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Biomedical subjects

M G Matera

Publications and source records attributed to M G Matera.

At least 73 records · Page 4Linked to original sources

Serum digoxin levels after concomitant ticarcillin and clavulanic acid administration.

Recently it has been recognized that steady-state serum digoxin concentrations may increase or fall to ineffective levels when the glycoside is administered together with several antibiotics. Our study was designed to assess if serum digoxin levels may be modified by the concomitant use of a ticarcillin and clavulanic acid. The study was carried out in 15 hospitalized patients suffering from exacerbation of their chronic bronchitis without liver disease and renal failure. Serum digoxin levels were not significantly modified by the concomitant use of a ticarcillin and clavulanic acid, although peak digoxin serum concentrations were slightly lower. However, the average time to achieve the maximum concentration and area under the curve over 24 h did not change.

Aged↗

Evaluation of lung tissue and hilar lymph node concentrations of azithromycin.

Since it is believed that most infections occur in the interstitial fluid, it has been suggested to measure the concentration of antimicrobial agents in pulmonary lymph that reflects the extracellular, extra-blood-vascular milieu in the lung. The aim of this study was to investigate the lung tissue and pulmonary lymph node penetration of azithromycin after 500 mg daily oral administration for three days in patients undergoing open thoracotomy. At the end of the treatment, each subject was assigned for 5 groups of 5 patients each according to thoracotomy time after the last dose (24, 48, 96, 120 and 144 h). Azithromycin was assayed by an agar diffusion method with Sarcina lutea Z114 (DRH) used as the test organism and the Antibiotic Assay Medium 1, pH 8.5 used as the medium. All patients had a detectable concentration of azithromycin in serum 24 h after the last dose (72 h after the first dose); the concentration fell below the detection limit (0.01 mg/l-1) after 96 h (168 h after the first dose). Peak concentrations in lung tissue and lymph nodes were found after 48 h (96 h after the first dose). Tissue and lymph node concentrations of azithromycin were much greater than serum concentrations and these tissue and lymph node concentrations persisted after serum concentrations declined. The concentrations in lung tissue of azithromycin were always higher than corresponding concentrations in hilar lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[The therapeutic prospects of ischemic cardiopathy].

Having thoroughly reviewed the risk factors and pathophysiologic features of ischemic heart disease, the authors describe therapeutic protocols at present in use and take stock of the perspectives opened by new drugs with different kinetic and dynamic and more advanced properties compared to those at present in use.

Cardiovascular Agents↗

Teicoplanin with other drugs: possible pharmacological interactions.

The contemporaneous employment of two or more drugs may present the risk of modifying the required therapeutic effect or producing adverse reactions. These interactions are of a pharmacokinetic and pharmacodynamic type. Teicoplanin is an antibiotic with a glycopeptide structure, produced by Actinoplanes teichomyceticus, active against both anaerobic and aerobic Gram-positive bacteria that are resistant to various chemotherapeutic drugs (beta-lactam and macrolide antibiotics, tetracyclines, co-trimoxazole). Then the aim of this work was to verify experimentally the possible pharmacological interactions between teicoplanin and oral hypoglycemic (phenformin and glibenclamide), or oral anticoagulant (warfarin) or bronchodilator (theophylline) drugs. Teicoplanin (3-15 mg/kg/die i.p. for 4 days) administration to the rat did not significantly (p > 0.05) modify the glycemia, prothrombin and partial thromboplastin times, the hypoglycemic effect of phenformin (2.5 mg/kg/die os for 4 days) and glibenclamide (0.5 mg/kg/die os for 4 days) or the anticoagulant effect of warfarin (0.5 mg/kg/die os for 4 days); moreover it did not significantly (p > 0.05) modify the pharmacokinetics of aminophylline (5 mg/kg i.v.) on the rabbit. In conclusion our results documented that teicoplanin does not interfere with phenformin, glibenclamide, or sodium warfarin activities nor with aminophylline pharmacokinetics.

