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Biomedical subjects

G Esposito

Publications and source records attributed to G Esposito.

At least 199 records · Page 11Linked to original sources

Free energies calculated according to Manning's polyelectrolyte model compared with Poisson Boltzmann predictions.

The values of the different terms contributing to the free energy of a polyelectrolyte in ionic solution, calculated according to Manning's model are compared with those predicted by the Poisson-Boltzmann(P-B) equation solved for the cell model. On this ground, the limits of applicability of Manning's model and some of its features are discussed. The comparison confirms the usefulness of Manning's model for low charge density polyelectrolytes, while for higher charge densities some care should be used due to the breakdown of the approximations underlying the model.

Computer Simulation↗

Homology model building of the thyroid transcription factor 1 homeodomain.

A possible structure for the homeodomain of rat thyroid transcription factor 1 is proposed on the basis of the homology with other homeodomains whose structures have been solved by X-ray crystallography. A structure very similar to the reference ones is feasible and may account for the observed DNA-binding specificity. Structural features of the model, which are likely to be shared by other homeodomains, are discussed and may help researchers in the field to analyse their own experimental data.

Amino Acid Sequence↗

The molecular basis of hereditary fructose intolerance in Italian children.

We investigated the molecular defects of the aldolase B gene in five unrelated patients affected by hereditary fructose intolerance. The techniques used were DNA amplification, direct sequencing and allele-specific oligonucleotide (ASO) hybridization. The most frequent substitutions found in the hereditary fructose intolerance alleles analysed were the A174D and the A149P mutations, which account for 50% and 30% of the alleles, respectively. In two unrelated families, we found a rare mutation, the MD delta 4 previously described only in one British family, which may be an important cause of the disease in Italy.

Base Sequence↗

Reconstruction of ischial pressure ulcers by skin expansion.

Ten patients, eight of whom were paraplegic, have had ischial pressure ulcers treated by skin expansion. Skin expanders 680 ml in size were inserted subcutaneously on the posterior aspect of the thigh. They were filled during a short period without complications, the filling being monitored with a cutaneous tonometer. At a second operation the ulcers were repaired easily with the expanded flaps. After a few weeks the patients were able to undergo a programme of rehabilitation that included sitting with the expanded flaps. No ulcers recurred during a median follow-up of 12 months (range 8-34).

Adult↗

[The effects of the selective intracoronary administration of nifedipine on left ventricular filling anomalies during coronary angioplasty].

Eighteen patients with isolated stenosis of left anterior descending artery, were randomly given 0.2 mg of nifedipine (Group II) or its solvent (Group I) via balloon catheter positioned across the lesion immediately prior balloon occlusion. Peak velocity of early (E peak) and late (A peak) filling, velocity flow integral at early (E area) and late (A area) filling and their ratios (by echo-Doppler) and heart rate, mean aortic and wedge (W) pressures were measured at baseline, 15 and 30 s during balloon occlusion and 10 min after balloon deflation. In Group I we observed a significant decrease in either E peak at 15 and 30 s (-24.7%, -29.3% respectively) and E area (-32.8%, -40.0% respectively) with a non significant increase in both A peak and A area. Accordingly, either E/A peak ratio and E/A area ratio decreased significantly. In Group II no significant changes were observed in the echo-Doppler parameters of left ventricular filling. Wedge pressure also significantly increased in Group I at 15 and 30 s (68.7% and 97.9% respectively), while a significant increase in Group II occurred only at 30 s (32.5%). Heart rate significantly increased only in Group I at 15 and 30 s (10.3% and 11% respectively), while aortic pressure remained unchanged in both groups. Thus, nifedipine given intracoronary in the post-stenotic area just before balloon occlusion prevents left ventricular filling dynamic alteration by preserving early filling.

Adult↗

[Coronary vasoconstriction induced by digoxin in normal subjects and in patients with coronary atherosclerosis].

This study evaluated the effects of digoxin infusion (0.014 mg/kg in 10 min i.v.) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (aged 47 +/- 12), divided in 3 groups were studied. The effects of digoxin infusion (after 10 and 20 min) and sublingual administration of isosorbide dinitrate were investigated in Group I (patients with angiographically normal coronary arteries, n = 9) and in Group II (patients with atherosclerotic coronary arteries, n = 8). In Group III (n = 5) to determine whether or not the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiographies were performed after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, i.v.). In Group I, 10 min after the end of digoxin infusion, cross-sectional area decreased from 7.7 +/- 4.1 mm2 to 6.0 +/- 2.2 mm2, and after 20 min to 5.6 +/- 2.6 mm2 (p < 0.05). Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (NS versus baseline). By 20 min after digoxin infusion heart rate was significantly reduced from 79 +/- 16 to 74 +/- 13 b/min (p < 0.01). Peripheral vascular resistances increased significantly 10 min after digoxin infusion (from 1396 +/- 693 to 1693 +/- 984 dyne*s*cm-5, p < 0.05), whereas cardiac output did not change. In Group II, minimal stenosis diameter decreased significantly 20 min after digoxin infusion from 1.6 +/- 0.5 mm to 1.4 +/- 0.5 mm (p < 0.05). Again, isosorbide dinitrate reverted digoxin-induced vasoconstriction as minimal stenosis diameter increased (NS versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Importance of cleansing in the topical treatment of skin lesions. A parallel study carried out in 20 patients and 30 rats].

