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Biomedical subjects

E Boschetti

Publications and source records attributed to E Boschetti.

At least 55 records · Page 3Linked to original sources

Predictive factors of delayed emesis in cisplatin-treated patients and antiemetic activity and tolerability of metoclopramide or dexamethasone. A randomized single-blind study.

To prevent delayed emesis induced by cisplatin (mean dose 90 mg/m2), 120 consecutive patients were randomized to receive, in a 7-day crossover design, oral metoclopramide (20 mg q.i.d.), dexamethasone (1 mg q.i.d.) or placebo (two tablets q.i.d.) starting 24 hours after the end of chemotherapy. Complete protection from nausea, but not from vomiting. was significantly increased by both dexamethasone and metoclopramide with respect to placebo. Important prognostic factors favoring the appearance of delayed emesis were incomplete protection from vomiting during the first 24 hours after cisplatin, female gender, and highest cisplatin doses. Tolerability of both drugs was good. Larger and randomized controlled trials are necessary to identify better preventive treatment of delayed emesis induced by cisplatin.

Cisplatin

Large scale production of human albumin: three years experience of an affinity chromatography process.

Immobilized Cibacron Blue is a well-known tool for the separation of a number of proteins and enzymes. Among them, human plasma albumin was easily purified from crude plasma and consequently, this approach represents an interesting way for a production scale. Our data describes about three years of experience in the production of human albumin using large columns of immobilized Cibacron Blue. The amount of albumin produced per cycle was about 250 g on a column of about 50 l. Over 500 cycles the final purity of albumin was very high and constant (98-100%). The albumin yield of the chromatographic fractionation was approximately 82%. The column performance remained acceptable when regeneration operations were applied to the sorbent. The long life of the sorbent renders this approach very attractive and economically acceptable for large scale applications.

Chromatography, Affinity

[Defined media for hybridoma culture: do they really replace serum and why are they attractive?].

The cell culture efficiency of serum free media is still the main question which limits the use of such a product. However, the experience due to a long usage of serum free media allows to certify that for hybridomas the proliferation growth is often similar to the levels attained with serum. Antibodies secretion is also good or superior to the one obtained with classical media used in different culture devices like flasks and cytocultures. Finally the higher purity degree of monoclonal antibodies in the cell culture supernatant is also a major advantage of serum free media.

Animals

Composite affinity sorbents and their cleaning in place.

Making large-scale affinity sorbents that are reusable under acceptable hygienic conditions implies specific treatments for cleaning in place with known aqueous solutions of chemical agents. However, common agents such as sodium hydroxide are frequently considered too drastic for the stability of macromolecular biologically active immobilized ligands. According to a large series of trials, it was found that only a mixture of sodium hydroxide and ethanol was actually effective in sterilizing a sorbent in a single step. When hydroxide or an ethanol-acetic acid mixture were used alone, they were not totally efficient in the inactivation of sporulated Bacillus subtilis. Conversely, they were efficient when used sequentially. All these solutions were able to remove pyrogens from chromatographic sorbents. As the sterilizing solutions contained a certain amount of ethanol, the most suitable chromatographic affinity sorbents had to be based on an incompressible matrix. When washing an affinity silica sorbent that had proteins as ligands with solutions such as sodium hydroxide, ethanol-acetic acid or ethanol-sodium hydroxide, it was found that certain sorbents were able to tolerate the treatments without a noticeable decrease in their biochemical activity.

Acetates

Effect of aspirin and dipyridamole treatment on prostacyclin production by human veins.

