[Sex hormones and male osteoporosis. A physiologic prospective for prevention and therapy]. / Ormoni sessuali ed osteoporosi maschile. Una prospettiva fisiologica di prevenzione e terapia.

BACKGROUND: Male osteoporosis is often an underestimate and non-acknowledged pathology because it is less frequent then post-menopausal women osteoporosis. The causes of osteoporosis in males were reviewed, considering the importance of the assessment of sexual hormones, even without symptoms of hypogonadism. METHODS: Sixty-two patients ranging in age from 45 to 75 years, males, were studied. None of them had assumed steroids nor other drugs causing osteoporosis. These patients have been subjected to bone mineral analysis (BMA) together with the following sexual hormones: LH, FSH, total testosterone, free testosterone, SHBG, estrone, estradiol. Two methods of BMA have been employed (Norland 2780 and UBA 575 Walker and Sonix). RESULTS: When osteoporosis or osteopenia were present, always there were modifications of sex hormones values. Statistic evaluation (linear regression, Pearson coefficient, Multiple regression, Backward Stepwise Multiple Regression), showed that there was a significant association between total testosterone and osteoporosis. CONCLUSIONS: Total testosterone resulted the most predictive sex hormone for the loss of bone mass; therefore, it is important to evaluate sex hormones in males with osteoporosis, for a correct and "physiological" therapy.

Revertant and potentiating activity of lonidamine in patients with ovarian cancer previously treated with platinum.

PURPOSE: Lonidamine (LND) is an energolytic derivative of indazol-carboxylic acid that has been shown to enhance cisplatin (CDDP) activity in both sensitive (A2780) and resistant (A2780/Cp8) ovarian cancer cell lines. The aim of this study was to confirm the potentiating or reverting activity of LND on CDDP activity obtained in experimental models in a phase II study of advanced ovarian cancer patients previously treated with platinum-based regimens. PATIENTS AND METHODS: Twenty-seven consecutive women with histologically proven and measurable ovarian cancer previously treated with platinum compounds were treated with CDDP plus LND. CDDP was administered at 1 mg/kg intravenously (IV) once weekly for 6 weeks and every 3 weeks thereafter until disease progression or toxicity. LND was administered at 450 mg daily (1 tablet every 8 hours) for the entire period of therapy starting 3 days before the first CDDP administration. In addition, a higher LND dosage was provided on the day of CDDP administration in an attempt to maximize the synergy of this drug with CDDP. RESULTS: Ten patients achieved a complete response (CR) or partial response (PR) for an overall response rate of 37% (95% confidence interval [CI], 19% to 55%). In particular, responses were observed in five of 18 (28%) refractory or early relapsed patients (one CR and four PRs) and in five of nine patients (55%) in the late-relapsed group (two CRs and three PRs). Grade 3 or 4 anemia, leukopenia, and thrombocytopenia were observed in 19%, 15%, and 11% of patients, respectively, whereas seven of 27 patients (26%) showed LND-related myalgia. Grade 3 renal toxicity was observed in two patients (8%). Neurotoxicity, often concealed by LND-related myalgia, was recorded as grade 1 or 2 in six patients (22%) and as grade 3 in one (4%). CONCLUSION: The 37% response rate observed in this study (28% in refractory or early-relapsed patients), suggests that the synergism between CDDP and LND observed in vitro against ovarian cancer cell lines can be clinically confirmed. However, larger series and randomized studies are needed to assess definitely the revertant activity of LND on CDDP-refractory patients.

Correlation between HPLC-determined lonidamine serum levels and clinical response in patients with advanced ovarian cancer.

Lonidamine is an energolytic derivative of indazolcarboxilic acid which has been demonstrated to enhance cisplatin activity in ovarian cancer cell lines either sensitive or resistant to this drug, thus suggesting the potential reverting activity of the mechanisms of drug resistance. A study was performed on nine patients with advanced ovarian cancer treated with lonidamine (LND) plus cisplatin (CDDP) as salvage therapy after the failure of first-line platinum containing chemotherapy. Serum LND was determined with a high-performance liquid chromatography (HPLC) method. The objective clinical response included one complete and three partial responses (overall response 44%). High LND serum levels were observed in three of four responding patients. The serum LND concentrations for these patients, detected one hour after the first and second dose administrations, were 15.2 +/- 1.1 and 14.6 +/- 1.4 micrograms/ml, respectively. Toxicity was mild to moderate, except for myalgia. The high serum levels of lonidamine detected in three of four responding patients suggests that the syngerism between LND and CDDP observed ovarian cancer cell lines may be confirmed in clinical practice. However, the potential role of LND in enhancing CDDP activity can be definitely established in large randomized trials.

An on-line semi-automated solid-phase extraction procedure for high-performance liquid chromatographic determination of lonidamine in serum.

