipo 2/sangre , Ácidos Grasos/sangre , Femenino , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Periodo Posprandial , Triglicéridos/sangre
6.
J Gastrointest Surg ; 8(3): 346-57, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15019933

RESUMEN

The effects of heme oxygenase (HO) inhibitors, zinc-protoporphyrin-IX (ZnPP-IX), and tin protoporphyrin-IX (SnPP-IX) and their interactions with L-arginine/nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways were investigated in postoperative ileus in rats. Intestinal transit was measured as Evans blue migration after skin incision, laparotomy or laparotomy plus gut evisceration and handling. Laparotomy and small intestinal manipulations increased blood plasma nitrites/nitrates level 1.88-fold. N(omega)-nitro-L-arginine methyl ester, indomethacin, a selective COX-1 blocker (resveratrol) and COX-2 antagonists (nimesulide, DuP-697, NS-398) reversed the additional inhibitory effects of gut manipulation subsequent to laparotomy. In contrast, N-(3-(aminomethyl)benzyl)acetamidine or S-methylisothiourea, highly selective inducible NOS blockers, remained ineffective. ZnPP-IX and SnPP-IX overturned the effects of laparotomy on dye propulsion, but were only partially effective after laparotomy and gut handling attenuating the additional inhibitory influences of gut manipulation, the intestinal transit reaching 89.21%, 92.87%, 53.46%, and 48.56% of respective controls transit. Salutary effects of L-NAME, ZnPP-IX, and SnPP-IX were dose-dependent, L-arginine or hemin (HO substrate) sensitive. Administration of indomethacin and resveratrol subsequent to SnPP-IX reversed the inhibitory effects of laparotomy and manipulation, amounting to 93.91% and 87.43% of controls. On the other hand, L-NAME injected after SnPP-IX abolished the salutary effects of the latter, study dye migration reached 25.18% of control rat. Therefore we demonstrated that nitric oxide, carbon monoxide, and prostanoids play a role in the pathogenesis of postoperative ileus albeit in different mechanisms. Laparotomy stimulated HO activity, whereas gut manipulation led to an excessive constitutive NOS stimulation accompanied by augmented prostanoid synthesis by COX-1. Unaffected synthesis of either NO or CO enables a return of gastrointestinal transit during postoperative period, whereas a pharmacological blockade of two complementary metabolic pathways provides a most effective measure against postoperative ileus development.


Asunto(s)
Monóxido de Carbono/farmacología , Ileus/etiología , Óxido Nítrico/farmacología , Complicaciones Posoperatorias/etiología , Prostaglandinas/farmacología , Animales , Arginina/farmacología , Ciclooxigenasa 2 , Inhibidores Enzimáticos/farmacología , Tránsito Gastrointestinal/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/antagonistas & inhibidores , Indometacina/farmacología , Isoenzimas/metabolismo , Laparotomía , Masculino , Metaloporfirinas/farmacología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Prostaglandina-Endoperóxido Sintasas/metabolismo , Protoporfirinas/farmacología , Ratas , Ratas Wistar , Resveratrol , Estilbenos/farmacología
7.
J Gastroenterol Hepatol ; 16(10): 1112-9, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11686837

RESUMEN

BACKGROUND AND AIM: We evaluated the effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid), a novel anti-ulcer drug, on indomethacin-induced small intestinal lesions in rats. METHODS: The animals were administered indomethacin (10 mg/kg, s.c.), and they were killed 24 h later. Rebamipide (30-300 mg/kg) was administered p.o. twice, 30 min before, and 6 h after indomethacin. RESULTS: Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied by an increase in enterobacterial translocation, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, as well as thiobarbituric acid (TBA) reactants, and these changes were significantly prevented by the supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2; 10 microg/kg, i.v.) or the pretreatment of animals with the antibiotic ampicillin. Treatment of the animals with rebamipide dose-dependently prevented the development of intestinal lesions, and this effect was mimicked by i.v. administration of superoxide dismutase (SOD: 3000 U/kg) + catalase (CAT: 5000 U/kg). The protection by rebamipide was accompanied by a significant suppression of the increase in both MPO and iNOS activities, and a complete inhibition of the increase in TBA reactants, while SOD + CAT significantly inhibited the increase of MPO activity and TBA reactants, but not iNOS activity. The bacterial translocation following indomethacin was also significantly decreased by either rebamipide or SOD + CAT. CONCLUSION: These results confirmed the importance of enterobacteria and iNOS/NO in the pathogenesis of indomethacin-induced small intestinal lesions, and suggested that rebamipide prevents the development of these lesions, probably by its radical scavenging action.


