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Biomedical subjects

P Simoni

Publications and source records attributed to P Simoni.

At least 37 records · Page 2Linked to original sources

Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study.

BACKGROUND: Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated. AIM: To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components. METHODS: One hundred and twenty-eight patients (68 males, 60 females, age 22-80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the 13C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities. RESULTS: All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT. CONCLUSIONS: (i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

Adult↗

Effects of body position on the carbon monoxide diffusing capacity in patients with chronic heart failure: relation to hemodynamic changes.

OBJECTIVE: Pulmonary diffusion has been found to be reduced in patients with congestive heart failure. The effects of postural changes on the diffusing capacity had been evaluated in healthy subjects, but not in patients with heart failure. The aim of this study was to evaluate the posture-induced changes in diffusing capacity in patients with chronic heart failure and their relation to the hemodynamic profile. METHODS: The pulmonary carbon monoxide diffusing capacity (DLCO) was measured in the supine position, with 20 degrees passive head elevation, and in the sitting position, both postures maintained for 10 min, in a group of 32 male patients with mild to moderate chronic heart failure due to left ventricular systolic dysfunction (ejection fraction <35%). On a separate day, in the absence of any changes in clinical status and therapy, the hemodynamic parameters were measured by right-heart catheterization. The sequence of postures was assigned randomly. RESULTS: The mean values of DLCO were slightly reduced and did not differ in the two positions (20.3 +/- 5.7 vs. 19.4 +/- 5.6 ml/min/mm Hg, 77 +/- 23 vs. 75 +/- 20% of predicted, respectively). The patients were then subdivided according to changes in DLCO from the supine to the sitting position: DLCO increased (+23%) in 9 patients (28%, group 1), decreased (-17.5%) in 17 patients (53%, group 2), and remained within the coefficient of reproducibility ( +/- 5 %) in 6 patients (group 3). As compared with group 2, group 1 patients showed a significant increase in mean pulmonary artery pressure (+7 vs. -15%, p < 0.01) and pulmonary capillary wedge pressure (+8 vs. -22%, p < 0.005) from the supine to the sitting position, while the cardiac index showed a smaller - but not significant - decrease in group 1 (-5 vs. -12%). The percent changes in DLCO significantly correlated with changes in pulmonary capillary wedge (r = 0.54, p < 0.0005) and mean pulmonary artery (r = 0.47, p < 0.005) pressures. CONCLUSIONS: In chronic heart failure postural changes may induce different responses in diffusing capacity. To a greater extent than in healthy subjects, the most common response is a decrease in DLCO in the sitting as compared with the supine position. The DLCO changes correlate with variations in pulmonary circulation pressure, probably due to changes in pulmonary vascular recruitment and pulmonary capillary blood volume.

Adult↗

In vivo determination of 5-bromo-2'-deoxyuridine incorporation into DNA tumor tissue by a new 32P-postlabelling thin-layer chromatographic method.

The halopyrimidine 5-bromo-2'-deoxyuridine (BUDR) can serve as one of many indicators of tumor malignity, complementary to histologic grade. We have developed a thin-layer chromatographic (TLC) technique that can assess tumor DNA base composition and analogue (BUDR) incorporation which vies with immunochemistry for BUDR. This requires post-labeling DNA by nick-translation and radioactive 5'-phosphorylation of representative 32P-alpha-dNMPs (deoxynucleotide monophosphates). Subsequent 3'-monophosphate digest exchanges a radioactive 32PO4 for the neighboring cold nucleotide. Separation in two dimensional PEI-cellulose TLC is carried out in acetic acid, (NH4)2SO4, and (NH4)HSO4. TLC of dNMPs was applied to control HeLa DNA, and HeLa cells receiving BUDR. BUDR is detected in 10(6) HeLa cells after 12-72 h incubations. Findings in HeLa DNA demonstrate normal TLC retention factors for all 32P-dNMPs. Two dimensional R(F) (x,y axes in cm) demonstrate: dAMP=1.4, 9.4; dCMP=10.0, 13.5; dGMP=4.6, 4.4; dTMP=9.0, 7.4; and BUDRMP 6.4, 6.6. This technique quantifies BUDR--which parallels tumor S phase, and serves as an indicator of labelling index (LI).

Bromodeoxyuridine↗

In vitro comparison of inhibiting ability of soluble TNF receptor p75 (TBP II) vs. soluble TNF receptor p55 (TBP I) against TNF-alpha and TNF-beta.

Tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin (LT, TNF-beta) are pleiotropic cytokines involved in diverse biologic processes, including immune and inflammatory reactions. The biologic responses to TNF are mediated through two forms of cell surface receptors, p55R and p75R. Both receptors exist in a soluble form (p55-sR or TBP I and p75-sR or TBP II), generated by the proteolytic cleavage of the extracellular regions of the molecule. These soluble forms may act by binding and, hence, neutralizing circulating TNF. In the present study, the murine A9 cell line in vitro bioassay was used to test TBP I and TBP II for their neutralizing activity against recombinant human TNF-alpha (rHu-TNF-alpha), and TNF-beta (rHu-TNF-beta) and recombinant murine TNF-alpha (rMu-TNF-alpha). Moreover, TBP I and TBP II were tested for their ability to displace TBP I in the TNF-TBP receptor binding assay (RIBA) against human and murine TNF-alpha as well as TNF-beta. TBP I, from either recombinant (from CHO and Escherichia coli) or urinary origin, was the most effective inhibitor with respect to rHu-TBP II (from CHO) against either human or murine TNF-alpha both in the A9 cells bioassay and in the RIBA assay. Both TBP I and TBP II preparations were less effective in protecting the A9 cells from the toxic effects of rMu-TNF-alpha than from those of rHu-TNF-alpha. The rHu-TBP II preparation was the most effective in inhibiting the cytocidal effect of rHu-TNF-beta on A9 cells and as active as TBP I in the RIBA assay. This result seems to indicate rHu-TBP II as the better soluble TNF receptor able to reverse the rHu-TNF-beta-induced toxicity, at least on A9 cells, leading to consideration of its therapeutic use in those diseases, such as multiple sclerosis, where a role for TNF-beta is indicated.

Animals↗

Long-term home care programmes may reduce hospital admissions in COPD with chronic hypercapnia.

Long-term oxygen therapy (LTOT) has been shown to improve survival in chronic obstructive pulmonary disease (COPD) patients. The clinical effectiveness of long-term home mechanical ventilation (HMV) is still discussed, nevertheless both LTOT and HMV are often included in the home care programmes of these patients. To evaluate the effectiveness of home care programmes including either HMV or LTOT, 34 COPD patients were studied. They were admitted to either HMV (Group A: 12 males and 5 females, aged 62 +/- 5 yrs), or LTOT (Group B: 9 males and 8 females, aged 62 +/- 8 yrs). They were compared to a historical group (Group C: 19 males and 10 females, aged 67 +/- 16 yrs) performing only their usual standard LTOT during the same period. Spirometry, maximal inspiratory pressure and arterial blood gas values were assessed at baseline and at 6, 12 and 18 months of follow-up. Mortality rate and number of hospital and intensive care unit (ICU) admissions and days of hospitalization were also assessed. Four out of 17 (23%) patients in Group A, 3 out of 17 (18%) in Group B, and 5 out of 29 (17%) in Group C died within 18 months. Of the lung function tests, only maximal inspiratory pressure in Group A showed a significant increase in the 18th month (50 +/- 4 to 56 +/- 7 cmH2O; p<0.01). In comparison to 18 months prior to the study, hospital admissions (from 2.2 +/- 0.6 to 1.3 +/- 1.1 and from 2.0 +/- 0.7 to 1.0 +/- 0.9 for Group A and B, respectively; p<0.005 for both), and days of hospitalization (from 60 +/- 34 to 34 +/- 40 and from 55 +/- 23 to 18 +/- 20 days in Group A and B, respectively; p<0.005 for both) significantly decreased only in the two groups submitted to the home care programme. We conclude that home care programmes may be effective in the long-term treatment of chronically hypercapnic chronic obstructive pulmonary disease patients in reducing hospital admissions.

Aged↗

Positive and negative effects of nuclear receptors on transcription activation by AP-1 of the human choline acetyltransferase proximal promoter.

