Effects of dopamine receptor blockade on cerebral blood flow response to somatosensory stimulation in the unanesthetized rat

Local cerebral blood flow (CBF) was determined in 30 cerebral structures, including four structures of the whisker-to-barrel cortex sensory pathway, by the quantitative autoradiographic [(14)C]iodoantipyrine method during unilateral vibrissal stimulation in rats administered 0.1 or 1.0 mg/kg haloperidol or its control vehicle intravenously. The low dose of haloperidol had no significant effects on resting CBF or its enhancement by vibrissal stimulation. By standard t tests, the high dose statistically significantly lowered baseline CBF in frontal and visual cortex, hippocampus, dentate gyrus, inferior olive, cerebellar cortex, and the ventral posteromedial (VPM) thalamic nucleus on the unstimulated side, and raised baseline CBF in the lateral habenula; however, these changes lost statistical significance after Bonferroni correction for multiple comparisons. Neither dose had any effects on the increases in CBF evoked by vibrissal stimulation in the principal sensory trigeminal nucleus and barrel cortex, but the higher dose statistically significantly enhanced the percent increases in CBF due to the sensory stimulation in the spinal trigeminal nucleus and VPM thalamic nucleus. These results do not support a role for direct dopaminergic vasoactive mechanisms in the increases in CBF associated with neuronal functional activation.     

Angiotensin receptor vaccines

Recent clinical studies have shown that RAS inhibitors are effective not only for the prevention of end-organ damage in hypertensive patients, but also for prevention of new-onset hypertension, diabetes mellitus, and atrial fibrillation. Vaccines against the RAS have been developed since the 1950s, and a recent phase IIa placebo-controlled study has confirmed that an angiotensin vaccine causes a significant decrease in blood pressure in hypertensive patients. The results of animal experiments from our and other laboratories have suggested that vaccination against the angiotensin type 1 (AT1) receptor causes a significant decrease in blood pressure in animal models of hypertension, and also ameliorates hypertensive end-organ damage. The angiotensin receptor may therefore be an important target for the development of vaccines for the prevention of hypertension and related complications.     

Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells.

Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. Recent evidence suggests that vasoconstrictive substances, such as angiotensin II (AII), may function as a vascular smooth muscle growth promoting substance. To explore the role of the counterregulatory hormone, atrial natriuretic polypeptide (ANP) in this process, we examined the effect of ANP (alpha-rat ANP [1-28]) on the growth characteristics of cultured rat aortic smooth muscle (RASM) cells. ANP (10(-7) M) significantly suppressed the proliferative effect of 1% and 5% serum as measured by 3H-thymidine incorporation and cell number, confirming ANP as an antimitogenic factor. In quiescent RASM cells, ANP (10(-7), 10(-6) M) significantly suppressed the basal incorporations of 3H-uridine and leucine by 50 and 30%, respectively. ANP (10(-7), 10(-6) M) also suppressed AII-induced RNA and protein syntheses (by 30-40%) with the concomitant reduction of the cell size. Furthermore, ANP also significantly attenuated the increase of 3H-uridine and leucine incorporations caused by transforming growth factor-beta (4 x 10(-11), 4 x 10(-10) M), a potent hypertrophic factor. These results indicate that ANP possesses an antihypertrophic action on vascular smooth muscle cells. Down-regulation of protein kinase C by 24-h treatment with phorbol 12,13-dibutyrate did not inhibit ANP-induced suppression on 3H-uridine incorporation. Based on the observation that ANP was more potent than a ring-deleted analogue of ANP on inhibiting 3H-uridine incorporation, we conclude that the ANP's inhibitory effect is primarily mediated via the activation of a guanylate cyclase-linked ANP receptor(s). Indeed 8-bromo cGMP mimicked the antihypertrophic action of ANP. Accordingly, we speculate that in addition to its vasorelaxant and natriuretic effects, the antihypertrophic action of ANP observed in the present study may serve as an additional compensatory mechanism of ANP in hypertension.     

Mediastinal Germ Cell Tumor Exhibiting a Discrepancy between Tumor Markers and Imaging: A Case Study

We report a mediastinal germ cell tumor (GCT) that exhibited a discrepancy between the time course of serum human chorionic gonadotropin (hCG) levels and clinical consequences. An otherwise healthy man, aged 34 years, was diagnosed with a nonseminomatous GCT, most likely embryonal carcinoma (EC), based on a mediastinal tumor biopsy. Standard chemotherapy resulted in an optimal decrease in serum hCG levels. However, multiple lesions in the liver continued to enlarge, which led to his death. Autopsy revealed few viable tumor cells in the liver, with the great majority of the tumor cells appearing to have undergone necrosis, suggesting that they responded to the chemotherapy. The residual tumor cells in the mediastinum and the liver were similar to syncytiotrophoblast cells, suggesting a cho-riocarcinoma (CC). On immunohistochemical analysis, the mediastinal tumor cells in the diagnostic biopsy specimen expressed both CD30 and hCG, whereas residual mediastinal and hepatic tumor cells in the autopsy specimen after chemotherapy also expressed hCG, but not CD30. These findings suggested that the patient suffered from a primary mixed GCT consisting of an EC and a CC. Both pre- and postchemotherapy tumors strongly expressed matrix metalloproteinase-2, supporting the aggressive and invasive features of the tumor phenotype. We speculate that the extremely invasive tumor destroyed normal liver structure, whereas chemotherapy and central necrosis reduced the number of viable cells themselves, causing a discordant decrease in serum hCG levels.Key Words: Nonseminomatous germ cell tumor, Serum human chorionic gonadotropin, Liver metastasis, Matrix metalloproteinase-2     

ESOPHAGOCARDIOPLASTY FOR ACHALASIA IN CLOSURE OF A COMPLICATED ESOPHAGOBRONCHIAL FISTULA

We report a rare case or benign esophagobronchial fistula associated with achalasia. The fistula healed spontaneously after esophagocardioplasty with a gastric patch, suggesting the utility of this procedure.     

Selective binding of sucralfate to endoscopic mucosal resection-induced gastric ulcer: evaluation of aluminium adherence

We evaluated the effect of sucralfate in patients with early gastric cancer in endoscopic mucosal resection (EMR)-induced gastric ulcers, and in rats with acetic acid-induced ulcers, by measuring concentrations of aluminium adhering to mucosal lesions. Twenty-two patients who underwent EMR received sucralfate with or without ranitidine and were examined endoscopically after 1 week, 2 weeks and 3 weeks. Gastric juice pH and concentration of aluminium in samples of ulcerated and normal mucosa were measured at various time-points. Good ulcer healing was observed in all patients. Significantly higher concentrations of aluminium were found in ulcerated tissue compared with normal mucosa. This selective binding of sucralfate was even found 12 h after drug administration and was confirmed in acetic acid-induced ulcers in 40 rats. Neutral rather than acid gastric juice was observed up to 12 h after the administration of sucralfate alone. These results suggest that sucralfate with or without ranitidine may contribute to the healing of EMR-induced ulcers by selectively binding to lesions.