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1.
Endocr J ; 63(3): 311-4, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26598136

RESUMEN

Diazoxide is a non-diuretic benzothiadiazine derivative, one of a group of substances introduced into clinical practice in the 1950s for the treatment of hypertension. Fajans reported the use of diazoxide for the treatment of insulinoma in 1979. Although patients with hyperinsulinemic hypoglycemia worldwide have been treated with diazoxide for more than 30 years, there are no recent reports about the adverse effects of this drug in Asian patients, including Japanese patients. Herein, we report the results of our retrospective clinical record review of 6 Japanese patients (3 females and 3 males, ranging in age from 58 to 91 years) with hyperinsulinemic hypoglycemia and inoperable insulinoma treated with diazoxide. Diazoxide improved control of hypoglycemic symptoms and maintained normoglycemia in 5 of the 6 patients, and was ineffective in one patient. Surprisingly, although all 6 patients received diazoxide according to the treatment strategy recommended in Western patients, 5 of the 6 patients developed edema and two developed congestive heart failure. Thus, when starting treatment with diazoxide in Japanese patients, the symptoms and signs of fluid retention should be evaluated carefully. Also, appropriate protocols for treatment with diazoxide should be evaluated by means of clinical trials in Japanese patients with hyperinsulinemic hypoglycemia.


Asunto(s)
Antihipertensivos/efectos adversos , Diazóxido/efectos adversos , Hiperinsulinismo/prevención & control , Hipoglucemia/prevención & control , Insulinoma/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Diazóxido/administración & dosificación , Diazóxido/uso terapéutico , Monitoreo de Drogas , Resistencia a Medicamentos , Edema/etiología , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Hiperinsulinismo/etiología , Hipoglucemia/etiología , Insulinoma/sangre , Insulinoma/fisiopatología , Japón , Masculino , Persona de Mediana Edad , Desequilibrio Hidroelectrolítico/inducido químicamente , Desequilibrio Hidroelectrolítico/fisiopatología
2.
J Clin Pharmacol ; 55(7): 831-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25677642

RESUMEN

This study aimed to compare the efficacy and safety of liraglutide versus insulin detemir plus sitagliptin in Japanese patients with type 2 diabetes treated with a basal-bolus insulin regimen. In this multicenter, open-label trial, 90 patients whose diabetes had been controlled well or moderately (glycated hemoglobin [HbA1c ] ≤ 7.3%) with basal-bolus insulin regimen were randomly assigned to a liraglutide group or a detemir group and were followed up for 24 weeks. The primary end point was HbA1c change from baseline to 24 weeks. Of the 90 enrolled patients, 82 completed this trial. At 24 weeks, the mean changes in HbA1c from baseline were 0.1% ± 0.9% versus 0.3% ± 0.8% in the liraglutide versus detemir groups, respectively (P = .46). The "overall" satisfaction score for the Diabetes Treatment Satisfaction Questionnaire changed from 25.2 ± 7.4 to 29.9 ± 5.3 (P < .001) and from 26.4 ± 6.1 to 28.3 ± 6.4 (P = .12) in the liraglutide and detemir groups, respectively. Although the mean change difference in HbA1c between both groups was not significant, switching from a basal-bolus insulin regimen to liraglutide once daily improved patient satisfaction levels without loss of glycemic control.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina Detemir/uso terapéutico , Liraglutida/uso terapéutico , Fosfato de Sitagliptina/uso terapéutico , Anciano , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Inyecciones , Insulina Detemir/administración & dosificación , Japón , Liraglutida/administración & dosificación , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Fosfato de Sitagliptina/administración & dosificación , Encuestas y Cuestionarios , Resultado del Tratamiento
3.
Hiroshima J Med Sci ; 60(2): 37-9, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21970186

RESUMEN

Patients on long-term hemodialysis are at risk of developing malnutrition,and poor nutrient intake is an important factor in this. In the present case, we encountered a 55-year-old Japanese woman with end-stage renal failure and a past history of schizophrenia. Severe systemic edema was observed. Hemodialysis was started, but after one year she suddenly became unable to consume food orally, despite provision of a dietary plan by the nutrition support team (NST). Tube feeding was eventually implemented. Because the systemic edema did not improve, we decided to remove body fluid by intense hemodialysis. Hypotension was often observed during this hemodialysis, requiring dopamine. Over approximately 2 months, the patient's dry weight fell from 73 kg to 62 kg, the patient's activity improved and she became able to eat orally again, allowing tube feeding to be stopped. Although the reason for the sudden anorexia has not been clarified, tube feeding and dry weight control was successful in the treatment of this malnourished hemodialysis patient.


Asunto(s)
Edema/terapia , Nutrición Enteral , Fallo Renal Crónico/terapia , Desnutrición/terapia , Diálisis Renal , Actividades Cotidianas , Dopamina/uso terapéutico , Edema/etiología , Edema/fisiopatología , Femenino , Humanos , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Desnutrición/etiología , Desnutrición/fisiopatología , Persona de Mediana Edad , Estado Nutricional , Diálisis Renal/efectos adversos , Simpatomiméticos/uso terapéutico , Resultado del Tratamiento , Pérdida de Peso
4.
Psychogeriatrics ; 11(3): 166-70, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21951957

RESUMEN

The present paper reports on a 68-year-old man with a 10-year history of parkinsonism who developed hallucinations and delusions after admission to an intensive care unit for the treatment of organophosphate intoxication. His initial diagnosis was delirium. On the basis of brain computed tomography findings and clinical symptoms, we diagnosed drug-induced psychosis in parkinsonism with multiple cysts in the bilateral striata.


