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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Guidelines on intestinal dysmicrobism (SIBO Small Intestine Bacterial Overgrowth)].

Bacterial flora consisting of Gram-positive and Gram-negative germs, aerobes and anaerobes, is distributed along the digestive tract in varying quantities from zero to a maximum of 10(12)/ml of endoluminal aspirate. This bacterial ecosystem counterbalances with the ecological niche of the host organism and harmonizes with the various digestive, secretory, motor, absorption and sensitivity functions of the entire intestine. This dynamic equilibrium between environment, bacterial flora and host may be interrupted due to a variety of complex reasons, leading to quantitative and qualitative modifications of the normal intestinal microbial flora that can cause Small Intestinal Bacterial Overgrowth (SIBO). SIBO is thus due to an invasion of the small intestine, from the upper part, by pathogenic strains of oro-alimentary origin, and from the lower part by colo-fecal germs through an incontinent Bauhin's valve. These germs alter the normal intestinal functions and give rise to a form of diarrhoea in which the characteristics of malabsorption prevail, with all the inherent diagnostic problems. The diagnostic gold standard is the culture of the duodenal-jejunal aspirate which, being difficult to perform and providing unreliable results, is not easily included in the daily clinical routine. Indirect tests include the breath test, which is widely accepted by patients but burdened by diagnostic doubts on the part of medical personnel. Diagnostic confirmation is therefore greatly conditioned by clinical subjectivity and objectivity, as well as by the response to medical therapy. In cases of declared malabsorption, medical therapy is necessary by means of appropriate diet, prebiotics, probiotics and antibiotics. The difficulty in identifying the specific bacterial population and the part of the digestive tract that is affected indicate the appropriateness of a broad-spectrum antibiotic therapy, capable of eradicating aerobes and anaerobes, preferably with a topical rather than a general action, frequently cause of undesired effects.

English Abstract↗
PubMed1998

Estrogen suppression as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia: evidence for its efficacy from studies with mepartricin.

Estrogen suppression has been introduced as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia. Recent negative results obtained in placebo-controlled trials with the aromatase inhibitor atamestane raised doubts about the efficacy of estrogen reduction. However, inhibition of aromatase not only reduces estrogens but also increases androgens which promote prostatic growth. In order to reevaluate the therapeutic efficacy of estrogen suppression, we summarize clinical trials investigating the therapeutic effects of mepartricin in the treatment of uncomplicated benign prostatic hyperplasia. Mepartricin has been reported to lower the levels of circulating estrogens without causing changes in other hormones such as androgens. By applying stringent inclusion criteria, 23 studies (including 7 placebo-controlled trials, 3 post-marketing surveillance studies, and 13 open trials) published between 1982 and 1996 were selected to be included in this report. In 79.9% of 4635 patients treated with mepartricin, its therapeutic effect was rated "good" or "excellent". In 6 out of 7 placebo-controlled trials, the therapeutic efficacy of mepartricin was significantly superior to that of placebo. Comparison of these data with results obtained with alpha 1-adrenoceptor antagonists or with the 5 alpha-reductase inhibitor finasteride indicates that mepartricin is as efficient as these widely accepted medical treatments for benign prostatic hyperplasia. Since mepartricin acts selectively upon estrogens, the present results show that estrogen suppression may be considered an efficient pharmacotherapeutic strategy in the medical treatment of uncomplicated benign prostatic hyperplasia.

Clinical Trials as Topic↗
PubMed1998

Defensive behaviors in wild and laboratory (Swiss) mice: the mouse defense test battery.

The development of laboratory rodent models for elicitation and measurement of a range of defensive behaviors raises the question of the relationship between defense in these animals and those of their wild congeners. To evaluate this relationship for mice, defensive responses to an anesthetized rat were compared for fourth-generation laboratory-bred wild mice and Swiss CD-1 (Swiss-Webster derived) laboratory mice in a Mouse Defense Test Battery. Wild mice showed enhanced levels of both freezing and flight, fleeing from distant approach of the predator in several situations and fleeing more quickly than the Swiss mice. However, Swiss mice did flee upon contact with the rat and also showed levels of several other defensive behaviors (risk assessment, defensive threat, and attack) that were often reliably higher than those of the wild mice. However, when wild mice were prevented from fleeing, their levels of defensive threat and attack were as high as, or at very short prey-predator distances higher than, those of the Swiss mice. These findings suggest that flight and freezing are the major defensive behaviors reduced in Swiss mice and that these reductions allow the appearance of higher levels of additional defensive behaviors in the laboratory animals. However, although Swiss mice do show lower levels of flight and freezing, their patterns of defensive behavior are sufficiently similar to those of wild mice that they provide adequate subjects for research on the biologic bases of defensive behavior. A final experiment indicated that when wild mice are familiarized with a chamber providing a place of concealment, they flee directly to this chamber on presentation of a rat, indicating that flight is a targeted response and not simply an abrupt increase in forward locomotion. Over 10 rat presentation trials with a blocked chamber entrance, however, this response declines.

