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Biomedical subjects

C Bianchini

Publications and source records attributed to C Bianchini.

At least 19 recordsLinked to original sources
PubMed2001

Absorption of calcium administered alone or in fixed combination with vitamin D to healthy volunteers.

Calcium supplementation is widely used in deficiency status and as an adjuvant in the treatment of osteoporosis. As usual with endogenous substances, the calcium absorption, distribution and elimination processes are strictly controlled by homeostatic equilibria. Free calcium ion is the most representative active fraction of the circulating ion. Ion excretion is controlled by a saturable tubular reabsorption process which leads to a renal threshold. Cumulative urinary excretion of calcium is the end-point of absorption, distribution and elimination processes, and is thus a good indicator of bioavailability. In order to increase the oral bioavailability of calcium, the ion is administered in association with vitamin D, which is known to enhance intestinal calcium absorption. The aim of this study was to evaluate the absorption of calcium administered alone and in fixed combination with cholecalciferol (vitamin D3, CAS 67-97-0). In accordance with the study protocol, calcium carbonate (CAS 471-34-1; 1500 mg = 600 mg as calcium ion) was administered as such (reference) and associated with cholecalciferol (400 IU) (test) for four days (2 doses/day) to 18 healthy male volunteers in a sequential pattern, namely reference followed by test. Urinary excretion of total calcium, and serum concentration of free and total calcium, 25-OH-vitamin D3 and parathyroid hormone were carefully analysed the day before (baseline) and on the 4th day of dosing, with validated methods. The effect of cholecalciferol in promoting calcium absorption was clearly observed from urinary excretion of total calcium, which with the test treatment showed a 16.6% increase in excretion (p = 0.025) compared with the reference treatment. The mean excretion values on the 4th day, expressed in mg, were 238.85 and 204.83 with test and reference respectively. Moreover, the results demonstrated an increased serum concentration of both free and total calcium after dosing with test and reference by comparison with the baseline situation. The area under the serum concentration-time curve of total calcium increased from day -1 to day 4 from 550.98 to 575.90 mg l-1 h with test and from 543.03 to 568.16 mg l-1 h with reference. Similarly, ionised calcium increased on day 4 with both the treatments. Parathyroid hormone showed the expected typical decreasing behaviour after dosing with the test and reference drugs. The results of this study suggest that calcium carbonate is absorbed through the intestine when administered either alone or in association with cholecalciferol. Cholecalciferol, however, showed the typical expected activity in promoting calcium absorption, which was evident from the cumulative urinary excretion of the ion. To the authors' knowledge, this study is the first published paper demonstrating the absorption and pharmacodynamic effect of short-term administration of vitamin D associated with calcium at the doses recommended for supplementation in a fixed-combination pharmaceutical product.

Adolescent↗
PubMed2000

1H- and 2H-T1 relaxation behavior of the rhodium dihydrogen complex [(triphos)Rh(eta 2-H2)H2]+.

Protonation of the classical trihydride [(triphos)RhH3] (2) at 210 K in either THF or CH2Cl2 by either HBF4.OMe2 or CF3SO2OH gives the nonclassical eta 2-H2 complex [(triphos)Rh(eta 2-H2)H2]+ (1) [triphos = MeC(CH2PPh2)3]. Complex 1 is thermally unstable and highly fluxional in solution. In THF above 230 K, 1 transforms into the solvento dihydride complex [(triphos)Rh(eta 1-THF-d8)H2]+ (5) that, at room temperature, quickly converts to the stable dimer trans-[[(triphos)RhH]2(mu-H)2]2+ (trans-6). In CH2Cl2, 1 is stable up to 240 K. Above this temperature, the eta 2-H2 complex begins to convert into a mixture of trans- and cis-6, which, in turn, transform into the bridging-chloride dimers trans- and cis-[[(triphos)RhH]2(mu-Cl)2]2+ at room temperature. Complex 1 contains a fast-spinning H2 ligand with a T1min of 38.9 ms in CD2Cl2 (220 K, 400 MHz). An NMR analysis of the bis-deuterated isotopomer [(triphos)RhH2D2]+ (1-d2) did not provide a J(HD) value. At 190 K, the perdeuterated isotopomers [(triphos)RhD3] (2-d3) and 1-d4 show T1min values of 16.5 and 32.6 ms (76.753 MHz), respectively, for the rapidly exchanging deuterides. An analogous 2-fold elongation of T1min is also observed on going from [(triphos)IrD3] to [(triphos)Ir(eta 2-D2)D2]+. A rationale for the elongation of T1min in nonclassical polyhydrides is proposed on the basis of both the results obtained and recent literature reports.

