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Biomedical subjects

G Corso

Publications and source records attributed to G Corso.

At least 19 recordsLinked to original sources
PubMed2002

Epidemiology of primary intracranial tumours in NW Italy, a population based study: stable incidence in the last two decades.

Data about the epidemiology of primary intracranial tumours (PIT) are still heterogeneous depending on different methodological approach in collecting data. In Valle d' Aosta, north west side of Italy, we have carried out a prospective consecutive population based study to calculate the incidence of PIT in the last decade (1992-1999) and to compare these rates with the previous period (1986-1991), data reported in a previous paper. The mean annual PIT incidence rate (ri) per 100,000 inhabitants was 25.48. The mean annual incidence rates in the two period of comparison were adjusted to the 1991 Italian population by the direct method. The standardised ratio was 26.43 in the previous period and 23.24 in the second decade. There is no statistically significant difference. The mean annual PIT incidence rates by tumour types were meningiomas 13.27/100,000 (men 9.77; women 16.7), neuroepithelial group 9.3 (men 10.62; women 8.1), adenomas 1.26, neurinomas 0.7. Mean annual incidence rates by tumour class were also stable. The stable incidence rate in the two periods and the similar incidence in England (21.04/100,000 person year), strengthen the evidence for a stable incidence rate of PIT in the last decade. These three papers used similar methodology. The homogeneous methodology allows comparison and further evaluation.

Adenoma↗
PubMed2001

Determination of RSD921 in human plasma by high-performance liquid chromatography-tandem mass spectrometry using tri-deuterated RSD921 as internal standard: application to a phase I clinical trial.

A fast, sensitive and specific method is presented for the quantification of RSD921 in human plasma by liquid chromatography coupled with tandem mass spectrometry using tri-deuterated RSD921 (3d-RSD921) as an internal standard. A single-step liquid/liquid extraction was performed with diethyl ether/hexane (80 : 20, v/v) using 0.5 ml of plasma. The plasma calibration curves were linear from 0.1 to 20 ng ml(-1) (r > 0.999). Between-run precision, based on the percent relative deviation for replicate (n = 40) quality controls, was < or =7.27% (0.5 ng ml(-1)), < or =7.39% (5.0 ng ml(-1)), and < or =5.06% (20.0 ng ml(-1)). Between-run accuracies, based on the relative error, were +/-2.59%, +/-1.23% and +/-1.64% respectively. The method was developed to evaluate the pharmacokinetic profile after 15 min of intravenous stepwise-ascending infusion dose of RSD921 in 18 healthy volunteers. A dissociation study of protonated RSD921 and 3d-RSD921 by collision-induced dissociation using in-source fragmentation and tandem mass spectrometry is also presented.

Anesthetics, Local↗
PubMed2000

Biochemical characterization of two crotamine isoforms isolated by a single step RP-HPLC from Crotalus durissus terrificus (South American rattlesnake) venom and their action on insulin secretion by pancreatic islets.

Crotamine, a neurotoxin present in the venom of the South American rattlesnake Crotalus durrisus terrificus exists as several polymorphic variants, as demonstrated by recombinant DNA technology (Smith and Schmidt, Toxicon 28 (1990) 575-585). We have isolated native crotamine by chromatography on Sephadex G75, and have purified two crotamine isoforms (F2 and F3) by a single step of RP-HPLC. Native crotamine and RP-HPLC fractions F2 and F3 produced skeletal muscle spasms and spastic paralysis in mice. At low glucose concentrations (2.8-5.6 mmol/l), none of the crotamines altered the insulin secretion by rat isolated islets. In the presence of 16.7 mmol glucose/l, F2 (5 microg/ml), but not F3, increased insulin secretion two-fold, whereas native crotamine (1.5, 5 and 16.5 microg/ml) potentiated the secretion dose-dependently. The increase in insulin secretion induced by F2 fraction (5 microg/ml) was similar to that obtained with 16.5 microg of native crotamine/ml. These results indicate that the mode of action of the F2 and F3 isoforms in beta-cells is different from that in muscle cells. This difference may be related to the binding affinity of each isoform for the Na(+) channels located in the beta-cell membrane. Crotamine isoforms may be valuable tools for studying the involvement of Na(+) channels in the mechanism of insulin secretion.

Animals↗
PubMed2000

Uterine morphology during the annual cycle in Chalcides ocellatus tiligugu (Gmelin) (Squamata: scincidae).

