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Biomedical subjects

D Bettega

Publications and source records attributed to D Bettega.

At least 37 records · Page 2Linked to original sources
PubMed1993

Shear-induced platelet aggregation is potentiated by desmopressin and inhibited by ticlopidine.

Shear-induced platelet aggregation is important in physiological hemostasis and in the pathogenesis of arterial thrombosis. It requires extracellular Ca2+, platelet membrane glycoproteins Ib/IX and IIb/IIIa, von Willebrand factor (vWF), and ADP. We studied the effects of desmopressin (DDAVP), which increases plasma vWF levels and shortens the bleeding time, and of ticlopidine, which inhibits platelet responses to ADP, on shear-induced platelet aggregation. Eleven healthy volunteers were given oral ticlopidine (250 mg b.i.d.) for 7 days. The same subjects were infused intravenously with DDAVP (0.3 micrograms/kg body wt) before the first and after the last doses of ticlopidine. The degree of platelet aggregation induced by shear stress at 25, 50, 75, and 100 dyne/cm2 in a cone-and-plate viscometer, plasma vWF levels, and the bleeding time were measured before and after each DDAVP infusion. Plasma vWF levels and the extent of shear-induced platelet aggregation increased after DDAVP and were correlated. Ticlopidine partially inhibited shear-induced platelet aggregation both before and after DDAVP infusion. The bleeding time, prolonged by ticlopidine, was shortened by DDAVP. Potentiation by DDAVP of shear-induced platelet aggregation may be one mechanism by which the drug shortens the prolonged bleeding time. Since shear-induced platelet aggregation can cause thrombotic occlusions in stenotic arterial vessels, our findings may explain the therapeutic efficacy of ticlopidine in arterial thrombosis.

Adult↗
PubMed1992

Patterns of development of tachyphylaxis in patients with haemophilia and von Willebrand disease after repeated doses of desmopressin (DDAVP).

When patients with mild haemophilia or von Willebrand disease (vWD) are repeatedly treated with desmopressin (DDAVP) at relatively short time intervals, some of them may become less responsive or unresponsive. The development of tachyphylaxis would limit the usefulness of DDAVP in clinical management of these patients. On the other hand, tachyphylaxis is not consistent, and its patterns of development are unknown. The aim of this study was to evaluate in controlled conditions the occurrence of tachyphylaxis by giving intravenous DDAVP (0.3 microgram/kg) on four consecutive days to a selected group of patients with mild haemophilia A (n = 22) and type I vWD (n = 15). After each dose, we measured parameters known to change after DDAVP, i.e. factor VIII coagulant activity, bleeding time, von Willebrand factor antigen, ristocetin cofactor and tissue-type plasminogen activator antigen. We found that on average the responses obtained after the second dose of DDAVP were approximately 30% less than those obtained after the first, but were not further reduced after the third and fourth dose. At all time intervals after DDAVP, patients with vWD responded relatively better than patients with haemophilia, and there were fewer vWD patients who responded poorly or became unresponsive. In vWD patients there were no significant changes in the bleeding time responses and in blood pressure and heart rate. The clinical implications of these findings are that repeated doses of DDAVP can be given efficaciously to many patients (particularly to those with vWD), even though responses lower than those seen after the first dose should be expected.

Adult↗
PubMed1992

Sustained correction of the bleeding time in an afibrinogenaemic patient after infusion of fresh frozen plasma.

We have evaluated the duration of the effect of replacement therapy with two different doses of fibrinogen on the prolonged bleeding time of an afibrinogenaemic patient and the relationship between changes in bleeding time and plasma and platelet fibrinogen concentrations. The infusion of 40 mg/kg fibrinogen, as fresh frozen plasma (FFP), corrected the prolonged bleeding time of the patient from longer that 30 min to 8 min. The bleeding time was still normal 9 d after infusion, at a time when the plasma and platelet fibrinogen levels were low (0.13 g/l and 27 micrograms/10(9) platelets; normal ranges 1.6-4.0 and 60-190). Two months later, the infusion of a smaller dose of fibrinogen (4 mg/kg) also corrected the bleeding time, which remained normal until the second day after infusion, despite the fact that plasma and platelet fibrinogen were very low (0.02 g/l and 3.4 micrograms/10(9) platelets). The bleeding time returned to the prolonged baseline values only by day 6 post-infusion, when plasma and platelet fibrinogen levels were 4 x 10(-4) g/l and 1.4 micrograms/10(9) platelets. Therefore, sustained correction of the prolonged bleeding time may be obtained in afibrinogenaemic patients with a single infusion of fibrinogen at lower doses than usually recommended.