Aggression↗
PubMed1998

Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken. METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included. RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH. CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents.

Anti-Bacterial Agents↗
PubMed1998

Latency of evoked neuromagnetic M100 reflects perceptual and acoustic stimulus attributes.

The latency of components of the auditory evoked neuromagnetic field has been shown to reflect, or encode, stimulus attributes. In particular, the M100 component, occurring approximately 100 ms post stimulus onset has a latency that depends on stimulus pitch, spectral complexity and presentation level. This study used magnetoencephalography to record neuromagnetic fields evoked by presentation of two-tone complexes consisting of various proportions of 100 Hz and 1 kHz energy. These are perceived categorically, as evidenced by classification and reaction time measurements. It is found that the M100 latency also varies categorically, that is, characterized by two plateau regions with a sharp interface. Thus, we find that not only does the M100 latency reflect acoustic attributes of a stimulus, but also such perceptual characteristics.

Acoustic Stimulation↗
PubMed1998

A genetic defect resulting in mild low-renin hypertension.

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) cause AME. Typical patients with AME have defective 11beta-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the HSD11B2 gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0-6% in typical patients with AME whereas the normal conversion is 90-95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C-->T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation. In vitro expression studies showed an increase in the Km (300 nM) over normal (54 nM). Because approximately 40% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the HSD11B2 gene.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Comprehensive study on structure-activity relationships of rifamycins: discussion of molecular and crystal structure and spectroscopic and thermochemical properties of rifamycin O.

The mechanism of action of rifamycins against bacterial DNA-dependent RNA polymerase has been explained on the basis of the spatial arrangement of four oxygens which can form hydrogen bonds with the enzyme. Structural descriptors are derived from X-ray diffraction crystal structures of 25 active and nonactive rifamycins. Principal component analysis is used to find the combination of structural parameters which better discriminate between active and nonactive rifamycins. Two possible mechanisms of molecular rearrangement are described which can convert nonactive into active conformations. The energy involved for conformational rearrangements is studied by molecular modeling techniques. Methyl C34 is found to play a key role for determining the geometry of the pharmacophore. Rifamycin O, reported to be active, is obtained by oxidation of rifamycin B and is studied by X-ray single-crystal diffractometry, by solution IR and NMR spectroscopy, and by thermal analysis. Surprisingly the oxidation process is totally stereospecific, and an explanation is given based on solution spectroscopic evidence. The conformation found in the solid state is typical of nonactive compounds, and molecular mechanics calculations show that a molecular rearrangement to the active conformation would require about 15 kcal/mol. Thermal analysis confirms that rifamycin O has a sterically constrained conformation. Therefore, it is likely that the antibiotic activity of rifamycin O is due either to chemical modification prior to reaching the enzyme or to conformational activation.

Calorimetry, Differential Scanning↗
PubMed1998

p125Fak focal adhesion kinase is a substrate for the insulin and insulin-like growth factor-I tyrosine kinase receptors.

