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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 163 records · Page 9Linked to original sources
PubMed1997

Plasma beta-endorphin, adrenocorticotropin hormone, and cortisol in autism.

Plasma levels of the hypothalamo-pituitary-adrenal axis hormones beta-endorphin (BE), adrenocorticotropin hormone (ACTH), and cortisol were measured in autistic (N = 48), mentally retarded/cognitively impaired (MR/CI, N = 16), and normal control (N = 26) individuals. Comparison of log transformed data from the three groups revealed that levels of BE and ACTH were significantly higher (p < .05) in the autistic individuals than in normal controls. The higher means in the autistic group were due to significantly higher plasma levels of BE and ACTH, indices of acute stress response, in the more severely affected individuals. The data support the idea that individuals with severe autism have a heightened response to acute stressors rather than chronic hyperarousal or elevated basal stress response system functioning.

Adolescent↗
PubMed1997

Ouabain-like factor quantification in mammalian tissues and plasma: comparison of two independent assays.

The resolution of controversies that concern the detectability of an endogenous ouabain-like factor (OLF) in mammalian tissues and plasma was approached by the application of a standardized method for its extraction and quantification. Two independent assays were used to quantify the OLF: (1) a radioimmunoassay, which used a polyclonal anti-ouabain antiserum, and (2) a radioenzymatic assay based on the inhibition of dog kidney Na+,K+-ATPase. Plasma and tissues were obtained from the Milan hypertensive strain (MHS) and the Milan normotensive strain (MNS) of rats and from healthy human volunteers. Results indicate that (1) a single high-performance liquid chromatography (HPLC) fraction identical to that of ouabain was identified by both assay methods in the rat hypothalamus and hypophysis and in both rat and human plasma; (2) dilution curves of OLF and standard ouabain were parallel and with a similar Kd, both in radioimmunoassay (3 nmol/L) and ATPase assay (14 nmol/L); (3) after HPLC, OLF was similarly quantified by the two methods in the hypothalamus, hypophysis, adrenals, and plasma of rats and in human plasma; (4) OLF was present in larger amounts in the hypothalamus, hypophysis, and plasma of MHS rats than that of MNS rats; (5) the HPLC fraction of human plasma was quantified similarly by both assays (range, 60 to 150 pmol/L); (6) recovery of standard ouabain in pre-HPLC plasma extracts was approximately 90%; and (7) pre-HPLC OLF concentrations in human plasma ranged between 0.05 and 0.75 nmol/L. Rat cerebral tissues and both rat and human plasma contained measurable amounts of OLF, which were quantified similarly by radioimmunoassay and ATPase assay, both before and after HPLC fractionation. The increased MHS tissue and plasma levels of OLF are in keeping with the pathogenetic role of this factor in MHS hypertension.

Adrenal Glands↗
PubMed1997

Oxoreductase and dehydrogenase activities of the human and rat 11beta-hydroxysteroid dehydrogenase type 2 enzyme.

The 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11betaHSD2) metabolizes glucocorticoids into their inactive 11-keto metabolites. Although the type 1 enzyme (11betaHSD1) displays both oxidative and reductive activity, to date 11betaHSD2 has been shown to have dehydrogenase activity only. In this study we compared both dehydrogenase and reductase characteristics of the cloned rat 11betaHSD1 and rat and human 11betaHSD2 for three different 11-hydroxysteroid substrates, cortisol (F), corticosterone (B), and dexamethasone (Dex), and the corresponding 11-keto metabolites, cortisone (E), 11-dehydrocorticosterone (A), and 11-dehydrodexamethasone (DH-Dex), respectively. In cell homogenates expressing either the rat or the human 11betaHSD2, the relative potency for the dehydrogenase reaction was B > F > Dex. Although there was no reduction of A or E, DH-Dex was readily converted to Dex with an equilibrium far on the side of the 11-hydroxy metabolite. DH-Dex reduction in homogenates was inhibited by both glycyrrhetinic acid and carbenoxolone, with a 50% inhibition at 80 and 100 nM, respectively. In intact cells transfected with rat 11betaHSD1, the equilibrium was on the reductase side for all substrates. Dehydrogenation of B or F was more potent with rat 11betaHSD2 than with rat 11betaHSD1. There was no detectable 11betaHSD1 oxidation of Dex. These data indicate that both the cloned human and rat 11betaHSD2 reduce DH-Dex and do this more readily than they oxidize Dex. Thus, 11betaHSD2 seems also to be a bidirectional enzyme, although no reduction of the physiological compounds A and E was observed.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Are the recent trends in liver cirrhosis mortality affected by the changes in alcohol consumption? Analysis of latency period in European countries.