Patients admitted for surgical removal of varicose veins were treated in a blinded manner for 48 hours prior to surgery with either placebo, low-dose aspirin (25 mg twice daily), dipyridamole (150 mg twice daily) or both. Segments of vein excised at surgery were incubated with or without sodium arachidonate and subsequent prostacyclin (PGI2) production was measured without knowledge of treatment given. During the first 5 minute period of incubation in the presence of arachidonate, veins from dipyridamole-treated patients demonstrated increased (by 75%) arachidonate-stimulated PGI2 production compared to placebo-treated patients. By contrast, PGI2 production was reduced by 64% by aspirin treatment and 67% by aspirin plus dipyridamole compared to placebo-treated patients (p = less than 0.05). In unstimulated vein segments incubated in the absence of arachidonate, spontaneous PGI2 production during the first 5 minute incubation period was increased 32% following dipyridamole treatment but was unchanged following aspirin treatment. By contrast, unstimulated (spontaneous) PGI2 production in patients treated with aspirin plus dipyridamole was reduced by 57% (p = less than 0.05), compared to both placebo- and aspirin-treated patients, and by 71% (p = less than 0.05) compared to dipyridamole-treated patients. With repeated change of incubation medium, the ability of vein walls to produce PGI2 declined. This exhaustion was not prevented by drug treatment. However, drug effects between patient treatment groups were consistent over successive incubation periods. These results suggest that certain therapeutic benefits that might be achieved by enhancement of PGI2 production from vascular endothelium following dipyridamole treatment may be reduced by simultaneous aspirin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin

Comparative effects of ibopamine and captopril in mild congestive heart failure. Focus on the long-term effects of inodilation on ventricular arrhythmias.

Twenty-three patients with mild heart failure (I-II NYHA classes) on digitalis and diuretics were assigned to the following treatment in a random and double-blind fashion: ibopamine-captopril, ibopamine-placebo, captopril-placebo, and placebo-placebo. The doses of captopril and ibopamine were respectively 25 mg t.i.d. and 100 mg t.i.d. The incremental exercise time (until exhaustion) and the peak VO2 (oxygen consumption), the indexes of left ventricular function (by echo and nuclear stethoscope) and ventricular arrhythmias (evaluated by prolonged Holter monitoring) were assessed before randomization, at 45 days and at 3 months. Ejection fraction, exercise time, peak VO2, ventricular arrhythmias and heart rate (at rest and during exercise) appeared to be equally unaffected by each treatment. Our results show that ibopamine exerts no significant effects on either heart rate or ventricular arrhythmias and that indexes of left ventricular function are not modified by any treatment in mild congestive heart failure.

Adult

Increased prostacyclin production from human veins by dipyridamole: an in vitro and ex vivo study.

The effect of dipyridamole on prostacyclin (PGI2) production in the presence or in the absence of sodium arachidonate was examined in human veins collected from otherwise normal subjects undergoing saphenous vein removal. Vein segments, maintained in ex vivo culture, that were removed from subjects treated with dipyridamole for two days prior to surgery synthesized 2.5 times more PGI2 (p less than 0.05) than veins that were removed from placebo-treated subjects when incubated in the presence of arachidonate. This difference decreased progressively when vein segments were washed repeatedly and then re-incubated in the presence of arachidonate. Direct addition of dipyridamole to vein segments incubated in vitro resulted in a dose-dependent increase in PGI2 production when the incubation was carried out in the presence of arachidonic acid. No effect of dipyridamole was observed in experiments performed in the absence of arachidonic acid. A mathematical analysis based on both ex vivo and in vitro experiments of the rate of decline of endothelial cell PGI2 biosynthesis suggested that the elevation of PGI2 with dipyridamole treatment resulted from increased PGI2 synthesis rather than decreased PGI2 catabolism. These data support the hypothesis that dipyridamole both ex vivo and in vitro enhances and prolongs PGI2 production by human vessels.

6-Ketoprostaglandin F1 alpha

[Isolation of human thrombin by affinity chromatography with silicate to be used in the preparation of biological glue].

At present the preparations of fibrin glue used a thrombin from equine or bovine origin. In order to remove the problems of antigenicity we developed a method of purification from acidified plasma. We used one affinity chromatography on benzamidine-Spherodex and compared three methods of elution: non specific (sodium chloride gradient) and biospecific competitors (arginin methylester or benzamidin). The yield is evaluated between 64 and 84% and the purification factor close to 160. The obtained thrombin is better than animal thrombin in the preparations of fibrin glue.

