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Biomedical subjects

R Palumbo

Publications and source records attributed to R Palumbo.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Pharmacokinetics and metabolism of N-(2-hydroxyethyl)-2,5-[14C]-pyrrolidine (HEP, Epolamine) in male healthy volunteers.

N-(2-hydroxyethyl)-pyrrolidine (HEP, Epolamine) is a strong base used to salify organic acids of pharmaceutical interest in order to improve their solubility in water. Diclofenac-HEP (Flector) is the first example of an epolamine salt of a drug. In this study, [14C]-HEP was administered by oral route (300 mg, about 50 microCi/subject) to 3 volunteers with the aim to investigate its plasma profile and to calculate the relevant pharmacokinetic parameters. The experimental data correlated with a two-compartment pharmacokinetic model. Total radioactivity in urine and faeces was also measured. The radioactivity was excreted preferentially by the faecal route (about 65% of the dose administered in the 0-72 h collection interval). Urinary excretion accounted for about 30% of the dose and occurred very rapidly (about 22% of the dose was in the 0-8 h collection interval). Metabolic investigations were carried out on urine samples. TLC analysis with radioscan detector indicated a main radioactive zone, accounting for about 98% of the radioactivity in the plate. After scraping off and purification of the radioactive areas, the compound isolated (Met I) was analysed by gas chromatography-mass spectrometry with electron-impact ionization process. The structure of the metabolite was postulated to be pyrrolidine N-oxide.

Adult↗
PubMedDate not supplied

Effect of an oxidative stress on methionine and S-adenosylmethionine metabolism in cultured bovine eye lens.

The sulphonium compound [Formula: see text] (AdoMet) plays a central role in many metabolic reactions of cellular metabolism, acting both as a propylamine donor in the biosynthesis of polyamines as well as a methyl donor in the transmethylation reactions. Moreover, AdoMet is a key intermediate of the transsulphuration pathway by which methionine is converted into cysteine, a precursor of glutathione. The aim of this study was to investigate the methionine and AdoMet metabolism in bovine lenses cultured in the presence of labelled methionine, upon treatment with H(2)O(2), as the experimental model for studying the molecular mechanisms responsible for the onset of senile cataract. The results reveal that one of the earliest changes following an oxidative stress is a severe impairment of protein synthesis. As far as the synthesis of AdoMet is concerned, a small but significant decrease in the conversion of labelled methionine into AdoMet occurs in treated lenses compared to the controls. In order to verify if the decreased AdoMet synthesis would lead in turn to alterations of methyl transfer reactions, we examined changes in the levels of various macromolecular methylations, such as protein methyl esterification and phospholipid methylation. The data clearly indicate that both the synthesis of AdoMet and the methyl transfer reactions could be significantly affected in eye lens upon an oxidative stress, suggesting that these alterations could be one of the biochemical events related to the ethiology of senile cataract. Finally, the question of whether or not H(2)O(2)-induced alterations of methionine and AdoMet metabolism could, in turn, affect some closely related metabolism, such as glutathione-associated reactions, is also discussed.

Journal Article↗
PubMedDate not supplied

(Iso) Prostaglandins in saliva indicate oxidation injury after radioiodine therapy.

UNLABELLED: As salivary glands concentrate radioiodine the radiation injury associated with 131I-therapy may result in sialoadenitis and xerostoma leading to a lasting impaired quality of life. Recently we reported about prostaglandin concentration changes as biochemical markers for radiation injury. Isoprostanes, a new family of prostaglandin-like compounds, have been demonstrated to be reliable markers for oxidation injury in vivo. PATIENTS AND METHODS: In this study we examined the levels of 8-epi-PGF2alpha, the major member of the isoprostane family in 24 patients undergoing 1311 treatment in different doses for hyperthyroidism and differentiated thyroid cancer. 6 healthy sex and age-matched volunteers were monitored in parallel. Saliva(iso)prostaglandins were determined before 131I treatment, as well as 1, 3, 7, 14, 21, and 28 days, and 2, 3, and 6 months after therapy. RESULTS: 8-epi-PGF2alpha showed a significant 1311 dose-dependent temporary increase. The alterations were comparable in all investigated patients and significantly higher in cigarette smokers. TXB2 and 6-oxo-PGF, showed a dose-dependent increase too. TXB2 was higher in cigarette smokers and 6-oxo-PGF1alpha lower as compared to non-smokers. CONCLUSION: These results clearly demonstrate a dose- and time-dependent tissue (TXB2, 6-oxo-PGF1alpha) and oxidation in-jury (8-epi-PGF2alpha) after 131I-therapy in the salivary glands.

