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Biomedical subjects

G Esposito

Publications and source records attributed to G Esposito.

At least 127 records · Page 7Linked to original sources
PubMed1997

Effects of allopurinol on striatal dopamine, ascorbate and uric acid during an acute morphine challenge: ex vivo and in vivo studies.

In the present study in vivo and ex vivo experiments were combined to evaluate the effects of allopurinol on the neurochemical changes induced by an acute morphine challenge (2 mg kg-1, s.c.). In samples from rat striatum, levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), ascorbate (AA), dehydroascorbate (DHAA), hypoxanthine, xanthine and uric acid (UA) were measured. Brain microdialysis experiments were carried out in freely moving rats. Striatal dialysate levels were assayed for DA, DOPAC + HVA, AA and UA using liquid chromatography followed by electrochemical detection. Morphine administration increased the striatal levels of DA metabolites, UA and DHAA and the extracellular concentrations of DA, DOPAC + HVA, UA and AA. Allopurinol (50 mg kg-1 by gavage), an inhibitor of xanthine oxidase which catalyses oxidation of xanthine to UA, decreased basal UA and AA concentrations and the morphine-induced increase in DA metabolites and AA oxidation. Since oxidation of DA and xanthines generates reactive oxygen species (ROS) and AA and UA are the main cellular antioxidants, these findings suggest that: (a) single morphine administration increases DA and xanthine oxidative metabolism with a consequent increase in ROS production, which may account for changes in concentrations of extracellular AA and tissue DHAA; (b) allopurinol decreases morphine-induced DA and xanthine oxidation; (c) UA and AA may act in concert to regulate levels of ROS in the brain.

Allopurinol↗
PubMed1997

Glutathione deficiency potentiates manganese toxicity in rat striatum and brainstem and in PC12 cells.

Levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), glutathione (GSH), ascorbic acid (AA), dehydroascorbic acid (DHAA) and uric acid (UA) were determined in the striatum and/or in the brainstem of 3-month-old male Wistar rats after subchronic oral exposure to MnCl2 (20 mg kg-1 daily) alone or associated to buthionine (S,R)sulphoximine-ethyl ester (BSO-E), an inhibitor of GSH synthesis. The NA, DA, DOPAC, GSH and glutathione disulphide (GSSG) concentrations were also determined in PC12 cells incubated with Mn alone or associated with either BSO-E or AA. When PC12 cells were incubated with AA, cellular AA and DHAA concentrations were also determined. It was found that BSO-E: (a) decreased GSH levels in the striatum and in the brainstem; (b) potentiated the Mn-induced increase in AA oxidation and uric acid formation in both brain regions; and (c) potentiated the Mn-induced DA and NA depletion in the brainstem. Moreover, the changes in striatal DA metabolism induced by the BSO-E association with Mn (decrease in DA, DOPAC and HVA levels and in the DOPAC + HVA/DA ratio) are consistent with the hypothesis of a loss of dopaminergic neurons. In PC12 cells, BSO-E decreased GSH and GSSG levels and potentiated the Mn-induced decrease-in DA and NA concentrations. On the contrary, AA antagonised the Mn-induced DA and NA depletion. AA antagonised also the Mn- and MN+ BSO-induced decrease in PC12 cells viability. In conclusion, the impairment of neuronal antioxidant system activity plays a permissive role in the oxidative stress-mediated Mn neurotoxicity.

Animals↗
PubMed1997

In vivo gene transfer: prevention of neointima formation by inhibition of mitogen-activated protein kinase kinase.

