RESUMEN
AIMS: The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen. METHODS: This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was administered first with fixed dose and injection times and then adapted to optimal dose after 3 months. RESULTS: Mean HbA(1c) (%) of all the subjects at months 4 to 6 of the study was improved compared with month 0 (7.34 ± 0.87, 7.28 ± 0.88, 7.25 ± 0.93 vs. 7.55 ± 1.18; p < 0.05 paired t-test). However, significant improvement was seen only among the patients who had previously used NPH as a basal insulin. Twice-daily injection of basal insulin increased among people in the type 1 previously injected insulin glargine. Total insulin dose increased in the type 1 glargine group. The mean body weight change in the highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6 months. Quality of life (QoL) relating to the patients' glycaemic control tended to improve without a change in frequency of hypoglycaemia. CONCLUSIONS: The results suggest that insulin detemir has a greater effect on glycaemic control in subjects with poor glycaemic control using NPH; can reduce or maintain body weight in obese patients; and obtains perceptive stability for patients with unstable glycaemic control.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Pérdida de Peso/efectos de los fármacos , Adulto , Anciano , Fármacos Antiobesidad/uso terapéutico , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Insulina Detemir , Insulina Glargina , Insulina Isófana/administración & dosificación , Masculino , Persona de Mediana Edad , Obesidad/prevención & control , Estudios Prospectivos , Resultado del TratamientoRESUMEN
In the present study, we investigated the effect of hydroxyl radical (.OH) produced by the Fenton reaction with FeSO(4) to H(2)O(2) on Ca2+ influx by measuring [(45)Ca2+] influx into mouse cerebral cortical neurons in primary culture.OH formed from 3 microM FeSO(4) and 0.01 microM H(2)O(2) significantly reduced 30 mM KCl-induced [(45)Ca2+] influx and this reduction was abolished by .OH scavengers such as N,N'-dimethylthiourea and mannitol. Nifedipine (1 microM), an inhibitor for L-type voltage-dependent Ca2+ channels (VDCCs) showed no additive effect on the reduction of the 30 mM KCl-induced [(45)Ca2+] influx, while the inhibitors for P/Q- and N-type VDCCs showed further suppression of the KCl-induced [(45)Ca2+] influx even in the presence of .OH. Bay k 8644, an activator of L-type VDCCs, dose-dependently stimulated [(45)Ca2+] influx, and this stimulation disappeared in the presence of nifedipine. Similarly, .OH also suppressed significantly [(45)Ca2+] influx induced by Bay k 8644. These inhibitory actions of .OH on the KCl- and Bay k 8644-induced [(45)Ca2+] influx were completely abolished by .OH scavengers. These results indicate that .OH has the activity to suppress Ca2+ influx through L-type VDCCs.
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Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Calcio/metabolismo , Corteza Cerebral/citología , Radical Hidroxilo/farmacología , Proteínas del Tejido Nervioso/efectos de los fármacos , Neuronas/efectos de los fármacos , Tiourea/análogos & derivados , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Canales de Calcio/clasificación , Canales de Calcio/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Células Cultivadas/efectos de los fármacos , Corteza Cerebral/metabolismo , Deferoxamina/farmacología , Compuestos Ferrosos/farmacología , Depuradores de Radicales Libres/farmacología , Peróxido de Hidrógeno/farmacología , Activación del Canal Iónico , Transporte Iónico/efectos de los fármacos , Quelantes del Hierro/farmacología , Manitol/farmacología , Ratones , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Nifedipino/farmacología , Cloruro de Potasio/farmacología , Tiourea/farmacología , omega-Agatoxina IVA/farmacología , omega-Conotoxina GVIA/farmacologíaRESUMEN
We investigated the mechanisms underlying the increase in diazepam binding inhibitor (DBI) and its mRNA expression induced by nicotine (0.1 microM) exposure for 24 h using mouse cerebral cortical neurons in primary culture. Nicotine-induced (0.1 microM) increases in DBI mRNA expression were abolished by hexamethonium, a nicotinic acetylcholine (nACh) receptor antagonist. Agents that stabilize the neuronal membrane, including tetrodotoxin (TTX), procainamide (a Na(+) channel inhibitor), and local anesthetics (dibucaine and lidocaine), dose-dependently inhibited the increased expression of DBI mRNA by nicotine. The nicotine-induced increase in DBI mRNA expression was inhibited by L-type voltage-dependent Ca(2+) channel (VDCC) inhibitors such as verapamil, calmodulin antagonist (W-7), and Ca(2+)/calmodulin-dependent protein kinase II (CAM II kinase) inhibitor (KN-62), whereas P/Q- and N-type VDCC inhibitors showed no effects. In addition, nicotine exposure for 24 h induced [3H]nicotine binding to the particulate fractions of the neurons with an increased B(max) value and no changes in K(d). Under these conditions, the 30 mM KCl- and nicotine-induced 45Ca(2+) influx into the nicotine-treated neurons was significantly higher than those into non-treated neurons. These results suggest that the nicotine-stimulated increase in DBI mRNA expression is mediated by CAM II kinase activation resulting from the increase in intracellular Ca(2+) through L-type VDCCs subsequent to the neuronal membrane depolarization associated with nACh receptor activation.