Adult↗
PubMed1992

Transformation of C3H 10T1/2 cells with 4.3 MeV alpha particles at low doses: effects of single and fractionated doses.

Oncogenic transformation of C3H 10T1/2 cells was determined after exposure to graded doses of 4.3-MeV alpha particles LET = 101 keV/microns. The source of alpha particles was 244Cm and the irradiation was done in an irradiation chamber built for the purpose. Graded doses in the range of 0.2 to 300 cGy were studied with special emphasis on the low-dose region, with as many as seven points in the interval up to 10 cGy. The dose-effect relationship was a complex function. Transformation frequency increased with dose up to 2 cGy; it seemed to flatten at doses between 2 and 20 cGy but increased again at higher doses. A total of 21 cGy was delivered in a single dose or in 3 or 10 equal fractions at an interval of 1.5 h. An inverse dose-protraction effect of 1.4 was found with both fractionation schemes. Measurements of the mitotic index of the population immediately before the various fractions revealed a strong effect on the rate of cell division even after very low doses of radiation. Mitotic yield decreased markedly with the total dose delivered, and it was as low as 50% of the control value after 4.2 cGy and 20% after 14 cGy with both fractionation schemes.

Alpha Particles↗
PubMed1991

Criteria and techniques for analysing cell survival data.

Cell survival was studied by analyzing the inactivation probability density function and its fundamental parameters. Mean D, variance sigma 2 and mode Dmode were evaluated and a set of equations relating these parameters to the usual parameters of the multitarget, multihit and linear-quadratic models Do and n, alpha and beta, kappa and lambda are reported. The multihit equation used was an extension of the usual equation, to allow parameter kappa to assume values that are not necessarily integers. In the multitarget curve, the mode of inactivation probability density function, proved to be the quasi-threshold dose Dq = Do ln(n). Relative variance, degree of asymmetry and degree of peakedness can be calculated from the shape parameters n in the multitarget model, kappa in the multihit model, and alpha/square root of beta in the linear-quadratic model. From an analysis of eight published cell survival sets of data, on C3H10T1/2 cells exposed to low LET radiations, it was found that D, sigma, and SF2 are the parameters which exhibit the least variation from experiment to experiment and the least variation in selecting the range of data available for estimation.

Analysis of Variance↗
PubMed1989

Growth kinetics of C3H10T1/2 cells exposed to low-LET radiation.

Growth curves and size of the colonies of C3H10T1/2 cells exposed to low-LET radiation (31 MeV protons) were determined after 0, 1, 3, 5, and 7 Gy. The data show that: cell density at confluence was 3.3 x 10(4) cells/cm2; the initial division delay was very small; in the first 15 h the increase in the cell number was essentially the same at all doses; at 100 h the colony size distribution was very large, ranging from 0 to 7 generations, even within the control population. The temporal dependence of the growth properties of surviving and non-surviving cells was represented by the equation N = N0(Fe(a(t - dD] + (1 - F)ea/bD(1 - e - bD(1 - e - bD(t - dD]) where F is the surviving fraction, t the time of sampling, a the growth rate, d the division delay per unit dose, b the rate per unit of dose at which the non-surviving cells lose their ability to divide. The resulting values were: a = 0.029 +/- 0.002 h-1; b = 0.0041 +/- 0.0009 h-1 Gy-1 and d = 1 +/- 0.8 h Gy-1. It was found that growth curves are affected by non-surviving progeny up to 150, 200 and 250 h after irradiation at 3, 5 and 7 Gy, whereas at longer times the population consists essentially of progeny of surviving cells.