Asunto(s)
Alanina/análogos & derivados , Alanina/farmacología , Antiulcerosos/farmacología , Inhibidores Enzimáticos/farmacología , Enfermedades Intestinales/prevención & control , Quinolonas/farmacología , Ampicilina/farmacología , Animales , Traslocación Bacteriana/efectos de los fármacos , Catalasa/farmacología , Relación Dosis-Respuesta a Droga , Enterobacteriaceae/efectos de los fármacos , Indometacina , Enfermedades Intestinales/inducido químicamente , Enfermedades Intestinales/enzimología , Peroxidación de Lípido , Masculino , Óxido Nítrico Sintasa/biosíntesis , Peroxidasa/biosíntesis , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/farmacología
8.
J Cardiovasc Pharmacol ; 38(6): 885-92, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11707692

RESUMEN

Hyperinsulinemia is closely related to coronary artery disease. Endothelial cells are important for the control of vascular tone, and dysfunction of endothelial cells has been implicated in coronary artery disease. The direct effects of insulin on coronary endothelial cells are nonetheless unknown. In this study, the acute effects of high-dose insulin were investigated on agonist-induced intracellular Ca(2+) concentration ([Ca(2+)](i)) in porcine coronary endothelial cells and coronary relaxation. Bradykinin (10 n M ) and cyclopiazonic acid (100 microM), an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, provoked large increases in [Ca(2+)](i) in coronary endothelial cells. This increase was dose-dependently inhibited by a 10-min preincubation with high doses of insulin (10, 30, 100 mU/ml). Under Ca(2+)-free conditions, bradykinin and cyclopiazonic acid provoked transient, small increases in [Ca(2+)](i). These increases were not affected by pretreatment with insulin (100 mU/ml). Bradykinin (1, 10, 100, 1,000 n M ) and cyclopiazonic acid (10 microM) significantly relaxed porcine coronary artery rings precontracted with histamine (1 microM). The vasodilator effects of bradykinin and cyclopiazonic acid were dose-dependently inhibited by insulin. These acute effects were not observed at physiologic concentrations. Our data indicate that high-dose insulin inhibits agonist-induced Ca(2+) response in coronary endothelial cells and attenuates agonist-induced coronary vasodilatation. The study suggests that hyperinsulinemia might be associated with coronary artery disease via derangement of endothelial Ca(2+)-dependent functions.


Asunto(s)
Calcio/metabolismo , Vasos Coronarios/fisiología , Endotelio Vascular/metabolismo , Hipoglucemiantes/farmacología , Insulina/farmacología , Vasodilatación/efectos de los fármacos , Animales , Bradiquinina/antagonistas & inhibidores , Señalización del Calcio/efectos de los fármacos , Células Cultivadas , Vasos Coronarios/citología , Técnicas de Cultivo , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Indoles/antagonistas & inhibidores , Insulina/administración & dosificación , Cinética , Porcinos , Vasodilatadores/antagonistas & inhibidores
9.
J Bone Miner Metab ; 19(5): 277-86, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11498729

