Perinatal asphyxia and heart problems

New bisantrene analogues were synthesized, bearing one or two 4,5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1,4 or 9 of the anthracene ring system. A 10-azabioisostere was also prepared. The position of substituents in structurally isomeric drugs modulates topoisomerase II poisoning and specificity, along with cytotoxicity.     

A trial of the long-term use of Sedacorone (amiodarone) under polyclinic conditions for the prevention of paroxysms of atrial fibrillation

Sedacorone (amiodarone) was given to 70 outpatients with coronary heart disease for 1.5-2 years to prevent paroxysms of cardiac arrhythmia after recovery of sinus rhythm. Sedacorone was administered initially in the dose 600 mg/day for 10-12 days, then the dose lowering was adjusted to the tolerance, heart rate and ECG readings. The minimal dose of 200 mg/day was taken for 5 days a week with a 2-day interval. In adequate individual dose Sedacorone prevented paroxysms of cardiac fibrillation or made the paroxysms less frequent in 91.4% of patients. Careful selection of patients and regular control helped avoid serious cardial and extracardiac complications. Sedacorone is recommended as a first-line medicine for outpatients with frequent paroxysms of cardiac fibrillations after recovery of the sinus rhythm to prevent the paroxysms recurrences.     

Hextend (hetastarch solution) decreases multiple organ injury and xanthine oxidase release after hepatoenteric ischemia-reperfusion in rabbits

OBJECTIVE: We hypothesized that multiple organ injury and concentrations of xanthine oxidase (an oxidant-generating enzyme released after hepatoenteric ischemia) would be decreased by the administration of a bolus of a colloid solution at reperfusion. DESIGN: Randomized, masked, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Fifty-four New Zealand white male rabbits, weighing 2 to 3 kg. INTERVENTIONS: Anesthetized rabbits were assigned to either the hepatoenteric ischemia-reperfusion group (n = 27) or the sham-operated group (n = 27). Hepatoenteric ischemia was maintained for 40 mins with a balloon catheter in the thoracic aorta, followed by 3 hrs of reperfusion. Each group was randomly administered a bolus of one of three fluids at the beginning of reperfusion: Hextend (hetastarch solution); 5% human albumin; or lactated Ringer's solution. The investigators were masked as to the identity of the fluid administered. MEASUREMENTS AND MAIN RESULTS: Multiple organ injury was assessed by the release of lactate dehydrogenase activity into the plasma and by indices of gastric and pulmonary injury. Circulating lactate dehydrogenase activity was significantly greater (p < .001) in animals receiving lactated Ringer's solution than in rabbits receiving either colloid solution. Gastric injury (tissue edema, Histologic injury Score) was significantly decreased (p < .01) by administration of both colloid solutions. Lung injury (bronchoalveolar lavage lactate dehydrogenase activity) was significantly decreased (p < .05) by the hetastarch solution administration. The hetastarch solution administration resulted in 50% less xanthine oxidase activity release during reperfusion compared with albumin or lactated Ringer's solution administration (p < .001). CONCLUSION: We conclude that multiple organ injury and xanthine oxidase release after hepatoenteric ischemia-reperfusion are decreased by colloid administration.     

The yeast HSM3 gene acts in one of the mismatch repair pathways

Mutants with enhanced spontaneous mutability (hsm) to canavanine resistance were induced by N-methyl-N-nitrosourea in Saccharomyces cerevisiae. One bearing the hsm3-1 mutation was used for this study. This mutation does not increase sensitivity to the lethal action of different mutagens. The hsm3-1 mutation produces a mutator phenotype, enhancing the rates of spontaneous mutation to canavanine resistance and reversions of lys1-1 and his1-7. This mutation increases the rate of intragenic mitotic recombination at the ADE2 gene. The ability of the hsm3 mutant to correct DNA heteroduplex is reduced in comparison with the wild-type strain. All these phenotypes are similar to ones caused by pms1, mlhl and msh2 mutations. In contrast to these mutations, hsm3-1 increases the frequency of ade mutations induced by 6-HAP and UV light. Epistasis analysis of double mutants shows that the PMS1 and HSM3 genes control different mismatch repair systems. The HSM3 gene maps to the right arm of chromosome II, 25 cM distal to the HIS7 gene. Strains that bear a deleted open reading frame YBR272c have the genetic properties of the hsm3 mutant. The HSM3 product shows weak similarity to predicted products of the yeast MSH genes (homologs of the Escherichia coli mutS gene). The HSM3 gene may be a member of the yeast MutS homolog family, but its function in DNA metabolism differs from the functions of other yeast MutS homologs.     

Isolation of an amino-terminal region of bovine papillomavirus type 1 E1 protein that retains origin binding and E2 interaction capacity

In vitro DNA binding results from a series of E1 proteins containing amino-terminal or carboxy-terminal truncations indicated that sequences between amino acids 121 and 284 were critical for origin binding. Additional binding experiments with E1 proteins containing internal, in-frame insertions or deletions confirmed the importance of the region defined by truncated E1 proteins and also demonstrated that downstream sequences were not required for binding activity in the context of the full-length E1 protein. On the basis of mapping results from the E1 mutants, a clone (pE1(121-311)) was constructed that expressed E1 amino acids within the approximate boundaries of the critical sequences for DNA binding. The E1(121-311) protein retained origin-specific DNA binding, confirming that this region was not only necessary but was also sufficient for origin recognition. In addition to origin binding, E1(121-311) bound E2 protein in a cold-sensitive manner. Therefore, DNA binding and E2 binding activities colocalize to a 191-amino-acid functional domain derived from the amino-terminal half of the E1 protein. Finally, three E1 proteins with mutations in this region all lacked DNA binding activity and were all defective for in vivo replication. Two of these E1 mutants retained E2 binding capability, demonstrating that origin recognition by E1 is critical for replication and cannot necessarily be rescued by an interaction with E2 protein.