There are frequent reports of the chronic nature of skin ulcers of varying etiology (burns, bedsores, wound diastasis, etc.); these heal with considerable difficulty probably due to problems related to the excessive use of disinfectants which, in spite of having a good bacterial action, interfere with re-epithelialisation processes. The aim of this study was to assess the value of simple wound cleansing instead of disinfection in those cases where there are no manifest signs of bacterial contamination. A widely sold solution, Katoderm (Devergè, Turin), was used in this study. The study was performed in two stages; the first in laboratory animals and the second in patients with small persistent lesions. The results of the study carried out in rats showed a significant prolongation of healing time in the group treated with polyvinylpyrrolidone-iodine compared to those in which lesions were only cleansed with Katoderm. The results of the clinical study also highlighted the faster speed of healing in patients treated with cleansing alone.

Administration, Topical↗

The gene encoding for MC56 determinant (drug-sensitivity marker) is located on the short arm of human chromosome 11.

A panel of mouse x human B- and T-cell hybrids was analyzed for the expression of MC56 determinant which marks the drug-sensitive state of CEM cells. Karyotypic and phenotypic analyses of the tested clones showed that the expression of MC56 determinant correlated to the presence of human chromosome 11 and segregated concordantly to the epitopes recognized by monoclonal antibodies in the CD44 cluster. By using a particular class of interspecific rodent x human-cell hybrids in which the human genome counterpart is represented in the different clones only by human chromosome 11 or its fragments, we showed that the gene encoding for MC56 determinant is located on the region p13-pter of the short arm of chromosome 11. Therefore, the hypothesized homology between the drug-sensitivity marker MC56 and the CD44 determinant is supported also by gene mapping studies.

Biomarkers↗

Effects of cortical ablation on apomorphine- and scopolamine-induced changes in dopamine turnover and ascorbic acid catabolism in the rat striatum.

Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid and dehydroascorbic acid (DHAA) were measured by HPLC in the striatum of rats whose fronto-parietal cortex had been unilaterally ablated after a single injection of apomorphine (1 mg/kg s.c.), scopolamine (0.6 mg/kg s.c.) or L-glutamate (500 mg/kg i.p.). Unilateral cortical ablation decreased striatal levels of glutamate in both striata ipsilateral (35%) and contralateral (17-25%) to the lesion. Apomorphine and scopolamine significantly increased (+94 and +122%, respectively) the DHAA/ascorbic acid ratio in the striata ipsilateral to the lesion in unoperated and sham-operated rats (+72 and +34%, respectively), but both drugs failed to increase it in ablated rats. L-Glutamate significantly increased the DHAA/ascorbic acid ratio in unoperated (+53%) and ablated rats (+37%). The increase in sham-operated rats (+34%) did not reach statistical significance. Apomorphine and scopolamine significantly decreased the DOPAC/DA ratio in the striata ipsilateral to the lesion of unoperated, sham-operated and ablated rats. The decrease in the DOPAC/DA ratio induced by apomorphine and scopolamine was greater in ablated rats than in sham-operated rats. L-Glutamate induced only minor changes in striatal DA and DOPAC levels. We conclude that the apomorphine- and scopolamine-induced increase in ascorbic acid oxidation in the striatum requires intact cortico-striatal glutamatergic pathways. Cortical ablation potentiates the apomorphine- and scopolamine-induced inhibition of striatal DA turnover.

3,4-Dihydroxyphenylacetic Acid↗

NMR structural characterization of the reaction product between d(GpG) and the octahedral antitumor complex trans-RuCl2(DMSO)4.

The reaction between the antitumor octahedral complex trans-RuCl2(DMSO)4 and d(GpG) leads to the formation of a stable compound characterized by a covalent bifunctional coordination of the bases to the metal center. The structure of the compound has been fully characterized by NMR and molecular modeling studies, showing the presence of two N7-coordinated guanine moieties in a head to head conformation, two dimethyl sulfoxide molecules, and one halogen atom in the coordination sphere of the ruthenium. The glycosidic chi angles are essentially in the anti range, the sugar puckering of the 5'G is 3'-endo (100% N), whereas that of the 3'G is more flexible but mainly in 2'-endo conformation (85% S), the two bases are strongly destacked. The compound shows structural features which are surprisingly similar to those exhibited by the corresponding cisplatin complex, indicating that such a way of interaction with DNA is not exclusive to Pt or to metals with square planar coordination geometries.