The uterus of the viviparous skink Chalcides ocellatus tiligugu was studied by SEM and LM during the annual cycle. Three functional phases were identified: preovulatory (spring), gestatory (summer), and quiescent (autumn-winter), characterized by changes in the uterine wall (mainly the endometrial layer). In the preovulatory phase, the uterine wall increases in thickness; its luminal epithelium has ciliated cells and two types of unciliated secretory cells. The first type secretes sulfated glycosaminoglycans (GAGs), which form the amorphous inner layer of the eggshell membrane; the second type secretes acidic glycoproteins that form the intrafibrillar matrix of the outer layer of the eggshell membrane. The lamina propria contains simple alveolar glands that secrete the collagen fibers of the eggshell membrane. During the gestatory phase, the glycoproteins produced by secretory cells of the second type have histotrophic activity for the developing embryo. The uterus widens to form incubation chambers with two hemispheres, one embryonic and the other abembryonic. Both a chorioallantoic placenta and an omphaloplacenta with histotrophic activity are present in late gestation. The chorioallantoic placenta, with aspects of a Weekes (1935) Type III placenta, develops in the embryonic hemisphere. The omphaloplacenta forms at the vegetative pole of the egg and shows cellular hypertrophy of the bilaminar omphalopleure and uterus. During the quiescent phase, the uterus gradually decreases in thickness and activity; its luminal epithelium does not show secretory activity. The annual variations in the myometrial layer involved the inner circular and the outer longitudinal muscle layers.

Animals↗
PubMed2000

Temporal trends of stroke in Valle d'Aosta, Italy. Incidence and 30-day fatality rates.

The objective of this study was to evaluate temporal changes of stroke in an Italian community by comparing the present incidence rates with those reported in the same area for 1989. The two studies were conducted by the same research group and met almost all the criteria proposed for an "ideal" stroke incidence study. The annual incidence rate per 1000 inhabitants increased (p < 0.01) by 29%, from 2.23 (95% CL, 1.96-2.50) in 1989 to 2.89 (95% CL, 2.58-3.20) in 1997. No statistically significant change was found when these rates were adjusted to the 1991 Italian population. The overall incidence rate was 2.40 (95% CL, 2.14-2.66) in 1989 and 2.65 (95% CL, 2.39-2.91) in 1997. The thirty-day case fatality rate declined dramatically (p < 0.001) from 31% (95% CL, 26-36) to 20% (95% CL, 16-24) between 1989 and 1997. Ageing of the population and better identification of cases could explain the high incidence rate, whereas the decrease of fatality rate may be due to a general improvement in acute care and inclusion of milder cases.

Adolescent↗
PubMed1999

Prevention of cardioembolic stroke: use of oral anticoagulants in patients with atrial fibrillation.

With the aim of quantifying the use of oral anticoagulant (OA) therapy in clinical practice, we surveyed 150 consecutive patients admitted with a diagnosis of atrial fibrillation (AF). Each patient was administered a questionnaire relating to the classic vascular risk factors and to the antithrombotic treatment received at home. The diagnosis of AF was formulated at the time of admission in 45 cases. Of the 105 cases with a previous diagnosis, OA therapy was relatively or absolutely contraindicated in 21 patients (20%), whereas the other 84 (80%) were ideal candidates for the treatment. Of these, 20 (24%) were actually receiving OA, 16 (19%) were on platelet anti-aggregants (PA), and 48 (57%) were receiving no antithrombotic treatment at all. Even lower percentages of OA use were found in the patients with a previous (20%) or recent (16%) history of cerebral ischemia. Upon discharge, of the 115 patients without contraindications to OA (84 with previously known and 31 with newly diagnosed AF), 50% were receiving OA and 20% PA. The results of this survey show that OA therapy is little used in the Valle d'Aosta Region for the prevention of ischemic stroke in AF patients at high risk for cerebral ischemia. The lack of knowledge among the general population, the difficulty of initiating the therapy in patients such as ours with severe comorbidities, and the absence of disorganization of centers for OA monitoring may be the main reasons underlying this low level of use. Population screening or a sensitization campaign could increase the identification of subjects at risk, whereas better organization of coagulation monitoring centers could encourage OA use in subjects at high risk for cerebral ischemia.

Administration, Oral↗
PubMed1999

Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure.