BACKGROUND: The mitogen-activated protein kinase kinase (MAPKK) is a protein downstream ras which is rapidly activated in cells stimulated with various extracellular signals. These proteins are believed to play a pivotal role in integrating and transmitting transmembrane signals required for cell growth. METHODS AND RESULTS: To study the effect of inhibition of MAPKK on smooth muscle cell (SMC) proliferation in vivo after vascular injury, we performed experimental balloon angioplasty using the standard Clowes technique in male Wistar rats 14-weeks old. The animals did not receive any treatment after vascular injury (N = 6) or were randomly assigned to receive, after balloon injury, a 30% (w/v) pluronic gel solution applied to the injured carotid artery, containing respectively: 1) no plasmid DNA (n = 10); 2) RSV-lacZ (encoding the beta-galactosidase gene) as control gene without effects on SMC proliferation (n = 10); 3) Tg-CAT (encoding cloramphenicol acetyl-transferase gene under the control of thyreoglobulin promoter) as an additional control gene without effects on SMC proliferation (n = 7): 4) a negative mutant of Mitogen-Activated Protein Kinase Kinase (MAPKK-) (n = 13). Fourteen days after vascular injury, carotid arteries were removed and cross sections were cut and stained with hematoxylin/eosin. Morphometric analysis demonstrated, in the MAPKK- treated rats, a significant reduction of both neointima (0.096+/-.018 mm2 vs. 0.184+/-0.019 mm2, p < 0.01) and neointima/media ratio (0.603+/-0.103 vs. 1.471+/-0.161, p < 0.01) compared to control DNA. CONCLUSIONS: The inhibition of MAPKK, by a dominant inhibitor mutant gene, prevents the SMC proliferation after vascular injury in vivo.

Animals↗
PubMed1997

Complications of pediatric laparoscopic surgery.

BACKGROUND: Surgical complications of laparoscopy most often occur during Veress needle or primary trocar placement. Veress needle punctures are insignificant and require no further treatment, whereas trocar-induced vascular injuries can be catastrophic. The frequency of vascular and viscus injuries is difficult to calculate because several complications are not reported in the literature. METHODS: During a 10-year-period (1984-1995), at the Division of Pediatric Surgery at "Federico II" University of Naples, 430 laparoscopic procedures were performed in 395 children with a mean age of 5 years. The incidence of complications related to laparoscopy was 1.8% with eight complications, one of which was rather severe. The complications included one abdominal wall hematoma, two perforations of abdominal viscus (stomach, ovary), one umbilical scar complication, one postoperative hydrocele, one subcutaneous emphysema, and one pneumothorax during a Nissen procedure. The only severe complication occurred in a young girl with neurologic problems and a kyphoscoliosis operated on via laparoscopy for a gastroesophageal reflux. She suffered injuries of both right common iliac vessels and several intestinal perforations due to blind introduction of the first umbilical trocar. RESULTS: In this case rapid conversion, complex vascular reconstruction, and multiple intestinal sutures were performed. The Nissen fundoplication with pyloroplasty was performed traditionally and the patient left the hospital free of symptoms after 20 days. The other seven complications were resolved without any problem intra- or postoperatively. CONCLUSIONS: The authors believe that the open approach with a blunt trocar is most important in helping to avoid complications in pediatric laparoscopy.

Adolescent↗
PubMed1997

Recombinant human antibodies specific for hepatitis C virus proteins.

Human antibodies to hepatitis C virus core, NS4A and NS3 were cloned in a prokaryotic vector and expressed as soluble Fab fragments and as phage-displayed Fabs. The recombinant Fabs were shown to be a suitable tool for immunohistochemistry, since they recognize the cognate antigen expressed in mammalian cells. The nucleotide sequence of the cDNA for the variable domains of these antibodies was determined and the V-gene usage was derived. On the basis of the deduced amino acid sequence, a structural model of the V domains of the Fabs was constructed.

Antibody Specificity↗
PubMed1997

Probing protein structure by solvent perturbation of NMR spectra: the surface accessibility of bovine pancreatic trypsin inhibitor.

In the absence of specific interactions, the relative attenuation of protein NMR signals due to added stable free radicals such as TEMPOL should reflect the solvent accessibility of the molecular surface. The quantitative correlation between observed attenuation and surface accessibility was investigated with a model system, i.e., the small protein bovine pancreatic trypsin inhibitor. A detailed discussion is presented on the reliability and limits of the approach, and guidelines are provided for data acquisition, treatment, and interpretation. The NMR-derived accessibilities are compared with those obtained from x-ray diffraction and molecular dynamics data. Although the time-averaged accessibilities from molecular dynamics are ideally suited to fit the NMR data, better agreement was observed between the paramagnetic attenuations of the fingerprint cross-peaks of homonuclear proton spectra and the total NH and H alpha accessibilities calculated from x-ray coordinates, than from time-averaged molecular dynamics simulations. In addition, the solvent perturbation response appears to be a promising approach for detecting the thermal conformational evolution of secondary structure elements in proteins.