A semi-automated solid-phase extraction procedure on-line with gradient elution reversed-phase chromatography permits the determination of lonidamine and its metabolite in human serum. The average recovery from serum at the 2.5 micrograms ml-1 level was (92.8 +/- 3.4)%. The limit of quantitation for a 100 microliter sample size was 50 ng ml-1. The within-day (n = 5) and between-day (n = 5) relative standard deviations for lonidamine determination in serum samples spiked at the 2.5 micrograms ml-1 level were 2.7% and 4.5%, respectively.

Stability of fumonisins (FB1 and FB2) in solution.

The stability of fumonisins B1 and B2 (FB1 and FB2) during 6 week storage was studied in acetonitrile:water (1:1) and methanol at four storage temperatures (-18, 4, 25 and 40 degrees C). Samples were analysed by HPLC with fluorescence detection after derivatization with o-phthaldialdehyde. Decomposition of fumonisins was evident in a methanol solution after 6 week storage at 4, 25 and 40 degrees C (signals for both toxins decreased by 5, 35 and 60%, respectively), whereas no losses were observed in samples stored at -18 degrees C. Both fumonisins were quite stable in acetonitrile:water solution at any of the four storage temperatures. The stability of fumonisins in acetonitrile:water (1:1) was confirmed over a period of 6 months at three temperatures (-18, 4 and 25 degrees C) in two solutions at different mass concentrations. No significant difference (t0.95-test) was observed between solutions stored in the dark at different temperatures and for different times (3 and 6 months). The overall coefficient of variation (n = 24, four measurements at each storage time and temperature) in each solution was < 3% for both toxins. Acetonitrile:water (1:1), unlike methanol, is a suitable solvent for fumonisin reference solutions.

Presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs. 2. 2-Phenoxy-, 2-(phenylthio)-, and 2-(phenylamino)alkanoic acid esters.

Further modifications of the leads ((R)-(+)-hyoscyamine and (p-chlorophenyl)propionic acid alpha-tropanyl ester), which show analgesic and nootropic activities as a consequence of increased central presynaptic ACh release, are reported. 2-Phenoxy- and 2-(phenylthio)alkanoic acid esters showed the best results. Several members of these classes possess analgesic properties which are comparable to that of morphine and at the same time are able to reverse dicyclomine-induced amnesia. Confirmation was found that the mechanism of action is due to an increase in ACh release at central muscarinic synapses and that both auto- and heteroreceptors controlling ACh release are very likely involved. According to the results obtained with (R)-(+)-hyoscyamine, analgesic activity is stereochemistry dependent, since the R-(+)-enantiomers are always more efficacious than the corresponding S-(-)-ones. On the basis of their potency and acute toxicity, compounds (+/-)-28 (SM21) and (+/-)-42 (SM32) were selected for further study.

[Association of infantile nephroblastomatosis and Wilms' tumor: discussion of a clinical case and therapeutic problems, analysis of the literature]. / Associazione della nefroblastomatosi infantile e tumore di Wilms: discussione di un caso clinico e delle problematiche terapeutiche, analisi della letteratura.

This is a case report of bilateral nephroblastomatosis in a 19 month child, who underwent a unilateral nephrectomy and chemotherapy. Further review of the nephrectomy specimen and biopsies of the contralateral kidney revealed mature features of nephrogenic rests progressing to Wilms' tumor. We have reviewed the literature and discuss the presentation and different therapeutic approaches.

Toxicity of some Fusarium section Sporotrichiella strains in relation to mycotoxin production.

The relationship between the toxicities of crude extracts and purified toxins of Fusarium spp. belonging to the section Sporotrichiella has been assessed. Toxicity was determined on the basis of death of Artemia salina larvae and of viability and blastogenic response of bovine and human lymphocytes. Trichothecene-producing strains of Fusarium sporotrichioides and Fusarium poae were toxic to A. salina and to lymphocyte blastogenesis. A strain of Fusarium tricinctum, producing visoltricin and chlamydosporol, induced differentiated activity in different bioassays (toxicity to A. salina but only minor activity against lymphocyte blastogenesis). Other, non-toxin-producing strains of Fusarium chlamydosporum, F. poae, and F. tricinctum were not active in the tested biosystems.

Immunomodulatory effects of fusarochromanones TDP-1 and TDP-2.

An in vitro peripheral lymphocyte blastogenesis system was used to investigate the biological activities of the fungal toxin fusarochromanone (TDP-1) and its monoacetyl derivative TDP-2. Briefly, cultures of human or bovine peripheral lymphocytes were exposed to TDP-1 or TDP-2 and a mitogen (PHA, Con A or PWM). After a standard incubation time, cell proliferation was quantified using the MTT bioassay. Human and bovine lymphocyte proliferation was inhibited by high concentrations of TDP-1; however, bovine lymphocyte proliferation was significantly increased at low concentrations of TDP-1. TDP-2 has similar but less pronounced effects on lymphocyte proliferation.