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Biomedical subjects

G Barone

Publications and source records attributed to G Barone.

At least 19 recordsLinked to original sources
PubMed1996

Temperature-induced denaturation of ribonuclease S: a thermodynamic study.

In this paper the thermal denaturation of ribonuclease S, the product of mild digestion of ribonuclease A by subtilisin, is deeply investigated by means of DSC and CD measurements. It results that at whatever pH in the range 4-7.5 the process if fully reversible but not well represented by the simple two-state N<-->D transition. Actually, a two-state model that considers both unfolding and dissociation, NL<-->D + L*, well accounts for the main features of the process: the tail present in the low-temperature side of DSC peaks and the marked dependence of denaturation temperature on protein concentration. This mechanism is strictly linked to the exact stoichiometry of RNase S. An excess of the protein component of RNase S, the so-called S-protein, shifts the system toward a more complex behavior, that deserves a separate treatment in the accompanying paper [Graziano, G., Catanzano, F., Giancola, C., & Barone, G. (1996) Biochemistry 35, 13386-13392]. The thermodynamic analysis leads to the conclusion that the difference in thermal stability between RNase S and RNase A is due to entropic effects, i.e., a greater conformational flexibility of both backbone and side chains in RNase S. The process becomes irreversible at pH 8.0-8.5, probably due to side-reactions occurring at high temperature. Finally, the influence of phosphate ion on the stability of RNase A and RNase S at pH 7.0 is studied and explained in terms of its binding on the active site of ribonuclease. The analysis enables us to obtain an estimate of the apparent association constant and binding enthalpy also.

Binding Sites↗
PubMed1996

The pharmacokinetics of a microemulsion formulation of cyclosporine in primary renal allograft recipients. The Neoral Study Group.

This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.

Adolescent↗
PubMed1996

The safety and tolerability of cyclosporine emulsion versus cyclosporine in a randomized, double-blind comparison in primary renal allograft recipients. The Neoral Study Group.

A 12-week, randomized, double-blind, multicenter pharmacokinetics study was conducted to compare the clinical safety and tolerability of cyclosporine capsules and oral solution for microemulsion and cyclosporine in 101 primary renal transplant recipients Cyclosporine emulsion has more complete absorption and improved bioavailability compared with cyclosporine, and dosing of both cyclosporine formulations was adjusted to achieve comparable whole-blood trough levels. Mean serum creatinine values were higher in the cyclosporine emulsion group at baseline, 8, and 12 weeks (P<0.05). The incidence of acute rejection was similar in both treatment groups although fewer patients required monoclonal antibody therapy in the cyclosporine group (31% vs. 82%, respectively). Despite the increased bioavailability of cyclosporine emulsion, no significant differences in the incidence of adverse events were observed; the safety, tolerability, and efficacy of cyclosporine emulsion and cyclosporine were comparable.

Administration, Oral↗
PubMed1996

Structural investigation of the polysaccharide fraction from the mucilage of Diceroaryum zanguebaricum Merr.

The polysaccharide fraction from the mucilage of Dicerocaryum zanguebaricum (Pedaliaceae) appears to be mainly constituted of a chemically homogeneous polysaccharide. By NMR and chemical degradative methods its structure appeared to consist of alternate-->4)-beta-D-GlcpA-(1--> and -->2)-alpha-D-Man p-(1-->units. Single branch units of beta-D-Xyl p and alpha-D-Gal p are linked to the O-3 positions of Man p and a significant number of Glc pA residues.

Africa↗
PubMed1996

Temperature-induced denaturation of beta-glycosidase from the archaeon Sulfolobus solfataricus.

The beta-glycosidase isolated from the extreme thermophilic archaeon Sulfolobus solfataricus, grown at 87 degrees C, is a tetrameric protein with a molecular mass of 240 kDa. This enzyme is barely active at 30 degrees C and has optimal activity, over 95 degrees C, at pH 6.5. Its thermal stability was investigated at pH 10.1 and 10.6 by means of functional studies, circular dichroism and differential scanning calorimetry. There was no evidence of thermal activation of the enzyme and the temperature-induced denaturation was irreversible and not well represented by the two-state transition model. A more complex process occurred, involving the dissociation and unfolding of subunits, and subsequent nonspecific association and/or aggregation. Denaturation temperature was around 85 degrees C, depending on protein concentration. The denaturation enthalpy change was between 7,500 and 9,800 kJ.mol-1, depending on the pH. The collapse of the native structure around 85 degrees C was confirmed by circular dichroism measurements and time-dependent activity studies. Finally, preliminary investigations were performed on the recombinant enzyme expressed in Escherichia coli.

