Initial degradation of deoxyribonucleic acid after injection in mammals.
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Animals↗
Biomedical subjects
C Paoletti
Publications and source records attributed to C Paoletti.
Smoking cessation rates 4 years after treatment by nicotine gum and acupuncture.
BACKGROUND: This study was done to estimate the smoking cessation rates 4 years after treatment with acupuncture and nicotine gum. METHODS: Participants were randomized in a 2 x 2 factorial design to four groups: double active treatments (nicotine gum and acupuncture), double placebo, and the combination of one active treatment and placebo. RESULTS: The success rates were quite similar in the four groups at the different points of follow-up. They sharply decreased between 1 month (around 23%) and 1 year (around 10%). The decrease slowed down thereafter to around 6% at 4 years. CONCLUSIONS: Results from our study suggest that the two treatments did not offer any long-term improvement over placebo. Additional investigations are necessary to estimate the magnitude of their long-term success rate.
Acupuncture Therapy↗
Measurement of recA protein induction in Salmonella typhimurium: a possible biochemical test for the detection of DNA damaging agents.
RecA protein was purified from S. typhimurium and its concentration was measured in crude extracts by an immunoradiometric assay. The dose-response relations and the kinetics of recA protein induction following treatment of the cells with ultra-violet light, nalidixic acid, mitomycin C, and cisplatin were studied in E. coli and S. typhimurium. The recA protein amplification was complete in a few hours and was stable for at least 3 hours. Dose-response curves showed a linear region for low doses of all the inducer agents tested. This direct relation between the recA protein level and the amount of inducer agent allows the quantification of the recA protein inducing potency of chemicals. The recA protein amplification was very sensitive to low doses of inducer agents: an UV dose of 0.25 J/M2, 500 ng of NAL or 50 ng of MMC induced a two-fold increase in cellular recA protein content. In addition, the measurement of RecA protein induction did not require the survival of the cells. These observations led us to suggest a new biochemical assay for detecting DNA damaging substances by the direct measurement of the recA protein level following treatment of the cells.
Antibiotics, Antineoplastic↗
Use of a new DNA intercalating fluorescing probe for studies on the mechanism of frameshift mutagenesis in Salmonella typhimurium.
As a general rule, ellipticine derivatives are mutagenic and intercalate into double-stranded nucleic acids. We have tested a new fluorescent ellipticine compound, 10[(1-carboxy-2-methylpropylidene)-amino]-9-hydroxy-2-methylell ipticinium (val-NMHE), for establishing the relationship between the amount of drug bound to nucleic acids in situ in Salmonella typhimurium and its biological effects: decrease of growth rate and mutagenesis. Val-NMHE is mutagenic only on Ames'strain TA 1977 which carries a + 1 frameshift mutation. On a per cell basis, the number of revertants is not linearly correlated to the amount of drug bound to nucleic acids: this number is relatively higher for increasing amounts of drug. This effect is not related to the mere probability of interaction between the drug molecule and its target, a GGGG/CCCC sequence. It might be explained by other hypotheses briefly discussed herein.
Alkaloids↗
Long-term survival in metastatic melanoma patients treated with sequential biochemotherapy: report of a Phase II study.
The overall survival for patients with metastatic melanoma is very poor, with a median survival of 8.5 months. In this Phase II trial, we assessed the efficacy, safety, and tolerability of a sequential biochemotherapy schedule, using dacarbazine as antiblastic agent and immunomodulant doses of interleukin-2 and interferon-alfa. Thirty-one eligible patients with metastatic melanoma received dacarbazine IV as antiblastic therapy and interluekin-2, plus interferon-alfa SC as sequential immunotherapy, for 6 months. Responding and nonprogressing patients were subsequently maintained on immunotherapy treatment for further 6 months. Twenty-nine patients had an adequate trial, and were assessable for both response and toxicities, with a median follow-up of 49 months. The overall response rate was 52 percent (3 CR and 12 PR), SD was 8 (27 percent) and PD were achieved in 6 patients (21 percent). The median survival duration of responders was 28 months, significantly longer (p < 0.001) than the 16 months of nonresponders. Therapy was well tolerated and produced a significant improvement in progressive-free survival. Further studies, thus, are recommended for larger groups of patients not only to confirm these results, but also to apply this biochemotherapy regimen as adjuvant postsurgical treatment in early stages of malignant melanoma.
