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Biomedical subjects

G Benedetti

Publications and source records attributed to G Benedetti.

At least 37 records · Page 2Linked to original sources
PubMed1998

Renoprotective effect of contemporary blocking of angiotensin II and endothelin-1 in rats with membranous nephropathy.

BACKGROUND: We previously showed that chronic administration of an angiotensin converting enzyme (ACE) inhibitor to rats with passive Heymann nephritis (PHN), a model of membranous nephropathy with proteinuria and increased renal synthesis of endothelin-1 (ET-1), reduces urinary proteins and partially limits the exaggerated ET-1 renal synthesis. Here we compared the effect of an ETA receptor antagonist and an ACE-inhibitor given as single therapies with a combination of the two drugs in uninephrectomized PHN rats. METHODS: PHN was induced with a single i.v. injection of rabbit anti-Fx1A antibody in 40 male Sprague Dawley rats. To accelerate the onset of renal damage rats underwent uninephrectomy seven days later and were subsequently treated until eight months with the ETA receptor antagonist LU-135252 (50 mg/kg b.i.d. p.o.) or the ACE-inhibitor trandolapril (1 mg/kg in the drinking water) or the combination of the two drugs. RESULTS: Either LU-135252 or trandolapril given alone prevented the increase in systolic blood pressure (SBP). Combined therapy was even more effective than single drugs. While LU-135252 and trandolapril reduced proteinuria by 23 to 25%, the drug combination resulted in 45% lowering of urinary proteins. Serum creatinine was significantly decreased by the combination, but not by the single drugs. Glomerulosclerosis and tubulointerstitial damage were more reduced by combined therapy than by LU-135252 or trandolapril alone. CONCLUSIONS: These data suggest that contemporary blocking angiotensin II (Ang II) and ET-1 in an accelerated model of PHN had an additive renoprotective effect than single blocking Ang II or ET-1 and would represent a therapeutic advantage for renal disease patients who do not completely respond to ACE inhibitors.

Angiotensin II↗
PubMed1998

Bindarit retards renal disease and prolongs survival in murine lupus autoimmune disease.

As an alternative to classical immunosuppressants in experimental lupus nephritis, we looked at bindarit, 2-methyl-2-[[1-phenylmethyl)-1H-indazol-3-y1]methoxy]propanoic acid, a novel molecule devoid of immunosuppressive effects, which selectively reduces chronic inflammation in rat adjuvant arthritis. Two groups of NZB/W mice (N = 55 for each group) were given bindarit, (50 mg/kg/day p.o.) or vehicle starting at 2 months of age. Mice were sacrificed at 2, 6, 8 and 10 months or used for survival studies. Bindarit delayed the onset of proteinuria (% proteinuric mice, bindarit vs. vehicle, 6 months: 0 vs. 33% and 8 months: 7% vs. 60%, P < 0.005; 10 months: 53% vs. 80%) and significantly (P < 0.05) protected from renal function impairment (serum BUN, bindarit vs. vehicle: 8 months, 30 +/- 3 vs. 127 +/- 42; 10 months, 53 +/-5 vs. 140 +/- 37 mg/dl). Appearance of anti-DNA antibodies was retarded and survival significantly (P < 0.0001) prolonged by bindarit (% survival, bindarit vs. vehicle: 8 months, 100% vs. 80%; 10 months, 87% vs. 40%; 12 months, 27% vs. 20%). Bindarit significantly limited glomerular hypercellularity, interstitial inflammation and tubular damage. Renal expression of monocyte chemoattractant protein (MCP-1) mRNA (Northern blot) markedly increased (7 - 12-fold in 8- 10-month-old mice vs. 2-month-old) during the progression of nephritis in association with mononuclear cell infiltration. Bindarit completely prevented MCP-1 up-regulation. In another series of experiments, bindarit (0.25% and 0.5% medicated diet, N = 16 for each group) when started at 4.5 months of age in NZB/W mice improved survival in respect to untreated mice (N = 17) in a dose-dependent manner (% survival: 8 months, 94% and 100%, respectively, vs. 47%; 10 months, 75% and 100% vs. 35%; 12 months, 31% and 75% vs. 12%). Survival was even more prolonged when bindarit (0.5% medicated diet) was combined with a low dose of methylprednisolone (1.5 mg/kg i.p.), which that only partially modifies proteinuria and survival of lupus mice, in an additional group of animals (N = 16). Thus, at 14.5 months when all mice given bindarit alone died, 50% of mice on combined therapy were still alive (P < 0.023). Studies are needed to establish whether bindarit may function as a steroid sparing drug in human lupus.