Animals↗

Clinical pharmacokinetics of theophylline during co-treatment with ticarcillin plus clavulanic acid in patients suffering from acute exacerbation of chronic bronchitis.

The effect of ticarcillin/clavulanic acid, taken for 7 days as vials containing 1000 mg of ticarcillin and 200 mg of clavulanic acid twice daily intramuscularly, on the steady-state pharmacokinetics of theophylline was studied in 12 patients suffering from acute exacerbation of chronic obstructive pulmonary disease. Initially, patients were treated for four days with theophylline as sustained-release formulation in the amount of 600 mg daily; on the last day, blood samples were taken for theophylline determination. Theophylline concentrations were measured serially for 12 hours by the method of polarized immunofluorescence (Abbott TDx system). Subsequently, while theophylline was continued at the same dosage, each patient received in addition ticarcillin/clavulanic acid vials every 12 hours. After seven days of this combined medication, the serial assays of plasma were repeated at the same time intervals as before. No influence of ticarcillin/clavulanic acid was detectable on the steady-state theophylline pharmacokinetics. It is concluded that both drugs can be administered concomitantly without any dosage adjustment of theophylline.

Bronchitis↗

Theophylline in the inhibition of angiotensin-converting enzyme inhibitor-induced cough.

Preliminary reports suggest that some pharmacologic agents may be effective in ameliorating angiotensin-converting enzyme (ACE) inhibitor-induced cough and, perhaps, allowing continuing use of ACE inhibitors in patients for whom this class of medication is important. We examined the effect of a once-a-day theophylline formulation on ACE inhibitor-induced cough and on the sensitivity of the cough reflex to capsaicin in 10 hypertensive patients who had developed cough during treatment with an ACE inhibitor. Theophylline did not induce bronchodilation but induced complete remission of clinical symptoms in 8 and attenuated the capsaicin-induced cough number in 7 subjects when compared with placebo. Theophylline may thus be effective in preventing ACE inhibitor-induced cough.

Adult↗

Contraction of bovine isolated bronchial airways: effects of epithelium removal.

The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylcholine, carbachol, 5-hydroxytryptamine and histamine was studied. Epithelium removal caused a significant leftward shift of the acetylcholine concentration-effect curve, pD2 values were 2.86 +/- 0.11 and 3.34 +/- 0.18 for intact and rubbed tissue, respectively (P < 0.05). However, there was no change in the acetylcholine maximal response. The sensitivity and responsiveness of the bovine bronchus to the other spasmogens were not significantly altered by removal of the epithelium. These results suggest that the epithelium of bovine bronchi modulates only acetylcholine-induced contraction.

Acetylcholine↗

Ondansetron, an antagonist of 5-HT3 receptors, in the treatment of antineoplastic drug-induced nausea and vomiting in children.

The aim of this study was to evaluate the efficacy and safety of ondansetron, an antagonist of 5-hydroxytryptamine type 3 (serotonin 3) (5-HT3) receptors, in controlling nausea and vomiting induced by antineoplastic therapy in children affected by cancer. Six patients affected by nausea and vomiting due to antineoplastic drugs were treated with ondansetron (4 mg/m2). Urinary samples for the assay of serotonin and 5-hydroxy-indoleacetic acid (5-HIAA) were collected 24 hr before antineoplastic drug treatment, 24 hours after the start of antineoplastic therapy and, 24 hr after the start of ondansetron therapy. All patients were affected by nausea and vomiting within two to four hr after the antineoplastic treatment. Urinary concentrations of serotonin and 5-HIAA were higher and statistically significant (P < 0.01) with respect to basal values. Treatment with ondansetron significantly reduced the number of episodes of nausea and vomiting, as well as the urinary values for serotonin and 5-HIAA.

Antineoplastic Combined Chemotherapy Protocols↗

Role of M1 muscarinic receptor subtypes in mediating airway smooth muscle contraction.

Muscarinic receptor subtypes have been identified on airways of several mammalian species, including humans. They are distributed in the lung over submucosal glands, airway ganglia and over the nerves; M1-receptors are found in airway ganglia, M2-receptors (autoreceptors) are present in cholinergic postganglionic nerves at the prejunctional level, whereas the muscarinic receptor subtypes found in airway smooth muscle are of the M3-receptor subtype. We had previously reported the presence of M1-receptors on the smooth muscle of large and small airways of patients suffering from chronic bronchitis, but only is the peripheral airways of healthy subjects; one possible explanation of these results is that the bronchial epithelium may play a role in bronchial responsiveness to relaxant muscarinic antagonists. To clarify this hypothesis we have studied in vitro the responses to acetylcholine (ACh), and some muscarinic selective (pirenzepine, PZ; p-fluorohexahydrosiladyphenidol, pFHHSiD) and non-selective (atropine, ATR) antagonists, on human bronchial smooth muscle in the presence and in the absence of epithelium. The absence of epithelium did not modify the responsiveness to ACh to any great extent and did not change the responsiveness to relaxant antagonists. Our results show that the M1-receptors may play a role in mediating contraction of airway smooth muscle; research is in progress regarding their function in disease.

Acetylcholine↗

Effects of some cephalosporins and teicoplanin on platelet aggregation.

Antibiotics may interfere with platelet (PLT) function, and beta-lactam antibiotics may interact with PLT aggregation, by inhibiting the binding of agonists of this aggregation (such as ADP and collagen) to specific receptor sites. In this study we have evaluated the relative in-vitro antiplatelet effects of some old and new cephalosporins (cefonicid, ceftazidime, ceftriaxone, cefotaxime, cefuroxime and flomoxef) and of teicoplanin, a new glycopeptide antibiotic. All the cephalosporins tested, and also teicoplanin, were found to have the potential to adversely affect human platelet aggregation only at high concentrations which are not achieved in vivo.

Adenosine Diphosphate↗

Relationship between zinc and obesity.

Zinc has important effects on metabolism, and on the thermoregulation of obese individuals. The aim of our investigation was to evaluate the serum zinc levels in obese patients before and after severe hypocaloric diets and to evaluate its correlation with the body mass index (BMI). Patients followed a severe hypocaloric diet (737 Kcal) for 60 days. Serum Zn levels and BMI were evaluated. Zn levels in obese patients were significantly (p < 0.01) lower than in controls, whereas the BMI values were significantly greater. At the end a severe hypocaloric diet, serum Zn and BMI levels returned to normal values. Our data show a possible relationship of the serum Zn levels with the anabolic and catabolic mechanisms in obesity, although the exact metabolic role of this bio-element remains unclear.

Adult↗

Flomoxef, a new oxacephem antibiotic, does not cause hemostatic defects.

Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Responsiveness and sensitivity to cholinergic agonists and antagonists in bovine isolated bronchial muscle.

1. Airways derived from different levels of the lung exhibit a difference in the reactivity and sensitivity to agonists. We have evaluated the effect of acetylcholine and cholinergic selective (pirenzepine, gallamine and 4-dipherylacetoxymethyl piperidine [4-DAMP]) and non-selective (atropine) antagonists on bovine proximal and distal smooth muscle preparations. 2. The distal preparations are more sensitive to acetylcholine than proximal bronchi. The relaxant effect of three selective antagonists on the distal and proximal tissues was the same when the results for each drug were compared. 3. Atropine and 4-DAMP were more potent than pirenzepine and gallamine in relaxing both proximal and distal bovine smooth muscle preparations. 4. These data suggest that the muscarinic sites on the smooth muscle of bovine airways are of the M3 subtype.

Acetylcholine↗

Antiflammins suppress the A23187- and arachidonic acid-dependent chloride secretion in rabbit distal colonic mucosa.

