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Biomedical subjects

B Bruni

Publications and source records attributed to B Bruni.

At least 19 recordsLinked to original sources
PubMed2005

Solid-state study of mepivacaine hydrochloride.

Different crystalline forms of the local anaesthetic mepivacaine hydrochloride (MH) were revealed by Fourier transform infrared spectroscopy (FT-IR), not by conventional differential scanning calorimetry (DSC). The existence of two polymorphic anhydrous modifications was discovered and further characterized by X-ray powder diffraction and thermal analysis: Form II, the commercial one, and the more stable Form I, obtained by re-crystallization from Form II. Two pseudopolymorphs were also obtained: Form III, a solvate crystallized from ethanol and Form IV, a solvate crystallized from methanol. Single crystal X-ray diffraction data for both solvates were collected and their structures were determined. Form II, metastable and monotropically related to Form I, generates through desolvation of Form III, very often present in industrial processing, where crystallization from ethanol solution is a common practice. For the sake of clarity, the presence of polymorphic forms should be reported in the drug master files of MH. However, since MH is readily water soluble, the observed polymorphism has no relevance to its typical clinical use as aqueous solutions.

Anesthetics, Local↗
PubMed2000

Clinical relevance of office underestimation of usual blood pressure in treated hypertension.

Average 24-h blood pressure (BP) is more representative of usual BP than office BP. However, the clinical relevance of 24-h BP in treated hypertensive subjects is incompletely known. Thus, we studied 395 uncomplicated hypertensive subjects (209 men, 53+/-10 years) who were receiving antihypertensive drug therapy from >1 year. All subjects underwent 24-h ambulatory BP monitoring and M-mode echocardiography. Subjects were classified by tertile of the difference between observed and predicted 24-h systolic BP (the latter determined by regressing 24-h systolic BP on office systolic BP): higher-than-predicted (III tertile), around the regression line (II tertile), and lower-that-predicted (I tertile) 24-h BP. Despite similar office BP (144/89, 141/88, and 144/89 mm Hg in the III, II, and I tertile, P = not significant), age, body mass index, and duration of hypertension, left ventricular mass was greater in the subjects with higher-than-predicted 24-h systolic BP (50+/-14 g x m(-2.7)) than in the other two groups (46+/-13 g x m(-2.7) and 42+/-10 g x m(-2.7), both P < .05). The III tertile also showed a more concentric left ventricular geometric pattern (relative wall thickness was 0.42+/-0.08, 0.40+/-0.07, and 0.38+/-0.07 in the III, II, and I tertile, P < .001) and a reduced systolic function at the midwall level (16.8+/-3, 17.7+/-3, and 18.2+/-3, P < .001). In conclusion, treated hypertensive subjects whose 24-h BP is notably higher than one would predict from office BP are more likely to develop left ventricular hypertrophy, a strong adverse prognostic marker. In a sizable subset of treated hypertensive subjects, BP measured in the physician's office underestimates usual BP and its impact on left ventricular structure.

Antihypertensive Agents↗
PubMed2000

Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study.

BACKGROUND: The long-term effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on ambulatory blood pressure and cardiac performance have never been examined comparatively. OBJECTIVE: We compared losartan and enalapril in their long-term effects on office and ambulatory blood pressure, cardiac structure and function, and routine biochemical tests. DESIGN: In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, 22 hypertensive subjects were studied with ambulatory blood pressure monitoring and echocardiography before and after an average of 3.3 years of treatment with losartan 50mg daily. These subjects were matched in a 1:3 ratio with a group of 66 subjects treated with enalapril 20mg daily. Case-control sampling was based on age (+/-5years), sex, pre-treatment office blood pressure (+/-5mmHg) and ambulatory blood pressure (+/-5mmHg), and duration of treatment (+/-6months). An additional group of subjects who interrupted their treatment with enalapril (n=18) or losartan (n =2) because of unwanted effects before execution of the follow-up study was not included in the analysis. RESULTS: Hydrochlorothiazide was added during follow-up in order to optimize blood pressure control (office blood pressure <140mmHg systolic and 90mmHg diastolic) in 10 subjects (45%) in the losartan group and 34 subjects (52%) in the enalapril group. Office and ambulatory blood pressures were lowered to a similar extent by losartan and enalapril. Left ventricular mass decreased from 98 to 87g/m(2) with losartan (P <0.01) and from 98 to 89 g/m(2) with enalapril (P <0.01). The change in left ventricular mass over time was more closely associated with the change in ambulatory blood pressure than with office blood pressure in both groups. Left ventricular internal diameter did not change with either drug. The endocardial shortening fraction, mid-wall shortening fraction and Doppler indexes of active diastolic relaxation did not change with either drug. None of the biochemical parameters showed a significant change. Serum uric acid showed a slight and non-significant reduction only in the losartan group. CONCLUSION: In this case-control study in uncomplicated subjects with essential hypertension, losartan and enalapril, alone or combined with a diuretic, effectively and equally lowered office and ambulatory blood pressure and induced a significant reduction in left ventricular mass during long-term treatment. Left ventricular systolic and diastolic function remained unchanged with either regimen.