The focal adhesion kinase p125(Fak) is a widely expressed cytosolic tyrosine kinase, which is involved in integrin signaling and in signal transduction of a number of growth factors. In contrast to tyrosine kinase receptors such as the platelet-derived growth factor and the hepatocyte growth factor receptors, which induce p125(Fak) phosphorylation, insulin has been shown to promote its dephosphorylation. In this study, we compared p125(Fak) phosphorylation in insulin-stimulated cells maintained in suspension or in an adhesion state. We found that, in nonattached cells, insulin promotes p125(Fak) phosphorylation, whereas dephosphorylation occurred in attached cells. This was observed in Rat-1 fibroblasts overexpressing the insulin receptor, as well as in Hep G2 hepatocytes and in 3T3-L1 adipocytes expressing more natural levels of insulin receptors. Insulin-induced p125(Fak) phosphorylation correlated with an increase in paxillin phosphorylation, indicating that p125(Fak) kinase activity may be stimulated by insulin. Mixing of purified insulin or insulin-like growth factor-I (IGF-I) receptors with p125(Fak) resulted in an increase in p125(Fak) phosphorylation. Using a kinase-deficient p125(Fak) mutant, we found that this protein is a direct substrate of the insulin and IGF-I receptor tyrosine kinases. This view is supported by two additional findings. (i) A peptide corresponding to p125(Fak) sequence comprising amino acids 568-582, which contains tyrosines 576 and 577 of the kinase domain regulatory loop, is phosphorylated by the insulin receptor; and (ii) p125(Fak) phosphorylation by the insulin receptor is prevented by addition of this peptide. Finally, we observed that p125(Fak) phosphorylation by the receptor results in its activation. Our results show that the nature of the cross-talk between the insulin/IGF-I receptors and p125(Fak) is dependent on the cell architecture, and hence the interaction of the insulin/IGF-I signaling system with the integrin system will vary accordingly.

Amino Acid Sequence↗
PubMed1998

Effects of cachexia due to cancer on whole body and skeletal muscle protein turnover.

BACKGROUND: Data available in the literature regarding whole body protein (WBP) kinetics in patients with cachexia due to cancer are conflicting. Some authors have reported an increase of WBP synthesis and breakdown, whereas others have not found any significant changes; only a few researchers have investigated more compartments simultaneously. The main purpose of this study was to investigate WBP and skeletal muscle protein (SMP) turnover simultaneously in cachectic patients to understand better the mechanisms underlying the general wasting of the host present in cancer cachexia. METHODS: WBP and SMP synthesis and breakdown were studied in malnourished patients with advanced gastric carcinoma and in healthy volunteers. Protein turnover was evaluated in a postabsorptive state, using a model based on a primed constant infusion of L-[(2)H5] phenylalanine and L-[(2)H4]tyrosine, and by determining the isotopic enrichment and concentration in plasma during a plateau phase by gas chromatography and mass spectrometry. RESULTS: Rates of WBP synthesis and breakdown did not differ significantly between the two groups (whole body synthesis [WBS] of 4.35 +/- 0.2 g/kg/day and whole body breakdown [WBB] of 4.77 +/- 0.2 g/kg/day in the control group and WBS of 3.34 +/- 0.7 g/kg/day and WBB of 4.5 +/- 0.4 g/kg/day in the patient group). The skeletal muscle compartment of the patients showed a significantly lower synthesis compared with controls (patients, 9.6 +/- 1.8 nmol/100 mL/minute and control, 25.9 +/- 7.6 nmol/100 mL/minute; P < 0.05), whereas the breakdown was similar in the two groups. Such reduction in SMP synthesis in the gastric carcinoma patients resulted in a more negative net balance. CONCLUSIONS: Conflicting data in the literature may be accounted for by the different selection of patients and controls. Furthermore, WBP kinetics is the result of the metabolism of at least two compartments, the muscle and the nonmuscle compartments (including the tumor), which can change in opposite ways. In patients with cachexia due to cancer, the skeletal compartment appears to be the more compromised, with a significant decrease in SMP synthesis.

Adult↗
PubMed1998

Large-scale preparation, purification, and crystallization of UDP-N-acetylmuramoyl-L-alanine: D-glutamate ligase from Escherichia coli.

The UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli, an enzyme involved in the biosynthesis of the bacterial peptidoglycan monomer unit, was overproduced and purified to homogeneity on a large scale, yielding 4 mg of protein per liter of bacterial culture. Crystals of the complex with the substrate UDP-MurNAc-L-Ala were grown by the hanging drop method using ammonium sulfate as the precipitant. They are tetragonal with cell dimensions a = b = 65.5 A and c = 134.59 A, space group P4(1) or P4(3), and contain one monomer of 46,842 Da in the asymmetric unit. In order to use the multiple-wavelength anomalous diffraction method for phasing, a selenomethionine derivative of the protein has also been overproduced, purified, and crystallized.

Amino Acid Sequence↗
PubMed1998

Social learning of a food preference in male and female Mongolian gerbils is facilitated by the anxiolytic, chlordiazepoxide.