Calorimetry, Differential Scanning↗
PubMed1995

The liquid amide transfer model and the unfolding thermodynamics of small globular proteins.

In this paper, the solid cyclic dipeptide model developed by Murphy and Gill is analysed in order to point out that, apart from general thermodynamic features shown by well-characterized small globular proteins, only the polar and apolar contributions to the net denaturation heat capacity change are necessary to calculate the so-called protein stability curve, delta dGzero versus temperature. We propose that these specific heat capacity contributions can be determined in a reliable manner by a group additivity analysis of the transfer process of liquid amides from pure liquid phase into water. This suggests that the unfolding process, thought of as the transfer of amino acid residues from the protein 'core' to contact with water molecules, can be modelled based on the transfer process of organic amides. The reliability of the model is tested in comparison with literature data.

Amides↗
PubMed1994

Structural investigation of Ceratozamia spinosa mucilage.

The polysaccharide fraction from Ceratozamia spinosa appears to be made up mainly by a chemically homogeneous polysaccharide but with a wide range of molecular weight. By NMR and chemical degradative methods, it is shown to consist essentially of a backbone of alternate-->4)-beta-D-GlcpA-(1-->and-->2)-alpha-D-Manp-(1--> units. On the 4 position of the latter, beta-D-GlcpA residues are linked. End units of alpha-L-Araf, beta-D-Xylp, alpha-L-Rhap, and alpha-L-3-OMe-Rhap are linked to C-3 and/or C-4 positions of beta-D-GlcpA residues.

Adhesives↗
PubMed1994

Wound healing in forefoot amputations: the predictive value of toe pressure.

A retrospective study of 136 men undergoing forefoot amputation was done to test the hypothesis that preoperative toe pressure (TP) could predict the likelihood of wound healing. Demographic data included age, smoking history, diabetes mellitus (DM), hypertension, hyperlipidemia, and coronary artery disease. Clinical data included infection, preoperative arterial Doppler data, TP, wound disposition, concomitant revascularization (REV), and healing outcome. Among diabetics, no primary amputation healed with a preoperative TP < 38 mm Hg. Among REV diabetics, no healing occurred with a TP < 40 mm Hg after bypass, but no failures occurred either with a TP > 68 mm Hg or an increase in TP > or = 30 mm Hg after bypass. Nondiabetic patients exhibited no threshold TP values. Univariate analysis revealed that DM and REV were significantly different in the healed (N = 83) vs. nonhealed (N = 53) populations (p = 0.027 and 0.034). In healed patients mean TP (71.8 +/- 3.5 mm Hg SEM) was significantly higher than in nonhealed patients (45.1 +/- 4.3 mm Hg SEM, p = 0.000). Logistic regression analysis identified age > 60 years (p = 0.03), DM (p = 0.003), preoperative TP (p < 0.001), and REV (p < 0.001) as significant independent predictors of forefoot amputation healing. Healing probability was calculated and plotted vs. TP for subpopulations based on age, DM, and REV status for both primary forefoot amputation and amputation concomitant with bypass. In this study population, therefore, preoperative TP appeared to be a useful clinical tool for predicting the healing potential of both primary forefoot amputations and amputations plus concomitant bypass for any given patient.

Adult↗
PubMed1994

Hydration enthalpy of model peptides: N-acetyl amino acid amides.

Determination of hydration parameters for the solute-solvent interactions of model peptide molecules can provide quantitative information on the factors affecting the folding and stability of proteins in aqueous solutions. Standard hydration enthalpies are calculated by combination of the standard sublimation and solution enthalpy data, experimentally determined. The results for some N-acetyl amino acid amides, assumed as model for peptides, are reported and the trend of hydration enthalpies with increasing complexity of the model molecules is discussed on the basis of the group additivity method. Further the direct proportionality between hydration enthalpy and non-polar accessible surface area (ASA) of each amino acid residue is emphasized. Finally it is pointed out that there exists a convergence temperature for the enthalpy associated with the hydration process of these model compounds and its value TH* = 93 +/- 7 degrees C is close to that found for small globular proteins (i.e. TH* = 100 +/- 6 degrees C). This finding can give some insights to clarify the emergence of convergence behaviour in the unfolding process.