Benzamidines

Pharmacokinetics of vincristine in cancer patients treated with nifedipine.

The pharmacokinetics of vincristine (VCR) after an intravenous bolus dose of 2 mg were studied in patients with cancer with and without a concomitant treatment with the calcium-entry blocker nifedipine (NIF). VCR concentrations were determined by a sensitive radioimmunoassay. Pharmacokinetic data were analyzed by a nonlinear weighted least-square regression program (SAS-NLIN). A tri-exponential model fitted the raw data better than a bi-exponential model in five of 14 (35%) patients treated with VCR alone and in seven of 12 (58%) patients treated with VCR plus NIF (P = NS). The T1/2 alpha was shorter in NIF-treated patients, whereas the T1/2 gamma was longer in the NIF-treated group. The NIF-treated group showed an increase in the AUC O-infinity and AUC 1 to 96 hours, and a decrease in the AUC 0 to 1 hour. Total plasma clearance of VCR and 7-day urinary excretion of VCR was reduced in the NIF-treated patients. These data suggest that, when VCR is administered to NIF-treated patients with cancer, there is a decrease in VCR clearance from the body. Theoretically, a greater cytotoxicity may be anticipated.

Aged

Polyacrylamide derivatives to the service of bioseparations.

Though acrylamide polymers are widely used in electrophoretic and chromatographic techniques, many research works aim at optimizing these media. As polyacrylamide presents some drawbacks, new acrylic monomers with particular properties are proposed. In this paper, we describe some approaches for obtaining polymers which are more porous, more hydrophilic and more resistant in alkaline solutions. Moreover, we also detail the synthesis of particular functionalized monomers, explaining the concept of 'polymer design' applicable to the techniques of protein separation.

Acrylic Resins

[Purification of human thrombin by affinity chromatography for its use in preparations for biological coagulation].

Biological glue is obtained by mixing different specific plasma proteins including a serine protease, thrombin. Surprisingly at present the thrombin used in such a mixture is from equine or bovine origin while all other components are from human. In this paper we described a particular efficient and specific chromatographic method for the purification of human thrombin usable as a serine protease in the preparation of biological glue. A pure and active thrombin is obtained from a plasma fraction after adsorption on benzamidine-Spherodex followed by an elution with non specific (sodium chloride gradient) or biospecific competitors (arginine methylester or benzamidine). The obtained thrombin with a yield close to 80% and a purification factor close to 160, showed good properties in the replacement of animal thrombin in the condition of biological glue.

Benzamidines

[Optimization of the purification of human plasma fibronectin by double affinity chromatography using gelatin and heparin Trisacryl LS].

The authors described an optimized method of preparation to obtain pure human plasma fibronectin. The new performances related to the chromatographic and concentration steps, where the saving of time is about 40% and the lyophilization step where the saving of energy is also about 40%. The final product is without any less of either physical and biological activities. The size of the columns, the volumes of the chromatographic supports (gelatin and heparin-Trisacryl LS) and the quantity of the treated plasma are very much important and also the quantities of the final product are very increased.

Acrylic Resins

Round table on antiasthmatic drugs; beta-agonists and theophylline. Workshop on pathogenesis and therapy of bronchial asthma Cortina d'Ampezzo/1-4 April, 1987.

Beta 2-agonists and theophylline compounds are first line drugs and are extensively used in the treatment of acute bronchial asthma. Beta 2-agonists are continuously expanding as a class of drugs. Recent research has increased the available knowledge of their cardiovascular and metabolic effects. Cardiovascular effects might be due to direct stimulation of beta 2-receptors sited in the atrial muscle. Metabolic effects (i.e. increase in blood glucose, insulin and non-esterified fatty acid (NEFA), decrease in plasma potassium) are, at least partly, a consequence of direct or reflex stimulation. Despite recent progress, slow-release theophylline compounds remain a basic approach to asthma management. Future progress in this field will probably be concerned with a more complete knowledge of 'ultra-slow' theophylline compounds (level of the plasma concentration fluctuation and patient compliance) and more complete results regarding the influence exerted by food (and gastric pH) on the rate and extent of absorption.