Journal Article↗
PubMed2000

Constitutive activation of the Ras/MAP kinase pathway and enhanced TCR signaling by targeting the Shc adaptor to membrane rafts.

The Shc adaptor is responsible for coupling receptor tyrosine kinases and tyrosine kinase-associated receptors to the Ras/MAP kinase pathway. Shc is believed to be regulated by a change in subcellular localization from the cytosol to the plasma membrane, where it recruits Grb-2/Sos complexes and hence permits juxtaposition of the guanine nucleotide exchange factor Sos to Ras, resulting in GDP/GTP exchange and Ras activation. Shc has been recently shown to inducibly colocalize in detergent-resistant membrane rafts together with the activated TCR and associated signaling molecules. To understand whether Shc localization in membrane rafts is sufficient to regulate Shc function, we constructed a Shc chimera containing the Ras membrane localization motif at the C-terminus. We show that membrane targeted Shc was constitutively localized in the plasma membrane of T-cells, and was mostly compartmentalized in lipid rafts. Membrane targeted Shc was phosphorylated on tyrosine residues and bound Grb-2/Sos in the absence of TCR engagement. Furthermore, expression of membrane targeted Shc resulted in constitutive downstream signaling, including Erk2 activation and enhancement of TCR dependent activation of the TCR responsive transcription factor NF-AT. Hence localization of Shc in membrane rafts is sufficient for Shc to acquire a signaling competent state. Interestingly, a membrane targeted Shc mutant lacking both Grb-2 binding sites was not only incapable of signaling in the absence of TCR triggering, but transdominantly inhibited endogenous Shc, supporting a non redundant role for Shc in the activation of the Ras/MAP kinase pathway in T-cells.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Safety and pharmacologic activity of a new nitrate ester, ITF 296, after intravenous administration in healthy volunteers.

To evaluate the safety and pharmacologic activity of ITF 296 in humans, three groups of healthy male normotensive subjects were studied. The first two groups (six subjects each) received, in ascending order, three dose levels of ITF 296 by 30-min intravenous infusion (group I, 0.1, 0.5, 1.0 microgram/kg/min; group II, 2.0, 4.0, 6.0 micrograms/kg/min). The third group of eight subjects received, in ascending order, four dose levels of ITF 296 (10, 20, 40, 80 micrograms/kg) by 1-min i.v. injection. The study was double-blind, and placebo-controlled according to a within-patient, incomplete, unbalanced block design, such that each subject received the placebo once. Hemodynamics were assessed by means of Dynamap and BOMED. The following parameters were evaluated at different times before and after ITF 296 administration: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke volume index (SVI), cardiac index (CI), and systemic vascular resistance index (SVRI). Blood samples for kinetic assessment of ITF 296 were taken before and at different times after ITF 296 administration. The drug was well tolerated. Only a few mild (except for one, moderate) side effects (mainly headache and dizziness) were reported, usually at the higher dose levels. All safety clinical chemistry and hematologic parameters were unaffected. After i.v. infusion of ITF 296, blood pressure started to fall at the dose of 2 micrograms/kg/min, DBP being significantly reduced at doses above 1 microgram/kg/min. The effect lasted for up to 60 min after the end of the infusion. The increase in heart rate was only modest, although apparently dose-dependent. SVI was only slightly reduced, and the other hemodynamic parameters did not change. After bolus administration of ITF 296, SBP was significantly reduced starting at a dose of 20 micrograms/kg with higher doses producing a more marked effect (up to -15 mm Hg). DBP was significantly reduced only at the higher dose level of 80 micrograms/kg. The effect lasted for up to 60 min after bolus administration. HR was slightly increased after doses of 40 and 80 micrograms/kg. SVI was slightly reduced and a small transient decrease in CI was observed, whereas SVRI did not change. Satisfactory, linear kinetic correlation was found between total doses administered and AUCs measured. ITF 296 in healthy male normotensive volunteers was effective and well tolerated. The results of this study justify the planning of further studies in patients in order to test the anti-ischemic activity of the compound.

Adolescent↗
PubMed1995

Hemodynamic and humoral effects at rest and after head-up tilt tests during 24-hour infusion of a new nitrate ester, ITF 296, compared with ISDN and placebo in healthy volunteers: a double-blind, randomized, within-subject study.