Animals↗
PubMed1989

Cell density dependence of transformation frequencies in C3H10T1/2 cells exposed to X-rays.

The effects of cell density on transformation frequencies were studied in C3H10T1/2 cells exposed to 0.5 and 7 Gy of 200 kVp X-rays. Initial cell density strongly influenced transformation frequency; this decreased by a factor of between 4 and 10 when the initial seeding density was changed from 50 to 2500 cells/10 cm diameter Petri dish. The data were fitted with two equations: (a) an allometric function represented on a log-log scale by a straight line and (b) a sigmoidal function with plateaux between 50 and 250 cells/dish and above 600. The two curves are compared and their probabilities discussed. Our data indicate that the region between 50 and 250 cells/dish would be the most suitable region for dose-effect measurements. A study of the growth curves at 0.5 and 8.5 Gy shows that cell growth rates are not influenced by initial cell density.

Animals↗
PubMed1987

Effects of split-dose irradiation on survival and oncogenic transformation induced by 31 MeV protons in C3H10T1/2 cells.

Survival and oncogenic transformation were studied in C3H10T1/2 cells exposed to 31 MeV protons. Total doses of 0.5, 1 and 7 Gy were delivered as single and two equal fractions with various time intervals up to 10 h between doses. With split doses as compared with single doses to a total dose of 7 Gy, survival increased by a factor of 2.5 +/- 0.2, whereas the frequency of transformation per surviving cell declined by a factor of 3.1 +/- 0.5. Maximal split-dose recovery occurred within the first 5 h for both endpoints. Further, the transformation frequency decreased by factors of 3.1 +/- 0.6 and 1.5 +/- 0.3 respectively for total doses of 0.5 and 1.0 Gy split into two equal fractions. The data for 1 and 7 Gy are compatible with data in the literature for other low LET radiations.

Animals↗
PubMed1985

In vitro cell transformations induced by 31 MeV protons.

Experimental data are presented on the frequencies of transformations in C3H10T1/2 cells exposed to 31 MeV protons (LET = 1.83 +/- 0.02 keV/mum in tissue) in a dose interval between 0.25 and 7.0 Gy. The transformation frequency per surviving cell curve showed a marked change in slope over the dose range used. At higher doses, above about 2 Gy, it steepened very sharply in comparison with the lower dose range. If fitted to a power of the dose, the power in the higher range was about five times that in the lower range.

Animals↗
PubMed1984

[Radiosensitivity and effect of dose fractionation in cultured cells].

Survival, division delay and repair of sublethal damage were studied as a function of the cellular age in cells of EUE line exposed to 31 MeV protons, (LET of 1.83 keV/micron in tissue). The findings are compared with data reported in the literature on various mammalian cell lines exposed to X and gamma rays, common behaviours are pointed out and the characteristics parameters quantified. Survival varies with cell age and reaches a maximum value at mid S and its minimum at late G1; the ratio between maximum and minimum ranges between 1.5 and 15 depending on the survival level. Division delay resulted to be equal to 6 and 12% of the generation time per Gy for mid G1 and mid-late S respectively. All the investigated lines are able to repair as much as 50% of the sublethal damage within one hour.

Cell Division↗
PubMed1981

Energy deposition by proton beams of up to 31 MeV in microscopic volumes.

The frequency distributions of energy deposition in microscopic volumes for proton beams of various energies and energy spreads were determined by means of a "rossi type" proportional counter. Tissue equivalent spherical volumes of 0.6, 0.72, 0.80, 1.00, 1.25, 1.50, 1.75, 2.00 micrometer diameter were simulated. Frequency distributions of energy deposition per unit pathlength are reported and their behavior as a function of the simulated pathlength, beam energy and energy spread is discussed. The results indicate that energy deposition distributions in microscopic volumes for protons in the range 8-31 MeV are skewsymmetric distributions with a tail on the high energy side, and that degraded beams behave differently from monoenergetic ones. Dose mean lineal energy values have been quoted for beams used in radiobiological experiments.