RESUMEN

To test the hypothesis that 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) suppresses bone resorption after ovariectomy (ovx) by inhibiting osteoclastogenic potential in bone marrow cells, the bilateral tibiae of ddY mice, 8 weeks of age, subjected to ovx were obtained. 1alpha(OH)D3, at doses of 0, 0.2 (low dose), or 0.4 microg/kg body weight (high dose), was administered orally by canula three times a week for 2 or 6 weeks. Histomorphometric analysis of the proximal tibiae revealed that 1alpha(OH)D3 administration had no significant effect on trabecular bone volume of ovx limbs, which was reduced after ovx. The bone formation rate, increased by ovx, was significantly decreased by the administration of high-dose 1alpha(OH)D3. The ovx-induced increases in osteoclast number and surface at 2 weeks postsurgery were suppressed by the administration of high-dose 1alpha(OH)D3. With regard to bone marrow cells, the number of nonadherent cells per tibia obtained from ovx limbs increased, and this increase was suppressed by the administration of low- and high-dose 1alpha(OH)D3. The formation of mineralized nodules in marrow cultures obtained from ovx limbs was increased after surgery and unaltered by 1alpha(OH)D3 administration. The number of osteoclast-like multinucleated cells obtained from ovx limbs was reduced by low- and high-dose 1alpha(OH)D3 administration alike. The number of colony forming units-fibroblast and the number of colony forming units for granulocytes and macrophages was unaltered by ovx or the administration of 1alpha(OH)D3. The present study clearly demonstrates that high-dose 1alpha(OH)D3 suppresses osteoclast numbers and surface after ovx. The inhibitory effects of low- and high-dose 1alpha(OH)D3 on bone marrow cells after ovx were marked in the differentiation from osteoclast precursors to mature osteoclasts. Administration of 1alpha(OH)D3 suppressed ovx-promoted trabecular bone resorption by inhibiting osteoclastogenic potential in bone marrow cells.


Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Resorción Ósea , Hidroxicolecalciferoles/farmacología , Ovariectomía , Tibia/citología , Fosfatasa Alcalina/metabolismo , Animales , Análisis Químico de la Sangre , Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/genética , Ensayo de Unidades Formadoras de Colonias/métodos , Femenino , Glicoproteínas/efectos de los fármacos , Glicoproteínas/genética , Glicoproteínas de Membrana/efectos de los fármacos , Glicoproteínas de Membrana/genética , Ratones , Ratones Endogámicos , Osteoclastos/efectos de los fármacos , Osteoprotegerina , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/genética , Receptores del Factor de Necrosis Tumoral , Tibia/efectos de los fármacos , Tibia/metabolismo
10.
Digestion ; 63(3): 171-9, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11351144

RESUMEN

BACKGROUND/AIM: We examined the healing process of chronic gastric ulcers in adjuvant-induced arthritic rats and investigated the mechanism for delayed ulcer healing in arthritic rats, in relation to acid secretion and basic fibroblast growth factor (bFGF). METHODS: Arthritis was induced in male dark Agouti rats by a single injection of Freund's complete adjuvant (FCA), while gastric ulcers were induced by thermal cauterization (70 degrees C for 30 s) 7 days after FCA injection. RESULTS: Injection of FCA induced severe arthritis in all animals with a marked acid hypersecretion. The healing of gastric ulcers was significantly delayed in arthritic rats as compared with normal rats. Daily administration of indomethacin delayed ulcer healing in both normal and arthritic rats, but this effect was more pronounced in the latter. In contrast, the healing of gastric ulcers was significantly promoted in both normal and arthritic rats by omeprazole at a dose that inhibited acid secretion completely. The delayed healing of gastric ulcers was not influenced by twice daily administration of N(G)-nitro-L-arginine methyl ester, aminoguanidine or FR167653 (IL-1/TNF-alpha synthesis inhibitor), but was significantly accelerated by CS-23 (recombinant human bFGF) in a dose-dependent manner, without effect on the acid secretion. The expression of bFGF was markedly increased after ulceration, but this response was decreased in arthritic rats. CONCLUSION: The healing of gastric ulcers was delayed in arthritic rats, and this mechanism may be partly attributable to both acid hypersecretion and less expression of bFGF.