Adult↗
[Bipolar disorder: clinical trials with fluoxetine].
Sixty patients (39 females and 21 males) aged between 20 and 65 (average 48.5) with bipolar disorder in the depressive phase, according to the DSM III-R diagnostic criteria, were treated with fluoxetine (20-60 mg/die) for 8 weeks. Evaluation of therapeutical efficacy was performed at 0 time and after 14, 28, 42, and 56 days, using the following psychometric tests; HAM-D, SCL-90, CGI. At the end of treatment 42 patients (70%) showed a reduction of the HAM-D score over 50%. Clinical results suggest that fluoxetine is affective in bipolar disorder. Tolerability was judged good and very good in 76% of patients. Side effects were very mild and in any case of rapid regression.
Adult↗
[Fluoxetine and depression in the elderly. Clinical experience].
Eighty-six patients aged between 60 and 80 years and affected with major depression according to the diagnostic criteria of the DSM III-R were treated with fluoxetine per os at the single dosage of 20 mg/die. At prearranged intervals psychometric reagents were administered for the evaluation of any variations in the depressive symptomatology. Already at the 1st examination after 14 days' treatment a considerable improvement in the psychopathological picture was observed. This improvement remained constant at the subsequent examinations and the follow-up after 90 days. The tolerability was excellent and the side effect mild, with a tendency to regress after the first days of therapy. The clinical assessment and the psychometric findings both suggest that fluoxetine has a useful action on major depression in the elderly.
Aged↗
[Efficacy and tolerance of aniracetam in elderly patients with primary or secondary mental deterioration].
The study was carried out on 60 patients (mean age 69.9 +/- 10.3 years) suffering from slight-moderate brain pathology primary or secondary to vascular forms. Patients were treated with 1500 mg/day per os of Aniracetam or placebo. Drug efficiency evaluation was performed utilizing the following psychometric tests: Blessed Scale, figures repetition test, Benton test, Corsi test, Rey test, Pieron test, phrases construction test, verbal fluency test. They were carried out during basal visit after two and four month treatment. In Aniracetam treated group the score showed a significant improving during the first and second control. In placebo treated group no change statistically considerable happened in any test. Aniracetam has proved to be a useful drug in slight-moderate brain decay treatment of the elderly.
Aged↗
[Evaluation of the efficacy and tolerability of fluoxetine in major depression, Multicenter clinical study].
In an Italian multicenter study, 296 patients (115 males, 181 females) affected with major depression diagnosed according to the criteria of the DSM III-R, were treated for 8 weeks with 20 mg/die fluoxetine (Fluoxeren-Menarini s.r.l.). At the end of the therapy the mean scores on the Hamilton Depression Scale had improved considerably, going down from 27.42 to 10.05. 69.6% of the patients had improved by at least in the 50% in the HAM-D scores (responders). At the CGI the overall improvement was evaluated with a mean score of 2.05 (marked improvement), while the patients assessed themselves at the end of treatment as being from "improved" to "greatly improved". No significant differences in efficacy were found to depend on age, type of depression or response to previous treatment, though younger patients (18-40 years), and those with single or recurring episodes, with atypical depression and good response to other antidepressants, showed a more marked improvement. The tolerability of the drug was found to be good. The laboratory tests, ECG and body weight stayed within normal limits.
Adolescent↗
The effects of desogestrel and ethinylestradiol combination in normal and hyperandrogenic young girls: speculations on contraception in adolescence.
Hormone profile and ovarian morphology were studied in two groups of adolescents (group 1:19 girls with slight signs of hyperandrogenism; group 2: 14 normal adolescents) in basal conditions and during a contraceptive combination of 30 micrograms ethinyl estradiol (EE) and 150 micrograms desogestrel (D). Treatment was associated with a low incidence of side effects in both groups. In group 1, acne generally improved within 12 months while hirsutism was only reduced in some subjects (58%) after 12 months of therapy (basal hair score 8.50 +/- 1.60 vs 5.81 +/- 1.53 p less than 0.001). Significant falls in plasma levels of LH, total and free testosterone and an increase in sex-hormone-binding globulin levels were observed during treatment especially in group 1. High percentage of multifollicular ovaries (75%) characterized hyperandrogenic subjects. Ovarian volume and number of follicles, higher in group 1 than 2 in basal conditions, showed a significant reduction in both groups and normal ovarian morphology was restored in hyperandrogenic subjects. Considering the high incidence of hyperandrogenemia in adolescence and its implications, our data suggest that the EE.D combination suits adolescent biological condition and is one of the suitable contraceptive methods in adolescents which also has therapeutic effects.