Animals↗
PubMed1998

Twenty-four-hour energy balance in Crohn disease patients: metabolic implications of steroid treatment.

Several hypotheses have been proposed to explain the nutritional deficiencies seen in Crohn disease patients, including inadequate food intake, decreased assimilation and increased loss of nutrients, and increased energy expenditure. To assess the effect of steroid therapy on body composition, energy expenditure, and fuel selection in Crohn disease, we compared 12 patients (6 men and 6 women) with biopsy-proven ileal Crohn disease with 11 healthy volunteers (6 men and 5 women). Five patients [Crohn's disease activity index (CDAI) = 98.4 +/- 3.78] took no medication and seven patients (CDAI = 283.9 +/- 22.5) were administered 29 +/- 18 mg prednisone/d. Body composition was evaluated by isotopic dilution and bioelectrical impedance analysis, and 24-h energy expenditure and basal metabolic rate were measured in a respiratory chamber. Fat-free mass was not significantly different among groups, whereas fat mass was lower in patients than in control subjects. Energy intake was higher in treated patients than in both untreated patients (P = 0.004) and control subjects (P = 0.005). Fecal losses were not significantly different between untreated patients and control subjects, but were higher (and proportional to the CDAI) in treated patients than in control subjects (P = 0.001). Metabolizable energy was not significantly different among groups, whereas energy balance was significantly higher in treated patients than in both control subjects (P = 0.0057) and untreated patients (P = 0.018). Nitrogen balance was mildly negative in treated patients compared with both control subjects and untreated patients, but not significantly so. In conclusion, prednisone treatment in Crohn disease patients stimulates food intake, promoting an overall positive energy balance despite large fecal nutrient losses.

Adult↗
PubMed1998

A surgical option for familial chylomicronemia associated with insulin-resistant diabetes mellitus.

BACKGROUND: The goal of the present work is to present an effective surgical approach for the treatment of a medically-resistant form of hyperlipidemia. METHODS: Two siblings with familial lipoprotein-lipase deficiency and subsequent hyperchylomicronemia, widespread skin xanthomas and severe insulin-resistant diabetes mellitus came to our observation after several unsuccessful attempts at medical treatment. In order to lower plasma lipids through lipid malabsorption, a modified bilio-pancreatic diversion operation was employed. The rationale in deciding to use this surgical approach was based also on the likely hypothesis that diabetes, in these subjects, was secondary to high circulating and tissue levels of lipids. Insulin sensitivity in the two treated subjects, as well as in 24 healthy volunteers constituting the control group, was assessed by euglycemic hyperinsulinemic clamp and indirect calorimetry, obtaining total end-clamp glucose uptake (M) and end-clamp glucose oxidation (ECGO) rates. RESULTS: Within 3 weeks of surgery, plasma triglycerides and cholesterol levels had decreased from 4500 and 500 mg/dl (with dietary restrictions) to lower than 450 and 150 mg/dl (on a free, lipid-rich diet) respectively. Fasting plasma glucose levels had decreased from above 300 (under daily repeated subcutaneous injections of insulin) to 80-100 mg/dl (without administration of insulin or oral hypoglycemic agents). Body weight and fat free mass were maintained in both subjects after surgery. In both patients, before surgery M and ECGO were significantly lower than in normal subjects, while after surgery they were not significantly different from normal subjects, confirming the positive metabolic effect of the operation. CONCLUSION: The surgical option used in these patients may represent an interesting and effective new possibility for treatment of those severe cases of hyperlipemia leading otherwise to metabolic complications and a low quality of life.

Adolescent↗
PubMed1998

Xylose absorption and metabolic status in urinary intestinal orthotopic reservoir: ileocecal compared with ileal neobladder.

PURPOSE: We compare the absorption of D-xylose and vitamin B12, and the metabolic status in ileocecal and ileal orthotopic neobladders. MATERIALS AND METHODS: D-xylose plasma levels after an oral load, body composition, plasma vitamin B12, acid base and electrolyte balance were studied in 33 patients with an ileocecal reservoir and 13 patients with an ileal reservoir. Mean followup was 55 months. Results of both types of operation and a healthy control group were compared. RESULTS: Plasmic levels of D-xylose and vitamin B12 were significantly lower in the ileal reservoir than in ileocecal reservoir group and normal controls. CONCLUSIONS: Despite an acceptable body composition, intestinal malabsorption could be present in patients with an ileal reservoir but the ileocecal tract appears to be safe.

