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Biomedical subjects

M Eandi

Publications and source records attributed to M Eandi.

At least 19 recordsLinked to original sources
PubMed2003

Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma.

Previous works showed that exposure to static and extremely low frequency (ELF) magnetic fields (MF) over 3 mT slows down the growth kinetics of human tumors engrafted s.c. in immunodeficient mice, reducing their metastatizing power and prolonging mouse survival. In the experiments reported here, immunocompetent mice bearing murine Lewis Lung carcinomas (LLCs) or B16 melanotic melanomas were exposed to MF and treated respectively with two commonly used anti-cancer drugs: cis-diamminedichloroplatinum (cis-platin) and N,N-bis (2-chloroethyl)tetra-hydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (cyclophosphamide). The experiment endpoint was survival time. The survival time of mice treated with cis-platin (3mg/kg i.p.) and exposed to MF was significantly (P<0.01) longer than that of mice treated only with cis-platin or only exposed to MF, superimposing that of mice treated with 10mg/kg i.p. of the drug, showing that MF act synergically with the pharmacological treatment. On the contrary, when mice treated with cyclophosphamide (50mg/kg i.p.) were exposed to MF no synergic effects were observed, the survival curve being exactly the same as that of mice treated with the drug alone. No clinical signs or toxicity were seen in any of the mice exposed to MF alone or along with cis-platin or cyclophosphamide treatment, compared to mice given only the two known drugs.A possible explanation for the synergic effect of MF being found in mice treated with cis-platin could be that the platinum ion stimulates radical production and that MF enhance active oxygen production bringing about changes in tumor cell membrane permeability, influencing positively the drug uptake. Alternatively, or in addition to this, it has been demonstrated that the rate of conversion of cis-platin to reactive species able to bind to DNA, is increased by localized production of free radicals by MF.

Animals↗
PubMed2002

Simultaneous HPLC determination of 5-fluorouracil and its metabolites in plasma of cancer patients.

5-Fluorouracil (5-Fu) is a commonly used anticancer agent for treatment of solid tumours. Certain studies have reported conflicting results between individual plasma concentration levels and toxicity or therapeutic effects. For this reasons some authors proposed to evaluate the plasma levels of 5-Fu metabolites 5-fluorouridine, 5-fluoro-2'-deoxyuridine and 5-fluoro-5,6-dihydro-uracil. The aim of the present work is to develop and validate a new HPLC method simultaneously determining 5-fluorouracil and its three metabolites, to be used to study the plasma levels, therapeutic effects and toxicity in cancer patients. The analytes were separated on a 4.6 x 250 mm ODS1 (5 micro m) not end-capped column, operating at room temperature. Elution was performed under isocratic conditions, employing a 1.5 mM K(3)PO(4) mobile phase (pH 5). 5-Bromo-5,6-dihydro-uracil was used as internal standard. The limits of quantitation were 0.5 micro g/mL for 5-fluorouracil, 1 micro g/mL for 5-fluoro-5,6-dihydro-uracil, 3 micro g/mL for 5-fluoro-2'-deoxyuridine and 5-fluorouridine; the stability, recovery, linearity, accuracy and specificity of the compounds were evaluated according to the criteria widely accepted. Using this method we measured plasma samples of 18 cancer patients treated with folinic acid (100 mg/m(2)) by intravenous administration, followed by an i.v. bolus of 5-Fu (400 mg/m(2)). The concentration levels of 5-fluorouracil and for 5-fluoro-5,6-dihydro-uracil were detectable in all the subjects while 5-fluorouridine and 5-fluoro-2'-deoxyuridine were present only in eight patients.

Antimetabolites, Antineoplastic↗
PubMed2000

Determination of Ibuprofen in human plasma by high-performance liquid chromatography: validation and application in pharmacokinetic study.

A specific method for the simultaneous determination of S-(+)Ibuprofen and R-(-)Ibuprofen enantiomers in human plasma is described. Adopting a high-performance liquid chromatographic (HPLC) system with spectrofluorometer detector, the compounds were extracted from plasma in alcohol medium and were separated on C18 column, using a solution of acetonitrile-water-acetic acid-triethylamine as mobile phase. The limit of quantitation was 0.1 microg/mL for both compounds. The method was validated by intra-day assays at three concentration levels and was used in a kinetic study in healthy volunteers. During the study we carried out inter-day assays to confirm the feasibility of the method.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Plasma erythropoietin concentrations in patients receiving intensive platinum or nonplatinum chemotherapy.