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Canales de Calcio Tipo L/metabolismo , Proteínas Portadoras/genética , Neuronas/enzimología , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Anestésicos Locales/farmacología , Animales , Unión Competitiva/fisiología , Bloqueadores de los Canales de Calcio/farmacología , Radioisótopos de Calcio/farmacocinética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Células Cultivadas , Corteza Cerebral/citología , Inhibidor de la Unión a Diazepam , Dibucaína/farmacología , Inhibidores Enzimáticos/farmacología , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Hexametonio/farmacología , Lidocaína/farmacología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones , Neuronas/química , Neuronas/citología , Nicotina/metabolismo , Agonistas Nicotínicos/metabolismo , Antagonistas Nicotínicos/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Procainamida/farmacología , ARN Mensajero/metabolismo , Sulfonamidas/farmacología , Tetrodotoxina/farmacología , Tritio , omega-Agatoxina IVA/farmacología , omega-Conotoxina GVIA/farmacologíaRESUMEN
Effects of N-methyl-D-aspartate (NMDA) on diazepam binding inhibitor (DBI) and its mRNA expression in mouse cerebral cortical neurons were examined. A significant increase in DBI mRNA expression was observed 1 day after the exposure to 0.1 microM NMDA and the maximal expression occurred 2 days after the exposure, whereas transient exposure to 0.1 microM NMDA for 15 min, 1 and 3 h produced no changes in the expression. Similarly, no changes in the expression were found by the concomitant exposure to NMDA and MK-801, a NMDA receptor antagonist, for 72 h subsequent to the incubation with NMDA alone for 3 h. Such NMDA-induced increases in DBI mRNA expression were dose-dependently inhibited by MK-801. Moreover, neuronal DBI content significantly increased by treatment with NMDA, which was completely abolished by MK-801. These results indicate that continuous activation of NMDA receptors is an essential factor for increasing DBI expression in the neurons.
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Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Corteza Cerebral/citología , Neuronas/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Inhibidor de la Unión a Diazepam , Maleato de Dizocilpina/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Ratones , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , ARN Mensajero/análisisRESUMEN
The effect of heparin was studied histologically and immunohistochemically. Tooth germs from 15-day-old mouse embryos were cultured with or without heparin. After 6 days of culture in control medium, mesenchymal cells underlying the inner enamel epithelium had differentiated into odontoblasts and secreted predentine. In medium with heparin, mesenchymal cells were undifferentiated. In medium with other glycosaminoglycans such as chondroitin sulphate, dermatan sulphate or hyaluronate, tooth germs were similar to those in control medium, as were those in medium with heparin-Sepharose absorbed serum. After 12 days of culture in the heparin medium, mesenchymal cells in some cusps had differentiated into odontoblasts and secreted predentine but in other cusps remained undifferentiated. Immunohistochemically, exogenous heparin did not prevent the deposition of type IV collagen, laminin and fibronectin in the basement membrane and extracellular matrix. These results suggest that exogenous heparin retards differentiation of odontoblasts but not by disruption of the basement membrane nor inactivation of heparin-binding growth factors present in serum.
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Heparina/farmacología , Odontoblastos/efectos de los fármacos , Germen Dentario/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Sulfatos de Condroitina/farmacología , Colágeno/análisis , Papila Dental/efectos de los fármacos , Papila Dental/patología , Papila Dental/fisiopatología , Dermatán Sulfato/farmacología , Órgano del Esmalte/efectos de los fármacos , Órgano del Esmalte/patología , Órgano del Esmalte/fisiopatología , Epitelio/efectos de los fármacos , Epitelio/patología , Epitelio/fisiopatología , Fibronectinas/análisis , Ácido Hialurónico/farmacología , Técnicas para Inmunoenzimas , Laminina/análisis , Mesodermo/efectos de los fármacos , Mesodermo/patología , Mesodermo/fisiología , Ratones , Ratones Endogámicos , Odontoblastos/patología , Odontoblastos/fisiología , Técnicas de Cultivo de Órganos , Germen Dentario/patología , Germen Dentario/fisiologíaRESUMEN
We report a case of hepatic angiosarcoma that is usually difficult to differentiate from cavernous hemangioma on computed tomography. The present case suggests that early central enhancement and arterioportal shunting on dynamic computed tomography might be helpful for distinguishing hepatic angiosarcoma with a solid growth pattern from benign vascular neoplasms of the liver such as cavernous hemangioma.