Adult↗
PubMedDate not supplied

Combination chemotherapy using vincristine, adriamycin, cyclophosphamide (VAC) alternating with ifosfamide and etoposide (IE) for advanced soft tissue sarcomas: a phase II study.

Chemotherapy options in patients with advanced soft tissue sarcomas (STS) remain presently inadequate. In this phase II study the activity and toxicity of a combined alternating VAC/IE regimen in advanced and/or metastatic STS was evaluated. VAC (vincristine, total dose of 2 mg, adriamycin 70 mg/m2 and cyclophosphamide 600 mg/m2) was given as intravenous bolus infusion on day 1, followed after 21 days by IE (ifosfamide, 1.8 g/m2 infused over 1 h, daily for 5 consecutive days, with mesna uroprotection, plus etoposide at 500 mg/m2 infused over 2 h on the first day). Courses were repeated every 3 weeks. Twenty patients were treated, 12 of whom had previously been given chemotherapy for advanced and/or metastatic disease. Treatment was feasible in ambulatory setting, with good patient compliance. Myelosuppression, overall acceptable, was the major dose-limiting toxicity, while non-hematological side effects were minimal. An overall response rate of 45% was observed (95% CI, 26%-66%), with 2 complete and 7 partial remissions, achieving 75% in the subset of untreated patients. Median survival time was 10 months in the whole group (range, 4-26+ months) and 14 months in responder patients (range, 9-26+ months).

Adult↗
PubMedDate not supplied

Liposomal doxorubicin (Caelyx) in advanced pretreated soft tissue sarcomas: a phase II study of the Italian Sarcoma Group (ISG).

BACKGROUND: Doxorubicin remains one of the few drugs with consistent single agent activity in advanced Soft Tissue Sarcomas (STS), with a demonstrated dose-response relationship. Liposomal-encapsulated Doxorubicin (LED) has been shown to be at least as active as free doxorubicin in experimental models, and phase I and II human studies indicate that this novel strategy of drug delivery my have less myocardial toxicity. Few clinical trials in adult STS have been published until now, with disappointing and often contrasting results. PATIENTS AND METHODS: Twenty-five consecutive patients with measurable advanced and/or metastatic STS, previously pretreated with anthracycline-based chemotherapy, were enrolled into the trial. LED (Caelyx) was administered over 1-hour intravenous infusion at the dose of 30 mg/m2 in the first 5 patients, then at the fixed dose of 50 mg/m2 in the subsequent 20 patients. Treatment was given on ambulatory basis, at 3-week intervals. Antiemetics were generally not required and only used if indicated. RESULTS: A total of 98 courses of chemotherapy were given (median 4 per patient, range 2 to 5). Amongst the 25 evaluable patients, there were 3 partial responses (12%, 95% confidence interval 4.2% to 29.9%) lasting 3-9+ months and all occurring in patients treated at 50 mg/m2/cycle. In addition, 2 minor responses (4+ months) and 17 stable disease (2-7+ months) were observed; the remaining 3 patients progressed while on therapy. The median delivered drug dose-intensity was 13.3 mg/m2/week (range 10 to 16.6 mg/m2/week). Treatment was well tolerated, with no patient requiring dose reduction or therapy delay because of toxicity. Only 2 cases of WHO grade 3 toxicity occurred, consisting of neutropenia and scrotal skin toxicity; respectively; no cardiotoxicity was seen. CONCLUSIONS: This study shows that Caelyx has some activity in advanced, anthracycline-pretreated STS, with favourable toxic profile. From the analysis of available experiences it emerges that liposomal doxorubicin has not been tested at doses adequate to exploit the antitumor effects of the drug, being the reached dose-intensity being even lower than those deemed critical for obtaining optimal responses to free doxorubicin. We suggest that further and better addressed studies be performed in STS, including patients with less advanced stages of disease, focused on attempting to delivery the drug at optimal doses.

