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Biomedical subjects

G Benedetti

Publications and source records attributed to G Benedetti.

At least 55 records · Page 3Linked to original sources
PubMed1994

Normalization of Insulin Sensitivity in the Obese Patient after Stable Weight Reduction with Biliopancreatic Diversion.

Insulin resistance is a common feature in obese patients. To evaluate the modifications in insulin sensitivity after a bariatric operation such as Bilio-pancreatic diversion (BPD), three groups of subjects (14 normal controls (N); seven ex-obese patients (X) with at least 2 years at weight-stable conditions after BPD surgery; and eight morbidly obese patients (0)) were studied with intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The ratio of the area under the curve (AUC) for glucose over that of insulin was used as a measure of insulin sensitivity. All the following tests were conducted as Bonferroni-corrected pairwise t-tests, in case overall ANOVA was significant. No significant difference was found between N and X subjects, while obese patients showed a reduced AUCg/AUCI ratio with respect to the normal controls (O vs N: 0.01164 +/- 0.00039 vs 0.02392 +/- 0.0039, p < 0.05). IVGTT, AUCS: significant differences were found in each case: N vs X: 0.0591 +/- 0.0075 vs 0.1402 +/- 0.0399, p < 0.05; N vs 0:0.0591 +/- 0.0075 vs 0.0223 +/- 0.0031, p < 0.01; X vs 0:0.1402 +/- 0.0399 vs 0.0223 +/- 0.0031, p < 0.05. IVGTT-derived data were also analyzed using the minimal model of glucose kinetics; with this method, glucose effectiveness was significantly different between normal subject and obese subjects (0.0248 +/- 0.00288 Vs 0.00906 +/- 0.00135 per min, p < 0.001). The insulin sensitivity index was not significantly different between normal and ex-obese subjects, while both of these groups were significantly different from obese patients (N vs 0: 12.04 x 10&sup5; +/- 2.61 x 10&sup5; vs 3.29 x 10&sup5; +/- 0.61 x 10&sup5;, p < 0.066; X vs 0: 16.42 x 10&sup5; +/- 4.23 x 10&sup5; vs 3.29 x 10(1)+/- 0.61 x 10&sup5; per min per pM, p < 0.02). In conclusion, the present study indicates that, after a body weight reduction operation capable of almost re-establishing ideal body weight like BPD, obese individuals with a family history of obesity show a normalization of insulin response to glucose load.

Journal Article↗
PubMed1994

Selection and characterization of early hematopoietic progenitors using an anti-CD71/S06 immunotoxin.

Most recently reported methods to select early hematopoietic cells basically rely on the depletion of committed progenitors. This task is generally accomplished by laborious procedures, which are sometimes difficult to reproduce. To simplify the selection method, we took advantage of the expression of the transferrin receptor (CD71) by proliferating committed progenitors and the lack of CD71 on noncycling immature progenitors. A monoclonal antibody (MAB) reactive with CD71 has been conjugated to the Saponaria officinalis seed ribosome-inactivating protein (SO6). The immunotoxin (IT) complex was used at increasing concentrations on normal non-phagocytizing bone marrow cells. A complete and reproducible killing effect on myeloid (colony-forming unit-granulocyte/macrophage [CFU-GM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitors was observed for IT concentrations of 1 x 10(-7) M. Unconjugated SO6 or anti-CD71 MAB had no effect on cell growth and viability. IT-resistant cells were able to generate CFU-GM after 7, 14, and 21 days of suspension culture in the presence of 5637 CM. Maximal CFU-GM values were obtained at day 21 and nearly approached the pretreatment values (mean 2587 vs. 3877 CFU-GM/mL). Growth factor enhancement of CFU-GM yield was obtained only by stem cell factor (SCF) at day 7; SCF, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), had an enhancing effect at days 14 and 21. IT toxicity on highly immature progenitors was ruled out by evaluating the growth of long-term culture-initiating cells (LTC-IC) from IT-treated cultures. LTC-IC frequency was found to be 1 out of 1506 seeded cells, which is within the range of normal untreated BM cells. In conclusion, anti-CD71 IT allows a simple and complete depletion of committed progenitors while sparing immature hematopoietic cells. The high CD71 expression by leukemic cells makes the procedure potentially suitable for in vitro purging.

Antibodies, Monoclonal↗
PubMed1993

[Role of the endogenous opioid system in the modulation of anginal pain].