Protons↗
PubMed1981

Chromosome aberrations induced by protons up to 31 MeV in cultured human cells.

Chromosome aberrations were induced in cultured human cells by proton beams of 31, 12, and 8 MeV. The frequencies of isochromatid breaks and dicentrics have been analysed as a function of proton energy and dose. Both effects are largely dependent on proton energy; isochromatid breaks increased linearly with the dose, whereas dicentrics show a definite parabolic behaviour. The experimental data were fitted to the analytic form Y = KDn and Y = alpha D + beta D2 and the best fitted values of the parameters are reported and discussed. The values of RBE for the isochromatid breaks are in the ratio 1.7:1.3:1 for 8, 12, and 31 MeV respectively. In the case of the dicentrics the RBE values are dose-dependent function of the type CD-n. The three distributions of dicentrics among the cells do not fit a Poisson distribution.

Cell Line↗
PubMed1981

[Parameters of a cell population synchronized for radiosensitivity studies (author's transl)].

Human cultured cells (EUE) were synchronized by the method of the mitotic harvest and the degree of synchronization, during the first duplication interval, determined by various tests which include growth curves, mitotic index cell-size distributions. Values of synchronization index initially greater than 90% and desynchronization rate of about 2%/hour were evaluated. The survival after 1.75 Gy of 31 MeV protons irradiation shows a sensitive period in the late G1 followed by an increase in radioresistance to a maximum in S.

Cell Cycle↗
PubMed1980

Multinucleate cells and micronucleus formation in cultured human cells exposed to 12 MeV protons and gamma-rays.

Cultured human cells of the EUE line were exposed to different doses of 12 MeV protons, plated and allowed to grow for 8 days; colonies were then scored for the presences of multinucleate cells and micronuclei. The frequency of both effects is an increasing function of the dose; the evaluated exponents of the dose-response equation (e = bDn) are n = 1.0 %/- 0.1 for multinucleate cells and n = 1.6 +/- 0.1 for micronuclei. By comparison with the results obtained with gamma irradiations, r.b.e. values were obtained for both effects. The correlation between the logarithm of the surviving fraction and the yield of the studied effects has been proved to be statiscally significant.

Cell Count↗
PubMed1977

Influence of neutron collimation on the energy deposition in a tissue equivalent sphere.

The influence of neutron collimation on the shape of energy deposition spectra was investigated using a spherical walled proportional counter. Experimental dose averaged lineal energies were obtained and compared with theoretical values. The fractions of total absorbed dose corresponding to various intervals of lineal energies were also deduced from the measured distributions.

Fast Neutrons↗
PubMedDate not supplied

Exercise training in mild hypertension: effects on blood pressure, left ventricular mass and coagulation factor VII and fibrinogen.

The aim of this study was to assess the effects of aerobic exercise on resting and 24-hour blood pressure (BP), left ventricular mass (LVM), plasma fibrinogen and factor VII (FVII). For this purpose 14 sedentary subjects with untreated diastolic BP between 90 and 104 mm Hg completed a 12-week supervised exercise program. At the end of this period, 8 subjects resumed a sedentary life-style and were reexamined 2 months later (detraining). Baseline, posttraining and postdetraining examinations included resting BP assessment, ambulatory BP monitoring, cardiopulmonary stress test, echocardiography and measurements of plasma fibrinogen and FVII. Exercise-mediated increase in aerobic fitness (VO2 max + 24%) was associated with a significant reduction in resting systolic and diastolic BP (p < 0.01), mean systolic and diastolic 24-hour BP (p < 0.001) and LVM index. As for the coagulation parameters only the concentration of fibrinogen significantly decreased (p < 0.01) whereas FVII remained unchanged. The 8 subjects that resumed a sedentary life-style were reexamined 2 months later: their resting BP, 24-hour BP and fibrinogen concentration returned to baseline values; only the effect on LVM was conserved. Our study underlines the usefulness and safety of regular physical exercise in mild hypertension. Most of the patients (11 of 14) had their BP normalized and a significant reduction in LVM and fibrinogen concentration was observed, leading to an overall improvement in coronary risk profile.

Adult↗