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Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the cardiac function of hamsters

Cardiovascular effects of (2'R)-4'-O-tetrahydropylanyladriamycin X HCl (THP) and doxorubicin (adriamycin, ADM) were studied in hamsters. In experiments to observe acute effects, THP was administered intravenously at a dose of 12.5, 25.0 or 50.0 mg/kg, and ADM at 1.56, 3.13 or 6.25 mg/kg was given to different subjects. The THP caused slight ECG alterations at a dose of 12.5 mg/kg. At a dose of 25.0 mg/kg or 50.0 mg/kg, THP caused moderate to remarkable alterations in ECG like a widening of PR and PRc interval, A-V block, ST segment depression and T wave flattening. The ADM caused moderate to remarkable alterations in ECG at a dose of 3.13 mg/kg or 6.25 mg/kg, including arrhythmia, bradycardia, A-V block, ST segment changes and T wave flattening. These changes caused by THP and ADM recovered within 5 approximately 10 minutes after injection. Alterations in the ultrastructure of the myocardium caused by THP at a dose of 50.0 mg/kg included some cells with slight changes like swelling of mitochondria, focal intracellular edema, and enlargement of myofibrils. The ADM, at a dose of 3.13 mg/kg, induced severer swelling of mitochondria than THP, dilatation of sarcoplasmic reticulum, intracellular edema, and disorganization of myofilaments. At a dose of 6.25 mg/kg of ADM, these changes became more pronounced. In experiments to observe subacute effects, hamsters were treated with THP or ADM by daily intraperitoneal injections for 15 consecutive days, and then allowed to be recovered for 15 days. Dose levels of THP or ADM were 0.125, 0.25, 0.5 and 1.0 mg/kg. General toxicity, ECG, hematological and blood biochemical analysis, and electron microscopic examination were studied. In the ECG study, THP-treated hamsters showed a reversible elevation of R wave amplitude at a daily dose of 0.5 mg/kg. Widening of PR and PRc interval, elevation of R and S wave amplitude, and reduction of T wave amplitude were observed at a daily dose of 1.0 mg/kg of THP. Hamsters treated with ADM showed increase of heart rate, reduction of T wave amplitude, and shortening of PR and PRc interval at a daily dose of 0.5 mg/kg. Severe changes were observed at a daily dose of 1.0 mg/kg of ADM including an increase of heart rate, elevation of R wave amplitude, reduction of S and T wave amplitude, and shortening of QT interval. The electron microscopic examination revealed that THP-treated hamsters showed separation of intercalated discs, formation of myelin structure, and dilatation of T-tubules at a daily dose of 1.0 mg/kg. Similar changes were caused by ADM at a daily dose of 0.25 to 1.0 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)     

Physical activity is associated with a low prevalence of musculoskeletal disorders in the Royal Norwegian Navy: a cross sectional study

Background  

Despite considerable knowledge about musculoskeletal disorders (MSD) and physical, psychosocial and individual risk factors there is limited knowledge about physical activity as a factor in preventing MSD. In addition, studies of physical activity are often limited to either leisure activity or physical activity at work. Studies among military personnel on the association between physical activity at work and at leisure and MSD are lacking. This study was conducted to find the prevalence of MSD among personnel in the Royal Norwegian Navy and to assess the association between physical activity at work and at leisure and MSD.     

Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone.

The CAMPATH-1 (CDw52) antigen has been purified from human spleen. The antigenic epitope is heat stable but sensitive to mild alkali treatment. Experiments with phosphatidylinositol-specific phospholipase C indicate that it is anchored by a glycosylphosphatidylinositol (GPI) anchor. An N-terminal sequence of 11 amino acids was determined, followed by an abrupt stop. Using short overlapping mixed oligonucleotide primers, cDNA synthesized from the mRNA of a human B cell line was amplified by the polymerase chain reaction. The product was used to isolate cDNA clones and the full amino acid sequence of the CAMPATH-1 antigen was deduced. It consists of 37 amino acid residues plus a 24-residue signal peptide. It has all the features expected for a GPI-anchored membrane protein except that the predicted mature protein is remarkably short, comprising no more than 18 residues and possibly as few as 12 (depending on the GPI linkage site). Potential attachment sites for carbohydrate are present and it is shown that the antigen contains N-linked oligosaccharide(s). This structure accounts for the known properties of the antigen, though the exact reasons why it is such a good target for cell lysis in vitro and in vivo are not yet clear.     

