Effects of DA-9701, a Novel Prokinetic Agent, on Phosphorylated Extracellular Signal-Regulated Kinase Expression in the Dorsal Root Ganglion and Spinal Cord Induced by Colorectal Distension in Rats

BACKGROUND/AIMS: DA-9701, a standardized extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that exhibits an analgesic effect on the abdomen. We investigated whether DA-9701 affects visceral pain induced by colorectal distension (CRD) in rats. METHODS: A total of 21 rats were divided into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root ganglion (DRG) and spinal cord was determined by immunohistochemical staining and Western blotting. RESULTS: The proportions of neurons in the DRG and spinal cord expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK was lower than that in group B. Western blot results for p-ERK in the spinal cord indicated a higher level of expression in group B than in group A and a lower level of expression in group C than in group B. CONCLUSIONS: DA-9701 may decrease visceral pain via the downregulation of p-ERK in the DRG and spinal cord.

Effect of different durations of overdistention on rat bladder function and morphology

We investigated the contribution of the duration of overdistention (DOD) to rat bladder function and morphology and explored its possible molecular mechanisms. Bladder overdistention was induced in male Sprague-Dawley rats (200-250 g) by an infusion of saline. Forty rats were divided into 5 groups submitted to different DOD, i.e., 1, 2, 4, and 8 h, and control. Bladder function was evaluated by cystometry. Morphological changes were observed by light and transmission electron microscopy. Compared to control (44.567 ± 3.472 cmH2O), the maximum detrusor pressure of groups with 2-, 4- and 8-h DOD decreased significantly (means ± SEM): 32.774 ± 3.726, 31.321 ± 2.847, and 29.238 ± 3.724 cmH2O. With the increase of DOD, inflammatory infiltration and impairment of ultrastructure were more obvious in bladder tissue. Compared to control (1.90 ± 0.77), the apoptotic indexes of groups with 1-, 2-, 4-, and 8-h DOD increased significantly (6.47 ± 2.10, 10.66 ± 1.97, 13.91 ± 2.69, and 18.33 ± 3.28%). Compared to control (0.147 ± 0.031/0.234 ± 0.038 caspase 3/β-actin and Bax/Bcl-2 ratios), both caspase 3/β-actin and Bax/Bcl-2 ratios of 1-, 2-, 4-, and 8-h DOD increased significantly (0.292 ± 0.037/0.508 ± 0.174, 0.723 ± 0.173/1.745 ± 0.471, 1.104 ± 0.245/4.000 ± 1.048, and 1.345 ± 0.409/8.398 ± 3.332). DOD plays an important role in impairment of vesical function and structure. With DOD, pro-apoptotic factors increase and anti-apoptotic factors decrease, possibly contributing to the functional deterioration and morphological changes of the bladder.

Infarto elétrico: alterações elétricas graves com mínimo dano miocárdico associado à ectasia coronariana / Electrical infarct: severe electrical alterations with minimal myocardial damage associated with coronary ectasia

Ectasia coronariana é situação pouco comum na prática clínica, sendo definida como dilatação anômala de segmentos coronarianos. Essa condição apresenta diferentes etiologias, sendo a mais comum a doença ateroesclerótica. Frequentemente acomete a artéria coronária direita e sua presença está relacionada a fenômenos tromboembólicos, como o infarto agudo do miocárdio. Relata-se um caso de infarto agudo do miocárdio com supradesnivelamento do segmento ST ocorrido em homem jovem, portador de ectasia de segmento proximal de coronária esquerda que evoluiu com grave distúrbio da condução elétrica pós-trombólise e mínimo dano miocárdio.

Accidente cerebro-vascular en la enfermedad de Fabry: algo más que una simple estenosis / Stroke in Fabry disease: more than a simple stenosis

Se analiza la evidencia existente a la fecha sobre los mecanismos fisiopatológicos que puedem generar accidentes cerebrovasculares en la enfermedad de Fabry. Esta entidad es el resultado de la deficiencia de alfa-galactosidasa A, lo que resulta en depósito patológico de glicoesfingilípidos en distintas poblaciones celulares. Asociados a la insuficiencia renal y cardíaca, los accidentes cerebrovasculares pueden derivar en la muerte de los pacientes. Durante mucho tiempo el único mecanismo generador de daño vascular informado fue la oclusión vascular por depósito lipídico a nivel endotelial. En la actualidad se describen otros mecanismos. El advenimento de la terapia de reemplazo enzimático ha generado gran expectativa en cuanto la posibilidad de reversión de estos mecanismos. Si bien la evidencia es escasa y son necesarios más estudios a largo plazo, algunos informes demuestran que luego de meses, el tratamiento ha logrado revertir algunos de los mecanismos implicados

The objective is to analyze the updated evidence on the physiopathological mechanisms that can generate cerebrovascular damage in Fabry disease. Fabry disease is the result of the deficiency of alpha-galactosidasa A, which causes pathological storage of glycosphingolipids, in different cells. Associated to renal and cardiac insufficiency, cerebrovascular complications can derive in the death of the patients. During a long time the only reported mechanism was the vascular occlusion by deposit of lipids at endothelial level. At the present time, other mechanisms are postulated. The arrival of enzyme replacement therapy has generated great expectation on the possibility of reversion of these alterations. Although the evidence is scarce and more long-term studies are necessary, some reports demonstrate that after months, the treatment has managed to revert some of the mechanisms involved

Takotsubo, discinesia apical transitoria: presentación de 4 casos y revisión de la literatura / Takotsubo, reversible apical ballooning of the left ventricle: report of 4 cases

A syndrome of apical ballooning, with ECG mimicking acute myocardial infarctation, mild or no enzymatic changes, and normal coronary angiogram was described in 1990. It presents mainly in middle aged and elderly women and it is preceded by stress triggering circumstances. Several mechanisms have been proposed although the precise cause remains unclear. The most accepted theory proposes the interaction of catecholamines and an inadequate inotropic response. We report four cases that presented with chest pain and sudden onset of heart failure, all patients had physical or emotional stress as a triggering factor. On ECG, ST segment elevation and inverted T waves were observed in the acute phase. All patients had typical echocardiogram image and normal coronary angiogram. Both ECG and echocardiogram returned to normal within two weeks.