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Hemangiosarcoma/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Anciano , Femenino , Hemangiosarcoma/patología , Humanos , Neoplasias Hepáticas/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND/AIMS: Percutaneous microwave coagulation therapy (PMCT) has recently been introduced as a new treatment for hepatocellular carcinoma (HCC) in Japan. This study was performed to evaluate its efficacy and safety. METHODOLOGY: Thirteen patients with 17 nodules of unresectable HCC were subjected to PMCT under ultrasonic guidance. The tumors ranged from 1.2-4.4 cm in size. Assessment of the efficacy of PMCT was made by follow-up with dynamic computed tomography (CT). RESULTS: In the patients with small HCC (< or = 2.0 cm), 8 of 10 nodules (80%) showed complete remission after PMCT. In small nodules located on the liver surface, 3 out of 4 nodules (75%) showed complete remission. However, in the patients with larger HCC (> or = 2.1 cm), 5 out of 7 nodules developed local recurrence after PMCT. Regarding assessment of the necrotic area after PMCT, dynamic CT revealed enhancement that was possibly caused by congestion of the liver parenchyma surrounding the area of necrosis due to PMCT in the early phase of the treatment. Therefore, the necrotic area must be assessed carefully. Although a slight heat sensation and/or pain during microwave irradiation (a common effect of PMCT) occurred in all patients, there were no serious adverse effects. CONCLUSIONS: Complete remission of small HCC (< or = 2 cm in diameter) can be achieved with PMCT alone, but there seem to be limitations to its effectiveness with larger HCC (> or = 2.1 cm). There were no serious adverse effects from PMCT and the therapy can be safely carried out even in patients with poor liver function.
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Carcinoma Hepatocelular/terapia , Hipertermia Inducida , Neoplasias Hepáticas/terapia , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Two cases of liver metastasis from colon cancer were treated by percutaneous ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year later, recurrence of liver tumor was detected, and PEI and PAI were performed for the metastatic lesions of the liver. Tumor regression and histopathological examination revealed coagulative necrosis. The patient died of lung metastasis 2 years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending colon cancer and liver metastasis, who received surgery, and chemotherapy with intraarterial 5-FU infusion was continued. Four months later, recurrence of liver metastasis with elevation of serum CEA was noted. The patient received PEI three times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis at the site of PEI. The patient has been alive for 1 year and 6 months with a new recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem to be useful for the treatment of unresectable liver metastasis.
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Ácido Acético/administración & dosificación , Neoplasias del Colon/patología , Etanol/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Antígeno Carcinoembrionario/sangre , Colon Sigmoide/cirugía , Neoplasias del Colon/cirugía , Femenino , Hepatectomía , Humanos , Inyecciones Intralesiones , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana EdadRESUMEN
A case of rapidly progressive periodontitis combined with plasma cell gingivitis with marked enlargement of the gingiva was presented. Clinically, in the plasma cell gingivitis, the gingiva appear red, friable and bleed easily; usually it does not induce loss of attachment. Histologically, a dense infiltration of the normal plasma cells in the connective tissue is a common finding. A hypersensitivity reaction to some antigens, often flavorings or spices, is generally recognized. In this case, a rapidly progressive loss of attachment was observed, so rapidly progressive periodontitis was diagnosed. Differential diagnosis of the plasma cell gingivitis could be determined by histological and ultrastructural examination. Allergens, however, could not be identified. Conventional periodontal therapy, including intensive plaque control, could not cure the plasma cell gingivitis completely but recurrence of gingival enlargement and loss of attachment could be well controlled.