Asunto(s)
Dominancia Cerebral/fisiología , Encefalomalacia/diagnóstico , Neostriado/patología , Trastornos Parkinsonianos/diagnóstico , 3-Yodobencilguanidina , Anciano , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/uso terapéutico , Antipsicóticos/uso terapéutico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Delirio/diagnóstico , Delirio/tratamiento farmacológico , Deluciones/diagnóstico , Deluciones/tratamiento farmacológico , Diagnóstico Diferencial , Dibenzotiazepinas/uso terapéutico , Quimioterapia Combinada , Encefalomalacia/tratamiento farmacológico , Alucinaciones/diagnóstico , Alucinaciones/tratamiento farmacológico , Humanos , Levodopa/efectos adversos , Levodopa/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Neostriado/irrigación sanguínea , Examen Neurológico , Intoxicación por Organofosfatos , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Psicosis Inducidas por Sustancias/diagnóstico , Psicosis Inducidas por Sustancias/tratamiento farmacológico , Fumarato de Quetiapina , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X
5.
J Med Invest ; 58(3-4): 252-4, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21921427

RESUMEN

Acute appendicitis often presents as right lower quadrant (RLQ) pain, severe tenderness at the point of McBurny or Lanz, and Blumberg's sign. Scrotal events with appendicitis are very rare. In our case, a 63-year-old Japanese man presented with severe RLQ pain and high fever. Physical examination revealed severe tenderness (including both points of McBurny and Lanz) and Blumberg's sign. The scrotum was slightly swollen and showed local heat with severe testicular pain. Abdominal computed tomography revealed ascites in a pelvic space and the right side of the spermatic cord was swollen. Emergency operation was performed and the final diagnosis was catarrhal appendicitis and acute epididymitis. This is the first report of acute appendicitis concomitant with acute epididymitis.


Asunto(s)
Abdomen Agudo/etiología , Apendicitis/complicaciones , Epididimitis/complicaciones , Humanos , Masculino , Persona de Mediana Edad
6.
J Med Invest ; 58(3-4): 255-8, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21921428

RESUMEN

Fournier's gangrene (FG) is rapidly progressing acute gangrenous infection of the anorectal and urogenital area. FG needs precocious diagnosis and aggressive treatment with the use of wide spectrum antibioticus and surgical debridement. In our case, a 91-year-old Japanese female who had rehabilitation after treatment of pneumonia and her past history was rheumatoid arthritis treated with steroid and chronic heart failure. Her activities of daily living was bedridden with dementia. Necrotic skin was observed in urogenital and anorectal area and skin redness enlarged to the hip with high fever. Surgical debridement was performed. Both Peptostreptococcus Sp. and Fusobacterium Sp. was cultured from resected necrotic tissue. We used antibioticus, PAPM and PIPC, which had sensitivity for them. But unfortunately, disseminated intravascular coagulation occurred after 4th day of operation, and finally she died after 10th day of operation. We discussed the treatment for FG in patient with complication.


Asunto(s)
Gangrena de Fournier/terapia , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Desbridamiento , Femenino , Gangrena de Fournier/complicaciones , Humanos
7.
Brain Res ; 1287: 184-91, 2009 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-19559010

RESUMEN

Mild cognitive impairment (MCI) is considered the transitional stage between normal cognition and dementia. The aim of this study was to use tractography based analysis to elucidate alterations in subjects with MCI compared with subjects with early Alzheimer's disease (AD) and controls. Seventeen subjects with early AD, 16 with MCI and 16 controls underwent magnetic resonance diffusion tensor imaging (DTI) and neuropsychological assessment. Diffusion tensor tractographies were computed and fiber-tract maps were generated using "dTV II" DTI software. We measured mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the uncinate fasciculus (UNC), posterior cingulate fasciculus (PCF) and corticospinal tract (CST). There were statistically significant differences in the FA and ADC values of the UNC and PCF between subjects with early AD and controls. Subjects with MCI exhibited significantly lower FA values on both sides of the PCF relative to controls. However, there were no significant differences between subjects with early AD and MCI for any measurement. Our results suggest that alterations in the PCF precede the onset of dementia.