We have examined the 5'-flanking region (944 bp) of the human choline acetyltransferase (hChAT) gene for sequences that modulate its transcriptional activity and identified a sequence 5'-TGACCCA-3' which confers c-Jun/c-Fos (AP-1) inducibility of homologous and heterologous promoters. Using transient transfections in neuroblastoma NE-1-115 and COS-1 cells, we show that ligand-activated estrogen receptor (HEGo) represses the transcriptional activation by c-Fos/c-Jun. Testing HEGo mutants in transfection assays reveals that the ligand-binding domain is crucial for this repression, whereas the N-terminal (A/B) region and the DNA-binding domain are not essential. Gel retardation assays show that the hChAT AP-1 recognition sequence binds in vitro baculovirus-produced c-Jun/c-Fos proteins. This binding is inhibited by addition of baculovirus-produced HEGo. In contrast to HEGo, ligand-activated glucocorticoid, androgen, and retinoic acid receptors (RARs) enhance the transcription activation induced by c-Jun/c-Fos. All three types of RARs--RAR alpha, beta, gamma--and RXR alpha are able to stimulate AP-1 activity on the proximal hChAT promoter. Several mechanism possibilities involving protein-protein interaction are discussed to explain the phenomena.

Cells, Cultured↗

Quantification of nucleolar organiser regions in canine perianal gland tumours.

The proliferative activity in 28 canine perianal gland tumours was examined by the quantitative evaluation of the nucleolar organiser regions associated with argyrophil proteins (AgNORs). These regions were stained with a specific silver stain and quantified directly by light microscopy and by computerised image analysis. The relationships between some of the parameters used (the number of AgNORs per nucleus, the area of AgNORs per nucleus and the ratio of the area of AgNORs to the area of the nucleus) were also examined in relation to the histopathological grades of the tumours. All the parameters showed a high correspondence with the tumours' proliferative activity, and the ratio of the area of AgNORs to the area of the nucleus was the most significantly correlated with the tumours' histological patterns.

Adenocarcinoma↗

Bioavailability study of a new, sinking, enteric-coated ursodeoxycholic acid formulation.

A new enteric-coated ursodeoxycholic acid (UDCA) formulation which sinks in the stomach and releases the drug only at a pH > or = 6.5 was developed. In 12 healthy subjects we measured, using a specific enzyme immunoassay, the serum levels of UDCA after a single oral dose of 450 mg of UDCA in three different formulations; enteric coated sinking tablet, stomach-floating enteric coated hard gelatin capsule and conventional gelatin capsule. The drug was given after a meal. Results are expressed as mean +/- SD. The area under the curve [AUC, mumol l-1 (8 h)] following oral administration of enteric-coated, sinking UDCA (39.0 +/- 8.5) was significantly higher than that obtained after both conventional UDCA (30.5 +/- 4.9) and floating enteric coated UDCA (29.3 +/- 3.4). Moreover, the maximum UDCA serum concentration (Cmax) was significantly higher with the enteric coated sinking UDCA formulation when compared to the other two formulations, while the time of maximum UDCA serum concentration (tmax) occurred later. These results may be explained by the hypothesis that the sinking tablet is expelled in the latter phase of gastric emptying along with the solid content. It therefore reaches the intestine at the highest alkalization phase caused by sustained biliary and pancreatic secretions. When released, the protonated insoluble UDCA is promptly solubilized by the alkaline pH thus giving a higher UDCA concentration gradient which facilitates its passive absorption. On the other hand, the floating capsule reaches the intestine too early, still in presence of an acidic pH; and in this condition UDCA is almost insoluble and consequently may be malabsorbed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

An "occupational miliary" due to nitrous gases.

The authors report the case of a patient suffering from chemical pneumonia due to nitrous gases of occupational origin which was mistakenly taken for military tuberculosis. Anamnestic, clinical and anatomopathological aspects of this disease, which successively analysed, often make the diagnosis difficult due to their complexity and lack of specificity.

Adult↗

Acquired gallstone opacification during cholelitholytic treatment with chenodeoxyholic, ursodeoxycholic, and tauroursodeoxycholic acids.