Adrenergic beta-Agonists

p-Benzylthiocarbamoyl-aspartyl-daunorubicin-substituted polytrisacryl. A new drug acid-labile arm-carrier conjugate.

A new type of drug acid-labile arm-carrier is described. A hydrophilic polymer [polytrisacryl, or poly(acryloyl 2-amido-2-hydroxymethyl-1,3-propanediol)], used as a model, is substituted with p-nitrobenzyl groups. The nitrobenzyl groups are reduced to aminobenzyl and transformed into benzylisothiocyanate groups which are allowed to react with aminoacyl daunorubicin. The excess of benzylisothiocyanate is transformed into benzylthiocarbamoyl N-methyl glucamine. A conjugate containing benzylthiocarbamoyl-aspartyl daunorubicin is stable at neutral pH, and releases free daunorubicin when it is exposed to pH 5 or below. This conjugate is about 200-fold less toxic than free daunorubicin, on a molecular basis, when it is added to the medium of Lewis lung carcinoma (3LL) cells in culture.

Acrylates

Application of chromatographic methods to the analysis of macrophage factors induced by Nocardia opaca cell walls.

Cell walls from Nocardia opaca induce the production of mitogenic factors by mouse peritoneal macrophages in vitro. These factors stimulate thymocytes from C3H/HeJ mice. Supernatants of peritoneal cell culture exhibiting this activity were fractionated by chromatographic procedures such as gel filtration and metal chelate affinity chromatography and the biological activities assayed. These fractionation studies indicate that several biologically active products occur in the supernatant. Four factors monokines (M) with different apparent molecular masses M1 (100,000), M2 (50,000), M3 (16,000) and M4 (7000) were obtained, one of which (M3) was identical to interleukin 1 (IL1). Several of the biochemical parameters of one of these factors, M2, were analyzed. It was found that this monokine had many properties in common with IL1: stimulation of proliferation of thymocytes from C3H/HeJ mice, similar amino acid composition and mobility during isoelectric focusing.

Amino Acids

Sympathetic activation on effort in patients with chronic heart failure. Long term effects of captopril.

Ten patients with congestive heart failure (CHF) (NYHA II-IV) on adjusted doses of digitalis and diuretics underwent a careful clinical assessment including an evaluation of exertion dyspnoea and the usual echocardiographic indices of cardiac performance. A cardiopulmonary exercise test with an increment of 20W every 3 minutes was prolonged until exhaustion. Systemic arterial pressure, ECG, VO2, VCO2 and VE were monitored throughout. Gas tensions, plasma catecholamines and lactate were measured in blood samples taken at the first and third minute of each exercise stage. The above measurements were carried out before and after 3 months of treatment with Captopril, 50 mg b.i.d. or t.i.d. A highly significant correlation between arterial lactate and plasma norepinephrine (NE) was observed in each patient during both exercise tests (r = 0.77 to 0.99; p less than 0.05 at least). Left ventricular end-diastolic dimensions were reduced by Captopril (from 69.9 +/- 1.7 to 65.2 +/- 1.4 mm, p less than 0.01) along with a concomitant increase in percent fractional shortening. Most of the patients were reclassified at a lower NYHA class and a significant decrease in dyspnoea score was observed. The exercise time was significantly increased (from 11.2 +/- 1.8 to 12.9 +/- 1.9 min; p less than 0.05), but the peak values of NE, arterial lactate and VO2 were not affected by the treatment. The predicted value of VE at a VCO2 of 1 L/min, regarded as an index of dyspnoea, was significantly decreased by Captopril (from 41.4 +/- 2.9 to 38.9 +/- 2.7 L/min; p less than 0.05). The positive effects of long-term treatment with Captopril on cardiac performance in CHF are confirmed. Sympathetic activity is linked to anaerobic muscular metabolism during exercise and seems to be independent of pharmacological ACE inhibition. The discrepancy between the exercise tolerance and the peak VO2 might be explained by a better utilization of the available energy.

Adult