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Encía/patología , Gingivitis/microbiología , Periodontitis/microbiología , Adolescente , Femenino , Gingivitis/patología , Humanos , Periodontitis/patologíaAsunto(s)
Ascitis/inmunología , Productos Biológicos/uso terapéutico , Neoplasias Intestinales/inmunología , Picibanil/uso terapéutico , Neoplasias Gástricas/inmunología , Adulto , Anciano , Ascitis/tratamiento farmacológico , Ascitis/etiología , Ensayos Clínicos como Asunto , Femenino , Humanos , Neoplasias Intestinales/complicaciones , Neoplasias Intestinales/mortalidad , Intestino Grueso , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Picibanil/efectos adversos , Pronóstico , Pruebas Cutáneas , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/mortalidad , Linfocitos T/inmunologíaAsunto(s)
Diferenciación Celular/fisiología , Ciclinas/genética , Hepatocitos/citología , Hepatocitos/fisiología , Ciclo Celular/fisiología , Línea Celular Transformada , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/metabolismo , Técnica del Anticuerpo Fluorescente , Vectores Genéticos , Humanos , Sistemas de Lectura Abierta , Proteínas Recombinantes de Fusión/metabolismo , Mapeo Restrictivo , Albúmina Sérica/análisisAsunto(s)
Regulación de la Expresión Génica , Hígado , Glicoproteínas de Membrana/genética , Receptores de Superficie Celular/genética , Secuencia de Bases , Línea Celular , Línea Celular Transformada , Cartilla de ADN , Proteínas de Unión al ADN , Endotelio/fisiología , Hepatocitos/fisiología , Humanos , Hígado/citología , Hígado/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Telomerasa/genética , Receptor Toll-Like 4 , Receptores Toll-LikeAsunto(s)
Anticuerpos/análisis , Embarazo , Rubéola (Sarampión Alemán)/inmunología , Adolescente , Adulto , Factores de Edad , Pueblo Asiatico , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Japón , Persona de Mediana Edad , Complicaciones Infecciosas del Embarazo/prevención & controlRESUMEN
The present study was carried out to investigate histological and ultrastructural changes, particularly changes of the epithelium-connective tissue junction, in rat gingival wounds treated with Caffeine or NaCl. Light Microscopy The animal had an incision in the lingual gingiva of lower incisors. Immediately after incision, the wounds of Groups A, B and C were treated with distilled water, caffeine (2.5%) and NaCl (25%), respectively. The gingivae were examined histologically at 1, 2, 4, 6, 8, 12 and 28 days after treatment. Electron Microscopy Groups a, b and c received the same treatment as those of Groups A, B and C, respectively. The gingivae were examined ultrastructurally at 4 and 28 days after treatment. 1. Light Microscopic Observations (1) Group A. On all experimental days, the wounds were covered by the epithelium. At 1 and 2 days, the connective tissues exhibited depositions of fibrin, but, at 4, 6 and 8 days, they showed the granulation tissues. At 12 and 28 days, the connective tissues appeared normal. (2) Group B. On all experimental days, the wounds were covered by the epithelium. At 1 and 2 days, the connective tissues exhibited depositions of fibrin. At 4, 6 and 8 days, they displayed granulation tissues. At 12 and 28 days, the connective tissues appeared normal. (3) Group C. On all experimental days, the wounds were covered by the epithelium. At 1 and 2 days, the connective tissues exhibited depositions of fibrin. At 4, 6, 8 and 12 days, they displayed granulation tissues. At 28 days, the connective tissue was normal. (4) Histometrically, at 6 days, Groups A, B and C exhibited the highest, intermediate and lowest number of fibroblasts per unit area, respectively. There were no differences in the number of inflammatory cells between all three groups. 2. Electron Microscopic Observations (1) Group a. At 4 days, the normally-formed gingival basal lamina was observed rather frequently just beneath the basal surfaces of basal cells. On occasions, the basal lamina exhibited various changes such as detachments, breaks, thickenings and duplications. Moreover, absence of the basal lamina was observed. At 28 days, the irregular types of basal laminae decreased in number, and most of the basal laminae appeared normal in structure. (2) Group b. At 4 days, the normally-formed gingival basal lamina was observed less frequently as compared with those of Group a. The above-mentioned various changes of the basal lamina were found rather frequently.(ABSTRACT TRUNCATED AT 400 WORDS)
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Cafeína/farmacología , Cloruro de Sodio/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Encía/lesiones , Encía/ultraestructura , RatasRESUMEN
The purpose of the present study was to study histologically and histometrically the inhibitory effect of aspirin on root resorption induced by mechanical injury of the periodontal soft tissues in rats. Resorption lacuna in the root surface of the molar in animals given both mechanical injury and aspirin administration contained fewer odontoclasts and was smaller in length and area than that in animals given only mechanical injury. The result of the present investigation indicated that the administration of aspirin might suppress root resorption induced by mechanical injury of the periodontal soft tissues.
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Aspirina/uso terapéutico , Encía/lesiones , Ligamento Periodontal/lesiones , Antagonistas de Prostaglandina/uso terapéutico , Resorción Radicular/prevención & control , Animales , Aspirina/farmacología , Masculino , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Antagonistas de Prostaglandina/farmacología , Ratas , Ratas Wistar , Resorción Radicular/etiología , Heridas Penetrantes/complicacionesRESUMEN
OBJECTIVE: Percutaneous microwave coagulation therapy was recently introduced as a new treatment for hepatocellular carcinoma in our country. We performed this study to evaluate the efficacy and safety of this therapy for treatment of hepatocellular carcinoma, especially for tumors located on the surface of the liver. CONCLUSION: Percutaneous microwave coagulation therapy can be performed safely even in patients with cirrhosis and can achieve complete remission of small hepatocellular carcinomas (< or = 2.0 cm) located on the surface of the liver.