BACKGROUND: Supplementation with L-arginine (ARG) strikingly ameliorates proteinuria and glomerulosclerosis in remnant rats by overcoming nitric oxide (NO) deficiency. Whether or not the same holds true in humans is unknown. This study aimed at evaluating the effects of ARG on the NO system and renal function in proteinuric patients with moderate chronic renal failure (CRF). METHODS: We measured plasma arginine, urinary and plasma NO3 (an index of NO synthesis), and urinary cGMP (an intracellular mediator of NO), as well as proteinuria and renal functional reserve (RFR) in CRF patients orally treated for six months with either ARG (0.2 g/kg body wt/day, CRF-A group) or the control vehicle (CRF-C). Normal subjects (NOR) were also included for basal comparisons. RESULTS: In CRF patients at baseline, plasma arginine was within the normal range; similarly, the urinary excretion of NO3 was comparable to the NOR value (CRF, 0. 440 +/- 0.02; NOR, 0.537 +/- 0.08 micromol/min, P = NS). The plasma NO3 levels were higher than in NOR (CRF, 74 +/- 6; NOR, 27 +/- 2 micromol/liter, P < 0.001), and consequently the renal clearance of NO3 resulted as being reduced. During the six months of treatment, although a remarkable steadiness of ARG and NO3 levels was detected in the CRF-C group, the CRF-A group was characterized by a marked and immediate increase of plasma ARG. This was associated, however, with a delayed increment in urinary and plasma NO3 levels and no change in urinary cGMP. In CRF-A, as in CRF-C, blood pressure, proteinuria, glomerular filtration rate, and renal plasma flow did not vary. Likewise, RFR, which was reduced at baseline in CRF, did not improve after ARG. CONCLUSIONS: In moderate CRF, the tonic release of NO is constant and, likely, not impaired, and ARG supplementation does not lead to an enhancement of NO activity, thus resulting in no renal effect.

Adolescent↗
PubMed1999

Fluconazole bioequivalence study: quantification by tandem mass spectrometry.

To develop a new method for quantifying fluoconazole in human plasma and to compare the bioavailability of two fluconazole capsule formulations, an open, randomized, two-period crossover study with a one-week washout interval was conducted in 24 healthy volunteers. Plasma samples were obtained up to 168 hours after drug administration and the serum fluconazole concentrations were analyzed using electrospray tandem mass spectrometry coupled to liquid chromatography using multiple reaction monitoring mode. The pharmacokinetic parameters obtained for fluconazole after the administration of each formulation included the Area under the curve (AUC)(0-168h), AUC(0-infinity), Cmax, Cmax/AUC(0-168h), Tmax, elimination rate constant (Ke), and half-life (T1/2). Within- and between-run imprecision was less than 2.3% and 8.2%, respectively. Inaccuracy within and between runs was -1.5% and -9.7%, respectively. The pharmacokinetic parameters for bioequivalence showed a normal distribution, and the variance of AUC(0-168h), AUC(0-infinity), and Cmax were homoscedastic. The geometric mean for the Fluconal/Zoltec (Fluconal; Libbs Farmacêutica Ltda, São Paulo, Brazil; Zoltec; Laboratórios Pfizer Ltda., São Paulo, Brazil) individual percent ratio was 94.9% for AUC(0-168h), 94.7% for AUC(0-infinity), 80.1% for Cmax, 102.6% for Ke, 97.5% for T1/2, and 0.93 for Tmax (arithmetic mean of individual differences). We have developed a method in which liquid chromatography is coupled with electrospray tandem mass spectrometry to improve the pharmacokinetic analysis of fluconazole. Because the 90% CI AUC is within the interval proposed for the Food and Drug Administration, we concluded that Fluconal is bioequivalent to Zoltec in terms of absorption. The CV was 27.5% for the Cmax parameter, indicating that fluconazole's absorption rate is highly variable. The European Union Regulatory Agency accepts an interval of 70-143%, and because the 90% CI for Cmax is within the interval proposed for the European Union agency, we conclude that Fluconal is bioequivalent to Zoltec for the rate of absorption.

Administration, Oral↗
PubMed1999

Streaminglike diffusion in the low-dimensional stochastic pump model.

In this paper we analyze a diffusion phenomenon in a few-dimensional Hamiltonian system of coupled mappings in which the principal component of diffusion occurs along resonances. The result is that the diffusion can have power-law dependence in coupling parameter mu and be independent of the stochastic parameter K. For the same range of parameters, the usual analytical Arnold diffusion across resonances is dependent on K and can be much smaller than resonance streaming diffusion. The results are used to qualitatively explain recent results in multidimensional coupled standard maps.