Amino Acid Sequence↗
PubMed1997

Hydrogen-deuterium exchange studies of the rat thyroid transcription factor 1 homeodomain.

The 1H NMR solution structure of the rat thyroid transcription factor 1 homeodomain (TTF-1 HD) showed that the molecule folds like classical homeodomains. The C-terminal extension of helix III (fragment 51-59) appeared to adopt a helical geometry, albeit not as rigid as the preceding portion, but the hydrogen-deuterium exchange of backbone amides and the NOE data provided evidence of a discontinuity between the two moieties of helix III at the highly conserved fragment Asn51-His52-Arg53. Analysis of quantitative measurements of isotope exchange rates allows one to recognize the general occurrence, in that region of HD motifs, of opposite effects to helix III stability. Asparagine, histidine and arginine residues occur most frequently at the beginning and end of protein helices. In TTF-1 HD a local fluctuation is observed in the fragment 51-53 which either kinks or tightens the alpha-helix. A search through the protein structure database reveals that the three most common variants of HD fragments 51-53 are often involved in helices and, frequently, in helix initiation or termination. For homeodomains in general, the nature of the fragment 51-53 may be related to the conformational dynamics of their DNA-recognition helix (helix III). Besides the specific results on fragment 51-53, the complete isotope exchange analysis of TTF-1 HD data shows that the partially solvent-exposed recognition helix is stabilized by hydrophobic interactions, like most of the structured regions of the molecule. Hydrophobic stabilization of the contacting regions meets the requirements of a DNA-interaction mechanism which, as shown with other DNA-protein complexes, should entail negative heat capacity variations due to changes in solvent exposure of the nonpolar protein surface.

Amides↗
PubMed1997

Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury.

Injury of the arterial wall induces the formation of the neointima. This structure is generated by the growth of mitogenically activated smooth muscle cells of the arterial wall. The molecular mechanism underlying the formation of the neointima involves deregulated cell growth, primarily triggered by the injury of the arterial wall. The activated gene products transmitting the injury-induced mitogenic stimuli have been identified and inhibited by several means: transdominant negative expression vectors, antisense oligodeoxynucleotides, adenovirus-mediated gene transfer, antibodies and inactivating drugs. Results of our study show that local administration of 3',5'-cyclic AMP and phosphodiesterase-inhibitor drugs (aminophylline and amrinone) to rats markedly inhibits neointima formation after balloon injury in vivo and in smooth muscle cells in vitro. The growth inhibitory effect of aminophylline was completely reversed by the inhibition of cAMP-dependent protein kinase A (PKA). These findings indicate an alternative approach to the treatment of diseases associated with injury-induced cell growth of the arterial wall, as stimulation of cAMP signaling is pharmacologically feasible in the clinical setting.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Oestradiol and testosterone blood levels in patients with viral cirrhosis and hepatocellular carcinoma.