Clinical efficacy of sulbactam/ampicillin in the field of pediatrics

Sulbactam (SBT) is a new derivative of the basic penicillin nucleus. It effectively and irreversibly inhibits several important bacterial beta-lactamases and displays synergistic effects against the resistant organisms when co-administered with ampicillin (ABPC). SBT/ABPC, which is a fixed combination of SBT and ABPC in a 1:2 ratio, was studied for clinical efficacy in the field of pediatrics. Patients treated were infants and children ranging from 12 days to 13 years and 2 months old suffering from acute tonsillitis in 2 cases, acute bronchitis in 2 cases, septicemia in 2 cases, acute enteritis, acute pyelonephritis and osteomyelitis in 1 case each, a total of 9 cases. SBT/ABPC was administered 100-300 mg/kg in daily doses and durations of treatment ranged from 4 to 17 days. Clinical results were "excellent" in 6 and "good" in 2: the efficacy rate was 88.9% or 8 cases out of 9. Neither clinical side effects nor abnormal laboratory findings obviously attributable to SBT/ABPC were observed in any cases.     

Induction of NK1.1(+) alpha beta TCR(+) T cells by bypassing TCR signals in ZAP-70 deficient mice

The mechanism of development of a unique subset of T cells, thymic NK1.1(+) alpha beta T cells, has been poorly understood. We found that the development of thymic NK1.1(+) alpha beta T cells was defective in mice deficient in ZAP-70. Instead, an accumulation of NK1.1(+) TCR beta(-) NK-like population was detected in the thymus and spleen of the ZAP-70 deficient (ZAP -/-) mouse. In the present report, we examined whether biochemical treatments that replace TCR-mediated positive selection signals could restore the generation of thymic NK1.1(+) alpha beta T cells in ZAP -/- mice using the thymus organ culture. We found that a higher concentration of phorbol ester (PMA) than that required for CD4(+) T cell generation and ionomycin induced the generation of NK1.1(+) alpha beta T cells. Phenotypic analysis of the induced NK1.1(+) alpha beta T cell population suggested that these cells expressed CD8 but not CD4 molecules, which is a different characteristic from ordinary thymic NK1.1(+) alpha beta T cells. These results suggest that differential signaling is required for the generation of mainstream T cells and thymic NK1.1(+) alpha beta T cells.     

Does breastfeeding protect children from asthma? Analysis of NHANES III survey data.

We sought to determine whether breastfeeding (yes/no) or its duration protects against the development of childhood asthma, its severity or age of onset. We conducted a secondary analysis of youth files of the National Health and Nutrition Examination Survey III (1988-94), and reviewed data from 6,783 children age 2 months to 6 years (3,316 breastfed), excluding children with a history of low birth weight or treatment in a neonatal intensive care unit. Study participants were breastfed an average of 157 days. The average age at onset of asthma was 14.3 months. In the logistic regression model, "ever breast-fed" was not a significant protective factor for developing asthma. Significant predictive factors were the mother's age at child's birth (beta = -0.08, p < 0.01), and a parent having asthma or hayfever (beta = 0.46, p < 0.01). In the linear regression model, the duration of breastfeeding was not a predictor for age at onset of asthma (beta = 0.01, p = 0.53). Only maternal smoking during pregnancy was a significant predictor of age at onset of asthma (beta = -7.59, p < 0.01). Breastfeeding does not appear to prevent asthma, delay its onset, or reduce its severity. However, breastfeeding is still recommended for its many other benefits.