Journal Article↗
PubMed1999

Fluoxetine bioequivalence study: quantification of fluoxetine and norfluoxetine by liquid chromatography coupled to mass spectrometry.

In this study, the authors assessed the bioequivalence of two fluoxetine tablet formulations in 24 healthy volunteers of both sexes who received a single 20 mg dose of each fluoxetine formulation, and a new sensitive method for the quantification of fluoxetine and norfluoxetine in human plasma was developed. The study was conducted using an open, randomized, two-period crossover design with a 4-week washout interval. Plasma samples were obtained over a 672-hour period. Plasma fluoxetine and norfluoxetine concentrations were analyzed by combined liquid chromatography coupled to mass spectrometry (LC-MS) with positive ion electrospray ionization using selected ion recording (SIR). Kolmogorov-Smirnov's test, histograms, probit plots, and the correlation between norfluoxetine AUC(0-infinity) and fluoxetine AUC(0-infinity) were used to analyze the population distribution. The limit of quantification was 0.15 ng.ml-1 and 0.50 ng.ml-1 for both fluoxetine and norfluoxetine, respectively. Within- and between-run imprecision was less than 13% and 17%, respectively. The pharmacokinetic parameters obtained for fluoxetine and norfluoxetine after the administration of each formulation included AUC(0-672 h), AUC(0-infinity), Cmax, Cmax/AUC(0-672 h), tmax, t1/2, and Ke. The AUC values for fluoxetine were not consistent with a normal distribution, reflecting the existence of two different populations (poor and extensive metabolizers). The mean pharmacokinetic parameters for extensive fluoxetine metabolizers were 27.0 ng ml-1 for Cmax, 2064.0 ng h ml-1 for AUC(0-infinity), and 85.4 h t1/2. The mean pharmacokinetic parameters for norfluoxetine (in extensive metabolizers only) were 2532.0 ng h ml-1 for AUC(0-infinity) and 8.4 ng ml-1 for Cmax. For fluoxetine bioequivalence, the 90% CI of the individual ratio geometric mean for Psiquial/Prozac (including both extensive and poor metabolizers) was 101.6% to 121.1% for AUC(0-672 h) and 86.1% to 102.6% for Cmax. For norfluoxetine, the 90% CI of the individual ratio geometric mean for Psiquial/Prozac (including both extensive and poor metabolizers) was 90.3% to 108.3% for AUC(0-672 h) and 84.5% to 106.3% for Cmax. The new method developed (LC-MS) presented high sensitivity, specificity, and short chromatographic run for the quantification of both fluoxetine and norfluoxetine in human plasma. Since both 90% CI for AUC and Cmax geometric mean ratios were included in the 80% to 125% interval proposed by the U.S. Food and Drug Administration, Psiquial was considered bioequivalent to Prozac according to both the rate and extent of absorption. The finding that there were no significant differences in the bioequivalence assessed by either fluoxetine or norfluoxetine pharmacokinetic parameters indicates that future bioequivalence trials may be performed by quantifying fluoxetine only.

Adolescent↗
PubMed1998

Comparative bioavailability of two sertraline tablet formulations in healthy human volunteers after a single dose administration.

OBJECTIVE: To compare the bioavailability of 2 sertraline tablets formulations (Tolrest from Laboratórios Biosintética, and Zoloft from Laboratórios Pfizer, Brazil) in 24 healthy volunteers of both sexes (12 male and 12 female) who received a single 50 mg dose of each sertraline formulation. MATERIAL AND METHODS: The study was conducted open with randomized two-period crossover design and a 14-day washout period. Plasma samples were obtained over a 96-hour interval and sertraline concentrations were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using selected ion monitoring method. From the plasma sertraline concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(0-96h), AUC(0-infinity), Cmax, Cmax/AUC(0-96h), Tmax, ke, and t(1/2). RESULTS: Pharmacokinetic parameters presented normal distribution according to Probit' s plot and Kolmogorov Smirnov's test, and the variance of AUC(0-96h), AUC(0-infinity) or Cmax were homoscedastic. Geometric mean Tolrest/Zoloft individual percent ratio was 95.22% for AUC(0-96h), 99.87% for Cmax, 100.4% for AUC(0-infinity), 103.6% for Ke, 96.0% for t(1/2) and 93.7% for Tmax. CONCLUSION: Since the 90% CI for both Cmax and AUC(0-96h) mean ratio were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that Tolrest was bioequivalent to Zolof for both extent and rate of absorption in a single dose administration.

