Comparative study of d-diltiazem and its analogues as calcium antagonists in snail neurones

The blocking effects of d-diltiazem, its metabolites, deacetyl-d-diltiazem (d-M1), deacetyl-N-demethyl-d-diltiazem (d-M2), deacetyl-O-demethyl-d-diltiazem (d-M4) and deacetyl-N, O-demethyl-d-diltiazem (d-M6) and 1-diltiazem were investigated on the voltage-gated calcium current (ICa) of an Achatina neurone. Based on the IC50 values, the order of potency was: d-diltiazem (0.426 mM), d-M2 (0.456), d-M1 (0.491), 1-diltiazem (0.759) greater than d-M4 (1.212) greater than d-M6 (greater than 2.000). Assuming that the IC50 reflects the KD for resting Ca2+ channels (Kr), steady state activation studies gave KD values for the inactivated channels (Ki) and Kr/Ki ratios of 0.122 mM (Ki) and 3.52 (Kr/Ki) (d-diltiazem), 0.112 and 6.98 (1-diltiazem), 0.083 and 6.07 (d-M1) and 0.156 and 2.97 (d-M2). All drugs tested showed a certain degree of voltage-dependence. The further percentage reduction in the normalized ICa after high frequency stimulation demonstrated the use-dependence of: 1-diltiazem (27.5%), d-diltiazem (26.3) greater than d-M2 (19.2) greater than d-M1 (16.7) greater than d-M6 (9.8). The voltage- and use-dependence of these drugs are consistent with their Ca2+ antagonistic properties.     

A CASE OF METASTATIC YOLK SAC TUMOR OF TESTIS IN A CHILD

We report a case of testicular yolk sac tumor in a child aged 3 years and 6 months with multiple bulky metastases to lung and retroperitoneum (stage 11182). After three courses of chemotherapy with a PV 8 regimen (cisplatin, vinblastine and bleomycin). complete and partial responses were obtained for lung and retroperitoneal lymph node metastases, respectively. The patient was followed-up closely. However, on the basis of a re-elevated alpha-letoprotein (AFP) after 4 months' follow-up, he was treated with three courses of salvage chemotherapy with a modified VAB-6 regimen (cyclophosphamide. etoposide. actinomycin D, bleomycin and cisplatin), lollowed by retroperitoneal lymph node dissection. Histologically, only necrotic tissue was found. There is no evidence of recurrence 24 months after lymphadenectomy. There is very little information in the literature on the appropriate management of postchemotherapy residual mass in pediatric testicular tumors.     

Characterization of certain hepatocyte-proliferating and/or protective factors induced by the sensitization of freezing-thawing hepatic tissue

Although tumor cryosurgery would be expected to produce beneficial immunological effects from the enhancement of anti-tumor activity, under certain conditions the tumor may become enlarged and metastases promoted due to increased immunosuppressive activity and a high zone tolerance. In the present study, we examined whether hepatocyteproliferating factors were produced by the inoculation of freezing-thawing hepatic tissue (FTHT). Serum obtained from rats inoculated with FTHT increased DNA synthesis, according to measurement by [³H]thymidine incorporation in primary cultured rat hepatocytes. This increase was dependent on the serum concentration, with serum obtained on day 14 after the inoculation being the most potent for hepatocyte proliferation. The sensitized serum promoted DNA synthesis nearly as much as serum obtained from a 70% hepatectomized rat, but slightly less than 10ng/ml hepatocyte growth factor. The sensitized serum also protected hepatocytes from carbon tetrachloride (CCI₄)-induced hepatotoxicity. Optical density measured by the 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrozolium bromide (MTT) cytotoxicity assay was increased, and the release of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in medium was decreased by treating hepatocytes damaged by CCI₄ with the sensitized serum. These results suggest that certain hepatocyte-proliferating and protective factors are induced in serum by the inoculation of freezing-thawing hepatic tissue, and that the sensitized serum may be useful in the treatment of liver failure.     