A double-blind, randomized, three-way complete crossover study was carried out to compare pharmacodynamic effects and tolerability during a 24-h intravenous infusion of ITF 296, isosorbide dinitrate (ISDN), and placebo, in the supine position and during 70 degrees head-up tilt. Ten healthy men aged 21-34 years participated in the study to obtain complete data in nine. Dosing started at 1 microgram/kg/min and was titrated up during the first 30 min of infusion, to produce a 10% reduction in diastolic blood pressure (DBP). At least 6 days elapsed between consecutive treatments. Heart rate (HR) and blood pressure were measured at least half hourly throughout the infusion period and up to 2 h afterwards. Systolic time intervals were measured before and at 0.5, 1, 2, 3, and 24 h of infusion in the fasting state. Tilt tests (70 degrees head-up for 2 min) were performed at 1, 6, 12, and 24 h of infusion. From 60 min before tilt, during tilt, and up to 15 min after end of tilt, ECG was monitored and BP, HR, and b/a ratio were recorded by means of fingertip plethysmography. Plasma-renin activity and concentrations of epinephrine and norepinephrine were measured preinfusion, and before and after tilt tests. Subjects were questioned frequently about adverse events. General tolerability of ISDN in the nine subjects who completed the study was poor, with eight suffering from headache and four from symptoms suggesting postural hypotension during tilt tests. Tolerability of ITF 296 was better, with 5 of 10 subjects reporting headache and 2 of 10 symptoms of postural hypotension during the first tilt only. Both active treatments successfully reduced DBP by at least 10% in all subjects at similar dose levels (final infusion rates 2.8 and 2.3 micrograms/kg/min for ITF 296 and ISDN, respectively). Systolic blood pressure (SBP) was reduced by about 6-7 mm Hg by both treatments. HR was increased by about 5 beats/min by ISDN but not by ITF 296. Those changes in BP and HR persisted throughout the 24-h infusion and reversed when it was discontinued. Fingertip plethysmography showed a profound reduction of b/a ratio, which persisted throughout the 24-h infusion. ISDN had consistently greater effects than ITF 296, suggesting that ISDN has the greater effects on small arterial vessels. Both active treatments reduced QS2 index throughout the 24-h period. Both treatments also reduced left-ventricular ejection time (LVET) index up to 3 h of infusion, with ISDN having the greater effects on LVET index and ITF 296 being intermediate between ISDN and placebo. ISDN prolonged pre-ejection period (PEP) at 1 h, had no effect at 2 h, and shortened PEP at 3 and 24 h. ITF 296 decreased PEP consistently during the 24-h infusion. Plasma-renin activity, epinephrine, and norepinephrine were increased by ISDN substantially more than by ITF 296. These results show that both ITF 296 and ISDN had comparable effects on diastolic blood pressure at similar dose-levels. ISDN increased HR, whereas ITF 296 did not. b/a Ratio was reduced more by ISDN, suggesting a greater activity on small arterial vessels. Arterial effects were maintained throughout the 24-h infusion. ISDN had a greater effect on venous return than ITF 296. ITF 296 seemed to show more balanced effects on preload and afterload than ISDN. ISDN caused significantly greater neurohumoral counter-regulation than ITF 296. Hemodynamic response to tilt was attenuated, as judged by the fact that hypotension occurred only during the early hours of the infusion, but the variability in the response of BP to tilt does not allow any firm conclusions to be drawn about possible development of tolerance. Tolerability of ISDN was poor and that of ITF 296 was better.

Adult↗
PubMed1991

Blood binding of selezen (imidazole salicylate) in man.

The interactions of selezen (imidazole salicylate) with human blood components were studied by equilibrium dialysis. These interactions were limited to the binding of salicylate to human serum albumin (HSA). The binding was saturable and involved several classes of binding sites with different association constants. A competition study indicated that salicylic acid at high concentration was able to displace warfarin and digitoxin but not glibenclamide from their HSA sites. On the other hand, selezen serum binding was decreased in renal impaired patients and this result was probably linked to the decreases in HSA concentration. So the use of small dosage regimens of selezen to these patients can be proposed. The same recommendation may be done for cirrhotic patients, where the decrease of selezen binding percentage was observed and due to both hypoalbuminemia and hyperbilirubinemia.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Verapamil 240 SR versus verapamil 120 SR in arterial hypertension. A randomized double-blind, placebo-controlled study with 24-hour ambulatory blood pressure monitoring.