Asunto(s)
Artritis Reumatoide/complicaciones , Factores de Crecimiento de Fibroblastos/análisis , Ácido Gástrico/metabolismo , Omeprazol/administración & dosificación , Úlcera Gástrica/complicaciones , Úlcera Gástrica/patología , Úlcera Gástrica/fisiopatología , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/fisiopatología , Western Blotting , Modelos Animales de Enfermedad , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Indometacina/farmacología , Masculino , Ratas , Ratas Endogámicas , Úlcera Gástrica/tratamiento farmacológico , Factores de Tiempo , Resultado del Tratamiento
11.
J Biol Chem ; 276(28): 26260-8, 2001 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-11313351

RESUMEN

The molecular mechanism underlying the renal expression localization of the thiazide-sensitive Na-Cl cotransporter (TSC) gene was studied. The TSC gene was localized to chromosome 19p12-14. In cultured cells, tissue-specific transcription activity of the 5'-flanking region of the rat rTSC gene (5'FL/rTSC) was demonstrated, and the major promoter region was located between position -580 and -141. To further examine the tissue-specific transcription, transgenic rats harboring the 5'FL/rTSC fused upstream of the LacZ gene were generated. Immunohistochemical analysis clearly showed that LacZ gene expression was co-localized to distal convoluted tubules (DCT) with TSC, indicating that the 5'FL/rTSC regulates the renal tubule-specific TSC expression. Because a transcription factor, HFH-3 (hepatocyte nuclear factor-3/folk head homologue-3), had also been localized to DCT, a possible role of the putative cis-acting element (HFH-3/rTSC, -400/-387 position) for HFH-3 binding in the tissue-specific transcription was examined. Deletion and mutation analyses suggested that transcription of the HFH-3/rTSC was actually responsive to HFH-3, and electrophoretic mobility shift assay showed a direct binding of in vitro synthesized HFH-3 to the HFH-3/rTSC. In conclusion, the rTSC gene is localized to rat chromosome 19p12--24. The transcription regulatory region of the TSC gene confers DCT-specific gene expression. DCT-specific transcription factor HFH-3 may be involved in the renal tubule-specific transcription of TSC gene.


Asunto(s)
Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Túbulos Renales/metabolismo , Receptores de Droga/genética , Receptores de Droga/metabolismo , Simportadores , Animales , Secuencia de Bases , Mapeo Cromosómico , Regulación de la Expresión Génica , Datos de Secuencia Molecular , Ratas , Alineación de Secuencia , Simportadores del Cloruro de Sodio , Miembro 3 de la Familia de Transportadores de Soluto 12 , Transcripción Genética
12.
Med Sci Monit ; 7(1): 20-5, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11208487

RESUMEN

Polaprezinc, N-(3-aminopropionyl)-L-histidinatozinc, has been shown to stimulate the production of insulin-like growth factor-1 (IGF-1) in mesenchymal cells, the polypeptide playing a role in the gastric epithelial wound repair. The present study was performed to examine the effect of polaprezinc on the impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats, in relation to IGF-1. Arthritis was induced in male Dark Agouti (DA) rats by a single injection of Freund's complete adjuvant (FCA), and the gastric ulcers were induced by thermal cauterization (70 degrees C for 30 sec) 7 days after FCA injection. Omeprazole (30 mg/kg) was administered p.o. once daily, while recombinant human IGF-1 (rhIGF-1) (30 micrograms/kg, s.c.) or polaprezinc (3-10 mg/kg, p.o.) was administered twice daily, starting from 3 days after ulceration for 14 days. The healing of gastric ulcers was significantly delayed in arthritic rats as compared to normal rats on day 10 and 17 following ulceration. The expression of IGF-1 mRNA was markedly increased in the ulcerated mucosa, but this response was apparently attenuated in arthritic rats. Repeated administration of polaprezinc accelerated the healing of gastric ulcers in both normal and arthritic rats, in a dose-dependent manner, and this effect was more pronounced in arthritic rats. Likewise, treatment with omeprazole also significantly promoted the healing of gastric ulcers in both normal and arthritic rats. On the other hand, rhIGF-1 significantly promoted the gastric ulcer healing in arthritic rats without any effect on that in normal rats. These results suggest that the impaired healing of chronic gastric ulcers in arthritic rats is, at least partly, accounted for by less expression of IGF-1, and the polaprezinc improves the delayed healing of gastric ulcers in arthritic rats, probably through an increase in IGF-1 production.


