Gastric mucosal damage induced by compound 48/80: Roles of serotonin and nitric oxide

The roles of nitric oxide (NO) and serotonin (5-HT) in the development of gastric mucosal lesions induced by compound 48/80 were investigated in rats. Repeated i.p. administration of 48/80 (1 mg/kg) produced damage in the stomach with severe oedema in the submucosa. The lesions induced by 48/80 were prevented by FPL-52694 (a mast cell stabilizer) and methysergide but not tri-pelennamine. The lesions were also inhibited by simultaneous administration of N ^G-monomethyl-L-arginine (L-NMMA), and this effect was mimicked by inducible NO synthase (iNOS) inhibitors, such as aminoguanidine or dexamethasone and significantly antagonized by coadministration of L-arginine. The mucosal myeloperoxidase activity, thiobarbituric acid reactants and vascular permeability in the stomach were all increased after 48/80 treatment and the changes were also attenuated by cotreatment with L-NMMA. Repeated s.c. treatment with 5-HT (20 mg/kg) provoked similar gastric lesions, which were also prevented by methysergide and iNOS inhibitors, as well as antioxidative drugs, such as allopurinol (a xan-thine oxidase inhibitor) and hydroxyurea (a neutrophil-reducing agent). The Ca²⁺-independent NO synthase (NOS) activity was increased in the gastric mucosa after administration of 48/80 or 5-HT and this change was inhibited by dexamethasone. These results suggest that: (i) the repeated administration of 48/80 induced inflammatory gastric lesions in the rat stomach, mediated by endogenous 5-HT; (ii) NO/iNOS is involved in the pathogenic mechanism of 48/80-induced gastric lesions, in addition to oxyradical formation; and (iii) the deleterious role of NO in this lesion model can be accounted for by a cytotoxic action of peroxynitrite that is formed in the presence of superoxide radicals.     

Antitumour Effects and Pharmacokinetics of Combination of Vinblastine with a Staurosporine Derivative,NA-382, in P388/ADR-bearing Mice

The effects of a staurosporine derivative, N-ethoxycarbonyl-7-oxostaurosporine (NA-382), on the pharmacokinetics of vinblastine were evaluated, compared with those of verapamil, in multidrug-resistant P388/ADR-bearing mice. At first, the in-vitro experiments indicated that NA-382 permeated into the cells better and were more effective in combined cytotoxicity with vinblastine and on accumulation of vinblastine than with verapamil in P388/ADR cells. In combined intraperitoneal injection with vinblastine (200 μ kg^?1) into P388/ADR-bearing mice, NA-382 in a suspension form (10 mg kg^?1) prolonged the life-span of the mice near to that of P388/S-bearing mice treated with vinblastine alone, but verapamil even at the maximum tolerated dosage (30 mg kg^?1) barely affected the in-vivo antitumour effect of vinblastine. When simultaneously administered with vinblastine to P388/ADR-bearing mice, NA-382 maintained significantly higher vinblastine levels in the tumour cells for 24 h and gave a larger area under the time-intracellular vinblastine concentration curve (0 to 24 h) than those receiving vinblastine alone, with long retention of the agent in ascitic fluid. Verapamil increased the cellular vinblastine content for only 6 h, accompanying a rapid elimination of the agent from the ascitic fluid. This study indicates that NA-382 is more effective against multidrug-resistance than verapamil, and its suspension is also advantageous for cancer chemotherapy of multidrug-resistant tumours.     

Comparison of the effects of KRN2391 and other coronary dilators on porcine isolated coronary arteries of different sizes

Abstract— The present study was performed to determine whether KRN2391 (N-cyano-N′-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulphonate), a novel vasodilator, shows different effects on porcine isolated coronary arteries of different sizes. The vasodilating effects of KRN2391 on porcine large (2·5–3·0 mm outer diam.) and small (0·8–1·0 mm) coronary arteries were also compared with those of cromakalim, nicorandil, nifedipine, nitroglycerin and adenosine. The relaxant effects of these drugs were examined in coronary arteries contracted by 25 Mm KCl. Nitroglycerin caused greater relaxation in large vessels than in small vessels. In contrast, adenosine, nifedipine and cromakalim caused greater relaxation in small vessels. However, there was no difference between large and small vessels in the relaxing effects of KRN2391 and nicorandil. These unique features of KRN2391 and nicorandil appear to be beneficial in ischaemic heart disease.     