Fifteen patients (6 males, 9 females), age range 36-70 years, were enrolled in a randomized, double-blind, placebo-controlled study according to a Latin-square design, with the aim of comparing 24-hour blood pressure profiles after three 15-day treatment periods with placebo, verapamil SR 120 mg (V120 SR) given twice daily (bid), and verapamil SR 240 mg (V240 SR) given once daily (od). All of the patients were diagnosed as mild or moderate essential hypertensives on the basis of standard casual recordings. Noninvasive 24-hour ambulatory blood pressure (BP) monitoring was performed with an ICR Spacelab 5200 automatic device. In comparison with placebo, a clinically and statistically significant reduction in both systolic and diastolic BP over 24 hours was obtained with both active treatments. Comparison of the two active treatments shows that V240 SR led to a greater reduction in systolic and diastolic BP than V120 SR. No changes in heart rate were observed. Both treatments were well tolerated. In conclusion, both verapamil regimens proved to be effective and safe in treating essential hypertensives, with V240 SR giving better 24-hour BP control.

Adult↗
PubMed1989

Calcium-channel blockade (nitrendipine) in combination with ACE inhibition (captopril) in the treatment of mild to moderate hypertension.

The antihypertensive efficacy of a combination of calcium-channel blockers and angiotensin-converting-enzyme (ACE) inhibitors in severe primary hypertension is well known, but a synergistic action of this drug combination in mild to moderate primary hypertension is still not established. Therefore, the aim of the present study was to evaluate the efficacy and tolerability of monotherapy with nitrendipine (20 mg) or captopril (100 mg), and of their combination (nitrendipine 10 mg plus captopril 50 mg), in patients suffering from mild to moderate primary hypertension, according to a single-blind, randomized, placebo-controlled design. After the first 4-week monotherapy period, both nitrendipine and captopril induced a significant decrease in systolic and diastolic blood pressure (BP) (p less than 0.001). Furthermore, nitrendipine caused a significant increase in heart rate (HR), while no change in HR was observed in patients treated with captopril. Several side effects were observed, both in the nitrendipine-treated patients (facial flushing, headache, malleolar edema) and in the captopril-treated patients (initial hypotension, dizziness, gastrointestinal disorders). However, these side effects were mild and were well tolerated. In the second combined 4-week therapy period, systolic and diastolic BP of patients treated with 10 mg nitrendipine combined with 50 mg captopril continued to decrease to a degree significantly lower (p less than 0.001) than that observed at the end of the monotherapy period. Simultaneously, no change in HR values occurred when compared to basal values. Furthermore, the incidence and intensity of some side effects observed during the combined therapy period were lower than those of the monotherapy period.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1989

Acute cardiovascular and renal effects of human calcitonin gene-related peptide.

Acute cardiovascular and renal effects of 25 micrograms IV human calcitonin gene-related peptide (hCGRP) have been studied in four normotensive and untreated subjects, in the absence and the presence of indomethacin, a prostaglandin synthesis-blocking agent. Intravenous infusion of hCGRP, alone, caused a transient but significant increase in heart rate (HR), hypotension, and facial flushing. Along with these effects, a positive inotropic action of hCGRP was documented by a noninvasive poligraphy. Furthermore, a significant increase in the catecholamines (norepinephrine and epinephrine), in the cyclic nucleotide (cyclic AMP and cyclic GMP) plasma levels, and a small decrease in total calcium with no change in inorganic phosphorus serum levels, occurred. Also acute renal hCGRP induced effects were observed, as a significant increase in urinary volume and in the urinary calcium, sodium, potassium, and chloride excretion. Indomethacin did not affect all the cardiovascular, metabolic, and renal hCGRP-induced effects. These results are in agreement with the hypothesis that hCGRP acts on the heart, vessels, and kidney, directly or indirectly, by the mediation of other vasodilating agents or systems excluding the prostaglandin system.

Adult↗
PubMed1989

Tolerability profile of the antiinflammatory compound imidazole salicylate: a metanalysis of safety data in 1408 patients.