The Authors make an analysis of the complex interactions occurring between peripheral and central factors in the regulation of anginal pain. As for the role of the endogenous opioid system, results obtained in a study using a particular methodological approach have demonstrated that patients with asymptomatic ischemic heart disease have a higher endogenous opioid tone at the level of the central nervous system.

Angina Pectoris↗
PubMed1993

[The variability of the heart rate in patients with a myocardial infarct undergoing systemic fibrinolysis interventions].

Although heart rate variability is a very important prognostic factor in patients with myocardial infarction, the mechanism for the reduction in the vagal cardiac activity is unknown: myocardial infarction can cause local areas of sympathetic or parasympathetic denervation that leads to catecholamine hypersensitivity; the destruction of local ventricular receptors of the autonomic system may alter feedback to the higher centres, impairing autonomic regulation; the mechanical distortion consequent to the infarction can give rise to sympathetic overactivity. Effective thrombolysis in myocardial infarction could reduce myocardial necrosis and, therefore, cause less reduction of vagal activity and/or less sympathetic stimulation. To determine whether systemic thrombolysis has some effect on heart rate variability we studied 40 patients with a first transmural myocardial infarction. Enrollment criteria were very strict: all the patients with conditions potentially influencing heart rate variability were excluded from this study. Between day 15 and day 25 from the infarction patients had an Holter monitoring. A program we developed provided for the automatic identification of R wave, for the calculation of RR interval, and for the recognition of pause, extrasystolic and post-extrasystolic beats, that could be thus excluded from the analysis. Patients were divided in 2 groups: 17 patients treated with thrombolysis and 23 subjects treated traditionally. There were no difference between the 2 groups with regard to the age and cardiac function, except for the less echo score in the fibrinolytic treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography, Ambulatory↗
PubMed1992

Endogenous opioid system modulation in anginal pain: demonstration of its central activity.

Plasma beta-endorphin levels provide controversial results on the role of endogenous opioid system in modulation of anginal pain. As an alternative, the action of plasmatic luteinizing hormone after administration of naloxone was investigated: naloxone blocks the tonic endogenous opioid system inhibition of gonadotropin release; thus, the level of luteinizing hormone after naloxone administration is an index of central endogenous opioid system activity. Twenty patients with coronary artery disease and positive results of stress tests were selected: 10 had angina (group I) and 10 did not (group II). Ten healthy subjects were also studied as a control group (group III). In all patients basal plasma beta-endorphin levels, basal luteinizing hormone plasma levels (every 15 minutes for 1 hour) and luteinizing hormone plasma levels after administration of 0.1 mg/kg naloxone over 4 minutes (every 15 minutes for 2 hours) were determined. In 15 patients the test was performed after luteinizing hormone releasing hormone was given. The integral concentration time of luteinizing hormone plasma level during baseline (LHiB) and after administration of naloxone (LHiN) or luteinizing hormone releasing hormone (LHiRH), the ratio (LHiN:LHiB and LHiRH:LHiB) and the differences (LHiN-LHiB and LHiRH-LHiB) between the postinfusion period and baseline were calculated. No difference was found in beta-endorphin plasma levels and luteinizing hormone response after luteinizing hormone releasing hormone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Recognition of the folding consensus in RNA secondary structures by the topological-filtering method.

Functionally homologous RNA sequences can substantially diverge in their primary sequences but it can be reasonably assumed that they are related in their higher-degree structures. The problem to find such structures and simultaneously satisfy as far as possible the free-energy-minimization criterion, is considered here in two aspects. Firstly a quantitative measure of the folding consensus among secondary structures is defined, translating each structure into a linear representation and using the correlation theorem to compare them. Secondly an algorithm for the parallel search for secondary structures according to the free-energy-minimization criterion, but with a filtering action on the basis of the folding consensus measure is presented. The method is tested on groups of RNA sequences different in origin and in functions, for which proposals of homologous secondary structures based on experimental data exist. A comparison of the results with a blank consisting of a search on the basis of the free energy minimization alone is always performed. In these tests the method shows its ability in obtaining, from different sequences, secondary structures characterized by a high-folding consensus measure also when lower free energy but not homologous structures are possible. Two applications are also shown. The first demonstrates the transfer of experimental data available for one sequence, to a functionally related and therefore homologous one. The second application is the possibility of using a topological probe in the search for precise structural motifs.

Algorithms↗
PubMed1991

Endoscopic injection sclerotherapy in non-variceal upper gastrointestinal bleeding. A comparative study of polidocanol and thrombin.