Asunto(s)
Antiulcerosos/uso terapéutico , Artritis Experimental/fisiopatología , Carnosina/análogos & derivados , Carnosina/uso terapéutico , Mucosa Gástrica/fisiopatología , Factor I del Crecimiento Similar a la Insulina/fisiología , Omeprazol/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/fisiopatología , Cicatrización de Heridas/efectos de los fármacos , Animales , Artritis Experimental/complicaciones , Peso Corporal/efectos de los fármacos , Cauterización , Edema/fisiopatología , Adyuvante de Freund , Mucosa Gástrica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Masculino , ARN Mensajero/genética , Ratas , Ratas Endogámicas , Proteínas Recombinantes/farmacología , Úlcera Gástrica/complicaciones , Factores de Tiempo , Transcripción Genética/efectos de los fármacos , Compuestos de Zinc
13.
Arch Otolaryngol Head Neck Surg ; 126(8): 997-1000, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10922234

RESUMEN

OBJECTIVES: To examine the possible correlation between the amount of antigen and the level of soluble tumor necrosis factor receptor (sTNFR), and to assess its biologic significance in allergic reactions. DESIGN: Randomized control trial. SUBJECTS: Twelve volunteers with Japanese cedar pollinosis and 10 healthy volunteers. INTERVENTIONS: The levels of p55 sTNFR (sTNFR1) and p75 sTNFR (sTNFR2) in samples of serum and nasal epithelial lining fluid (ELF) from 12 subjects with pollinosis and 10 healthy subjects were measured 4 times (preseason, early season, midseason, and postseason) in low (total, 415/cm( 2) per season) and high (total, 19,935/cm(2) per season) pollen-count periods, and the results were compared among the 4 groups. RESULTS: In the low-pollen-count period, increased levels of sTNFR1 and sTNFR2 were observed in ELF samples from the allergic subjects during the midseason. In contrast, in the high-pollen-count period, those levels were already elevated during the preseason and reduced during the midseason. Especially, the levels of sTNFR2 in ELF samples from the allergic subjects during the midseason in the high-pollen-count period were significantly lower than those in the low-pollen-count period. Moreover, a significant negative correlation (sTNFR1, R = -0.82; sTNFR2, R = -0. 73) was found between the levels of sTNFR1 and sTNFR2 in ELF samples and the scores of symptoms in the allergic subjects in the high-pollen-count period, but not in the low-pollen-count period. CONCLUSION: In patients with pollinosis, the amounts of antigen regulate the local levels of sTNFRs, possibly inhibiting nasal allergic inflammation.


Asunto(s)
Antígenos/inmunología , Antígenos/metabolismo , Receptores del Factor de Necrosis Tumoral/inmunología , Receptores del Factor de Necrosis Tumoral/metabolismo , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/metabolismo , Adulto , Ensayo de Inmunoadsorción Enzimática , Humanos , Polen/efectos adversos , Polen/inmunología , Rinitis Alérgica Estacional/etiología , Estaciones del Año , Índice de Severidad de la Enfermedad , Regulación hacia Arriba
14.
Kurume Med J ; 47(2): 165-8, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10948655

RESUMEN

Schwann cell tumor occurring in the intestines is rare. A 68-year-old female came to our hospital because of hematemesis. Barium enema and colonoscopic examination revealed submucosal tumor in the sigmoid colon. Laboratory data showed mild anemia. No other abnormal finding was found in the blood chemistry. Tumor marker levels of carcinoembryonic antigen (CEA), CA19-9, alpha feto protein (AFP) and neuron specific enolase (NSE) were within normal limits. The exploratory laparotomy confirmed a large sigmoid colon tumor. She received sigmoid colectomy. The resected specimen was a submucosal tumor with central depression, measuring 4.7 x 3.5 x 3.0 cm in size. The cut surface of the tumor was yellowish hue with necrosis. Histological examination showed spindle-shaped tumor cells with palisading comma-shaped nuclei and the nuclear pleomorphism. Immunohistochemical examination revealed that the tumor was positive for S-100 protein staining, and negative for Actin and for H.H.F. staining. These findings showed that this tumor was of Schwann cell origin. We report here the case in detail of a schwannoma in the sigmoid colon.