OBJECTIVES: The appearance of gallstone opacification during oral bile acid administration indicates that stones are no longer susceptible to dissolution and represents, therefore, a definitive treatment failure. Ursodeoxycholic acid (UDCA) has been imputed to facilitate gallstone opacification; however, data regarding the comparative occurrence of gallstone opacification during UDCA and chenodeoxycholic acid (CDCA) administration are not yet available. Our objectives were to evaluate the frequency of acquired opacification in gallstone patients taking UDCA and in gallstone patients taking CDCA, to verify whether or not gallstone opacification is a peculiar side effect of UDCA treatment and, further, to evaluate gallstone opacification in gallstone patients receiving tauro-UDCA (TUDCA) to verify whether the administration of the more soluble tauroconjugate might prevent the deposition of calcium salts on the stone surface. METHODS: 106 gallstone patients on UDCA, 125 gallstone patients on CDCA, and 31 gallstone patients on TUDCA were evaluated. Before treatment, all patients had radiolucent gallstones as assessed by oral cholecystography; further cholecystographic evaluations were performed every 6 months during treatment. RESULTS: The frequency of gallstone opacification was 13.2% (14/106) in UDCA patients, 8.8% (11/125) in the CDCA patients, and 12.9% (4/31) in the TUDCA patients. The differences were not statistically significant (p = NS). Sex, stone size, dose of bile acid, and duration of treatment were not significantly related to an increased frequency of gallstone calcification in any of the treatment groups. The frequency of gallstone opacification appeared to be higher in older patients. CONCLUSIONS: 1) UDCA rich bile is not a major predisposing factor for acquired gallstone opacification; 2) the administration of TUDCA does not prevent gallstone opacification; 3) opacification could be related to the natural history of gallstone disease.

Adolescent↗

A previously unidentified choline acetyltransferase transcript in the human foetal brain.

To identify choline acetyltransferase (ChAT) transcript(s) in human foetal brain we used the reverse polymerase chain reaction including different couples of oligonucleotide primers. The analysis indicated the presence of a new choline acetyltransferase transcript containing at its 5' end an untranslated exon (E1A) of 57 nucleotides in length extending from Nt 3771 to Nt 3828. It differs in the 5'-non coding region from the M-N-R type mRNA previously described in mouse and rat.

Brain↗

Trans-activation by thyroid hormone receptors of the 5' flanking region of the human ChAT gene.

Fusion gene constructs containing the human choline acetyltransferase 5' flanking region are stimulated by thyroid hormone (T3) in neuronal NG108-15 and NE1-115 cells but not in non neuronal COS-1 and JEG-3 cells. To identify potential T3 receptor binding elements (T3RE), chimeric plasmids containing various lengths of the 5' end of the hChAT gene linked to the CAT reporter gene were assayed by transient transfections into NG108-15, NE1-115 and COS-1 cells. We show that regulation is T3 specific as estrogen, dexamethasone, dihydrotestosterone, all-trans-retinoic acid and 9-cis-retinoic acid have no effect. We localized several potential T3REs and characterized the most proximal T3RE (position 3280-3291) which contains two hexameric half-sites arranged as a direct repeat without a base pair spacer. An oligonucleotide containing this sequence confers T3 responsiveness to a heterologous promoter. The transcriptional response of this T3RE is markedly reduced after mutation of the first or second half-site indicating that both half-sites are required for a maximal T3 response. We have found that RAR alpha, RXR alpha and COUP-TF do not enhance T3 responsiveness and therefore they may not interact with T3R alpha in NG108-15 cells on this regulatory sequence. T3R monomer and dimer specific binding to the proximal T3RE is demonstrated by gel-retardation DNA binding assays and by methylation interference experiments. In COS-1 cells, T3R inhibits transcriptional activation by the transcription factor AP-1 whereas in NE1-115 cells T3R enhances AP-1 mediated activation in a T3 dependant fashion. It is likely that these effects involve protein-protein interactions. These results suggest that the T3 receptor can act as a positive transcriptional regulatory factor on the hChAT gene.

Amino Acid Sequence↗

Improved intestinal absorption of an enteric-coated sodium ursodeoxycholate formulation.

A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycoursodeoxycholate were measured by specific enzyme immunoassay after oral administration of their sodium salts in an enteric-coated formulation at equimolar doses of 475 and 540 mg. The same subjects also received in separate experiments ursodeoxycholic acid, sodium ursodeoxycholate, and glycoursodeoxycholic acid in gelatin capsules. The mean area under the curve (mumol/L.hr) following administration of enteric-coated sodium ursodeoxycholate (45 +/- 8) was significantly higher than that of either ursodeoxycholic acid (26 +/- 5; P < 0.01) or sodium ursodeoxycholate (25 +/- 6; P < 0.001) administered in a conventional gelatin capsule. No differences were found when glycoursodeoxycholic acid was administered as an enteric-coated sodium salt or in acid form in gelatin capsules. Ursodeoxycholic was administered at a dose of 10 mumol/min/kg over 1 hr to bile fistula rats both intraduodenally (i.d.) and intravenously (i.v.). The experiment included administration of the sodium salt in solution and the acid as a suspension. A similar experiment was performed with glycoursodeoxycholic acid. The ratio of the amount recovered from bile in the i.d. to that in the i.v. experiment is almost 1 for the sodium salt of ursodeoxycholate in solution, while it drops to 0.55 for ursodeoxycholic acid. No differences were found between i.v. and i.d. administration when glycoursodeoxycholic acid was administered in acid form and as a soluble sodium salt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Professional figures in intermediate intensive units.