OBJECTIVE: A striking reduction of alcohol-related problems, such as liver cirrhosis death rates, has been observed in many western countries in recent years. It might be expected that these declines are accompanied by a lagged reduction in per capita alcohol consumption, since many years of intake are required for cirrhosis of the liver to develop (lag theory). The main aim of this study is to verify the validity of the lag theory, taking as target populations those resident in European countries. METHOD: Changes in liver cirrhosis death rates in 22 European countries between 1970 and 1089 were regressed onto changes in per capita alcohol consumption (1961-89) to evaluate the latency period between trends of these variables. RESULTS: Eastern countries had a latency period between trends in alcohol consumption and in mortality rates of many years, whereas in northern, western and southern Europe cirrhosis mortality rates were explained by their relationship with per capita alcohol consumption, which lagged a few years. In some countries, an immediate contemporary appearance of the two phenomena was observed. CONCLUSIONS: These results suggest that the lag theory cannot fully explain the relationship between changing alcohol consumption and cirrhosis mortality and that other factors, such as alcoholism treatment rates, are involved in the wide geographical variability of the latency periods.

Adolescent↗
PubMed1997

Isolation and structure elucidation of 7,8-dideoxy-6-oxo-griseorhodin C produced by Actinoplanes ianthinogenes.

A novel product, isolated from a culture broth of Actinoplanes ianthinogenes fermented for producing purpuromycin, was purified and its structure established on the basis of physico-chemical data and chemical reactions. The new product resulted to be structurally related to griseorhodins, a group of hydroquinonic antibiotics obtained from Streptomyces californicus. This compound showed a weak activity against Gram-positive and resulted inactive against Gram-negative bacteria and Candida albicans.

Anti-Bacterial Agents↗
PubMed1997

Substitution of amino acids 1 and 3 in teicoplanin aglycon: synthesis and antibacterial activity of three first non-natural dalbaheptides.

The replacement of amino acids 1 and 3 of glycopeptide antibiotics (dalbaheptides) with new amino acids or other chemical entities suitable to interact with both glycopeptide-resistant (D-Ala-D-Lactate) and susceptible (D-Ala-D-Ala) targets is one of the chemical strategies currently followed to pursue activity against highly glycopeptide-resistant VanA enterococci while maintaining activity against glycopeptide-susceptible Gram-positive bacteria, particularly methicillin-resistant staphylococci. As a preliminary approach, the substitution of amino acid 1 of deglucoteicoplanin (TD) with D-lysine or D-methylleucine and of its amino acid 3 with L-phenylalanine or L-lysine was investigated. In this paper, the synthesis and in vitro antibacterial activities of first non-natural dalbaheptide methyl ester aglycons MDL 63,166 (D-Lys1-Phe-3-TD-DHP-Me), MDL 64,945 (D-Lys1-Lys3-TD-DHP-Me), and MDL 64,468 (D-MeLeu1-Lys3-TD-DHP-Me) are described. These compounds, which were obtained from intermediate TD-derived tetrapeptide methyl ester (TDTP-Me) according to a 9-step overall procedure, had excellent anti-staphylococcal activity. The most active derivative against staphylococci, MDL 64,945 (MIC: 0.063 microgram/ml for S. aureus, S. epidermidis and S. haemolyticus) was inactive against VanA enterococci, while MDL 63,166 and MDL 64,468 were somewhat active against VanA strains of E. faecalis; MDL 64,468 was also moderately active against one VanA isolate of E. faecium and had marginal activity as TD against E. coli.

Anti-Bacterial Agents↗
PubMed1997

[Aging of the vitreous body. Role of glycation and free radicals].

The vitreous body plays an important role in the structure and in the function of the eye. Its bio-rheological properties contribute crucially to the mechanical resistance and optical transparency of ocular tissues. The composition and structure of the vitreous body change during aging and more rapidly in diabetes. These changes may have deleterious consequences such as functional disturbances and retinal detachment. The mechanical and optical properties of the vitreous are the result of its particular macromolecular architecture composed of a hyaluronan gel supported by a fine collagen meshwork, essentially of type II and IX. These are held together by proteoglycans and by fibronectin. All these macromolecules are susceptible to free radical damage produced by UV and visible light, by metabolic processes as well as the Maillard reaction. The mechanisms by which Maillard products and free radicals play a role in the physiological or accelerated aging of the vitreous are discussed in this review.

Aged↗
PubMed1997

A comparative study of defense styles of bulimic, anorexic and normal females.