Asunto(s)
Neoplasias del Colon/diagnóstico , Neurilemoma/diagnóstico , Anciano , Neoplasias del Colon/patología , Femenino , Humanos , Inmunohistoquímica , Neurilemoma/patología
15.
Biochim Biophys Acta ; 1464(2): 219-30, 2000 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-10727609

RESUMEN

A cDNA clone encoding a Na(+)- and Cl(-)-dependent high affinity taurine transporter was isolated from a common carp cell line, Epithelioma papulosum cyprini (EPC), as a hyperosmotic stress-inducible gene by RNA arbitrarily primed PCR. The clone contained a 2.5-kb cDNA fragment including an open reading frame of 1878 bp encoding a protein of 625 amino acids. The deduced amino acid sequence of carp taurine transporter shows 78-80% identity to those of cloned mammalian taurine transporters. The functional characteristics of the cloned transporter were analyzed by expression in COS-7 cells. Transfection with the cDNA induced Na(+)- and Cl(-)-dependent taurine transport activity with an apparent K(m) of 56 microM. The Na(+)/Cl(-)hepatopancreas. Taurine transporter mRNA level increased up to 7.5-fold on raising the ambient osmolality from 300 to 450 mosmol/kgH(2)O. These data suggest the significant role of taurine as an osmolyte in carp cells.


Asunto(s)
Carpas/genética , Proteínas Portadoras/genética , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana , ARN Mensajero/biosíntesis , Taurina/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células COS , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/química , Línea Celular , Cloruros/farmacología , Clonación Molecular , ADN Complementario/aislamiento & purificación , Soluciones Hipertónicas , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/química , Datos de Secuencia Molecular , ARN Mensajero/análisis , Alineación de Secuencia , Sodio/farmacología , Transfección
16.
J Med Chem ; 43(4): 649-63, 2000 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-10691691

RESUMEN

A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit 1a led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 10(6) L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead 1a. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS, 8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.


Asunto(s)
Anticoagulantes/síntesis química , Pirrolidinas/síntesis química , Inhibidores de Serina Proteinasa/síntesis química , Tiofenos/síntesis química , Trombina/antagonistas & inhibidores , Animales , Anticoagulantes/química , Anticoagulantes/farmacocinética , Anticoagulantes/farmacología , Sitios de Unión , Cristalografía por Rayos X , Evaluación Preclínica de Medicamentos , Humanos , Técnicas In Vitro , Modelos Moleculares , Pirrolidinas/química , Pirrolidinas/farmacocinética , Pirrolidinas/farmacología , Ratas , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/farmacocinética , Inhibidores de Serina Proteinasa/farmacología , Relación Estructura-Actividad , Tiofenos/química , Tiofenos/farmacocinética , Tiofenos/farmacología , Trombosis/sangre , Trombosis/metabolismo
17.
Aliment Pharmacol Ther ; 13(6): 833-40, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10383515