Antineoplastic Agents↗

The effects of cortical ablation on d-amphetamine-induced changes in striatal dopamine turnover and ascorbic acid catabolism in the rat.

Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels were determined by HPLC in the striatal synaptosomal fraction and in the whole striatum of rats, whose fronto-parietal cortex had been bilaterally ablated, after a single injection of d-amphetamine (2.0 mg/kg i.p.). d-Amphetamine significantly increased the DHAA/AA ratio in unoperated and sham-operated rats, but failed to increase it in ablated rats, as compared to pertinent saline-treated groups. In the synaptosomal fraction, d-amphetamine significantly decreased the DHAA/AA ratio in unoperated, sham-operated and ablated rats. d-Amphetamine significantly decreased the DOPAC/DA ratio in the whole striatum and significantly increased it in the striatal synaptosomal fraction in all experimental groups. Cortical ablation greatly increased d-amphetamine-induced motor hyperactivity. We conclude that the d-amphetamine-induced increase in AA striatal oxidation requires integrity of the cortico-striatal glutamatergic pathways. Further, AA oxidation occurs in the extracellular space. The cortico-striatal glutamatergic pathways exert an inhibitory modulation on d-amphetamine behavioral effects.

3,4-Dihydroxyphenylacetic Acid↗

Probing protein structure by solvent perturbation of nuclear magnetic resonance spectra. Nuclear magnetic resonance spectral editing and topological mapping in proteins by paramagnetic relaxation filtering.

Soluble spin labels, which "bleach" the surface proton resonances of a protein to n.m.r. measurements, can provide useful information about protein conformation and dynamics. The use of the soluble nitroxide, TEMPOL, has been explored to show the correlation of the paramagnetic perturbations of protein two-dimensional n.m.r. data with proton exposure to the free radical in hen egg-white lysozyme. The results demonstrate that the nitroxide approaches the protein randomly, and that the extent of the observed paramagnetic effects reflects the native folding pattern of the protein. A correlation of spectral simplification with the known tertiary structure establishes the feasibility of new strategies for topological mapping of surface and buried protons of the protein. Application to the elucidation of protein structure and to the study of dynamical processes is discussed.

Amino Acid Sequence↗

Double-blind controlled trial of progesterone vaginal cream treatment for cyclical mastodynia in women with benign breast disease.

The clinical effectiveness and safety of vaginal micronized progesterone treatment in mastodynia were evaluated in a double-blind placebo controlled study. Eighty regularly menstruating women affected by severe cyclical mastodynia were randomly assigned to two groups of 40 patients. One group was treated for 6 cycles from the 19th to the 25th day of the cycle with 4 g of vaginal cream containing 2.5% natural progesterone. The other group was similarly treated with placebo. The treatment was preceded by a control cycle. All patients reported every day their breast pain on a 100 mm visual linear analogue scale (VAS). The response of breast tenderness and nodularity to treatment was assessed by clinical examination. Vaginal progesterone resulted significantly more efficacious than placebo in reducing mean ratings of breast pain on VAS and mean scores of breast tenderness to touch. Success of treatment, defined as reduction greater than 50% of basal mean score of breast pain on VAS, was achieved in the 64.9% of patients treated with progesterone and in the 22.2% of patients receiving placebo (p < 0.01). Conversely, at the end of treatment, the improvement in breast nodularity showed a not statistically significant difference between the two groups. No major side-effects were detected.

Adult↗

Induced crossing-over in Drosophila melanogaster germ cells of DNA repair-proficient and repair-deficient (mei-9L1) males following larval feeding with 5-azacytidine and mitomycin C.

The effects of 5-azacytidine (5-AZ) and mitomycin C (MMC), administered by larval feeding, on crossing-over were measured in Drosophila melanogaster male germ cells of a DNA repair-proficient and a repair-deficient (mei-9L1) strain. Both 5-AZ and MMC are effective inducers of male crossing-over. The estimated number of induced recombination events was higher in repair-proficient than in mei-9L1 males. The apparently lower sensitivity of mei-9L1 males to crossing-over induction may be the result of an incomplete crossing-over process.

Animals↗

Management of patients with ovarian cancer using monoclonal antibodies.