Social transmission of a food preference in Mongolian gerbils (Meriones unguiculatus) depends on the presence of a social bond between the interacting animals. An "observer" gerbil can acquire a preference for a novel food item from a familiar and, or related "demonstrator" animal. However, exposure to an unfamiliar and unrelated demonstrator gerbil does not lead to acquisition of a food preference, even though the extent of social interaction and likelihood of transmission of food information is unaffected. Likewise, individual preexposure to a novel food does not affect diet preference in individual animals. Here we show that oral, nongavage, administration of the benzodiazepine anxiolytic, chlordiazcpoxide (CDP, 2.5, 5, and 10 mg/kg) has significant dose-associated differential facilitatory effects on social learning in male and female gerbils, while having no significant effects on either individual learning or total food consumption. These results suggest that the CDP mediated reduction of the anxiety associated with the interactions between unfamiliar/unrelated gerbils facilitates social learning. These findings also rise the possibility of sex differences in socially related anxiety and the effects of CDP on social learning in gerbils.

Animals↗
PubMed1998

Free radical depolymerization of hyaluronan by Maillard reaction products: role in liquefaction of aging vitreous.

The degradation of hyaluronan was followed by viscosimetry and by HPLC in order to study the possible role of Maillard products (lysine-glucose) on the alteration of the vitreous gel in aging and diabetes. Lysine-glucose generated Maillard products produced a decrease of viscosity and of the number average molecular weight (Mn) of hyaluronan during a 1 h incubation at 37 degrees C. This effect was comparable to that produced by 1 U/ml of testicular hyaluronidase but was weaker than the effect of a Fenton-type reagent (Udenfriend's reagent). The polydispersity of hyaluronan incubated with Maillard products appeared higher than with hyaluronidase suggesting a more random reaction. Antioxydant enzymes (SOD, catalase), the iron chelators (desferrioxamine, transferrin) and the free radical scavengers (uric acid, carnosine) inhibited the degradation by Maillard products confirming its free radical nature and the intervention of trace metals. Maillard products have been detected in diabetic vitreous and may play a role in its accelerated modifications (liquefaction) in diabetes as compared to normal aging.

Aging↗
PubMed1998

A multistep therapy with subcutaneous low dose recombinant interleukin-2, 5-fluorouracil and leucovorin prolongs the response of metastatic colorectal cancer patients: a pilot study.

Data from 12 metastatic colorectal cancer patients who were submitted to a pilot study with a multistep subcutaneous (sc) low dose recombinant interleukin-2 (rIL-2), 5-fluorouracil (5-FU) and leucovorin (LV) administration were compared with those from 13 historical controls who were comparable for the major prognostic indices. All 12 patients in the pilot study were subjected initially to six to eight courses of 5-FU-LV by endovenous (ev) bolus consistent with the Machover schedule alternating with 6 weeks of rIL-2 cycles. At the progression of metastatic disease, the patients were given 500 mg/m2 per day of 5-FU by continuous infusion (ci) for 5 days every 4 weeks and in case of further progression, 2,600 mg/m2 of 5-FU by 24-h ci once a week for 6 weeks. The control patients were treated with 5-FU-LV by the Machover schedule until progression and then observed. As yet, two patients in the pilot study and three control patients are currently alive. In the pilot study, the patients' response rate (CR + PR) and overall response rate (CR + PR + SD) were much higher than in the controls (50 vs 23% and 92 vs 54%, respectively). Time duration of response and survival from primary surgery were more prolonged in the pilot study than in the historical control, although not significantly (10.5 vs 6 and 41.5 vs 29 months, respectively). Time from starting therapy to progression and survival from relapse were significantly in favour of the pilot study (11.5 vs 4 and 31 vs 13.5 months; P < 0.01 and P < 0.05 unpaired t-test, respectively). Low dose s.c. rIL-2 cycles were well tolerated and no interruption occurred. In the pilot study sporadic grade 3 toxicity (diarrhoea or leucopenia) was responsible for the reduction of 5-FU doses to 80% of the previous infusion, but no treatment was postponed. In conclusion, these preliminary data suggest the opportunity to initiate large prospective randomized trials using a multistep therapy with rIL-2, 5-FU ci at conventional and at high dose in metastatic colorectal cancer.

