The apoptosis-triggering properties of vitamin E succinate (VES, RRR-alpha-tocopheryl succinate) for human LNCaP and PC-3 prostate carcinoma cells and normal PrEC human prostate epithelial cells were investigated. LNCaP and PC-3 cells were sensitive to VES-induced apoptosis, with 100% and 60% of cells undergoing apoptosis after three days of treatment with 10 micrograms of VES/ml, respectively. PrEC cells were resistant to VES-induced apoptosis. Treatment of prostate cells with agonistic anti-Fas antibody triggered apoptosis in approximately 50% of PC-3 cells within 48 hours, whereas LNCaP and PrEC cells were resistant. Prostate cells simultaneously treated with VES and agonistic anti-Fas antibodies revealed 1) no effect on PrEC cells, 2) an additive effect on Fas-sensitive PC-3 cells, and 3) a synergistic effect on LNCaP cells. VES treatment of LNCaP cells caused depletion of cytosolic 43-kDa Fas, enhanced membrane levels of 43-kDa Fas, and induced Fas sensitivity. PC-3 cells expressed high levels of membrane 43-kDa Fas that were enhanced by VES treatments. Fas ligand expression by LNCaP cells was enhanced by VES treatments. In summary, VES triggers apoptosis in human prostate carcinoma cells but not normal prostate cells in vitro, and VES modulates Fas signaling.
The RRR-alpha-tocopheryl succinate derivative of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of three metastatic human prostatic cancer cell lines, LNCaP, PC-3, and DU-145. LNCaP is a lymph node-derived androgen-sensitive prostate cell line; these cells are defective for response to transforming growth factor-beta (TGF-beta) but are normal for cell cycle-related tumor suppressor genes: p53 and retinoblastoma (Rb). PC-3 is a bone marrow-derived androgen-insensitive prostate cell line; these cells are defective for both p53 alleles but normal for both Rb alleles. DU-145 is a brain-derived androgen-insensitive prostate cell line; these cells are defective for both p53 and both Rb alleles. VES at 5, 10, and 20 micrograms/ml inhibited DNA synthesis in the three cell lines in a dose-dependent manner. Purified TGF-beta 1 at 1 ng/ml inhibited DNA synthesis of PC-3 cells within 24-72 hours and DU-145 cells at 72 hours but did not inhibit DNA synthesis of LNCaP cells. Previous studies in our laboratory showed that VES growth-inhibited tumor cells secrete biologically active antiproliferative factor TGF-beta s, suggesting that VES's mechanism of growth inhibition may involve the TGF-beta system of growth control.(ABSTRACT TRUNCATED AT 250 WORDS)
Bactericidal and opsonic activities in convalescent-phase sera from patients with disseminated gonococcal infection (DGI) were analyzed with use of the patients' infecting strains and other strains of Neisseria gonorrhoeae. Serum from a patients with C8 deficiency was opsonic for her first DGI isolate grown on solid medium or in chick embryos; with added complement the serum was bactericidal (at a dilution of 1:320). Her serum was not bactericidal for nine other isolates from patients with DGI. Only one of the other patients with DGI had detectable serum bactericidal activity (dilution, 1:2,5) against her own isolate; this patient's serum was also active against one other DGI isolate. Opsonization was detectable only in sera that were potentially bactericidal and could be distinguished from bactericidal activity only with C8-deficient serum. The isolates from patients with DGI were of an auxotype different from that of most other gonococci, and most of the isolates tested were not killed by sera from patients with uncomplicated gonorrhea, even though these wera killed other gonococci. Thus, isolates from patients with DGI appeared to be significantly different from other gonococcal isolates.
The pharmacology and toxicology of tobramycin in animals and humans are reviewed. After intramuscular and intravenous administration, tobramycin diffuses throughout most body tissues and tissue fluids. Therapeutic concentrations can be obtained by intravitreal or intradural injections. Dogs tolerate intracisternal doses of 0.2 mg/kg without adverse reaction. The half-life of tobramycin in cochlear fluid of guinea pigs and in renal tissues of rats is significantly longer than the serum half-life in these species and is reflected in the ototoxic and nephrotoxic potential of tobramycin and other aminoglycosides. In man, the serum half-life of tobramycin is 2 hr; renal clearance, apparent volume of distribution, and recovery from urine are similar to those parameters for gentamicin. The serum half-life in neonates in prolonged (4.5-8.7 hr). Concentrations of tobramycin in serum are effectively reduced by hemodialysis, but peritoneal dialysis is less efficient in elimination of the antibiotic. Tobramycin crosses the placenta and is concentrated in the kidney and urine of the fetus.
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