Asunto(s)
Enfermedad de Alzheimer/patología , Trastornos del Conocimiento/patología , Imagen de Difusión por Resonancia Magnética/métodos , Giro del Cíngulo/patología , Tractos Piramidales/patología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/psicología , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/psicología , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad
8.
J Pharmacol Exp Ther ; 322(1): 23-9, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17468300

RESUMEN

Tobacco and alcohol are the most commonly used drugs of abuse and show the most serious comorbidity. The mesolimbic dopamine system contributes significantly to nicotine and ethanol reinforcement, but the underlying cellular signaling mechanisms are poorly understood. Nicotinic acetylcholine (nACh) receptors are highly expressed on ventral tegmental area (VTA) dopamine neurons, with relatively low expression in nucleus accumbens (NAcb) neurons. Because dopamine receptors D(1) and D(2) are highly expressed on NAcb neurons, nicotine could influence NAcb neurons indirectly by activating VTA neurons to release dopamine in the NAcb. To investigate this possibility in vitro, we established primary cultures containing neurons from VTA or NAcb separately or in cocultures. Nicotine increased cAMP response element-mediated gene expression only in cocultures; this increase was blocked by nACh or dopamine D(1) or D(2) receptor antagonists. Furthermore, subthreshold concentrations of nicotine with ethanol increased gene expression in cocultures, and this increase was blocked by nACh, D(2) or adenosine A(2A) receptor antagonists, Gbetagamma or protein kinase A (PKA) inhibitors, and adenosine deaminase. These results suggest that nicotine activated VTA neurons, causing the release of dopamine, which in turn stimulated both D(1) and D(2) receptors on NAcb neurons. In addition, subthreshold concentrations of nicotine and ethanol in combination also activated NAcb neurons through synergy between D(2) and A(2A) receptors. These data provide a novel cellular mechanism, involving Gbetagamma subunits, A(2A) receptors, and PKA, whereby combined use of tobacco and alcohol could enhance the reinforcing effect in humans as well as facilitate long-term neuroadaptations, increasing the risk for developing coaddiction.


Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico/fisiología , Etanol/farmacología , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/fisiología , Nicotina/farmacología , Núcleo Accumbens/efectos de los fármacos , Receptor de Adenosina A2A/fisiología , Receptores de Dopamina D1/fisiología , Receptores de Dopamina D2/fisiología , Área Tegmental Ventral/efectos de los fármacos , Animales , Células Cultivadas , Técnicas de Cocultivo , Activación Enzimática , Expresión Génica/efectos de los fármacos , Núcleo Accumbens/enzimología , Subunidades de Proteína , Ratas , Ratas Sprague-Dawley , Elementos de Respuesta/fisiología , Área Tegmental Ventral/enzimología
9.
Proc Natl Acad Sci U S A ; 102(24): 8746-51, 2005 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-15937104

RESUMEN

The nucleus accumbens (NAc) is central to heroin addiction. Activation of opiate receptors in the NAc dissociates G(i/o) into alpha and betagamma subunits. Galpha(i) inhibits cAMP production, but betagamma regulates several molecular pathways, including protein kinase A (PKA). We show in NAc/striatal neurons that opiates paradoxically activate PKA signaling by means of betagamma dimers. Activation requires Galpha(i3) and an activator of G protein signaling 3 (AGS3). AGS3 competes with betagamma for binding to Galpha(i3)-GDP and enhances the action of unbound betagamma. AGS3 and Galpha(i3) knockdown prevents opiate activation of PKA signaling. In rats self-administering heroin, AGS3 antisense in the NAc core, but not shell, eliminates reinstatement of heroin-seeking behavior, a model of human relapse. Thus, Galpha(i3)/betagamma/AGS3 appears to mediate mu opiate receptor activation of PKA signaling as well as heroin-seeking behavior.


Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Dependencia de Heroína/metabolismo , Núcleo Accumbens/metabolismo , Receptores Opioides/metabolismo , Transducción de Señal/fisiología , Animales , Western Blotting , Encéfalo/patología , Células Cultivadas , Subunidades beta de la Proteína de Unión al GTP/metabolismo , Subunidades gamma de la Proteína de Unión al GTP/metabolismo , Vectores Genéticos , Técnicas Histológicas , Inmunoprecipitación , Masculino , Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Simplexvirus
10.
Biochim Biophys Acta ; 1625(3): 246-52, 2003 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-12591611

RESUMEN

Human glia maturation factor-gamma (hGMFG) was recently identified as a gene that is homologous to glia maturation factor-beta (GMFB). In this study, we determined the organization of the 9.5-kb hGMFG gene and characterized its promoter activity. The 5'-flanking region of the first exon has putative elements for binding transcription factors Sp-1, GATA-1, AML-1a, Lyf-1 and Ets-1, but there were no TATA or CAAT boxes within a 226-bp sequence upstream from the initiation codon. Primer extension analysis and 5'RACE (rapid amplification of cDNA 5' ends) identified multiple transcription initiation sites within the region -84 to -70 nucleotides from the first ATG codon in a Kozak consensus sequence. A core promoter region was determined by transfecting a series of deletion constructs with a dual luciferase reporter system into rat astrocyte-derived ACT-57 cells. We found that 226 bp of the core promoter region exhibited bidirectional promoter activity.


Asunto(s)
Factor de Maduración de la Glia/genética , Regiones Promotoras Genéticas/fisiología , Secuencia de Bases , Sitios de Unión , Línea Celular , Clonación Molecular , Genes Reguladores , Factor de Maduración de la Glia/biosíntesis , Humanos , Datos de Secuencia Molecular , Sitio de Iniciación de la Transcripción
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