Aged↗
PubMed1997

Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids.

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after reaching stable body weight, at least 2 years after surgery POII. A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91 mumol.kg-1.min-1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/- 77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of total decrement), rather than in the early postoperative period (Ob to POI 135.25 +/- 14.99 to 124.28 +/- 11.22 kg, 17% of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance.

Adult↗
PubMed1997

Vitamin B12 and folic acid plasma levels after ileocecal and ileal neobladder reconstruction.

OBJECTIVES: To compare the plasma levels of vitamin B12 and folic acid following resection of ileocecal or ileal segments used for orthotopic bladder substitution. METHODS: Hemoglobin, hematocrit, and plasma levels of vitamin B12 and folic acid were measured in 34 patients with ileocecourethrostomy (ICUS) and in 16 patients with ileal reservoir (IR), with a mean follow-up of 59.8 +/- 41.9 months. The results were compared with regard to both the type of operation and the length of time since surgery. RESULTS: The level of folic acid was normal in all patients. The mean level of vitamin B12 in the ICUS group was 413.67 +/- 160.45 ng/mL compared to 257.63 +/- 121.36 for the IR group. This difference was statistically significant. In the IR group, 18.75% of the patients had a level of vitamin B12 below normal. CONCLUSIONS: There is a tendency for vitamin B12 levels to fall in patients in whom the ileum is used. Resection of the ileocecal segment including the junction does not alter the level of vitamin B12.

Aged↗
PubMed1997

Dodecanedioic acid infusion induces a sparing effect on whole-body glucose uptake, mainly in non-insulin-dependent diabetes mellitus.

Even-numbered dicarboxylic acids (DA) have been proposed as an alternative fuel substrate in parenteral nutrition. In particular, dodecanedioic acid (C12) shows a rapid plasma clearance from tissues, a very low urinary excretion compared with other DA and a high oxidation rate. The aim of the present study was to investigate the effect of C12 infusion on insulin-stimulated glucose uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM) compared with healthy volunteers. A primed-constant infusion of C12 (0.39 mmol/min) was administered over 240 min, and at 120 min a 2 h euglycaemic hyperinsulinaemic clamp was performed. Blood specimens were sampled every 30 min and fractioned urines were collected over 24 h. The levels of C12 were measured by HPLC. Indirect calorimetry was performed continuously during the entire session. Body composition was assessed in all subjects studied to obtain fat-free mass (FFM) values. Whole-body glucose uptake decreased significantly during C12 infusion in both groups, although this effect was much more evident (P < 0.01) in NIDDM patients (52.4 (SD 15.8) % decrease compared with saline) than in controls (25.9 (SD 12.1) % decrease). The M value (mumol/kgFFM per min) was reduced by C12 to lower levels in NIDDM patients than in normal controls (12.6 (SD 3.9) v. 25.9 (SD 4.5), P < 0.01). Urinary excretion of C12 over 24 h was significantly lower in NIDDM patients than in controls (4.26 (SD 0.30) mmol v. 5.43 (SD 0.48), P < 0.01), corresponding to less than 3% of the administered dose. The infusion of C12 decreased non-protein RQ significantly in both groups of patients. In conclusion, this study shows, for the first time, that C12 significantly reduces glucose uptake in both normal controls and NIDDM patients, although this sparing effect on glucose uptake is much more pronounced in diabetic patients. These data suggest that C12 decreases glucose uptake and oxidation, mainly through a mechanism of substrate competition. Thus, it might be a useful alternative substrate in enteral or parenteral nutrition, sparing glucose utilization and increasing glycogen stores, in those clinical conditions, like NIDDM, where reduced insulin-induced glucose uptake and oxidation are observed.

Blood Glucose↗
PubMed1996

A graph-topological approach to recognition of pattern and similarity in RNA secondary structures.

Secondary and tertiary RNA structures play an important role in many biological processes. Therefore the necessity arises to find similar higher-order structures for different but functionally homologous RNA sequences. We propose here a graph-topological approach to the problem, which shows two main features: simplified graph representation which allows the recognition of similarity of RNA secondary structures with the same branching look despite minor differences. This allows comparison among foldings from different sequences, and "pruning" of the secondary structures not shared by all the sequences since the early stages of the search. (b) The graph representation is encoded by the Randić topological index, and the search for the folding similarity is reduced to checking the identity of single numbers. These characteristics make this approach significantly different, less depending on empirical criteria, and less computationally heavy then previous methods, where the folding consensus has been measured by an alignment procedure or correlation of strings representing the secondary structures. Some U2 snRNA and viroid sequences are studied by this approach, which is imbedded in our previous search method based on genetic algorithms.