Adult↗
PubMed2000

Persistence of increased left ventricular mass despite optimal blood pressure control in hypertension.

BACKGROUND: Left ventricular hypertrophy is an adverse risk marker in essential hypertension and its regression has a favorable effect on prognosis. It is unclear whether blood pressure normalization induced by long-term therapy is able to normalize left ventricular mass completely. METHODS: In the setting of a prospective cohort study, 107 consecutive hypertensive patients who achieved blood pressure normalization (clinic blood pressure < 140/90 mmHg on > or = 3 consecutive visits) under long-term (1-10 years, average 2.9) drug treatment were individually matched with 107 healthy normotensive controls by gender, age (+/- 5 years), body mass index (+/- 3 kg/m2), and clinic systolic blood pressure (+/- 5 mmHg) in a case-control design. All subjects underwent 24-hour blood pressure monitoring and M-mode echocardiography. RESULTS: Treated hypertensive patients and normotensive controls did not differ by age, body mass index, clinic blood pressure (128/82 vs 128/81 mmHg), and 24-hour blood pressure (120/77 vs 120/76 mmHg). Left ventricular mass and relative wall thickness were greater in the hypertensive than in the normotensive group (97 +/- 24 vs 86 +/- 17 g/m2 and 0.40 +/- 0.08 vs 0.37 +/- 0.08, both p < 0.001). CONCLUSIONS: Left ventricular mass is greater in well-controlled hypertensive patients than in normotensive controls matched by age, obesity, gender, and clinic and 24-hour blood pressure. This finding is consistent with the lower than epidemiologically expected reduction in coronary heart disease risk during antihypertensive therapy and might reflect the persistent effect on left ventricular mass of hemodynamic and/or non-hemodynamic factors other than blood pressure in treated patients with essential hypertension.

Antihypertensive Agents↗
PubMed1995

Crystal structure of reduced bovine erythrocyte superoxide dismutase at 1.9 A resolution.

Cu,Zn superoxide dismutase was investigated crystallographically in the reduced form. Co-ordinate errors were estimated by comparing two independently refined models, based on two different data sets. This gave a detailed error estimation as opposed to the standard sigma A and Luzzati plots, which estimate only the overall error. The high quality of the final model, obtained after scaling together the two data sets, combined with the error estimates allowed a detailed analysis of the protein and solvent structures. An automatic procedure for building and refining solvent structure was tested and found to give reproducible results. Contrary to results obtained from spectroscopic studies, the co-ordination of the metal ions in the catalytic site is preserved in the crystal structure of the reduced enzyme, as compared with the crystal structure of the oxidised form. Analysis of the solvent reveals a well-defined chain of closely packed, hydrogen-bonded water molecules filling the active site groove. This structural feature could serve as a hydrogen bond relay for efficient delivery of protons to the active centre. Analysis of electron density suggests that Glu119 is covalently modified. The modification, if originated in vivo, could have a role in the catalytic mechanism and could affect the overall electrostatic field in the active site. There are significant differences between the active sites of the two crystallographically independent monomers. They are explained in terms of local differences in the crystal environment.

Amino Acid Sequence↗
PubMed1994

X-ray, NMR and molecular dynamics studies on reduced bovine superoxide dismutase: implications for the mechanism.

Single crystals of the reduced form of Cu, Zn superoxide dismutase (space group P2(1)2(1)2(1), one dimer per asymmetric unit) have been obtained and their X-ray structure refined at 1.9 A resolution. The structure shows that the imidazolate bridge is maintained in the present crystalline form. It is confirmed that in solution the bridge is broken and the involved histidine is protonated on the side of copper. Based on the NOE constraints, and with the aid of molecular dynamics calculations, a structural model is proposed for the molecule in solution. Both structures are considered significant as far as the enzymatic mechanism is concerned.

Animals↗
PubMed1992

Acute respiratory effects of sublingual buprenorphine: comparison with intramuscular morphine.