AIMS: Platinum chemotherapy has been shown to have potent antineoplastic activity against various tumours, especially testicular, bladder, ovarian, head and neck cancers. This activity is accompanied by side-effects of nephrotoxicity and cumulative myelosuppression, the latter frequently presenting as severe anaemia. Cisplatin and carboplatin nephrotoxicity might lower erythropoietin (Epo) secretion and, by this mechanism, contribute to the anaemia that follows therapy with this chemotherapeutic agent. The aim of the present work is to study the plasma immunoerythropoietin and haemoglobin levels of cancer patients treated with platinum or 5-fluorouracil-based chemotherapy. METHODS: Plasma was obtained from 25 patients who were about to receive chemotherapy for advanced malignancy: 15 treated with cisplatin or carboplatin and 10 with nonplatinum drugs. Blood was collected on the first day (before drug administration) and around day 15 of every chemotherapy course. Complete blood count, creatinine and immunoreactive Epo levels were also measured in 22 healthy volunteers. RESULTS: An increase in Epo levels occurred following every course of 5-FU or platinum based chemotherapy in patients with steady concentrations of creatinine and decreased levels of haemoglobin (Hb). In particular, we observed an increase after about 15 days of the chemotherapy treatment and the Epo levels declined toward normal just before the following course. This phenomenon was evident in every course. CONCLUSIONS: Our results suggest that chemotherapy administration, using the current standards of hydration and forced diuresis, slightly lowered Hb levels but did not depress Epo production, both in 5-FU and in platinum treated subjects.

Adult↗
PubMed1998

Economic impact of resistance in the community.

Antimicrobial resistance is assumed to be an important health problem and an economic burden to society. However, the relationship between the emergence of in vitro microbiological resistance and its clinical and socioeconomic consequences has not yet been satisfactorily determined for either nosocomial or community-acquired infection. In the case of both nosocomial and community-acquired infection, previous exhaustive reviews of published and unpublished reports concluded that mortality, likelihood of hospitalization, and length of hospital stay were usually at least twice as great for patients infected with drug-resistant strains as for those infected with drug-susceptible strains of the same bacteria. However, evaluation of the economic impact of resistance is still problematic and the adverse economic and health effects of drug-resistant bacterial infections can only be roughly quantified. Decision analysis models, such as decision trees, can aid evaluation of the impact of resistance on health and economic outcomes from the perspective of a given decision maker. A model of cost analysis should be based on a knowledge of the incremental consumption of resources specifically dependent on the dynamics of antimicrobial resistance in a given clinical setting (e.g. home care or hospital care). In general, we can assume that the increased rate of isolation of resistant strains from community-acquired infections correlates positively with an increase in morbidity, mortality, risk of hospitalization and the need for additional days in hospital and for more expensive and powerful antibiotics. We implemented and simulated a general decision-tree model to analyse the influence of antibiotic resistance on the economic outcomes of community-acquired lower respiratory tract infections, from the perspective of both society and the health-care local organization (HCLO). This model allows simulation of the impact of different degrees of resistance on the direct costs of an antibiotic therapy as well as on the cost-effectiveness of antibiotics with different degrees of resistance.

Community-Acquired Infections↗
PubMed1997

Preliminary pharmacokinetic study of ibuprofen enantiomers after administration of a new oral formulation (ibuprofen arginine) to healthy male volunteers.

The pharmacokinetics of ibuprofen enantiomers were investigated in a crossover study in which seven healthy male volunteers received single oral doses of 800 mg racemic ibuprofen as a soluble granular formulation (sachet) containing L-arginine (designated trade name: Spedifen), 400 mg (-)R-ibuprofen arginine or 400 mg (+)S-ibuprofen arginine. Plasma levels of both enantiomers were monitored up to 480 minutes after drug intake using an enantioselective analytical method (HPLC with ultraviolet detection) with a quantitation limit of 0.25 mg/l. Substantial inter-subject variability in the evaluated pharmacokinetic parameters was observed in the present study. After (+)S-ibuprofen arginine, the following mean pharmacokinetic parameters +/-SD were calculated for (+)S-ibuprofen: tmax 28.6 +/- 28.4 min; Cmax 36.2 +/- 7.7 mg/l; AUC 86.4 +/- 14.9 mg.h/l; t1/2 105.2 +/- 20.4 min. After (-)R-ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S-ibuprofen and (-)R-ibuprofen, respectively: tmax 90.0 +/- 17.3 and 50.5 +/- 20.5 min; Cmax 9.7 +/- 3.0 and 35.3 +/- 5.0 mg/l; AUC 47.0 +/- 17.2 and 104.7 +/- 27.7 mg.h/l; t1/2 148.1 +/- 63.6 and 97.7 +/- 23.3 min. After racemic ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S- and (-)R-ibuprofen, respectively: tmax 30.7 +/- 29.1 and 22.9 +/- 29.8 min; Cmax 29.9 +/- 5.6 and 25.6 +/- 4.4 mg/l; AUC 105.1 +/- 23.0 and 65.3 +/- 15.0 mg.h/l; t1/2 136.6 +/- 20.7 and 128.6 +/- 45.0 min. Tmax values of S(+)- and (-)R-ibuprofen after a single dose of 400 mg of each enantiomer did not differ significantly from the corresponding parameters obtained after a single dose of 800 mg of racemic ibuprofen arginine, indicating that the absorption rate of (-)R- and (+)S-ibuprofen is not different when the two enantiomers are administered alone or as a racemic compound. An average of 49.3 +/- 9.0% of a dose of the (-)R-ibuprofen arginine was bioinverted into its antipode during the study period (480 minutes post-dosing). The percent bioinversion during the first 30 minutes after (-)R-ibuprofen arginine intake averaged 8.1 +/- 3.9%. The mean AUC of (+)S-ibuprofen calculated after 800 mg racemic ibuprofen arginine (105.1 +/- 23.0 mg.h/l) was lower than the mean AUC value obtained by summing the AUCs of (+)S-ibuprofen after administration of 400 mg (+)S-ibuprofen arginine and 400 mg (-)R-ibuprofen arginine (133.4 +/- 26.6 mg.h/l). In conclusion, the administration of Spedifen resulted in very rapid absorption of the (+)S-isomer (eutomer) with tmax values much lower than those observed for this isomer when conventional oral solid formulations such as capsules or tablets of racemic ibuprofen are administered. This characteristic is particularly favourable in those conditions in which a very rapid analgesic effect is required.