BACKGROUND: Patients with alcoholic cirrhosis show hypogonadism and feminization associated with sex hormone imbalance due to enhanced aromatization of testosterone and subsequent reduced testosterone and increased oestradiol blood levels. Because oestrogens modulate hepatocyte proliferation and oestrogen receptors are present in liver cirrhosis and hepatocellular carcinoma, it has been proposed that sex hormone imbalance can play a role in liver carcinogenesis. Trials with the oestrogen receptor antagonist tamoxifen have been performed with conflicting results. OBJECTIVES: To investigate oestradiol and testosterone blood levels in men with viral cirrhosis and hepatocellular carcinoma and also to investigate changes in sex hormone circulating levels induced by tamoxifen treatment. PATIENTS AND METHODS: Oestradiol and testosterone blood levels were evaluated in 32 male patients with postviral cirrhosis and hepatocellular carcinoma at the time of diagnosis and during the follow-up, and in 20 healthy controls. In eight patients, hormone levels were also assayed during treatment with tamoxifen (40 mg/day). No patient had a history of high alcohol intake. RESULTS: Oestradiol values observed at the time of diagnosis were 56.1 +/- 54.5 pmol/l, while testosterone values were 13.6 +/- 8.0 pmol/l. There was no relationship between oestrogen values and age, while higher oestradiol values were observed in patients with advanced cirrhosis (Child B and C); conversely, testosterone levels progressively and significantly decreased from cirrhosis Child A (15.1 +/- 9.7) to C (7.7 +/- 7.1) (P < 0.05). Tamoxifen treatment (40mg/day) for 1 month in eight patients increased oestradiol values (62.2 +/- 77.0 vs. 156.4 +/- 83 pmol/l, P < 0.05), while testosterone levels decreased (15.1 +/- 6.8 vs. 8.5 +/- 10.6 pmol/l). However, these changes were not associated with clinical signs or symptoms of feminization. Oestrogen levels decreased after 6 months of tamoxifen treatment. No significant change in hormone levels was observed in patients not treated with tamoxifen. Unlike patients with alcoholic cirrhosis, in male patients with viral cirrhosis and hepatocellular carcinoma there were no significant alterations in blood oestradiol and testosterone levels, although a certain degree of sex hormone imbalance was observed in those with advanced cirrhosis. Treatment with tamoxifen (40 mg/day) did not induce clinical manifestations of sex hormone imbalance.

Age Factors↗
PubMed1997

Longitudinal monitoring of bone mineral density in thalassemic patients. Genetic structure and osteoporosis.

The changes in bone mineral density (BMD) measured by single photon absorptiometry (SPA) using two observations conducted over a period of 2 years were examined in 54 thalassemic subjects [30 F(A) and 24 M(B)] with a chronological age ranging from 2.6 to 22.6 years and in 27 sex- and age-matched controls (C). Each category (A, B and C) was divided into three groups according to pubertal signs: pre-pubertal subjects (A1, B1 and C1); peri-pubertal subjects (A2, B2 and C2) and pubertal subjects from the first observation (A3, B3 and C3). Furthermore, each group of patients was divided into sub-groups on the basis of haematological phenotypes, those with a more severe form were called beta0/beta0 while those with other forms were called "others". The most significant findings were the following: the presence of a more severe reduction of the bone mineral density in patients with the beta0/beta0 phenotype than in patients with the "others" phenotype; patients with hypogonadism corresponded to the beta0/beta0 phenotype, while those with spontaneous puberty corresponded to the "others" phenotype. In conclusion, since puberty and the degree of bone mineral density are related to the haematological phenotype, puberty (spontaneous or induced) positively influences the bone mineral density only at the start of puberty, while subsequently, the degree of osteoporosis is the expression of widespread and chronic systemic damage due to the haematological phenotype.

Adolescent↗
PubMed1997

Laparoscopic adjustable silicone gastric banding: preliminary results of the University of Naples experience.

BACKGROUND: Laparoscopic adjustable silicone gastric banding (LASGB) is a minimally invasive surgical procedure indicated for the treatment of patients with morbid obesity. METHODS: From January 1996, eight patients successfully underwent the video-laparoscopic procedure. RESULTS: Preoperative body mass index was 44.4 +/- 4.7 (range 37.9-53.3). Mean operative time was 255 +/- 73 minutes (range 150-360). Mean hospital stay was 3 +/- 1 days. Intraoperative complications were absent. CONCLUSION: Preliminary results have been satisfactory, and encourage us to continue with LASGB.

Adult↗
PubMed1997

[Implantation of the Palmaz-Schatz stent in coronary vessels irrigating and non-irrigating necrotic myocardial areas: comparison of acute results and at mid-term].