Aged↗
PubMed1998

Exploring the combined action of lifetime alcohol intake and chronic hepatotropic virus infections on the risk of symptomatic liver cirrhosis. Collaborative Groups for the Study of Liver Diseases in Italy.

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables. a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.

Adolescent↗
PubMed1998

Catalase in the stratum corneum of patients with polymorphic light eruption.

UV radiation generates reactive oxygen species, which may be involved in polymorphic light eruption. The endogenous enzymatic defense system includes catalase in the epidermis. Thirteen patients with a history of polymorphic light eruption, but free from lesions, and 13 controls were investigated from November to March. Catalase was analysed in the upper horny layer according to Colin et al.'s spectrophotometric technique. In polymorphic light eruption, catalase values were about 30% lower than in control subjects. Such deficiency was observed in patients free from the disease and not recently sun-exposed. The diminished skin catalase in irradiated polymorphic light eruption makes it possible that a longer restoration time of catalase is involved in the pathogenesis.

Adolescent↗
PubMed1998

Echo-guided SWL of vesical stones with Dornier MPL 9000 lithotripter in obstructed and unobstructed patients.

Sixty-one patients with vesical stones (38 with underlying obstructive conditions and 23 unobstructed) underwent SWL using ultrasound targeting under no regional or general anesthesia. A foley catheter was not routinely employed, and the bladder was filled in a physiologic way. Complete resolution was obtained in 47 patients (78%); in particular, 66% of the obstructed patients and 96% of the unobstructed patients became stone free in one to four SWL sessions. The average number of sessions for all patients was 1.28+/-0.63. Fragments were completely evacuated also in some patients with severe obstruction and in all three patients with neurogenic bladder dysfunction. The size and number of stones did not seem to play a limiting role in SWL effectiveness: the principal limiting factor was the hardness of the stone. No severe complications occurred. However, in six patients (10%), some fragments stopped in the urethra, causing acute urine retention, and endoscopic extraction was necessary. Echo-guided SWL of bladder stones is safe and highly effective in nonobstructed patients and can be considered the elective monotherapy method. In obstructed patients, SWL efficacy is lower, but the method may be suggested for patients who refuse or delay other, more invasive techniques.

Adolescent↗
PubMed1998

Endothelin-1 infusion inhibits plasma insulin responsiveness in normal men.

OBJECTIVES: Elevated plasma endothelin (ET)-1 levels have been described in insulin-resistant states such as syndrome X, obesity, non-insulin-dependent diabetes mellitus, and in some studies in essential hypertension. To investigate whether increases in circulating ET-1 to levels observed in insulin-resistant states can modulate insulin levels and/or insulin sensitivity in humans, we assessed these variables during low, non-pressor-dose ET-1 compared with placebo infusion. DESIGN: In a randomized, single blind, crossover design, 10 lean normotensive male subjects received either an intravenous infusion of subpressor doses of ET-1 dissolved in polygeline or a control infusion of polygeline only (placebo). Using dynamic assessment by the minimal model approach with the modified frequent sampling intravenous glucose tolerance test (FSIGT) the following and other parameters were measured: insulin sensitivity; acute insulin response to glucose (AIR(G)) calculated as the average of the three peak values between 2 and 5 min after injection of glucose from which the basal insulin levels were subtracted; the initial area under the curve (AUC(1-19)) from insulin values between time 0 and 19 min and the first-phase insulin secretion (phi1) from insulin kinetics parameters. RESULTS: ET-1 infusion reduced AIR(G) (to 34.85 +/- 4.27 compared with 49.3 +/- 6.9 microU/ml during placebo, P=0.017) and the acute C-peptide response to glucose (to 2.33 +/- 0.41 compared with 3.1 +/- 0.44 ng/ml, P=0.018), decreased plasma insulin levels during the FSIGT compared with placebo (analysis of variance P<0.0001) and decreased the AUC(1-19) (to 2.1 +/- 0.2 compared with 2.9 +/- 0.3 U/l per 20 min, P<0.01) while phi1 tended to be lower. S1 measured during ET-1 infusion was unaltered (11.11 +/- 1.91 x 10(-4) versus 10.88 +/- 2.11 10(-4)/min per mU per l, NS). CONCLUSIONS: These findings demonstrate that an increase in circulating ET-1 to levels observed in insulin-resistant states acutely diminishes the insulin secretory response but does not significantly modify insulin sensitivity.

Adult↗