RESUMEN

AIM: To examine gastric mucosal ulcerogenic responses to indomethacin and HCl/ethanol in adjuvant arthritic (AA) rats. METHODS AND RESULTS: Arthritis was induced in male Dark Agouti (DA) rats by injection of Freund's complete adjuvant (FCA) into the right hind paw. The gastric ulcerogenic response to indomethacin was markedly worsened in AA rats, depending on the degree of arthritic change. This aggravation of indomethacin-induced gastric lesions in AA rats was significantly prevented by NG-nitro-L-arginine methyl ester (L-NAME) and amino-guanidine as well as dexamethasone. In contrast, the mucosal ulcerogenic response to HCl/ethanol was inhibited in AA rats. The suppression of HCl/ethanol-induced gastric lesions in AA rats was reversed almost totally by L-NAME and aminoguanidine as well as dexamethasone and partly by indomethacin. The expression of inducible nitric oxide synthase (iNOS) mRNA was observed in the stomach of AA rats but not of normal rats. Moreover, the luminal releases of nitric oxide (NO) metabolites as well as prostaglandin (PG) E2 were significantly increased in AA rats. CONCLUSIONS: The gastric mucosal ulcerogenic responses were modified in AA rats, in different manners depending on the irritants; an increase in response to indomethacin and a decrease in response to HCl/ethanol. These changes may both be accounted for by increased production of NO by iNOS, and the latter is also partly related to increased production of PGs.


Asunto(s)
Artritis Experimental/metabolismo , Óxido Nítrico/fisiología , Úlcera Gástrica/inducido químicamente , Animales , Peso Corporal , Dinoprostona/metabolismo , Etanol/toxicidad , Ácido Gástrico/metabolismo , Indometacina/toxicidad , Masculino , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo I , Óxido Nítrico Sintasa de Tipo II , ARN Mensajero/análisis , Ratas
18.
J Comp Neurol ; 408(2): 147-60, 1999 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-10333267

RESUMEN

Pax-6, a transcription regulatory factor, has been demonstrated to play important roles in eye, nose, and brain development by analyzing mice, rats, and humans with a Pax-6 gene mutation. We examined the role of Pax-6 with special attention to the formation of efferent and afferent pathways of the cerebral cortex by using the rat Small eye (rSey2), which has a mutation in the Pax-6 gene. In rSey2/rSey2 fetuses, cortical efferent axons develop with normal trajectory, at least within the cortical anlage, when examined with immunohistochemistry of the neuronal cell adhesion molecule TAG-1 and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) labeling from the cortical surface. A remarkable disorder was found in the trajectory of dorsal thalamic axons by immunostaining of the neurofilament and the neural cell adhesion molecule L1 and DiI labeling from the dorsal thalamus. In normal rat fetuses, dorsal thalamic axons curved laterally in the ventral thalamus without invading a Pax-6-immunoreactive cell cluster in the ventral part of the ventral thalamus. These axons then coursed up to the cortical anlage, passing just dorsal to another Pax-6-immunoreactive cell cluster in the amygdaloid region. In contrast, in rSey2/rSey2 fetuses, dorsal thalamic axons extended downward to converge in the ventrolateral corner of the ventral thalamus and fanned out in the amygdaloid region without reaching the cortical anlage. These results suggest that Pax-6-expressing cell clusters along the thalamocortical pathway (ventral part of the ventral thalamus and amygdala) are responsible for the determination of the axonal pathfinding of the thalamocortical pathway.


Asunto(s)
Vías Aferentes/embriología , Corteza Cerebral/embriología , Proteínas de Unión al ADN/fisiología , Vías Eferentes/embriología , Desarrollo Embrionario y Fetal , Proteínas de Homeodominio , Tálamo/embriología , Vías Aferentes/citología , Animales , Axones/fisiología , Moléculas de Adhesión Celular Neuronal/análisis , Corteza Cerebral/citología , Contactina 2 , Proteínas de Unión al ADN/genética , Vías Eferentes/citología , Anomalías del Ojo/genética , Proteínas del Ojo/genética , Proteínas del Ojo/fisiología , Feto , Homocigoto , Inmunohistoquímica , Complejo de Antígeno L1 de Leucocito , Glicoproteínas de Membrana/análisis , Ratones , Moléculas de Adhesión de Célula Nerviosa/análisis , Factor de Transcripción PAX6 , Factores de Transcripción Paired Box , Mutación Puntual , Ratas , Ratas Sprague-Dawley , Proteínas Represoras , Tálamo/citología
19.
J Thorac Cardiovasc Surg ; 117(2): 375-82, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9918980