In this randomized, double-blind, placebo study, the respiratory effects of a single dose of sublingual buprenorphine (0.4 mg) were examined and compared with those induced by one dose of intramuscular morphine (10 mg) in a population of women, aged 25-65 years, admitted at the Hospital for Elective Surgery because of uterine fibromyomatosis. Some indices of control of breathing (P0.1, VT/TI, VE, VA, TI, TE, TI/TTot, RR), gas exchange parameters (D[A-a]O2, VD/VT, PAO2) and blood gases (PaO2, PaCO2) were measured in basal condition and at 30, 60, 90, 180 and 360 min after the administration of the drugs. No significant changes of the respiratory function were observed in patients who have received sublingual buprenorphine. In the morphine-group, however, mild PaO2 decrease and PaCO2 increase were found at 60 and 90 min (p less than 0.05), without any reduction of the respiratory drive activity, as shown by P0.1, VT/TI and VE. The significant FRC reduction, observed in the morphine-group (p less than 0.05), could have induced both TE shortening and RR increase with larger dead space ventilation and consequent fall of VA (p less than 0.05). These results suggest that the administration of one dose of sublingual buprenorphine (0.4 mg) does not cause any detrimental respiratory effect; on the other hand, an appreciable, although clinically trivial, worsening of the respiratory function results from intramuscular morphine (10 mg), in the absence of any obvious respiratory depression.

Administration, Sublingual↗
PubMed1990

Comparative evaluation of cardioselectivity of metoprolol OROS and atenolol: a double-blind, placebo-controlled crossover study.

Cardioselectivity of a single oral dose of metoprolol oral osmotic (OROS) (14/190 mg) and atenolol (100 mg) was compared in 12 patients with reversible obstructive airway disease by assessing the dose-response curve to increasing doses of inhaled salbutamol. The beta-blocking activity of the two drugs, which was determined by measuring heart rate, blood pressure, and derived indexes at peak plasma drug levels, was similar. Both metoprolol and atenolol significantly reduced forced vital capacity and peak expiratory flow, with no difference between drugs. Atenolol but not metoprolol also significantly reduced forced expiratory volume in 1 second and specific airway conductance. Both metoprolol and atenolol shifted the dose-response curve of specific airway conductance to the right. The results indicate that the new OROS delivery system for metoprolol, which produces a relatively constant plasma drug level, provides a cardioselectivity comparable to or greater than that of atenolol at maximum plasma levels.

Adolescent↗
PubMed1988

Treatment of allergy to heterologous monocomponent insulin with human semisynthetic insulin. Long-term study.

Eight type II (non-insulin-dependent) diabetic subjects (7 women, 1 man, aged 42-61 yr), initially treated with oral hypoglycemic agents and intermittently treated with conventional insulins, were identified as developing allergic reactions to porcine and mixed-species monocomponent insulin. Allergy was systemic (urticaria and nonthrombocytopenic purpura) and local delayed in two subjects and local immediate or biphasic in six subjects. Lipoatrophy was present in two subjects. After treatment with human semisynthetic insulin (Monotard HM and Actrapid HM), systemic allergy disappeared. Local allergy disappeared in five subjects and was reduced in three subjects. No lipoatrophy occurred in new injection areas. The clinical results were accompanied by a significant decrease in serum insulin-specific IgE after 6, 12, 18, 24, 30, and 36 mo. Insulin-specific IgG showed an evident decrease in five of eight patients, but the difference in mean values was not significant after 6, 18, 24, 30, and 36 mo. With one exception, intradermal skin tests were positive to human, bovine, and porcine insulin before and after human insulin treatment.

Adult↗
PubMed1988

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↗
PubMed1986

Acute on chronic comparative effects of a combination of fenoterol-ipratropium bromide and terbutaline in patients with chronic obstructive lung disease.

Twenty patients suffering from chronic obstructive lung disease (COLD) were examined in a randomized intra-individual single-blind study in order to compare the ventilatory response, tolerance and side-effects of a combination of 40 micrograms ipratropium bromide and 100 micrograms fenoterol (Duovent) with 250 micrograms terbutaline, both given by inhalation (2 puffs) three times a day. The ventilatory parameters FVC, FEV1, sGaw, RV and PaO2, tested on the 7th and 14th days at 0, 30, and 240 min after the morning administration of the two drugs, showed significant differences between treatments, revealing a greater persistence of bronchodilator effect and a more prolonged duration of action with Duovent than with terbutaline. We believe that the results obtained suggest the usefulness of a combination of anti-cholinergic and beta 2-agonist drugs in the treatment of reversible bronchial obstruction in COLD, where even the parasympathetic nervous system seems to play an important role. The observed clinico-functional effects (intensity and duration of bronchodilatation) together with the lack of side-effects permit us to affirm that Duovent is a rational pharmacologic combination which represents real progress in the difficult treatment of COLD patients.

Adult↗
PubMed1985

Effect of N-acetylcysteine in subjects with slow pulmonary mucociliary clearance.