En 1990 se describió un síndrome caracterizado por discinesia apical transitoria, cambios en el electrocardiograma(ECG), mínima elevación de enzimas cardíacas y arterias coronarias normales. Sepresenta con mayor frecuencia en mujeres añosas y es precedido por un evento de estrés, ya sea físico opsíquico. La fisiopatología aún no está aclarada y se proponen diversas teorías. La de mayor peso es la quepostula una afección secundaria a la descarga de catecolaminas desencadenada por el estrés, sobre un corazón incapaz de mantener una respuesta inotrópica adecuada. Se presentan cuatro casos de pacientes atendidos en nuestro hospital que se manifestaron con síntomas sugerentes de infarto agudo de miocardio asociadosa insuficiencia cardiaca, en el contexto de un episodio estresante. Los síntomas preponderantes fueron dolor precordial opresivo y disnea. En el ECG se evidenciaron tanto supradesnivel del segmento ST, como inversiónde la onda T. Todos los pacientes presentaron la imagen ecocardiográfica típica de discinesia apical, y todos tuvieron en la cinecoronariografía coronarias normales. Cabe destacar que tanto el ECG, como el ecocardiograma volvieron a la normalidad a partir de las dos semanas.

Mastite periductal: uma entidade controversa / Periductal mastitis: a controversial disease

A mastite periductal representa uma das entidades mais controversas na mastologia e os questiomamentos a respeito dessa doença vão desde sua etiologia ao seu tratamento. A faixa etária de maior ocorrência é a de 35 a 70 anos e sua etiopatogenia é controversa sendo defendida por vários autores como fase evolutiva da ectasia ductal, e por outros, como entidade à parte. Clinicamente é representada por processo inflamatório localizado, retroareolar, que pode evoluir para a formação de abscesso e posterior fistulização periareolar. Na fase inicial os patógenos encontrados com maior freqüência são os anaeróbios e gram-negativos; entretanto, na agudização, os gram-positivos, principalmente estafilococos, participam no processo. O diagnóstico é eminentemente clínico e os achados histológicos sempre revelam um processo inflamatório crônico. O tratamento deve ser iniciado com antibióticos capazes de reduzir o processo agudo. Todavia o procedimento cirúrgico representa a principal arma terapêutica, uma vez que, se não forem ressecados o ducto comprometido e o trajeto fistuloso, o processo infeccioso crônico recrusdescerá. Várias técnicas cirúrgicas têm sido propostas para o tratamento, sendo que a recidiva do processo é bem menos freqüente quando são ressecados o trajeto fistuloso e os ductos terminais

Ectasias vasculares del colon / Vascular ectasias of the colon

Antecedentes: Las ectasias vasculares del colon siguen siendo una patología controvertida y de difícil resolución por el especialista. Su gradual aumento obliga a normatizar conductas para su mejor diagnóstico y tratamiento. Objetivos: analizar en forma retrospectiva nuestros resultados en el diagnóstico y tratamiento de esta patología, y unificar criterios y conductas para evitar de esta forma confusiones y poder sacar conclusiones válidas en el futuro. Diseño: Observacional retrospectivo. Material y Métodos: Entre enero de 1987 y diciembre de 1998 fueron tratados en la Clínica Modelo de Lanús 25 pacientes portadores de ectasias vasculares del colon, todos los pacientes fueron sometidos a un mismo protocolo diagnóstico y terapéutico que incluyó a la arteriografía como principal método de estudio. Resultados: El tratamiento definitivo fue, conservador en 10 pacientes (40 por ciento), realizándose procedimientos intervencionistas en el 60 por ciento restante, 5 con goteo intraarterial de vasoconstrictores, y diez procedimientos quirúrgicos. La morbilidad de este grupo fue del 20 por ciento y la mortalidad nula. Conclusiones: Concluimos que la denominación de esta entidad debe ser ectasias vasculares, que su fisiopatología es adquirida y su forma de presentación es el sangrado digestivo bajo. El mejor estudio diagnóstico sigue siendo la arteriografía y que el tratamiento debe ser conservador una vez superado el episodio agudo.

Effect of esophageal and gastric distention on bronchial hyper-responsiveness in patients with bronchial asthma.

OBJECTIVE: Over-eating is said to aggravate asthma though the mechanism is still unclear. We tried to study the mechanism by causing distention in oesophagus and stomach. METHODS: Fifteen patients with nocturnal asthma were studied in a random cross-over design. The esophagus and stomach of the subjects were distended with a balloon. The effect of the distention on the airways was measured by taking forced expiratory volume one second (FEV1), forced vital capacity (FVC) and bronchial hyper-responsiveness (BHR). RESULTS: Distention of stomach caused significant reduction in FEV1 on FEV1/FVC ratio but similar distention of esophagus did not. Histamine PD20 was decreased by 0.43 (SEM 0.28) doubling dose with gastric distention. However, with oesophageal distention no significant change was observed in PD20. CONCLUSION: It can be concluded that gastric distention leads to broncho-constriction as measured by FEV1, FEV1/FVC ratio along with increase in BHR probably by inducing airway inflammation. Therefore asthmatic patients should be advised to avoid large meals.