Adult↗
PubMedDate not supplied

Concomitant radiation-doxorubicin administration in locally advanced and/or metastatic soft tissue sarcomas: preliminary results.

Doxorubicin was administered by continuous infusion at a dosage of 12 mg/sqm/day for 5 days concomitantly with radiation treatment (150 or 200 cGy/day for trunk or extremity lesions, respectively) for 5 days. The 5-day cycles were repeated every 3 weeks. Seventeen patients, 5 of whom were pretreated, entered the study; all were assessable for toxicity and 15 for response. The overall objective response rate was 46% (7/15): 1 complete and 6 partial responses. Response rate reached 54% in only non-pretreated patients (6/11) and 75% in patients with PS less than or = 2 (6/8). No disease progression was observed during treatment. The median duration of complete or partial responses was 28 weeks (range 5-86). Toxicity was low and treatment very well tolerated. In our preliminary analysis, the response rate obtained with this combined chemo-radiotherapic regimen was encouraging and the toxicity was acceptable.

Adult↗
PubMedDate not supplied

[Nocturnal changes in osteocalcin in children with constitutional growth retardation].

Growth Hormone (GH) and serum Bone GLA-Protein (BGP or Osteocalcin), a sensitive and specific marker of bone turnover, were measured in 5 children with growth retardation, during 12 h period from 8 p.m. every 30'. A nocturnal periodicity in Osteocalcin was found: BGP rose slightly during sleep in the patients studied, maximum concentration being reached between 3 and 5 a.m. There were no consistent correlations between Osteocalcin concentration and circulating levels of GH in the subjects tested. BGP determination may be of interest in the evaluation of children with short stature but standardized analytical conditions remain to be determined.

Child↗
PubMedDate not supplied

[Visualization of carotid and femoral atherosclerotic lesions using autologous lipoprotein reinjection containing apo-B marked with 131I: preliminary data].

Atherosclerotic lesions can be detected by several methods, such as angiography, B-mode ultrasonography, computed tomography and magnetic resonance. Radioisotopic techniques, recently introduced by using radiolabelled platelets and LDL (low-density lipoproteins), can give more informations about the "metabolic activity" of atherosclerotic lesions. The aim of this study was to detect atherosclerotic lesions in 7 hyperlipemic patients using autologous apo-B containing lipoproteins labelled with 131I in order to evaluate different functional patterns of these lesions. Carotid and femoral accumulations of this radiocompound were detected in the majority of patients. The method appears promising for evaluating the "in vivo" relationships between lipoproteins, which are involved in the pathogenesis of atherosclerosis, and the vessel wall.

Adult↗
PubMedDate not supplied

Efficacy of the association of 13-cis-retinoic acid (13cRA) and alpha-interferon 2a (alpha-IFN 2a) in moderate-severe cervical intraepithelial neoplasia (CIN II-III): a pilot study.

Recent in vitro studies have suggested a possible therapeutic synergism between alpha-IFN 2a and 13cRA in certain neoplasias, while encouraging in vivo findings strongly support the enhanced effectiveness of the two agents when used in combination. The specific aim of our study was to evaluate the efficacy and the toxicity of the association of 13cRA and alpha-IFN 2a in patients with CIN II and CIN III who refused surgical treatment. Twenty-one patients (aged between 25 and 58 years), of which 14 were CIN II and 7 CIN III, entered the study. 13cRA (orally at 0.5-1 mg/Kg/day) and alpha-IFN 2a (intramuscular at 3x10(6) I.U./day for the first 15 days, then 3 times/week for the following four weeks) were administered simultaneously for eight consecutive weeks. 13/21 (62%) histologically verified objective responses (6 complete and 7 partial) were achieved. We also obtained 8 stable diseases. Compliance was generally good and no delays in therapy due to toxicity were recorded (except for two patients presenting WHO degree III cutaneous and mucosal toxicity which regressed one week after suspending treatment). Human Papilloma Virus (HPV) was initially detected in 16/21 (76%) patients, while HPV negativization after treatment was observed in 3/16 (19%). Although preliminary and requiring long-term assessment, the encouraging results of this study confirm the need for further investigation on the role of systemic medical therapy in the treatment of CINs.

Adult↗