There is significant evidence that in the general population there are subjects either with fast or slow pulmonary mucociliary clearance rates. At the moment we do not know the physiological importance of such finding. Slow clearers should be regarded as a subpopulation at risk for bronchopulmonary diseases. Therefore, it would be of considerable interest if their mucociliary function could be stimulated by drugs for preventive purposes. Twelve apparently healthy subjects with slow mucociliary clearance rate, selected in an epidemiologic survey in a non-smokers population were given 0.6 g oral N-acetylcysteine/day/60 days in a double-blind cross-over randomized study. After treatment their mucociliary clearance rates increased by about 35% as compared with baseline values, and returned to pre-treatment values after the washout period. Subjects were unresponsive to placebo treatment. It would seem that slow clearers are protected against lung aggressions by prevention and/or mucus-active drugs.

Acetylcysteine↗
PubMed1981

Kinetic analysis of the response of plasma glucose, insulin, and C-peptide to glucagon injection in normal and diabetic subjects.

A compartmental model formed by plasma glucose, proinsulin, insulin, and C-peptide was proposed to allow a quantitative evaluation of the interrelationship among the different components of the system and to obtain a better discrimination between normal and pathologic subjects. In 11 control subjects, in 6 mild diabetics, and in 9 severe diabetics (insulin-dependent), the kinetics of plasma glucose, insulin, and C-peptide after an i.v. injection of glucagon (sampling for about 120 min) were fitted to the model which was solved with digital computing techniques. Since biphasic plasma insulin and C-peptide kinetics were demonstrated in many normals and mild diabetics, the effect of glucagon in the model was represented by a differential plus a proportional effect. The model (formed by 6 compartments and 14 transfer constants) takes into account the fact that insulin and C-peptide derive monomolecularly from proinsulin and that liver inactivates insulin. The values of the parameters obtained were submitted to stepwise discriminant analysis in order to obtain their relative importance in discriminating among the three groups of subjects. With respect to normal subjects, we found in diabetics an increased inflow of glucose into plasma; a decreased effect of glucagon in promoting the proinsulin response; a decreased effect of glucose in promoting the proinsulin response; a decreased glucose utilization; a lower coupling effect of insulin on glucose; and a higher disappearance rate of C-peptide. We observed a lower formation of insulin and C-peptide from proinsulin in severe diabetics.

Adult↗
PubMed1978

[Treatment with monocomponent semi-lente insulin in diabetes of difficult compensation].

According to personal experience, good clinical effects may be obtained by monocomponent insulin treatment, independently from strict immunological indications (i.e. high plasma-anti-insulin antibody titers). The present paper reports on a two daily injection treatment with monocomponent Semilente insulin (SeLe MC) in comparison with an earlier management with conventional retard insulins, in a group of 16 insulin dependent diabetics, selected among the most poorly controlled patients with unstable diabetes and/or high insulin requirement. In 6 subjects, after transfer to SeLe MC, it was observed a reduction in M bs, delta, and M delta indices of the glycemic regulation, indicating lower mean glycemic profiles with fewer irregularities. In 11 cases a marked improvement in the subjective symptomatology was noticed. Some minor hypoglycemic reactions induced to a reduction in the high insulin requirement in 8 cases. All but two patients had significant values of insulin IgG antibodies. The period of observation was too short to take in consideration an immunological modification, as an explanation of the present clinical results. However, these could be hypothetically referred to an amelioration in the releasing of endogenous insulin and/or in the hormone-receptor interaction as a consequence of treatment with monocomponent insulin preparations, in comparison to non purified conventional preparations. Treatment with SeLe MC seems to be suitable in particularly difficult control of the diabetes and in emergency situations.

Adolescent↗
PubMed1978

[Evaluation of diabetes control by new numerical indices of daily blood glucose values].

Attempts to assess the degree of diabetic control by numerical expressions of blood glucose behaviour have been performed by Schlichtkrull et Al. (M-Ms value) and by Molnar, Service et Al. (MAGE, MODD, MBG and FBG values). However these methods, partly derived from the results of continuous blood monitoring, fail to give qualitative information about the glycemic daily profile. In order to obtain a more complete estimation of the diurnal blood sugar curve, a simple set of three indices is introduced by our group: 1) the Mbs value (modified); 2) the mean difference (delta value) of the various Mbs/bs calculated with a HP 25 Hewlett-Packard, and 3) the mean of the differences, exceeding delta, which are between contiguous Mbs/bs (M delta value). This investigation was carried out in 103 diabetic observations, on the basis of eight blood-sugar daily determinations (Destrostix Reflectance Meter) on two successive twenty-four-hour periods, under standard conditions of diet, exercise and therapeutic regimen. As the results show, modified Mbs describes the mean level of the glycemic profile; delta indicates the amplitude of the glycemic variability field; M delta reports both maximal and minimal extremes of the curve. A correlation of these parameters is expressed by a formula, which might distinguish stable from unstabel ("brittle") diabetes and allow clinical comparison in different treatment conditions.

Aged↗