Bulbocavernosus reflex during the micturition cycle in normal male subjects

BACKGROUND: To investigate normal changes in the bulbocavernosus reflex (BCR) during the micturition cycle, we examined the change in BCR during the micturition cycle using an evoked potential reaction of the BCR (BCR-EP). METHODS: Fourteen normal subjects were examined in the study. The BCR-EP was recorded at empty bladder, filled bladder, during voiding and at empty bladder after voiding. To elicit the BCR-EP, the dorsal nerve of the penis was stimulated by two ring electrodes and an electromyogram of the external urethral sphincter was recorded. The maximum amplitude was measured to evaluate changes in the BCR. RESULTS: The amplitude of the BCR was increased by bladder filling and the ratio of the amplitude at filled bladder/amplitude at empty bladder was 1.32 +/- 0.39. The stable BCR-EP elicited by stimulation at empty bladder disappeared during voluntary voiding in 13 of 14 subjects. However, as stimulation was increased in seven subjects, the BCR-EP was again seen clearly. CONCLUSIONS: The BCR varies during the micturition cycle, although in normal subjects this variation occurs within a relatively narrow range. Changes in the BCR out of the normal range (e.g. large acceleration by bladder filling or insufficient inhibition during voiding) could suggest the existence of neurogenic disease.     

Macroreentrant Atrial Tachycardia in Patients without Previous Atrial Surgery or Catheter Ablation: Clinical and Electrophysiological Characteristics of Scar‐Related Left Atrial Anterior Wall Reentry

Scar‐Related Left Atrial Anterior Wall Reentry. Introduction: Macroreentrant atrial tachycardia (MRAT) has been described most frequently in patients with prior cardiac surgery. Left atrial tachycardia and flutter are common in patients who undergo atrial fibrillation ablation; however, few reports describe left atrial MRAT involving the regions of spontaneous scarring. Here, we describe left atrial MRAT in patients without prior cardiac surgery or catheter ablation (CA) and discuss the clinical and electrophysiological characteristics of tachycardia and outcome of CA. Methods and Results: An electrophysiological study and CA were performed in 6 patients (3 men; age 76 ± 6 years) with MRAT originating from the left atrial anterior wall (LAAW). No patient had a history of cardiac surgery or CA in the left atrium. Spontaneous scars (areas with bipolar voltage ≤ 0.05 mV) were observed in all patients. The activation map showed a figure‐eight circuit with loops around the mitral annulus (4 counterclockwise and 2 clockwise) and a low‐voltage area with LAAW scarring. The mean tachycardia cycle length was 303 ± 49 milliseconds. The conduction velocity was significantly slower in the isthmus between the scar in the LAAW and the mitral annulus than in the lateral mitral annulus (0.17 ± 0.05 m/s vs 0.94 ± 0.35 m/s; P = 0.003). Successful ablation of the isthmus caused interruption of the tachycardia and rendered it noninducible in all patients. Conclusion: Spontaneous LAAW scarring is an unusual cause of MRAT, showing activation patterns with a figure‐eight configuration. Radiofrequency CA is a feasible and effective treatment in such cases. (J Cardiovasc Electrophysiol, Vol. 24, pp. 404‐412, April 2013)     

Inactivation of Vesicular Stomatitis Virus by Serum from Patients with Hepatocellular Carcinoma

Vesicular stomatitis virus was inactivated by serum from tenpatients with hepatocellular carcinoma more strongly than bythe serum of ten healthy adults. This action of human serumwas also observed in an infant, a child, a patient with agammaglobulinemia(Bruton type) and the cord blood of three babies (lacking IgM).Serum samples treated with zymosan and by heating at 56°Cfor 30 min lost this ability only partially, although complementaction in the same samples was completely inactivated.     

Juvenile Thyroid Carcinoma with Metastasis to the Bilateral Cervical Lymph Nodes--A Case Report

A case of juvenile thyroid carcinoma with metastasis to thebilateral cervical lymph nodes in a 9-year-old male is reported.The clinical picture of juvenile thyroid carcinoma is characterizedby early metastasis to the lungs and cervical lymph nodes. InEurope, there have been many reports of thyroid carcinoma afterradiation. However, our patient had received no radiation. Surgeryconsisted of subtotal thyroidectomy and right modified neckdissection. The tumor was a papillary adenocarcinoma and metastasiswas seen in 24 out of 38 lymph nodes removed. The serum thyroglobulinlevel, determined by radioimmunoassay, was 184 ng/ml preoperatively,but by 8 months postoperatively the level fell to 48 ng/ml.No signs of recurrence have been found to date (30 months afterthe operation).