In order to evaluate the incidence of side-effects (S.E.), the withdrawal rate and the type of S.E. of the new antiinflammatory agent imidazole salicylate, we performed an analysis of 33 clinical trials involving 1408 patients treated with 750 mg t.i.d. (tablets or solution) or 1000 mg b.i.d. (granulated powder), taking into account all the factors (treatment duration, pharmaceutical form, indications, etc.) that could influence the type and incidence of S.E. Slight and transient episodes of pyrosis or epigastric pain represented the great majority of S.E. The overall rate of withdrawal was 1.8%. According to the duration of therapy, the incidence of S.E. was: 2-3 days, 3.3%; 5-7 days, 5.6%; 10-14 days, 8.8%; 30 days, 10.2%. The pharmaceutical forms, the treated pathologies and the various experimental designs adopted (double-blind, open, etc.) did not influence the S.E. rate. With imidazole salicylate the overall incidence of S.E. was always lower than other NSAID's ranging from 10% to 64% of that observed with the reference drugs (other salicylates, ibuprofen, naproxen, flurbiprofen, piroxicam, diclofenac). In conclusion, this analysis showed a linear relationship between S.E. and exposure time up to 10-12 days, followed by a clear trend toward a plateau of 10% of S.E. with treatments up to 30 days. Therefore the risk-benefit ratio, particularly when compared with that of the reference drugs, seems to be very favourable.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration.

The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.

Adult↗
PubMed1988

A two-year study of enteric infections associated with diarrhoeal diseases in children in urban Somalia.

A hospital-based systematic sample of 1667 children with severe diarrhoeal disease was studied in Mogadishu, Somalia, throughout 1983 and 1984. One or more enteric pathogens were found in 61% of the patients. Rotavirus (25%), enterotoxigenic Escherichia coli (11%), Shigella spp. (9%), Aeromonas hydrophila (9%), Giardia lamblia trophozoites (8%), Campylobacter jejuni (8%), and Vibrio cholerae non-O1 (6%) were the most frequently identified pathogens. Age-specific detection rates of enteric pathogens and helminths, seasonal patterns, and relationship of some specific infections with feeding status and main clinical features have been defined for all the sample examined.

Adolescent↗
PubMed1988

[Treatment of essential mild-to-moderate arterial hypertension with once-daily penbutolol. Controlled clinical study vs atenolol].

The anti-hypertensive and tolerance of penbutolol, a non-selective beta-blocker of long duration and endowed with an ISA effect were compared with those of atenolol, a cardioselective beta-blocker without ISA effect, in two groups of 20 patients each suffering from slight-to-moderate essential primary hypertension selected on the basis of a clinico-experimental design of open randomised type. The two drugs presented a similar anti-hypertensive effect which attained its peak expression in the second week of treatment. As for side-effects, penbutolol during treatment presented better tolerance than atenolol. Further, both penbutolol administered once daily at a dose of 40 mg/die, and atenolol, administered once daily at a dose of 100 mg/die proved to possess satisfactory anti-hypertensive activity justifying its use in a single daily dose.

Adult↗
PubMed1988

[Evaluation of the adrenergic and pressor response to the hand-grip test in young athletes].

Numerous factors may influence the sympathetic and pressure response to physical exercise, age, sex, type of activity carried on and training for example. Training, in particular is considered to reduce both adrenergic and pressure response. Plasma catecholamine levels and the haemodynamic response to the hand-grip test have therefore been evaluated in a group of young athletes, compared with a group of non-trained youths. The results confirmed that young athletes have a lower sympathetic and haemodynamic response to the isometric exercise and this is accompanied by improved cardiac performance. The value of the hand-grip test is underlined as a method of investigation able to evaluate the training level attained by the athlete.

Adult↗
PubMed1987

The prevalence and intensity of intestinal parasites in two Somalian communities.

About 85% of the population of two Somali communities harboured soil-transmitted intestinal nematodes and/or protozoa. The commonest parasite (75% in the Lafoole institution and 59% in the Afgoye institution) was Trichuris trichiura. Mixed infections were common. The source of infection is contaminated fields around dwelling quarters, because of indiscriminate defaecation. One of the factors responsible for the higher incidence of hookworm in Lafoole (45%) compared with Afgoye (1.5%) may be the different soil character of the surrounding fields.

Adolescent↗
PubMed1986

Circulating levels of catecholamines and cyclic AMP during the handgrip test in borderline hypertension.

Systolic and diastolic blood pressure, heart rate, and circulating levels of catecholamines and cyclic AMP were measured during the handgrip test in 18 borderline hypertensive patients, 22 stable hypertensive patients, and 20 normotensive control subjects. No difference was observed, at rest, for plasma levels of noradrenaline, adrenaline, dopamine, and cyclic AMP among the three groups. During the handgrip test in borderline hypertensive patients, the percentage of increase of plasma levels of noradrenaline, adrenaline, dopamine, and cyclic AMP were significantly more elevated with respect to the levels of control subjects but not when compared with those of stable hypertensive patients. These results are in agreement with the hypothesis that in both borderline and stable hypertension there is an exaggerated sympathetic response to the handgrip test.

Adult↗