In Italy, respiratory intermediate intensive care units (IICUs) are not yet considered as autonomous hospital departments. The IICU of the Rehabilitation Department of the Medical Centre of Gussago (12 monitored beds) provides care for respiratory and cardiac patients. Ventilatory assistance and noninvasive modalities both in treatment and monitoring suggest a multidisciplinary approach to the patient. Highly professional figures should, therefore, be singled out to provide care in a respiratory IICU. The medical staff is composed of one anaesthesiologist, one cardiologist and one pulmonologist, who can integrate care when respiratory complications occur in a cardiological patient, or when cardiac events affect a respiratory patient. Nurses are capable of specific activities, especially when ventilatory assistance is required. The presence of a physiotherapist reduces the nursing workload, especially for ventilated individuals. The psychological aspect is undertaken by a specialist. Finally, an expert in nutrition provides an individualized dietary regimen. Our 4 year experience encourages such a multidisciplinary approach. An ideal integration of the professional activities should provide adequate and individual care for patients admitted to an IICU.

Humans↗

HPLC study of the impurities present in different ursodeoxycholic acid preparations: comparative evaluation of four detectors.

The use of HPLC with different detectors has been investigated for the analysis of bile acid impurities present in four different commercially available ursodeoxycholic acid preparations. The bile acids were efficiently separated by C18 reversed-phase HPLC using methanol-water (3:2, v/v) as the mobile phase. The detectors used for bile acid detection were: UV at 200 nm refractive index (RI) and an evaporative light scattering mass detector (ELSD II). A prederivatization method with the formation of a fluorescent naphthacyl ester has also been used. GC-MS analysis of Me-TMS bile acid derivatives was included as a reference method. The four ursodeoxycholic acid samples were 98-99% pure. The main impurities present in the samples were chenodeoxycholic acid and to a lesser extent lithocholic acid. Only one sample was found to be almost 100% pure using all the detectors. Significant agreement of the data was found between RI, ELSD II detectors and the fluorescent method; the UV detector was unsuitable for use in this method. The analytical performances of the four detectors for bile acid analysis are reported and discussed. When the four-detector data were compared with the GC-MS method, reasonable agreement resulted. Discordant results were found in the quantitation of trace impurities like lithocholic acid and/or other minor bile acids present in amounts less than 0.1%.

Bile Acids and Salts↗

Identification and analysis of the human choline acetyltransferase gene promoter.

Choline acetyltransferase (ChAT) is the key enzyme responsible for the synthesis of the neurotransmitter acetylcholine and is reduced in various central neurodegenerative diseases. From a previously selected 12.6 kb human choline acetyltransferase (hChAT) genomic clone, we have identified and characterized a promoter region of 895 bp. Sequence analysis revealed the presence of a TATA-like box, a CAAT box and several putative regulatory responsive elements. Three transcription initiation sites were determined by primer extension analysis. The Northern blot of poly(A)+ RNA, showed a single band of 2300 Nt in the human nucleus accumbens and facial nucleus. By using transient transfections into NE-1-115 and COS-1 cells of the 5' flanking region of the hChAT gene we identified a sequence of 66 bp upstream of the transcription start site which confers responsiveness to proto-oncogenes c-Fos/c-Jun. These data suggest that the hChAT gene may be a physiological target of c-Fos/c-Jun and therefore may play a role in neuronal responses to various stimuli.

Base Sequence↗

Human choline acetyltransferase (CHAT): partial gene sequence and potential control regions.

Choline acetyltransferase (CHAT) (EC 2.3.1.6) is the biosynthetic enzyme for the neurotransmitter acetylcholine in the central and peripheral nervous systems. In this study, a human CHAT genomic clone has been isolated and partially sequenced at its 5' end. This fragment contains the first four exons with an ACG initiator codon and potential control regions including TATA, CAAT, GC boxes, and several transcription control sequences. A comparison of the primary structure of CHAT among pig, rat, mouse, and Drosophila is presented.

Amino Acid Sequence↗