Recent evidence suggests that higher restenosis rate is observed after coronary angioplasty of an infarct-related artery. Furthermore, angiographic restenosis seems associated with a deterioration of left ventricular function at follow-up. The aim of this study was to assess the acute results and angiographic restenosis following coronary artery stenting of infarct-related (Group 1) and non infarct-related coronary arteries (Group 2). We retrospectively analyzed the results of 381 consecutive patients treated with Palmaz-Schatz coronary stent implantation between May 1992 and January 1996. Stenting of the infarct-related artery was performed in 154 patients (Group 1), while 227 patients (Group 2) received stenting of the non infarct-related artery. Both groups had similar age, gender, clinical conditions and coronary angiographic pattern. There were no significant differences between groups, concerning type of stented coronary vessel (left anterior descending-LAD 52.4% vs non-LAD 47.6%, Group 1, LAD 59.5% vs non-LAD 40.5%, Group 2) and number of stents per patient (1.31 +/- 0.48 in Group 1, 1.18 +/- 0.56 in Group 2) and per coronary vessel (1.17 +/- 0.54 in Group 1, 1.09 +/- 0.46 in Group 2). The procedure was performed using similar maximal inflation pressures in both groups (13.3 +/- 2.9 atm in Group 1, 13.40 +/- 3.17 atm in Group 2). Technical success was achieved in 96.8% of Group 1 and in 96% of Group 2 patients. Acute coronary stenting success and major adverse events (acute myocardial infarction, emergency bypass, death) were similar in both groups of patients. No difference was found in restenosis rate at 6-month angiographic follow-up (Group 1 = 29.8%, Group 2 = 27%). In conclusion, this study indicates that stenting of infarct and non infarct-related coronary arteries has similar success and 6-month restenosis rates.

Coronary Circulation↗
PubMed1997

Pivagabine: a novel psychoactive drug.

Pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg) is a metabolically stable compound with a modulatory effect on some biochemical parameters involved in stress conditions (corticotropin releasing factor, neurosteroids). The compound, tested in several animal models, prevents stress-correlated behavioural deficits. Moreover, pivagabine has a highly significant therapeutic potential in clinical conditions characterized by manifestations of psychological distress due to an inadequate management of stressful events.

Animals↗
PubMed1996

Analysis of the solution structure of the homeodomain of rat thyroid transcription factor 1 by 1H-NMR spectroscopy and restrained molecular mechanics.

The solution structure of the rat thyroid transcription factor 1 (TTF-1) homeodomain has been elucidated by 1H-NMR and restrained modeling. The TTF-1 homeodomain folds in the same manner as classical homeodomains, with three helices, a loose loop between the first two helices, and a tight turn between helix II and helix III. The typical assembly of the hydrophobic core is maintained and N-capping motifs are identified in helix I and helix III. The N-terminal stretch of helix II exhibits some mobility, similar to the preceding loop region, which may be related to its anomalous capping. The N-terminal decapeptide and the C-terminal octapeptide of the molecule (68 residues long) are disordered. All the previous characteristics are shared by all known isolated homeodomain structures. An important difference among these structures occurs at the C-terminal extension of helix III, which is either disordered or helically folded. In the TTF-1 homeodomain, the C-terminal extension of helix III (residues 51-59) appears structured, albeit not as rigidly as the preceding portion. Analysis of the NOEs and hydrogendeuterium exchange of backbone amides provides evidence for discontinuity between the two moieties of helix III, which is introduced by a tightening or a kink of residues 51-53.

Animals↗
PubMed1996

A molecular code dictates sequence-specific DNA recognition by homeodomains.

Most homeodomains bind to DNA sequences containing the motif 5'-TAAT-3'. The homeodomain of thyroid transcription factor 1 (TTF-1HD) binds to sequences containing a 5'-CAAG-3' core motif, delineating a new mechanism for differential DNA recognition by homeodomains. We investigated the molecular basis of the DNA binding specificity of TTF-1HD by both structural and functional approaches. As already suggested by the three-dimensional structure of TTF-1HD, the DNA binding specificities of the TTF-1, Antennapedia and Engrailed homeodomains, either wild-type or mutants, indicated that the amino acid residue in position 54 is involved in the recognition of the nucleotide at the 3' end of the core motif 5'-NAAN-3'. The nucleotide at the 5' position of this core sequence is recognized by the amino acids located in position 6, 7 and 8 of the TTF-1 and Antennapedia homeodomains. These data, together with previous suggestions on the role of amino acids in position 50, indicate that the DNA binding specificity of homeodomains can be determined by a combinatorial molecular code. We also show that some specific combinations of the key amino acid residues involved in DNA recognition do not follow a simple, additive rule.

Animals↗