Acne Vulgaris↗
Isolation and characterization of the glutathione-elliptinium conjugate in human urine.
In a cancer patient given 100 mg/m2 elliptinium by intravenous infusion, the glutathione conjugate was found in urine. This metabolite was isolated after ion-exchange treatment and high performance liquid chromatography. Its structure was assessed by fast-atom bombardment mass spectrometry and comparison with an authentic sample.
Adult↗
[Mitochondrial DNA of malignant cells].
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Adenoviridae↗
[The structure of hemoglobins and its functional implications].
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Chemical Phenomena↗
Metabolism of ethidium bromide in rats.
The biliary excretion products recovered after iv administration of ethidium bromide to rats were found to consist of: unchanged drug, 8-acetylethidium, and an 8-acetylated hydroxylated metabolite. Proofs of structure were obtained by field desorption mass spectroscopy and 1H NMR, which indicated that the latter metabolite is probably substituted at position 2-. The yield of these various metabolites was critically influenced by pretreatment of the animals with inducers of the hepatic mixed function oxidases. Similar results were obtained in vitro, using various subfractions of differently pretreated rat liver. The role of each cellular fraction and order of completion of the acetylation and hydroxylation steps are determined and the putative occurrence of transient intermediates is discussed.
Animals↗
Identification of the glucuronide and glutathione conjugates of the antitumor drug N2-methyl-9-hydroxyellipticinium acetate (Celiptium). Comparative disposition of this drug with its olivacinium isomer in rat bile.
Two metabolites of the antitumor drug N-2-methyl-9-hydroxyellipticinium acetate (Celiptium) were isolated from bile of 10 mg/kg iv-treated rats. These metabolites were characterized by UV-visible, mass and proton-NMR data and identified as (i) 9-(O)-glucuronide conjugate and (ii) 10-(S)-glutathione adduct. Evidence for the same type of metabolites for the isomer N-2-methyl-9-hydroxyolivacinium acetate was supported by HPLC data. Despite their minor structural differences (change into a methyl position), the biliary excretion profile of these two drugs is rather different quantitatively: total metabolites excreted within a 12-hr period is 33 +/- 4% of the administered dose for ellipticinium and 70 +/- 6% for olivacinium. The major metabolite is the 9-(O)-glucuronide conjugate for those two drugs: 25 +/- 3% of the dose of ellipticinium and 67 +/- 5% for olivacinium derivative. In both cases, the presence of the 10-(S)-glutathione adduct as a minor metabolite [1.5 +/- 0.5 of the dose (ellipticinium) and 1 +/- 0.5 (olivacinium)] supports the hypothesis that a "biooxidative alkylation" process could occur in vivo.
Alkaloids↗
Metabolism and disposition studies of 9-hydroxyellipticine and 2-methyl-9-hydroxyellipticinium acetate in animals.
Radiolabeled 9-hydroxyellipticine (iv and ip routes) and the corresponding radioactive quaternary salt, 2-methyl-9-hydroxyellipticinium acetate (iv route), were administered to mice. Tissue distribution was then followed up to 64 hours by means of autoradiography. Both drugs accumulated in the kidneys, lungs, and liver; 9-hydroxyellipticine also accumulated in the spleen and bone marrow. The quaternary salt was concentrated in the gastrointestinal walls and the salivary and thyroid glands; none was found in the brain. Metabolic studies after administration of these antitumor drugs to rats and mice showed that 9-hydroxyellipticine is extensively metabolized, mainly to its glucuronide. Under our experimental conditions, the ellipticinium derivative was excreted unchanged in the bile (70%) and in the urine (30%). Pharmacokinetic studies in mice using either radioactivity measurements or selective extraction followed by spectrofluorometric quantitation have shown that blood levels drop very rapidly during the distribution phase followed by a much slower disposition phase, with a half-life of about 30 hours for the quaternary salt.
Alkaloids↗