Amino Acids↗
PubMed1993

Nortriterpenoid oligoglycosides from Chionodoxa luciliae.

Six new oligoglycosides of eucosterol derivatives were isolated from the bulbs of Chionodoxa luciliae Bossis. A chemotaxonomical relationship based on glycoside and homoisoflavanone content is revealed for some Muscari, Bellevalia, Chionodoxa and Scilla species.

Carbohydrate Sequence↗
PubMed1993

[Captopril administration before thrombolysis in patients with an acute myocardial infarct: a pilot study of the short- and long-term effects].

Several experimental studies, carried out on animals and on isolated heart, showed that captopril can reduce the post-ischemic reperfusion injury. Our study was aimed at checking the effects of captopril before thrombolysis in acute myocardial infarction (AMI) and included 204 patients, hospitalized within 4 hours from the onset of symptoms. Patients were randomly subdivided into 2 groups: the first group (105 patients, Group A: pretreatment) received 6.25 mg captopril orally about 15 min before iv administration of urokinase (2 million), the second group (99 patients, Group B: late-treatment) received captopril about 3 days after thrombolytic treatment. Captopril doses were later increased in both groups according to blood pressure. All patients were subdivided according to the localization of infarction. One hundred and thirty-seven patients showed anterior AMI (70 from Group A and 67 from Group B); 67 patients showed inferior AMI (35 from Group A and 32 from Group B). Ventricular hyperkinetic arrhythmias (VHA) due to reperfusion were evaluated during the first 2 hours. Ventricular hyperkinetic arrhythmias occurred in 11.4% of patients with anterior AMI in Group A versus 38.8% in Group B (p < 0.001). CK peak normalization time in the group with anterior AMI was achieved after 58 +/- 2 hours in Group A versus 72 +/- 2 hours in Group B (p < 0.01). Late arrhythmias, > Lown's class 2 was found to occur in 15.7% of patients with anterior AMI of Group A versus 32.8% in Group B (p < 0.05), at predischarge Holter test. One hundred and nineteen patients underwent a hemodynamic test about 3 weeks after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1992

Captopril and glutathione before thrombolysis in acute myocardial infarction: a pilot study.

This study is aimed at checking whether treatment with glutathione (GL) and captopril (CA) before thrombolysis can further improve the protective effects of ACE-inhibitors in cases with anterior acute myocardial infarction (AMI). Ninety-eight double blind randomized patients (86 men and 12 women) showing symptoms of AMI anterior and undergoing thrombolytic treatment were admitted to our study and subdivided into 4 groups. Group A (25 pts) received thrombolytic treatment only, Group B (23 pts) received 3 g GL intravenously 15 min before thrombolysis and for 2 h thereafter, Group C (26 pts) received 6.25 mg CA orally 15 min before starting thrombolytic treatment, Group D (24 pts) received 3 g GL intravenously before thrombolysis and for 2 h thereafter, and captopril as well like group C. On the third day after AMI onset groups A and B received CA also. In all groups, the doses of CA were gradually increased according to blood pressure values. The following features were considered: a) the occurrence of early (within the first 2 h after thrombolysis) ventricular hyperkinetic arrhythmias; b) CK peak; c) the normalization time of CK peak (NT); d) the occurrence of late ventricular hyperkinetic arrhythmias (VHA) in the predischarge Holter test (Lown's class 2); e) ejection fraction (EF) being measured in 60 pts undergoing haemodynamic test. The results were an follows: Group A: VHA early 13/25, CK peak 1982 +/- 282; NT 71 +/- 2 h; Late VHA 8/25; EF 53.5 +/- 2.5% (16 pts). Group B: VHA early 11/23; CK peak 1917 +/- 242 U/l; NT 69 +/- 3 h; late VHA 7/23; EF 54.5 +/- 5.4% (14 pts). Group C: VHA early 4/26; CK peak 1671 +/- 266 U/l; NT 58 +/- 3 h; late VHA 5/26; EF 55.5 +/- 3% (16 pts). Group D: VHA early 3/24; CK peak 1463 +/- 201; NT 56 +/- 4 h; late VHA 5/24; EF 57.6 +/- 4% (14 pts).

Aged↗
PubMed1991

The relevance of anatomic and hemodynamic factors to a classification of cerebral arteriovenous malformations.