Clinical effects of percutaneous cardiopulmonary support in severe heart failure: early results and analysis of complications.

Between January 1993 and December 2001, we employed percutaneous cardiopulmonary support (PCPS) in 35 patients. PCPS was used for postcardiotomy in 25 of these patients who could not be weaned from cardiopulmonary bypass (CPB) because of severe cardiogenic shock. In the other 10 patients, PCPS was used for a non-surgical disease. Twenty-nine patients (82.9%) were weaned from PCPS, and 28 (80.0%) survived. The other 7 patients (20.0%) died due to postoperative complications. The causes of death were multiple organ failure (MOF) due to wound bleeding, low cardiac output syndrome (LOS), myonephropathic metabolic syndrome (MNMS) with severe lower limbs ischemia, cerebrovascular accident (CVA), and sepsis. The first cause for the complications was postoperative sustained severe heart failure. To improve the survival rate, it was necessary to prevent bleeding and begin PCPS at an earlier stage.     

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Benastatins have been isolated as part of a program designed to find microorganism-produced inhibitors of glutathione S-transferase from Streptomyces sp. MI384-DF12. They were purified by chromatography of reversed-phase silica gel, silica gel and Capcell Pak C18 (HPLC) followed by solvent extraction and then isolated as yellow powders. Benastatins A and B have the molecular formulae, C30H28O7 and C30H30O7, respectively. They were competitive with 3,4-dichloronitrobenzene as the substrate, and the inhibition constants (Ki) of benastatins A and B were 5.0 x 10(-6) and 3.7 x 10(-6), respectively.     

Hollow microspheres for use as a floating controlled drug delivery system in the stomach.

Hollow microspheres (microballoons), loaded with drug in their outer polymer shells, were prepared by a novel emulsion-solvent diffusion method. The ethanol:dichloromethane solution of drug (tranilast or ibuprofen) and an enteric acrylic polymer were poured into an agitated aqueous solution of polyvinyl alcohol that was thermally controlled at 40 degrees C. The gas phase generated in the dispersed polymer droplet by the evaporation of dichloromethane formed an internal cavity in the microsphere of the polymer with the drug. The drugs incorporated in the solidified shell of the polymer were found to be partially or completely amorphous. The flowability and packability of the resultant microballoons were much improved compared with the raw crystals of drug. The microballoons floated continuously over the surface of acidic dissolution media containing surfactant for greater than 12 h in vitro. The drug release behavior of the microballoons was characterized as an enteric property, and drug release rates were drastically reduced depending on the polymer concentration at pH 6.8.     

A case report of mitral valve regurgitation due to the infective endocarditis associated with the straight back syndrome

A 54 year-old man was admitted to our hospital with a compliant of high fever following the dental treatment. He had the straight thoracic spine with absence of physiological kyphosis. Blood culture was positive for Streptococcus sanguis I. Echocardiography revealed the mitral valve regurgitation with some vegetation at the ruptured chordae tendinae of the posterior leaflet. The operation was performed after the sign of the inflammation was disappeared. We performed the mitral valve reconstruction following the Carpentier's technique. The half of the posterior leaflet was excised, and the annuloplasty and valvuloplasty was done with ease.     

Altemicidin, a new acaricidal and antitumor substance. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties

Screening of new insecticidal and acaricidal antibiotics was carried out with reference to anti-brine shrimp activity from actinomycete strains isolated from marine environments. Of 200 actinomycete isolates, one isolate was found to produce a new substance, altemicidin. The strain was isolated from sea mud collected at Gamo, Miyagi Prefecture, Japan, and identified as Streptomyces sioyaensis SA-1758. Altemicidin was purified by Diaion CHP-20P and Sephadex LH-20 column chromatographies. The molecular formula was determined as C13H20N4O7S by elemental analysis, MS and 13C NMR spectrum. Altemicidin showed not only acaricidal activity but also antitumor activity. The compound showed no antimicrobial activity except the inhibitory activity to Xanthomonas strains.