Administration, Oral↗
PubMed1997

Occurrence of the same peroxidative compounds in low density lipoprotein and in atherosclerotic lesions from a homozygous familial hypercholesterolemic patient: a case report.

Oxidative modification of low density lipoprotein (LDL) and its byproducts may play a fundamental role in atherosclerosis. We report an in vitro analysis of LDL peroxidative compounds in an homozygous familial hypercholesterolemic (HFH) patient who subsequently died. During the autopsy, we analyzed lipids extracted directly from different atherosclerotic plaques, and we also provided an immunocytochemical analysis using the specific monoclonal antibody MDA2 (directed against malondialdeyde-lysine epitopes of oxidized LDL). The results showed that the same species of peroxidative compounds were present both in LDL in vitro and in lipids extracted directly from atherosclerotic lesions. Moreover, the immunocytochemistry analysis revealed a positive staining of atherosclerotic plaques, confirming the presence of LDL oxidation-specific epitopes. Although observation of a single case is necessarily limited, our findings are consistent with the hypothesis that oxidative modification of LDL is involved in human atherogenesis.

Adult↗
PubMed1997

Pseudodiastrophic dysplasia type Burgio in a newborn.

Pseudodiastrophic dysplasia is a distinct disorder that differs from diastrophic dysplasia on the basis of elbow and proximal interphalangeal joint dislocations, platyspondyly, and scoliosis. We report on a new patient with this rare skeletal dysplasia and two previously undescribed major malformations: omphalocele and complex heart defect.

Bone Diseases, Developmental↗
PubMed1997

Effect of low density lipoprotein fatty acid composition on copper-induced peroxidation: 1H-nuclear magnetic resonance analysis.

Oxidation of low density lipoprotein (LDL) has been implicated in atherogenesis. An increased content of oleic acid in LDL and the substitution of monounsaturated for polyunsaturated fatty acids in the diet reduce LDL oxidation. With 1H-NMR analysis, all LDL modifications, including the production of copper-induced aldehyde products, can be evaluated simultaneously. The aim of the present study was to investigate whether the fatty acid composition of LDL affected the NMR evaluation of aldehyde compounds. The LDL of the samples utilized were rich in oleic fatty acid (26.9%). After 48 h of exposure to copper sulfate, the mean production of malonyldialdehyde (MDA) by LDL was 31.2 nmol/mg of protein. Moreover, in the present study NMR did not reveal large amounts of peroxidative compounds since the nanomolar amounts of MDA produced after exposure to copper sulfate could not be detected. This study also demonstrated that the fatty acid composition (i.e. the oleic:linoleic acid ratio) must be taken into account in the evaluation of LDL peroxidation by NMR. In particular, a high concentration of oleic acid may limit the formation of large amounts of peroxidative compounds generated after exposure to the oxidant copper sulfate.

Adult↗
PubMed1997

Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia.

Familial hypercholesterolemia was the first genetic disorder recognized to cause myocardial infarction. Patients with homozygous familial hypercholesterolemia have rapidly progressive coronary atherosclerosis with angina pectoris, myocardial infarction, or sudden death at a young age. Selective apheresis on dextran sulfate cellulose columns reduces mortality and may induce regression of coronary lesions. These patients have both increased levels and prolonged circulation residence time of low-density lipoprotein (LDL), which is not removed by cellular receptor. LDL oxidation may play a pivotal role in atherogenesis. LDL undergoes oxidation before being taken up by macrophages and then transformed into arterial wall foam cells. The aim of this study was to investigate LDL oxidation in eight homozygous patients with familial hypercholesterolemia during repeated LDL apheresis. LDL lipid peroxidation, estimated by conjugated-diene absorbance at 234 nm, lipid peroxides, and malondialdehyde showed an increased resistance against oxidation after repeated LDL apheresis. This phenomenon was also observed in the oxidative indexes of protein moiety of LDL (apolipoprotein-B100 fragmentation, trinitrobenzenesulfonic acid reactivity, and electrophoresis agarose mobility). Similarly, cholesteryl esterification was decreased after LDL apheresis. Thus selective LDL apheresis not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation. This phenomenon might contribute to reduce coronary atherosclerosis and thus mortality of these particular patients.

Apolipoprotein B-100↗