We have compared the defense styles of anorexic (N = 41), bulimic (N = 37) and normal females (N = 72) living in Paris, using the Bond Defense Style Questionnaire relating to 17 defenses: sublimation, anticipation, suppression, undoing, idealization, reaction formation, projection, passive aggression, acting out, isolation, devaluation, autistic fantasy, denial, displacement, dissociation, splitting and somatization. The objective of this study was to better understand the personality structure in terms of psychological defenses of adolescent girls and young women suffering from anorexia or bulimia nervosa (DSM-III-R). Data showed significant differences of psychological functioning between control subjects and eating disorder subjects, particularly for the projection, undoing and sublimation defenses. Anorexics differed from the bulimic females only on the passive aggression, isolation and devaluation defenses. These data are discussed in relation to the hypothesis that anorexics and bulimics can be situated on the same continuum ranging from normal to eating disorders with certain common psychological features as risk factors shared by the eating disorder females.

Adolescent↗
PubMed1997

[Molecular biology in bladder carcinoma: contributions of immunohistochemistry].

Despite the insights genetics and molecular biology have given to a better understanding of the mechanisms which lead to the onset and development of bladder carcinoma, the factors that influence its unpredictable and, at times, particularly aggressive outcome are still largely unknown. Also in bladder carcinoma the study of cellular differentiation markers has been replaced by that of genotypic alterations, and, mainly with the help of immunohistochemistry, of the expression of genes involved in cell proliferation and death, such as MTS1, TP53, Rb, c-myc, Bcl-2, c-erb-B2. So far, anyway, no independent and reliable indicator able to predict the outcome of the single tumour has been identified, and this issue seems to be best addressed by studies of the altered expression of more than one oncoprotein simultaneously. Fairly identical is the question arised by TP53 mutations, which, while worsening the evolution of advanced muscle-infiltrating tumours, hold a still unclear and debated meaning in superficial tumours. It is anyway clear that molecular analysis only may enable to reliably detect the presence of any TP53 mutations. As a matter of fact, the multiplicity of genetic mutations, the frequent transcript variations and the intrinsic limits of immunohistochemistry may explain the discrepancy between immunohistochemical and molecular analysis results, with specificity and sensitivity levels clinically not acceptable. To date, anyway, the biological and clinical meaning of this discrepancy has still to be clarified, as well as the clinical meaning, if any, of p53 overexpression in the absence of gene mutations.

Gene Expression↗
PubMed1997

[Flexibility of the surgical model of intestinal transplantation in swine].

AIM: To verify the feasibility to introduce variations in the technique of intestinal transplantation, we developed three different intestinal transplant models in pigs. EXPERIMENTAL DESIGN: Feasibility and comparative study. ENVIRONMENT: Pre-clinical organ transplant surgery. MATERIALS AND METHODS: Sixty outbread piglets (mean weight 27.1 +/- 4.4 kg) received a total orthotopic intestinal allograft from equivalent donors perfused through the aorta with UW solution at 4 degrees C. Intraluminal flushing of the graft was always avoided. The animals were divided in 3 groups according to the transplantation procedure adopted. Group 1 (n = 9): excision of small and large bowel and replacement with small bowel only; group 2 (n = 39): excision of small bowel and its replacement; group 3 (n = 12): excision of small and large bowel and their "en-bloc" replacement. The superior mesenteric artery and vein were anastomosed end-to-end in all groups. RESULTS: The lowest perioperative mortality occurred in group 2 (28%), followed by group 3 (58%) and group 1 (78%). However, in group 1 the incidence of perioperative deaths was influenced by our learning curve in surgical and anesthesiologic management. No significant differences were noted in terms of cold and warm ischaemia time of the grafts, length of operative time, histopathologic analysis of preservation injury. The addition of the colon in the transplanted graft resulted in a more critical hemodynamic profile at reperfusion. CONCLUSION: Three different experimental models of intestinal transplantation are feasible in pigs. The choice can be made based on the type of study needed.

Analysis of Variance↗
PubMed1996

Synthesis and quantitative structure-activity relationship of 17 beta-(hydrazonomethyl)-5 beta-androstane-3 beta,14 beta-diol derivatives that bind to Na+,K(+)-ATPase receptor.