RESUMEN

OBJECTIVE: The systemic inflammatory response is an important cause of organ dysfunction. The present study tested the hypothesis that 2 clinically used agents, amrinone and vesnarinone, would decrease inflammation and cardiac dysfunction in a relevant model of systemic inflammatory response activation. METHODS: Rabbits received intravenous endotoxin, alone or in conjunction with amrinone or vesnarinone. Systemic effects were assessed by death, fever, behavior, and acidosis. Measures of inflammatory signaling were (1) plasma tumor necrosis factor-alpha and interleukin-1 beta production, (2) lung tissue myeloperoxidase activity, and (3) myocardial inducible nitric oxide synthase activity. Indices of systolic and diastolic myocardial function were measured in Langendorff-perfused hearts. RESULTS: Vesnarinone, in particular, reduced mortality rates (19% vs 61% for lipopolysaccharide alone, P =.01) and acidosis in lipopolysaccharide-treated rabbits. Both agents markedly reduced systemic tumor necrosis factor and interleukin-1 concentrations, lipopolysaccharide-mediated effects on myocardial systolic and diastolic function and on myocardial inducible nitric oxide synthase activity. Vesnarinone, but not amrinone, (1) decreased fever and lethargy, consistent with decreased central nervous system effects of endotoxin, and (2) decreased lung leukocyte infiltration. CONCLUSIONS: Vesnarinone and amrinone, which are used clinically for their inotropic and vasodilating properties, may be useful to limit inflammatory activation and consequent organ dysfunction. Structure-activity and/or pharmacokinetic between the compounds may be important, particularly in preventing inflammatory signaling within certain tissues.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Amrinona/uso terapéutico , Inhibidores de Fosfodiesterasa/uso terapéutico , Quinolinas/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Animales , Evaluación Preclínica de Medicamentos , Endotoxemia/sangre , Endotoxemia/inducido químicamente , Endotoxemia/tratamiento farmacológico , Endotoxinas , Corazón/efectos de los fármacos , Corazón/fisiopatología , Mediadores de Inflamación/sangre , Interleucina-1/sangre , Pulmón/efectos de los fármacos , Pulmón/enzimología , Miocardio/enzimología , Óxido Nítrico Sintasa/efectos de los fármacos , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Pirazinas , Conejos , Salmonella typhimurium , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/inducido químicamente , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisis
20.
Arerugi ; 47(11): 1182-9, 1998 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-9893335

RESUMEN

Recently, it is pointed out that the incidence of Japanese cedar pollinosis has increased in children. We studied on the rate of sensitization and the onset of the disease in children under sixteen who visited allergy clinic in the Department of Otorhinolaryngology in Mie University Hospital. The percentage of positive rate of skin test and IgE antibodies of house dust mite was about 80 to 90% in 1981, 1991, and 1996. However, the percentage of positive rate of skin test and IgE antibodies of Japanese cedar pollen was 43% and 26%, respectively in 1981, but both increased to 58% in 1996. Most of Japanese cedar pollinosis patients also had house dust mite allergy. Among 115 pediatric patients who visited our allergy clinics in the past seven years, 32.2% were allergic to house dust mite alone, 8.6% were allergic to Japanese cedar pollen alone, 40.9% were allergic to both, and 6.1% were allergic to house dust mite, Japanese cedar pollen, and orchard grass pollen. 68% of the total 115 patients were boys, but significantly more girls had the pollinosis. 17.4% of those who are sensitized to the pollen were asymptomatic during the pollen season. Thus, it was confirmed that the rate of children sensitized to the pollen has apparently increased for the past twenty years. We should take care of those children who are sensitized to the pollen but asymptomatic during the pollen season.


Asunto(s)
Polen/inmunología , Rinitis Alérgica Estacional/epidemiología , Adolescente , Distribución por Edad , Animales , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina E/análisis , Incidencia , Lactante , Japón/epidemiología , Masculino , Ácaros/inmunología , Rinitis Alérgica Estacional/inmunología , Estaciones del Año , Pruebas Cutáneas , Árboles
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA