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Biomedical subjects

C Rossi

Publications and source records attributed to C Rossi.

At least 289 records · Page 16Linked to original sources
PubMed1986

Pharmacokinetics of etoposide in patients with abnormal renal and hepatic function.

Etoposide (VP16) pharmacokinetics was investigated in three groups of cancer patients: a control group of 18 patients with renal and hepatic function tests in the normal range; a group of 8 patients with renal insufficiency; and a group of 15 patients with abnormal hepatic function. In the control group plasma clearance (Clp), volume of distribution (Vd), and elimination half-life (t1/2 beta) of VP16 were, respectively, 22.8 +/- 1.0 (SE) ml/min/m2, 11.4 +/- 0.8 liters/m2, and 5.6 +/- 0.4 h. In patients with renal insufficiency Clp was 12.8 +/- 1.1 ml/min/m2, Vd was 20.8 +/- 4.9 liters/m2, and t1/2 beta was 19.2 +/- 4.7 h. A statistically significant correlation (P = 0.0000001) was found between VP16 Clp and creatinine clearance. In 12 of 15 patients with abnormal liver tests Clp, Vd, and t1/2 beta were, respectively, 27.9 +/- 2.7 ml/min/m2, 12.4 +/- 1.5 liters/m2, and 5.4 +/- 0.6 h and are thus similar to those of the control group. In the other three cases with abnormal liver function VP16 plasma levels were very low. In these cases VP16 t1/2 beta values were similar (5.1, 4.4, and 5.1 h) whereas Clp values (320, 87, and 96 ml/min/m2) and Vd values (142, 33, and 42 liters/m2) were much larger than in controls. These results suggest that VP16 doses should be reduced in patients with renal function impairment but not necessarily in patients with liver impairment. The high VP16 Vd and Clp values found in a subset of patients with liver impairment require further elucidation.

Adult↗
PubMed1985

Antimycin A- and hydroxamate-insensitive respiration in yeasts.

In this paper evidence is presented for the mitochondrial localization of the antimycin A (AA) + salicylhydroxamate (SHAM)-insensitive respiration of the yeasts Kluyveromyces lactis, Endomycopsis capsularis and Hansenula saturnus. Such a respiration, which can be sustained by NADH and NADPH but not by succinate, is inhibited by high concentrations of azide. AA + SHAM-insensitive respiration is not phosphorylating and its postulated physiological role is to oxidize NADH.

Antifungal Agents↗
PubMed1985

Horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of VP16-213. Identification of a new metabolite.

VP16 was submitted to oxidation catalyzed by horseradish peroxidase (HRP) and H2O2 in phosphate buffer (pH 7.0). The product of the reaction, which has a high performance liquid chromatographic (HPLC) retention time different from the previously known metabolites of VP16, was identified as 1,2,3,4-tetradehydro-VP16 by 1H-NMR and mass spectrometry (MS) analysis. It was found to result from the loss of four hydrogens and the formation of an aromatic ring (ring C of VP16). This new product retains, in the 4' position of the E ring of VP16, the hydroxy group which is crucial for the antitumoral activity of podophyllotoxin derivatives. The reaction was linear in a wide range of VP16 concentrations and was dependent on the concomitant presence of peroxidase and H2O2.

Acetylation↗
PubMed1985

Chronic traumatic aneurysms of the descending thoracic aorta.

Between 1970 and December 1984, 28 patients with post-traumatic chronic aneurysm of the descending thoracic aorta were consecutively operated on in our Division of Cardiac Surgery. Ages ranged from 16 to 66 years (mean 38 years); 25 were male and three were female. In all cases, a history of a major deceleration injury was documented. The interval between trauma and operation ranged from 2 to 50 years (mean 11.4 +/- 7.8). Twenty-three (82.1%) were asymptomatic. Only one operation was performed on an urgent basis for recurrent episodes of hemoptysis. All patients underwent resection with prosthetic tubulargraft (25 cases) and patch-graft (3 cases) replacements. In all patients but one, left heart bypass was employed. No hospital deaths, late deaths, paraplegia or graft-related complications occurred. Considering the risk of late rupture and the young age of most of the patients, surgery in chronic post-traumatic aneurysms of the descending thoracic aorta is always indicated. We consider left heart bypass a safe technique in preventing renal and medullar ischemic injuries.

Journal Article↗
PubMed1985

Pharmacokinetics of etoposide in gestochoriocarcinoma.

Etoposide (VP16) levels were determined by high-performance liquid chromatography assay in plasma, urine, and surgical specimens of patients with choriocarcinoma undergoing surgery after a dose of 100 or 200 mg/m2 given as a 1-hour infusion. The drug disappeared from plasma biexponentially, with a terminal half-life of 4.1 +/- 0.4 hours, an apparent volume of distribution of 9 +/- 1.1 L/m2, and clearance of 21.5 +/- 3.1 ml/minute/m2. Fifty and 740 minutes after the end of VP16 infusion, the drug concentrations in myometrial carcinoma or in normal myometrium were approximately 40%-50% of those in plasma; 25-180 minutes after the end of drug infusion, the concentrations of VP16 in lung metastases amounted to 19%-43% of those in plasma, whereas in normal lung, the concentrations of VP16 were 38%-61% of those in plasma. In subcutaneous tissue, VP16 levels were much lower than in plasma (about 5%-27%). About 50% of VP16 was eliminated in the urine as unchanged drug, glucuronide, or sulfate.

Choriocarcinoma↗
PubMed1985

[Comparative results in the carotid region. Venous or arterial digital angiography?].

A comparative evaluation between Digital Venous (DV) and Arterial (DA) studies of carotid arteries has been carried out in our institution in the last two years. DV study, in our experience, only in fourty percent of the cases shows good details (i.e. of true diagnostic value); this rate decreases to fifteen-twenty of intracranial sector, while DA offers optimal results in eighty percent and more of the patients. DV studies, highly invasive on a pharmacological point of view, based on the contrast medium amount, must be reserved only to surgical follow-up studies and patients with femoral/brachial bilateral occlusion, that involves technical impossibility for arterial catheterization.

Angiography↗
PubMed1985

[Digital subtraction angiography (DSA) of the renal-adrenal area. Methods of use and indications].

Our experience on 371 patients studied with DSA for reno-adrenal pathology in the last two years is reported. The purpose of this study was the evaluation of real possibilities of DSA in comparison with conventional angiography, particularly to specify diagnostic space of venous versus arterial approach in this region of interest. In our experience, DSA by venous approach is indicated only as a screening method for nefrovascular hypertension or post-surgery, post-PTA and post-embolization controls; in all other cases, DSA by arterial approach is preferable for its superior diagnostic accuracy and lesser pharmacological invasivity, in comparison both with venous DSA and conventional angiography.

Adrenal Gland Diseases↗
PubMed1985

Pharmacokinetics of teniposide in patients with ovarian cancer.

Pharmacokinetics of teniposide (VM26) after each of three doses were investigated by high-performance liquid chromatographic assay in eight patients with ovarian cancer with normal liver and renal functions. Treatment consisted of a first dose of 100 mg/m2 iv as a 1-hour infusion (Day 1), a second dose of 150 mg/m2 iv as a 1-hour infusion (Day 8), and a third dose of 150 mg/m2 as an approximately 1-day infusion (Day 22). Disappearance of VM26 from plasma followed a biexponential decay pattern. The mean terminal half-life (+/- SE) was 6.9 +/- 0.9 hours after the first dose, 6.1 +/- 0.7 hours after the second dose, and 9.7 +/- 1.4 hours after the third dose. VM26 levels in ascites were lower than those in plasma in the first hours after drug administration, but by 24 hours they were similar or slightly higher. Urinary elimination of VM26 as unchanged drug amounted to less than 10% of the dose.

Adult↗
PubMed1985

Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. I. Synthesis of 4H-s-triazolo[3,4-c]-1,4-benzothiazine and derivatives with potential CNS activity.

As a part of a program toward the synthesis and the pharmacological studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines, a number of 4H-s-triazolo[3,4-c]-1,4-benzothiazine derivatives were prepared and tested for their CNS activity. The syntheses of the new tricyclic compounds (VII) were performed via the 2H-1,4-benzothiazine-3(4H)-thiones (II) which were obtained by Lawesson's thiation of lactams (I). Compounds (II) and their S-methyl-thioethers (III), quantitatively obtained by PTC method, were reacted with acylhydrazines to give the title compounds. Some triazolobenzothiazines (VII) were also prepared from 3-hydrazinoderivatives (IV) by cyclization with either an aliphatic acid or the corresponding orthoesther.

Animals↗
PubMed1985

[Digital panangiography. Possibilities of digital angiography in estimating multifocal atheromatous vascular diseases].

Results obtained on 431 patients studied during thirty months (February '83-June '85) with DSA-whole body angiography are reported. On the basis of statistic evaluation, PAN-DSA certainly appears the best choice, especially with combined use of 150 mgI/ml and 300 mgI/ml contrast medium. A highly significant incidence of athero-sclerotic lesions found on target-territories, even in the presence of monofocal symptoms, suggests global radiological study (PAN-DSA) as indicated whenever diffuse vascular pathology is suspected.

Angiography↗
PubMed1984

1H-13C selective NOE studies of the decapeptide gramicidin S.

The cyclic decapeptide gramicidin S has been used as a model biopolymer to test the reliability of a structural method which is based on a relaxation analysis of heteronuclear selective NOEs. The observation of through-the-space dipolar couplings between intra- and inter residue amide protons and carbonyl carbons, perfectly consistent with the well established peptide solution conformation, confirms the effectiveness of this structural approach. As a corollary of the latter, carbonyl carbon resonances are unequivocally assigned. Moreover, a direct experimental proof of a Orn-NH2----Phe C = O hydrogen bonding is here given.

Biopolymers↗
PubMed1984

Biochemical studies on the ability of pentamethylmelamine to interact in vivo with DNA and proteins in a sensitive murine ovarian reticular cell sarcoma.

The metabolism of 14C-PMM and its irreversible interaction with DNA and proteins were studied in M5076/73A reticular cell sarcoma, a murine solid tumor previously shown to be sensitive to the drug. Metabolism and irreversible binding were determined 0.25, 1, 8 and 104 hours after a single i.p. injection of radiolabelled PMM, tumor and liver macromolecular binding were compared with two differently 14C-labelled PMM, i.e. ring- and methyl-PMM. Ring-PMM derived macromolecular binding appeared to have more relevance in vivo and had a similar time profile in both liver and tumor. Ring-PMM derived DNA binding was then related to metabolic steps between PMM and 2,2,4,6 TMM and 2,2,4,6 TMM itself and 2,4,6 TriMM.

Altretamine↗
PubMed1984

Pharmacokinetic study of VM26 given as a prolonged IV infusion to ovarian cancer patients.

Plasma levels of VM26 were assayed by HPLC in six ovarian cancer patients with normal renal and liver function who received the drugs as an initial 1-h IV infusion of 80 mg/m2 followed by a 24-h IV infusion of 120 mg/m2. These doses and infusion rates were chosen on the basis of mean VM26 clearance values found in a previous study, with the aim of reaching plasma steady-state levels of approximately 6 micrograms/ml in a short time. Plasma steady-state levels of 4-10 micrograms/ml, close to those predicted theoretically, were in fact attained at 4-9 h during the second, slower infusion. Mean half-lives and clearance values were 8.6 +/- 1.1 h and 0.78 +/- 0.08 l/h/m2. Six percent of the VM26 dose was recovered as unchanged drug in the urines collected up to 24 h after the end of infusion. The glucuronide of VM26 aglycone (4'-demethylepipodophyllotoxin) was identified in the urine of all patients, in amounts corresponding to about 8% of the drug dose.

Animals↗
PubMed1984

Proton relaxation mechanisms and the measurements of r phi, r psi and transannular interproton distances in gramicidin S.

Monoselective, Rio(SE), biselective, Rio(i,j), and nonselective proton spin-lattice relaxation rates have been measured for dilute solutions of gramicidin S in dimethyl sulfoxide and used to evaluate cross-relaxation rates (sigma ij = Rio(i,j)-Rio(SE)) and Fi ratios (Fi = Ri(NS)/Rio(SE)). The cross-relaxation parameters, sigma, and Fi ratios measured for backbone gramicidin S protons predict that the same correlation time, tau c = 1.2 X 10(-9)s, modulates all the dipolar proton-proton interactions and that these interactions represent the main source for the proton spin-lattice relaxation process. The larger relaxation rates for amide versus alpha-protons of the backbone are attributed to dipolar relaxation between 14N and its directly bonded protons and is an approximate measure of the extent of this. The intrabackbone proton-proton distances, evaluated from sigma values, were consistent with the antiparallel beta-plated sheet/beta II'-turn conformation previously proposed for gramicidin S in solution.

Gramicidin↗
PubMed1984

1H-NMR relaxation studies of glycopeptides: a dynamic structural investigation.

The Glycopeptide Man5GlcNAc4Asn (ACCB2) in water solution has been studied by means of 1H NMR relaxation techniques in order to define molecular structure and dynamics. From the analysis of selective and non-selective proton relaxation rates of selected ACCB2 protons, a lack of internal mobility along the polysaccharide chain was observed. The presence of a conformationally well-defined molecular structure for ACCB2 is proposed.

Carbohydrate Conformation↗
PubMed1984

Etoposide (VP-16-213) in malignant brain tumors: a phase II study.

Twenty-two consecutive patients with recurrent malignant brain tumors after radiation therapy and systemic combination chemotherapy with BCNU and vincristine, four of whom were not evaluable due to early death, were treated with etoposide (VP-16-213) (50-100 mg/m2 for five days every three weeks). Response, defined as improvement in both clinical examination and computed tomography scan in absence of glucocorticoids dosage increase, was observed in three (17%) of 18 evaluable patients, lasting greater than 21, seven, and two months, respectively. Six additional patients had stable disease for greater than 10, seven, four, four, three, and two months: all of them had improvement of clinical symptoms but no variation in their scans. Overall median survival from the start of VP-16-213 was 4.5 months (range, 1-23 + months), whereas patients with response or stable disease had a median survival of eight months. Overall, treatment was well tolerated. In 10 patients concomitant plasma and cerebrospinal fluid samples were evaluated with a high-performance liquid chromatographic method for drug assay. The concentration of VP-16-213 in cerebrospinal fluid was less than 1% that found in plasma, even in the two patients with response. The activity of etoposide in patients with malignant, lomustine-vincristine-resistant brain tumors suggests an interesting potential use for this drug.

Adolescent↗