Algorithms↗
PubMed1996

Increased resting lipid oxidation in Crohn's disease.

Resting energy expenditure (REE) was measured by indirect calorimetry and body composition was assessed by both direct (bioimpedance) and indirect (anthropometry) methods in 20 hospitalized patients with biopsy-proven ileal Crohn's disease and in a group of 16 healthy volunteers matched for sex, age, and height with the patient group. The Crohn's disease activity index was below 120 in all patients studied, who were treated with a low dose of corticosteroids (0.2-0.3 mg/kg body wt of prednisone). The average weight of Crohn's patients was significantly lower than that of controls (55.70 vs 70.50 kg, P < 0.001) due to both lower fat mass (9.97 vs 18.30 kg, P < 0.001) and lower lean body mass (45.72 vs 52.20 kg, P < 0.02). The average REE was significantly higher in the control group (1785.42 +/- 7.503 vs 1559.1 +/- 48.39 kcal/day, P < 0.001). However, these differences disappeared when REE was normalized by lean body mass (LBM) (34.49 +/- 2.56 vs 34.704 +/- 3.75 kcal/kg LBM P = NS). The nonprotein respiratory quotient was significantly lower in the patient group (0.823 +/- 0.031 vs 0.882 +/- 0.012, P < 0.025), indicating an increased lipid oxidation. This increased lipid oxidation might explain the reduced fat stores found in the group of Crohn's patients, suggesting also that a sufficiently lipid-rich diet could be useful in their nutritional management.

Adult↗
PubMed1995

An improved GLC method for a rapid, simultaneous analysis of both medium chain fatty acids and medium chain triglycerides in plasma.

An improved gas-liquid chromatographic (GLC) method for the direct, simultaneous analysis of both medium chain monocarboxylic acids (MCFA) and medium chain triglycerides (MCT) is reported. The calibration curve of MCFA and MCT is linear in the range from 30 ng to 1000 ng. Five nanograms for tricaproin (MCT-6), 10 ng for tricaprylin (MCT-8) and 15 ng for tricaprin (MCT-9) represent the GLC detection limits of MCT, while those of MCFA range from 40 to 15 ng depending on their chain length: the longer the chain length, the higher the detection limit. The recovery of MCFA range from 79 to 99% and that of MCT from 85 to 99%. An example of plasma concentration curves of MCT and MCFA after an intravenous bolus injection of an MCT emulsion (100 mg MCT/kgbw) in a patient with Crohn's disease is shown.

Adult↗
PubMed1995

A genetic algorithm to search for optimal and suboptimal RNA secondary structures.

Genetic algorithms are a search method used in solving problems by selection, recombination and mutation of tentative solutions, until the better ones are achieved. They are very efficient when the 'building block' hypothesis is effective for the solutions, which means that a better solution can be obtained by assembling short 'motifs' or 'schemata' that can be retrieved in some other worse solutions. The additive nature of the secondary structure free energy rules suggests the validity of this hypothesis, and therefore the likely power of a genetic algorithm approach to search for RNA secondary structures. We describe in detail an original genetic algorithm specific for this problem. The sharing function used to obtain differentiated solutions is also described. It results in a greater effectiveness of the algorithm in retrieving a large number of suboptimal RNA foldings besides the optimal one. RNA sequences of different length are used to test the method. The PSTV viroid sequence has been studied.

Algorithms↗
PubMed1995

Ethanol metabolism and aging: the role of "first pass metabolism" and gastric alcohol dehydrogenase activity.

To investigate the effect of age and gender on ethanol metabolism, first-pass metabolism (FPM) and gastric alcohol-dehydrogenase (ADH) activity were compared in 32 elderly and 30 young adult nonalcoholic subjects. The FPM was obtained from the difference between the area under the curve of ethanol blood concentration after intravenous or oral administration of ethanol 0.3 g/Kg b.w. The ADH activity was determined in samples of gastric mucosa obtained during diagnostic endoscopy. In the young adult group the FPM was higher in men than in women (3.3 +/- 2.3 vs 1.2 +/- 0.9 mmol/l/h, respectively, p < .01). In aged subjects FPM was found to be very low for men (1.1 +/- 0.8 mmol/l/h, p < .001); conversely, FPM was not significantly reduced in women (1.7 +/- 0.8 mmol/l/h, p = n.s.). The gastric ADH activity was significantly (p < .01) higher in young adult men than women, whereas in aged subjects the activities were low (p < .0001) in both sexes. Thus, gender-related FPM differences equalize in the elderly or are even reversed, most likely because of gastric mucosal atrophy, which occurs more in men than women.