Adult↗
PubMed1997

Pharmacoeconomic aspects of antibacterial treatment with cefotaxime.

Pharmacoeconomics is a relatively new discipline, which is becoming increasingly useful in the current climate of medical advances that continue despite limited access to healthcare resources. Pharmacoeconomics may be used as a tool, assisting healthcare decision makers to select clinically beneficial therapies and weigh clinical gain against expenditure. Cefotaxime has been shown in many studies to be a cost-effective antibiotic agent, its monetary value being augmented by its use in low dose, low frequency regimens. This cost-effectiveness, combined with a maintained broad spectrum of antibiotic activity, low propensity for selecting resistant bacterial strains and high therapeutic index, makes cefotaxime a suitable antibiotic agent in many indications involving mild-to-moderate infections by susceptible organisms.

Cefotaxime↗
PubMed1991

[Piroxicam in analgesia].

Piroxicam, a NSAID with a proved analgesic and antiphlogistic efficacy, largely used in rheumatic-orthopedic pathologies, has an antalgic action also in extra-rheumatic pathologies, such as postoperative and dental pain and primary dysmenorrhea. This is probably due both to a peripheral mechanism, at the injured site level, which is particularly widespread, and goes from prostaglandin inhibition to suppression of the synthesis of different algesiogenic substances (oxygen free radicals, lytic enzymes), and to a direct non endorphin-mediated action at central level. The data base considered in this review, concerning piroxicam in extra-rheumatic analgesia, is of about 2,500 patients, in 26 clinical studies, mostly with an experimental double-blind placebo-controlled design or vs other NSAIDs. The doses ranged from 5 to 40 mg in a single administration: the doses of 20 and 40 mg showed an immediate analgesic effect, with the onset of analgesia within 30 min./1 hour from the administration. Analgesic activity was intense, comparable or superior to that of other drugs (aspirin, codeine, other NSAIDs) and more prolonged, often lasting as long as 24 hours. Tolerability of this data base was very satisfactory and comparable to that of the placebo, incidence of side effects being negligible.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

[Ferroprotein succinylate: treatment of iron deficiency in obstetrics and gynecology].

Aim of this multicentric clinical trial was to evaluate the efficacy and tolerability of a new iron compound: iron proteinsuccinylate. 3,200 patients affected with iron deficiency due to obstetric or gynecologic etiology were treated with iron proteinsuccinylate, at a daily dose of 80 mg Fe3+, for at least 30 days. Iron proteinsuccinylate induced a statistically significant improvement (p less than 0.01) in mean values of hemoglobin and serum iron. The compound also caused a disappearance or improvement of subjective symptomatology (asthenia, anorexia) and of clinical conditions deriving from iron deficiency state (polypnea, cutaneous and mucous pallor). The treatment was well tolerated and caused a few slight side effects (diarrhea, epigastralgia, nausea) in 2.4% of patients.

Anemia, Hypochromic↗
PubMed1989

Pharmacokinetics, endocrine and antitumour effects of leuprolide depot (TAP-144-SR) in advanced prostatic cancer: a dose-response evaluation.