Potential prognostic anatomic and hemodynamic factors were evaluated in 248 patients with cerebral arteriovenous malformations (AVMs), all treated by direct microsurgical removal. The size of each AVM was calculated by its volume, obtained by the multiplication of the three AVM diameters by 0.52. A surgical classification of AVM location (in 11 groups) is proposed. Types of feeders and of drainage were classified as superficial or deep; the extent of the drainage system was classified according to a four-degree scale. The mean flow velocity in the main AVM feeder, detected using transcranial Doppler ultrasonography, was used as an indirect measure of AVM shunt flow in a small number of patients (n = 29). AVM volume was a very important prognostic factor: the incidence of hyperemic complications and the morbidity and mortality rate were significantly higher when the volume of the lesion was greater than 20 cm3 (P less than 0.0001 for hyperemic complications; P less than 0.001 for permanent morbidity and mortality). The incidence of hyperemic complications and the morbidity rate were higher in AVMs in rolandic, inferior limbic, and insular locations than in AVMs in other locations. As for other anatomic factors: a) the presence of deep feeders significantly increased the incidence of hyperemic complications, as well as the morbidity and mortality rate; b) the presence of deep drainage significantly increased permanent morbidity only; c) the extension of the venous system was significantly related to the development of hyperemic complications, and to morbidity and mortality. Transcranial Doppler examination showed that mean flow velocities greater than 120 cm/s in the main feeder were associated with a significantly higher rate of postoperative hematomas and transient deficits. A classification of cerebral AVMs that takes into account AVM volume and location, the type of feeders, the extent of the drainage system, and the main feeder flow velocity is suggested.

Adolescent↗
PubMed1991

Treatment of cerebral arteriovenous malformations with a combination of preoperative embolization and surgery.

Forty-nine patients with cerebral arteriovenous malformations (AVMs) were treated with preoperative embolization followed by resection using a microsurgical approach. In 27 patients, the AVM was located in an eloquent area; in 32 patients, the volume of the AVM was over 20 cm3. Preoperatively, flow-directed embolization was performed in 10 patients (28 procedures), selective embolization with threads was performed in 35 patients (46 procedures), and a combination of flow-directed and selective embolization was performed in 4 patients (12 procedures). The percentage of reduction of the AVM volume averaged 36% after embolization. Five minor complications (transient neurological deficits, in 2 cases associated with ischemic areas on the CT scan) were observed after embolization. The interval between the last embolization and surgery was as follows: within 10 days in 7 patients; between 11 and 20 days in 3 patients; between 21 and 30 days in 10 patients; between 31 and 60 days in 11 patients; and 2 months later in 18 patients. The efficacy of this combined treatment (embolization plus surgery) was evaluated by the incidence of hyperemic complications and the clinical outcome. Hyperemic complications occurred more frequently in patients with an AVM volume greater than 20 cm3. When compared with flow-directed embolization, selective embolization was linked with decreased bleeding during surgery; postoperatively, the incidence of cerebral edema was also lower. Clinical outcome was better after selective embolization, with no occurrence of major deficits and no mortality. When the percentage of reduction of the AVM volume after embolization was 40% or more, the incidence of intraoperative hyperemic complications was lower; moreover, new permanent deficits were never observed in patients with this volume reduction. A retrospective clinical comparison of two groups of patients with similar AVM volumes (greater than 20 cm3)--those given combined treatment (n = 32) versus those treated by direct surgery alone (n = 27)--showed that intraoperative bleeding appeared to decrease in patients treated by embolization; the incidence of postoperative hyperemic complications was not different in the two groups. New major deficits and deaths were less frequent in patients treated by embolization (P = 0.05 for the incidence of major deficits); postoperative epilepsy was also less common in these patients. In conclusion, combined treatment with selective preoperative embolization and direct surgery may help the neurosurgeon in the treatment of large, high-flow AVMs, reducing the risks connected with their surgical removal.

Adolescent↗
PubMed1991

Use of a tunneling device to aid in positioning of a graft.

A tunneling device can be used to ensure easy placement of a prosthetic or autogenous graft. This can be done without the danger of the graft twisting, kinking or having the clips and ties pulled off. The often frustrating problem of ensuring that the arterial graft lies properly in position can be greatly simplified with the use of this technique.

Anastomosis, Surgical↗