Adult↗
PubMed1995

Both early and committed haemopoietic progenitors are more frequent in peripheral blood than in bone marrow during mobilization induced by high-dose chemotherapy + G-CSF.

Haemopoietic growth factor administration following high-dose chemotherapy markedly amplifies progenitor cell pool in the peripheral blood (PB). Collection and reinfusion of these cells enable rapid haemopoietic reconstitution following autograft. Less is known on engraftment potentiality of bone marrow (BM) cells taken under analogous conditions. To investigate this tissue, PB and BM were evaluated simultaneously during maximal mobilization in a series of 14 patients undergoing the HDS chemotherapy programme. A significantly higher growth of committed progenitors was found from PB rather than from BM (663 +/- 123 v 267 +/- 40 CFU-GM/10(5) MNC, respectively). Also, significantly more CFU-GM could be collected by a median of three leukaphereses, compared to those harvested from BM (158 +/- 31 v 16 +/- 4 x 10(4) CFU-GM/kg, respectively). Most mobilized CFU-GM were phenotypically immature (CD15-); in addition, circulating cells included primitive progenitors, as assessed by LTC-IC assay, or by evaluation of non-proliferating pre-CFU-GM, selected by an anti-CD71 immunotoxin. The amount of pre-CFU-GM determined by both techniques was consistently higher in PB than in BM. Moreover, a direct correlation could be established between circulating CFU-GM and primitive precursors. Thus, during optimally induced mobilization, PB contains many more haemopoietic progenitors, of both committed and primitive stages, than does BM. Under such conditions, PB is probably the best source of material for graft purposes.

Adult↗
PubMed1995

[The Italian mortality map at the municipal level].

The Italian Atlas of mortality at municipality level is the result of a research project coordinated by the Emilia-Romagna region and supported by the Health Ministry. To the realisation of this project have collaborated the Institute of Medical Statistics of Milano and the CILEA under the supervision of Prof. Cesare Cislaghi. Compared to previous equivalent products, this Atlas contains a number of methodological and content innovations. This was a consequence of the development of new statistical methods and the need of achieving different aims. First of all, the Atlas was aimed at describing the mortality at small area level, which is obtained via Kernel estimates; secondly, the objective was to identify suspect clusters of deaths which may suggest the existence of high risk areas. The Mortality Atlas is formed by 31 tables, one for each of the analysed cause of death; each table has a circular shape of 100 hundred kilometers radius and contains a variable number of municipalities; each municipality may be present in more than one circle. The Atlas is available on magnetic support and for each cause of death are provided several statistical analyses and indicators included in different files. One of these files can be directly used to build high quality maps using the graphical package MAPINFO.

Cervical Atlas↗
PubMed1995

[Significance of lactose breath test in the newborn].

Lactose breath test have been performed in healthy newborns, in whom breath hydrogen excretion was preliminarily demonstrated by lactulose breath test. 27.5% of newborns showed positive lactose breath test, with no differences related to sex and gestational age, while a higher percentage of positive test has been found in < 2500 g and formula-fed neonates compared, respectively, to > or = 2500 g and breast-fed ones. In healthy newborns, without any clinical signs of lactose intolerance, it is possible to demonstrate hydrogen in expired air; this is not equivalent of lactose malabsorption, but, instead, depends on the phenomenon of colonic fermentation that allows energy and nutrient absorption.

Breath Tests↗
PubMed1995

[The Bleuler tradition of the schizophrenia concept and Burghölzli as the site for psychotherapy of schizophrenic patients].

The author, who worked for many years with Manfred Bleuler, summarises the essence of Bleuler's theory of schizophrenia: that healthy and disturbed psychic processes occur simultaneously; an understanding of the complexity of the schizophrenic person; understanding the psychosis in relation to a persons life, which arises from a disposition that becomes manifest in the conflicts that life entails; the importance of psychotherapy and social care. The author shows how his own work contributed to this theory.

History, 19th Century↗