Antiflammins are synthetic peptides with sequence homology to proteins inhibitory for phospholipase A2. The effects of antiflammins on chloride secretion induced by the calcium ionophore A23187, arachidonic acid (AA) and prostaglandin E2 (PGE2) were investigated in distal rabbit colonic mucosa mounted in Ussing-type chambers. 100 nM AF-2 (antiflammin 2, peptide HDMNKVLDL) fully prevented the increase in Isc, net chloride secretion, tissue PGE2 and second messenger cAMP induced by 5 microM A23187. AF-1 (antiflammin 1, peptide MQMKKVLDS) also inhibited, although to a lesser extent, the A23187-mediated increase in Isc. AF-2 inhibition began at doses of 100 nM (delta Isc -0.20 +/- 0.08, microEq h-1 cm-2, mean +/- S.E.M., N = 3) and was maximal at doses comprised between 200 and 250 nM (delta Isc -0.51 +/- 0.12, microEq h-1 cm-2, mean +/- S.E.M., N = 3). AF-2 also inhibited the increase in Isc and chloride secretion induced by the incubation with 10 microM AA and bradykinin but it was ineffective when tissues were stimulated with 10 microM PGE2. 100 nM AF-2 brought about an inhibition of the increase in AA-mediated increases in PGs and cAMP comparable to that of 10 microM of the cyclooxygenase inhibitor indomethacin. In vitro assay of colonic cyclooxygenase activity showed that 100 nM AF-2 and AF-1 inhibited cyclooxygenase activity (73 and approximately 30%, respectively), but they did not modify the in vitro activity of porcine phospholipase A2.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Impact of rokitamycin, a new 16-membered macrolide, on serum theophylline.

Side effects have been observed when 14-membered macrolides, erythromycin and troleandromycin, have been prescribed concurrently in patients receiving therapeutic doses of theophylline. Rokitamycin is a new 16-membered macrolide antibiotic. We have evaluated its effect on theophylline serum concentrations in 12 adult patients suffering from chronic obstructive pulmonary disease. Initially, six patients were treated for four consecutive days with theophylline as sustained-release formulation in the amount of 600 mg daily; six other patients received for four consecutive days a short term intravenous infusion of 240 mg aminophylline, given over a period of 30 min twice daily. On the last day, blood samples were taken for theophylline determination. Theophylline concentrations were measured serially for 12 hours after oral formulation and 4 hours after aminophylline by enzyme immunoassay technique. Subsequently, while theophylline and aminophylline treatments were continued at the same dosage, each patient received in addition rokitamycin tablets, 400 mg every 12 hours. After seven days of this combined medication, the serial assays of serum theophylline were repeated at the same time intervals as before. Concomitant administration of therapeutic doses of rokitamycin did not affect significantly the steady-state pharmacokinetics of oral theophylline and did not alter the (pseudo-) steady-state pharmacokinetics of intravenous aminophylline, showing that the two drugs may be coadministered without any theophylline dose adjustment.

Aged↗

[Cardiac function (angiocardioscintigraphic evaluation) and plasma catecholamine levels in non-insulin-dependent diabetics].

Cardiac mortality is more frequent in diabetic patients than in normal subjects and particularly heart failure occurs 4-6 times more frequently in these patients than in normals also excluding diabetics with coronary artery disease (CAD). To study cardiac function, 20 patients with type II diabetes mellitus (11 M and 9 F, mean age 48 +/- 9 years), and 13 normal subjects (6 M and 7 F, mean age 48 +/- 13 years), were submitted to radionuclide ventriculography with technetium 99m to evaluate some indices of cardiac function at rest and during effort. The diabetic patients were on good metabolic control testified by a satisfactory fasting and post prandial glycaemia, absence of glycosuria in the last 3 monthly controls and a normal value of glycosylate haemoglobin; they had no vascular or neurological complications; CAD was excluded submitting these patients to a maximal effort ECG on an ergometer. The normal subjects were comparable to diabetic patients for age, sex, mean arterial pressure, body mass index and body surface area. At rest, stroke volume, peak filling rate, cardiac output, ejection fraction (EF), were significantly lower in diabetic patients than in normal subjects. Systemic vascular resistances (SVR) were higher in diabetics than in normal subjects (p less than 0.01). Mean EF during effort increased in both normals and diabetics but 30% of diabetic patients showed no increase in EF during effort (less than 5%). Preload, represented by end-diastolic volume or blood volume, did not differ in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