To date several agents have been used to achieve haemostasis in patients with non-variceal upper gastrointestinal bleeding using endoscopic sclerotherapy techniques. Polidocanol has been widely used but local complications have been reported after treatment. We have compared the efficacy and safety of thrombin and polidocanol in 82 consecutive patients with ongoing or recent bleeding from duodenal, gastric, or anastomotic ulcers. Primary control of haemostasis from spurting vessels was achieved in 90% of cases using polidocanol and in 86.6% using thrombin. Definitive haemostasis was obtained in 80% of patients in both groups. When a non-bleeding vessel was visible, injection of polidocanol or thrombin effectively prevented rebleeding in 90.9% and 85.7% of cases, respectively. When a non-bleeding sentinel clot was present, injection of polidocanol or thrombin provided definitive haemostasis in 100% and 92.8% of cases, respectively. No statistically significant difference was evident between the two agents. In the polidocanol group, one local haemorrhagic complication was noted. No general or local complications were recorded in the thrombin group.

Duodenal Ulcer↗
PubMed1991

Three-dimensional folding of Tetrahymena thermophila rRNA IVS sequence: a proposal.

We studied the Tetrahymena thermophila rRNA IVS sequence with the aim of obtaining a model of the structure characterized by the bases proximity of the self-reactions sites. The considered sequence kept up those fragments essential for its catalytic activity as demonstrated by deletion mutants. The first step was the theoretical analysis with a computer method previously proposed, to find optimal free energy secondary structures with the required features, under the suitable constrains. Then we tried folding the obtained secondary structures, in low resolution tertiary models, which kept up the proximity of the catalytic sites also in the space. The proposed tertiary folding seems to provide for a better explanation to the transesterification mechanisms and moreover it is in good agreement with the experimental data (activity of mutants, enzymatic cleavages, phylogenetically conserved regions).

Animals↗
PubMed1991

Modifications induced by gestational diabetes mellitus on cellular membrane properties.

Alterations in erythrocyte plasma membrane properties (enzymatic activities and membrane fluidity) have been observed in patients affected by insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). In order to verify whether these alterations are present also in gestational diabetes mellitus (GDM) we studied the plasma membranes obtained from two different cellular types (erythrocyte from both mother and cord blood and placenta syncytiothrophoblast cell) of 16 healthy pregnant women and 15 women affected by GDM. The following determinations were performed on the membrane preparations: Na+/K(+)-ATPase activity, acetyl-cholinesterase (AchE) activity, membrane fluidity and cholesterol:phospholipid ratio. We observed a reduction of both enzymatic activities and a decrease of membrane fluidity in maternal and cord blood erythrocytes and in syncytiotrophoblast plasma membranes in GDM pregnant women in comparison with controls. The cholesterol to phospholipid ratio was significantly lower in the erythrocyte membranes of women affected by GDM than in normal pregnant women, while it was increased in the cord blood erythrocyte membranes and in placental membranes in GDM in comparison with controls. The present study found, in GDM patients, a membrane alteration similar to the abnormality reported in IDDM and NIDDM (i.e. decreased Na+/K(+)-ATPase activity), while opposite modifications were observed with regard to other membrane activities and properties. The different membrane alterations observed in GDM with respect to IDDM and NIDDM might be linked to the different degree of metabolic control, on the contrary the reduced Na+/K(+)-ATPase activity might be a primary event in the pathogenesis of diabetes mellitus per se and might constitute a signal of high risk of developing the disease later in the women affected by GDM during pregnancy.

Acetylcholinesterase↗
PubMed1991

In vitro effect of magnesium on the Na/K-ATPase isolated from human placenta.

Magnesium (Mg) is an activator of many cellular processes, among which is cation transport. An imbalance of cation transport may be involved in several diseases, as well as during pregnancy. Since the action of Mg in vivo in preventing gestational diseases is known, as well as its role in vitro on some cation transport activities, we studied the action of increasing concentrations of Mg on the activity of the enzyme Na/K-ATPase isolated from placental tissue of six normotensive women, at term. Incubation in a medium with increasing concentrations of Mg resulted in a significant activation of the enzyme, which was related to Mg concentration. The study demonstrates the action of Mg in vitro on isolated enzymes, and suggests the use of enzyme purification as a model for the study of cation transport in pregnancy.

Dose-Response Relationship, Drug↗
PubMed1991

Role of endogenous opioids on nociceptive threshold in patients with exercise-induced myocardial ischemia.