We describe in detail the current trend using monoclonal antibodies to diagnose ovarian cancer either in vitro or in vivo. The approach with such powerful reagents allows to differentiate in vitro tumor histotypes and to detect in peritoneal washings the presence of a few neoplastic cells which characterize the minimal disease. The detection of elevated sera levels of ovarian cancer-associated antigens, such as CA-125 and TAG-72, allows the monitoring, follow-up of these patients and the response to therapy with great accuracy. We focused our attention on the role in vivo of labelled monoclonal antibodies, mainly for diagnostic purposes. Radioimmunoscintigraphy has been found to be more reliable than CT and US to detect foci of disease mainly in patients already treated by surgery, overcoming all the problems usually encountered with these two procedures.

Antibodies, Monoclonal↗

Transforming growth factor beta 1 inhibits gonadotropin action in cultured porcine Sertoli cells.

In the present study, we have tested the effects of transforming growth factor beta 1 (TGF beta 1) on FSH action toward aromatase activity and lactate production in cultured Sertoli cells isolated from immature porcine testes. Whereas treatment of Sertoli cells with FSH resulted in a dose-dependent increase (about 7-fold) in aromatase activity (conversion of testosterone into estradiol) (ED50 = 80 ng/ml FSH), the addition of TGF beta 1 reduced this gonadotropin action. The inhibitory effect of TGF beta 1 on FSH aromatase activity was dose dependent (ED50 = 0.1 ng/ml, 4 pM TGF beta 1) with a maximal decrease (about 40%) observed after a long term (48-h) treatment. TGF beta 1 exerted its inhibitory effect on FSH action at the level(s) of cAMP accumulation, exerting no apparent effect on the gonadotropin receptor or at a site(s) related to cAMP action. TGF beta 1 (2 ng/ml) significantly (P less than 0.002) reduced (52% decrease) FSH-stimulated cAMP levels in cultured porcine Sertoli cells. However, such an inhibitory effect of the growth factor was no longer observed when stimulation of cAMP accumulation with FSH occurred in the presence of methyl isobutyl xanthine (0.5 mM), an inhibitor of cAMP-phosphodiesterase activity. This observation suggests that TGF beta 1 decreased cAMP levels by increasing catabolism of the cyclic nucleotide through an enhancement of cAMP-phosphodiesterase activity. The inhibitory effect of TGF beta 1 was not limited to the action of FSH on aromatase activity but also extended to the gonadotropin action (mediated by cAMP) on lactate production. As for the inhibitory effect of TGF beta 1 on FSH-induced aromatase activity, the inhibitory effect of the growth factor on FSH-stimulated lactate production was dose and time dependent with a maximal decrease (about 30%) observed in the picomolar range (1 ng/ml, 40 pM) after 48 h treatment with TGF beta 1. In conclusion, the present study demonstrates that TGF beta 1 attenuates FSH action on Sertoli cell activity and that such inhibitory action is potentially exerted through a decrease in cAMP levels. Because of the local production of TGF beta 1, it is suggested that the effects of the growth factor reported here might be exerted in the context of the testicular paracrine mechanisms.

1-Methyl-3-isobutylxanthine↗

[Effect of alpha-adrenergic receptor blockade on peripheral vasoconstriction induced by the cold pressor test. Evidence for functional integrity of alpha 1 and alpha 2 adrenergic receptors in patients with congestive heart failure].

Central sympathetic stimulation results in direct vascular vasoconstriction mediated by activation of alpha-adrenergic receptors. However, it is unknown whether this vasoconstriction is mediated by alpha 1 or alpha 2-adrenoceptor subtypes. In patients with congestive heart failure (CHF), both circulating and neuronally released catecholamines produces vasoconstriction via alpha-adrenergic stimulation. This vasoconstriction produces detrimental hemodynamic effect in CHF patients since it increases right and left ventricular filling pressures and pulmonary and systemic vascular resistances. While the myocardial alpha 1-adrenoceptors seems not to be down-regulated in heart failure, the functional integrity of vascular alpha 1 and alpha 2-adrenoceptors in CHF remains to be elucidated. Accordingly, the present study was designed to assess whether the limb vascular response to alpha 1 or alpha 2-adrenoceptor stimulation is impaired in patients with CHF. We studied 25 control subjects and 19 patients with CHF due to primary dilated cardiomyopathy. Forearm blood flow was measured by venous occlusion plethysmography. Sympathetic stimulation was produced by cold. The intraarterial pump-infusions of BHT 933 (a selective alpha 2-adrenoceptors agonist agent, 0.1, 1, 10 micrograms/kg/min for 5 min) produced the same peripheral vasoconstriction in CHF and in control subjects: 32 +/- 23.9%, 47.3 +/- 20% and 55 +/- 26.1% respectively at I, II, and III dose in CHF and 28.7 +/- 38.6%, 36 +/- 14.5%, and 57 +/- 13.8% respectively at I, II, and III dose in control subjects. The dose response to BHT 933 was not different in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