Anthracycline analogs: the past, present, and future.
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Biomedical subjects
Publications and source records attributed to M Russo.
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In six depressed epileptic patients stabilised on carbamazepine therapy, addition of the antidepressant agent viloxazine (300 mg/day for three weeks) induced a marked (average 55%) increase in steady-state plasma carbamazepine concentration. The concentration of the active metabolite carbamazepine-10,11-epoxide also increased during viloxazine therapy, but to a lesser extent (16%). In three patients, these effects were associated with symptoms of carbamazepine intoxication, which regressed rapidly when plasma carbamazepine and carbamazepine-10,11-epoxide levels returned to baseline values after discontinuation of viloxazine. In a seventh patient, viloxazine had to be discontinued after only two weeks because of severe side effects associated with a striking elevation of carbamazepine and carbamazepine 10,11-epoxide levels (by 197% and 137% respectively). Although viloxazine appears to be one of the few antidepressants which can be used safely in patients with epilepsy these results indicate that the drug should be prescribed with great caution in subjects treated with carbamazepine. The mechanism of the interaction probably involves inhibition of the metabolism of both carbamazepine and its active epoxide metabolite.
In the present study the coisogenic C5-sufficient B10.D2/nSn and C5-deficient B10.D2/oSn mice were used to determine the importance of the C5 molecule in the polymorphonuclear leucocyte accumulation in inflammatory sites. Peritoneal exudates were induced by carrageenin, glycogen, zymosan, endotoxin lipopolysaccharides (LPS) and via a passive immediate hypersensitivity reaction. It was found that the temporal profile of PMN accumulation induced by all inflammatory stimuli tested, except by high doses of LPS, is similar in C5-sufficient and C5-deficient strains of mice.
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An enzyme immunoassay for the detection of IgG and IgM anti-polymerized albumin autoantibodies (AAA) is described. It was found that polyalbumin receptors on HBsAg particles interfere in the detection of IgG AAA when polymerized human albumin (pHSA), but not polymerized bovine albumin (pBSA), is used as coating antigen. Polyalbumin receptors do not appear to interfere in the detection of IgM AAA, with either pHSA or pBSA as coating antigen. All normal sera showed evidence of AAA, of both IgG and IgM classes. Levels of IgG and IgM AAA in sera from most type A and type B acute hepatitis patients were above the range of normal controls. ELISA detection of AAA distinct from HBsAg reactivity can help in understanding the role of these autoantibodies in HBV infection.
Polyclonal antibodies to synthetic human pancreatic growth hormone-releasing factor [hpGRF(1-44)NH2] and rat hypothalamic growth hormone-releasing factor [rhGRF(1-43)OH] were produced in rabbits by injecting these weak immunogens, coupled to thyroglobulin and emulsified with complete Freund's adjuvant in the presence of activated charcoal, directly into the spleen. A subsequent booster injection by the conventional intramuscular route resulted in high-titer antibodies, which at a 1:20,000 dilution were used to develop highly sensitive and specific radioimmunoassays for these peptides. By using antibodies with an apparent Ka of 3.3 X 10(-12) (human) and 7.7 X 10(-11) (rat), the sensitivity of these assays in both human and rat was found to be less than 1 fmol. The antibody to hpGRF(1-44)NH2 is directed against the COOH-terminal region of the molecule, as shown by its crossreactivity with various hpGRF analogues: 140% with hpGRF(30-44)NH2; 1%-2% with hpGRF(1-37)OH, hpGRF(1-40)OH, and hpGRF(1-40)NH2; and none with hpGRF(1-29)NH2. Serial dilutions of human and rat hypothalamic extracts demonstrated parallelism with the corresponding species-specific standard and 125I-labeled tracer. There was no crossreactivity with other neuropeptides, gastrointestinal peptides, or hypothalamic extracts of other species. The hypothalamic content in fmol/mg (wet weight) of tissue was 3.6 +/- 0.2 for the human and 11.1 +/- 5.5 for the rat. Age-related changes in hypothalamic GRF content were present in rats, with a gradual increase from 2 to 16 weeks and a correlation between increasing body weight and GRF content. These radioimmunoassays will serve as important tools for understanding the regulation of growth hormone secretion in both human and rat.
The ultrastructure and contractile behavior of a new preparation of thrombin-activated human platelets is described. The preparation is referred to as the "platelet strip" because of its similarities to classical vascular smooth muscle strips. The platelet strip consists of a giant platelet aggregate 10 mm long, 4 mm wide, and 200 micron thick. To facilitate handling, the aggregate has a special high-compliance nylon mesh embedded in its mass. Each strip contains 7.3 X 10(8) platelets. Fibrin contamination is 150-fold lower than in platelet-rich plasma clots. Active isometric forces of up to 100 g/cm2 and 6-10 h viability are easily and reproducibly obtained. Platelet strips remain contracted after thrombin activation. The contraction is tonic and partial. Further small increases in force can be produced by depolarizing solutions or pharmacological agents, e.g., ADP, epinephrine, and endoperoxide analogues. These small increases are reversible on washout of the agents. Full relaxation is induced by agents such as prostaglandin E1 or papaverine, which increase adenosine 3',5'-cyclic monophosphate. However, after washout of these agents, recovery of tension is variable depending on the concentration of the drug and the degree of prestretching of the preparation.
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The purpose of the present study was to evaluate the possible electrophysiological effects of Indoprophene, a new non steroidal analgesic anti-inflammatory agent, which might be employed in the treatment of chest-pain from myocardial ischemia. Ten patient, who were undergoing a electrophysiological study for diagnostic purposes, were given 400 mg of indoprophene by intravenous rapid bolus. The A-V conduction times were recorded in basic condition and 30 minutes after administration of the drug. The data we collected show that Indoprophene does not influences either normal or prolonged A-V conduction times. We conclude that the drug, as it has a good effect on pain and lacks haemodynamic consequences and effects on conduction and excitability, is recommendable for the treatment of chest-pain from myocardial ischemia.
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Serum samples from 22 patients with proven typhoid fever, 60 febrile nontyphoidal patients, and 120 healthy subjects were tested for immunoglobulin A (IgA), IgG, and IgM anti-Salmonella typhi lipopolysaccharide antibodies by an enzyme-linked immunosorbent assay. The levels of all three classes of immunoglobulin anti-lipopolysaccharide were higher in typhoid patients than in controls; the test for IgM anti-lipopolysaccharide gave the best discrimination between typhoid and nontyphoidal sera. The absorbance values obtained with the enzyme-linked immunosorbent assay for IgM anti-lipopolysaccharide were highly correlated to the titers of anti-O agglutinins. However, the enzyme-linked immunosorbent assay was much more specific than the Widal test, and hence it could be a useful tool for the serological diagnosis of typhoid fever with a single blood sample.
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ADA and PNP levels were measured in T-enriched and T-depleted subpopulations of peripheral mononuclear cells from patients with typhoid fever. ADA activity was significantly increased in T-enriched, but normal in T-depleted preparations of typhoid patients. Elevated levels of ADA in T cells were observed from the initial phase up to 30 days from the onset of the disease. Unlike ADA changes, PNP modifications were transitory, and affected both T-enriched and T-depleted subpopulations. The usefulness of ADA determination in T cells to detect and follow up T-cell activation during typhoid fever is suggested.