To evaluate whether endogenous opioids (EO) play a role in the perception of anginal pain, a randomized double blind clinical trial, using naloxone (N) and placebo (P) and measuring beta-endorphin (beta-ep) plasma levels, was performed. We studied 10 patients with angiographically assessed coronary artery disease (CAD) and stable exercise-induced myocardial ischemia (established by 2 preliminary bicycle ergometric tests) of whom 5 symptomatic (SYM) and 5 asymptomatic (ASYM) and 5 subjects without CAD as a control group (CON). On a third exercise test the beta-ep plasma level (fmol/ml) was measured at rest (SYM 5.4 +/- 2.3 vs ASYM 7.2 +/- 2.3 vs CON 6.8 +/- 2.6, NS), at peak exercise (SYM 4.4 +/- 1.8 vs ASYM 8.0 +/- 4.2 and vs CON 6.2 +/- 2.7, NS) and during recovery (SYM 7.5 +/- 4.2 vs ASYM 7.2 +/- 3.0 vs CON 6.7 +/- 2.5, NS). On 2 subsequent tests patients received N (0.2 mg/kg) or P intravenously and chest pain was evaluated on an analogue scale (score from 1 to 10). After N compared to P we observed: an increased perception of chest pain in SYM (6.8 +/- 1.5 vs 4.2 +/- 1.0; p less than 0.01) without significant changes of the ischemic threshold (total work, heart rate-blood pressure product, ST segment changes, 2D-echocardiographic wall motion abnormalities); no modifications in ASYM and CON.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Modifications induced by general anesthetics on Na+/K+ ATPase obtained from human placenta.

Previously it was demonstrated that thiopental in vivo anesthesia didn't affect the Na+/K(+)-ATPase activity of syncythiotrophoblast plasma membrane, while affecting other enzymatic activity. The aim of the present work was to investigate if this lack of effect of thiopental on the Na+/K+ ATPase activity might be due to its specificity of action on definite membrane proteins or if the binding sites of the anesthetic to this enzyme might be masked within the membrane. Temperature dependence of the Na+/K(+)-ATPase activity and of a spin label paramagnetic maleimide derivative (MSL,2,2,6,6-tetramethylpiperidin-1-oxyl-4-maleimide), which shows a selective binding to the reduced sulfhydryl groups of proteins were investigated. This report shows that a Na+/K(+)-ATPase membranous preparation obtained from placental tissue is strongly inhibited by thiopental.

Anesthetics↗
PubMed1990

Quality of life of COPD patients treated by long-term oxygen.

The three main dimensions of quality of life (physical function, social activities, and psychological status) were evaluated by a questionnaire in 41 COPD patients with severe respiratory failure treated by long-term oxygen. The results were compared with those obtained in patients suffering from COPD without chronic respiratory failure and in patients suffering from severe diabetes and/or atherosclerosis. A relevant impairment of the indexes of quality of life was found in the group of subjects with chronic respiratory failure. The extent of the impairment was significantly higher in these subjects than in the two other groups of patients.

Combined Modality Therapy↗
PubMed1990

Secondary structures of Tetrahymena thermophila rRNA IVS sequence involved in its self-splicing reactions: a new computer analysis.

The secondary structures of Tetrahymena thermophila rRNA IVS sequence involved in the self-splicing reactions, are theoretically investigated with a refined computer method previously proposed, able to select a set of the deepest free energy RNA secondary structures under constraints of model hypotheses and experimental evidences. The secondary structures obtained are characterized by the close proximity of self-reactions sites and account for double mutations experiments, and differential digestion data.

Animals↗
PubMed1990

5-Fluorouracil and high-dose folinic acid as second-line chemotherapy in head and neck cancer.

Experimental and clinical data support the concomitant use of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA). To verify the role of such a combination in far advanced head and neck cancer, we performed a phase II study employing weekly HDFA, 500 mg/m2 in 2-h infusions, and 5-FU, 600 mg/m2 bolus injection. Twenty-seven evaluable patients with recurrent disease entered the study. One complete response, seven partial responses, 10 stable disease, and nine progressions were observed: the overall response rate was 29.6%. Oral mucositis and diarrhea were major side effects; five patients discontinued the treatment due to toxicity; no deaths correlated to the treatment were detected. Considering the characteristics of our patients, the 5-FU/HDFA combination has shown a satisfactory antitumoral activity, but toxicity was similar to other chemotherapy regimens.

Aged↗