Twenty-two patients with advanced prostatic cancer and one with benign prostatic hypertrophy were given the GnRH analogue leuprolide in the form of a slow-release depot formulation by subcutaneous injection at doses of 3.75, 7.5, 15 or 30 mg. Following the first dose, drug levels were measured by a double-antibody RIA over an observation period of 5 weeks. Thereafter patients continued long-term subcutaneous treatment at the same dose every 4 weeks. Serum levels of leuprolide showed a rapid increase immediately after injection, reaching a peak proportional to dose within 3 h (range of mean values 13.1-54.5 ng/ml). Subsequently, mean drug levels declined to a plateau proportional to dose (0.49-1.99 ng/ml at 5 weeks). A significant dose-dependent increase in the area under the serum concentration-time curve from zero to 35 days (AUC0-35 days) from 541.7 to 1653.9 ng/ml.h was also noted (p less than 0.01). With all doses there was an initial rise in serum LH and FSH, followed by a rise in testosterone and dihydrotestosterone, then a sharp decrease within 3 weeks. FSH inhibition was achieved in all the 20 evaluable patients and was maintained in 17 of them (85%) over 5 weeks. Fifteen subjects (75%) had marked suppression of LH levels. In 13 of them (65%) this condition continued for the entire observation time. Castration levels of serum testosterone and dihydrotestosterone, however, were maintained in all patients for up to 5 weeks. Two of the 21 evaluable patients (10%) had a complete response; 15 a partial response (71%) and 3 stable disease (14%). No significant differences were observed in relation to dose. Clinical improvement and serum hormonal changes support this as a new and superior method of administration of leuprolide at a dose as low as 3.75 mg.

Aged↗
PubMed1989

[Clinico-pharmacologic study of a new sustained-release oral salbutamol preparation in patients with obstructive airway disease].

A new sustained release preparation of oral salbutamol (8 mg) was compared to salbutamol (8 mg) and placebo in 15 patients suffering from chronic obstructive airways disease in a randomized double-blind cross-over trial. Changes in airways resistance and amplitude of finger tremor as well as subjective assessment of side effects (tremors, unrest, palpitations) revealed a longer lasting effect following the sustained release preparation of salbutamol.

Adult↗
PubMed1988

Drug monitoring study of a product containing ferritin.

A drug monitoring study was carried out co-operatively by industry, a university department of clinical pharmacology and a randomly selected sample of general practitioners throughout Italy to collect case history and clinical data on over 10,000 patients with anaemia treated for 2 to 4 months with a preparation containing ferritin plus vitamin B12 co-enzyme and folinic acid. Analysis of the data generated, whilst confirming the effectiveness and tolerability of the study medication, highlighted the usefulness of the research methodology for describing the pattern of use of a drug widely prescribed in general medicine.

Adolescent↗
PubMed1987

Congenital deficiency of alpha-2-adrenoceptors on human platelets: description of two cases.

The biochemistry and functionality of platelets from two related subjects (mother and son) with alpha-2-adrenoceptor-deficient platelets has been evaluated. Radioligand binding experiments with the specific alpha-2-adrenergic-receptor antagonist, 3H-yohimbine, showed a drastic reduction of alpha-2-adrenoceptors in platelets from both subjects in comparison with the control values. Electron microscopy studies revealed a normal morphology and a normal number of alpha granules and dense bodies. Levels of adenine nucleotides; 5-hydroxytryptamine; B-thromboglobulin; platelet-factor-4 and thromboxane A2 production were within normal limits. Platelet aggregation and 5-hydroxytryptamine production in response to adrenalin (at concentrations up to 50 microM) were absent, whereas ADP, AA, PAF, collagen and thrombin-induced aggregation, secretion, Ca++ flux and thromboxane A2 production were normal. The inhibitory effect caused by different concentrations of prostacyclin on Ca++ flux, aggregation, secretion and thromboxane A2 production of platelet functionally lacking of alpha-2-adrenoceptor was not distinguishable from control platelets and platelets preincubated with yohimbine.

Adult↗
PubMed1985

[Cefoperazone: microbiological, kinetic and clinical studies].

In vitro cefoperazone proved more active against the tested gram-negative bacteria than either piperacillin or mezlocillin. When administered in 1 g venous bolus the antibiotic achieved high plasmatic concentrations that were still adequate after 8 hours. 33.2% was excreted by the kidneys and a considerable amount by the biliary way. Cefoperazone produced a clinical cure in 35/36 patients (97.22%). A disulfiram-like effect was noted in 18.18%.

Bacterial Infections↗
PubMed1984

[Antitubercular agents].

Author resume the most important stages of the antitubercular struggle. Then they consider the action mechanisms of single drugs, often not well known, such the action mechanism of pyrazinamide. At present, the criteria of effectiveness, tolerance, availability and economy allow to use rationally and not arbitrarily the antitubercular drugs and these criteria also assure the best therapeutic results.

Antimetabolites↗