A series of 17 beta-(hydrazonomethyl)-5 beta-androstane-3, beta,14 beta-diol derivatives was synthesized and evaluated in the displacement of [3H]ouabain binding from Na+,K(+)-ATPase. The data were explored with multiple linear regression and partial least-squares to find possible quantitatives structure-activity relationships. Good correlations were found between binding to the receptor and van der Waals volumes or molar refractivities of the 17 beta-hydrazonomethyl substituents and pKa values of the compounds. Equivalent results were obtained using the proton affinity (calculated using MOPAC) of the hydrazone residues instead of experimental pKa. As basicity or related electronic factors of the substituents explain a significant portion of the observed changes in the activity, an ion-pair interaction between a carboxylate residue of the enzyme and the protonated 17 beta-hydrazonomethyl group, as postulated by Thomas, plays an important role in the interaction of the ligand to the Na+,K(+)-ATPase receptor.

Androstane-3,17-diol↗
PubMed1996

Rat 11 beta-hydroxysteroid dehydrogenase type 2 enzyme is expressed at low levels in the placenta and is modulated by adrenal steroids in the kidney.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) protects the non-discriminating mineralocorticoid receptor from occupation by glucocorticoids. In man the enzyme is also highly expressed in the placenta where it is thought to also protect the fetus from the high circulating levels of maternal glucocorticoids. Mutations in the HSD11B2 gene have recently been shown to account for the syndrome of apparent mineralocorticoid excess. In the present study we have used a rat 11 beta HSD2 cDNA to study the distribution and regulation of this enzyme. The rat protein is highly homologous to the mouse, rabbit and human enzymes, except for the carboxy-terminal region which displays extensive divergence between species beyond residue 382. Northern blot analysis of rat total RNA showed that the single copy gene is highly expressed in kidney and adrenal with lower levels in the colon; surprisingly, there was no detectable signal in the placenta. There was also no detectable mRNA in the liver, heart, hippocampus, testis, thymus and pancreas. Nuclease protection analysis revealed the presence of moderate 11 beta HSD2 message levels in the parotid and exceedingly low levels in the placenta. Regulation studies showed that administration of dexamethasone, deoxycorticosterone and 9 alpha-fluorocortisol to adrenalectomized rats for 7 days increased renal enzyme activity 33%-50%, while message levels decreased 35%-70%, suggesting that the increased enzyme activity may represent activation of latent enzyme.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Hypertension-associated point mutations in the adducin alpha and beta subunits affect actin cytoskeleton and ion transport.

The adducin heterodimer is a protein affecting the assembly of the actin-based cytoskeleton. Point mutations in rat adducin alpha (F316Y) and beta (Q529R) subunits are involved in a form of rat primary hypertension (MHS) associated with faster kidney tubular ion transport. A role for adducin in human primary hypertension has also been suggested. By studying the interaction of actin with purified normal and mutated adducin in a cell-free system and the actin assembly in rat kidney epithelial cells (NRK-52E) transfected with mutated rat adducin cDNA, we show that the adducin isoforms differentially modulate: (a) actin assembly both in a cell-free system and within transfected cells; (b) topography of alpha V integrin together with focal contact proteins; and (c) Na-K pump activity at V(max) (faster with the mutated isoforms, 1281 +/- 90 vs 841 +/- 30 nmol K/h.mg pt., P < 0.0001). This co-modulation suggests a role for adducin in the constitutive capacity of the epithelia both to transport ions and to expose adhesion molecules. These findings may also lead to the understanding of the relation between adducin polymorphism and blood pressure and to the development of new approaches to the study of hypertension-associated organ damage.

Actins↗
PubMed1996

Point mutations abolish 11 beta-hydroxysteroid dehydrogenase type II activity in three families with the congenital syndrome of apparent mineralocorticoid excess.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts cortisol into mineralocorticoid receptor inactive cortisone, thus preventing occupation of the non-selective mineralocorticoid receptor by glucocorticoids in the kidney. Mutations generating inactive enzymes have been described in the HSD11B2 gene in the congenital syndrome of apparent mineralocorticoid excess (AME), although proof of mutant protein synthesis was not provided. In the present study we have examined the metabolism of cortisol in mammalian cells transfected with plasmids expressing the wild type and mutant enzymes from three additional families of patients with mutations in the HSD11B2 gene. These studies revealed that the mutants were enzymatically inactive in intact mammalian cells expressing significant levels of both full length and truncated proteins. This is the first study to definitively show that point mutations in the HSD11B2 gene abolish 11 beta HSD2 enzymatic activity in the syndrome of AME.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

The 11 beta-hydroxysteroid dehydrogenase type II enzyme: biochemical consequences of the congenital R337C mutation.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts cortisol to cortisone, allowing the non-selective mineralocorticoid receptor to bind aldosterone. When the activity of this enzyme is compromised, as occurs in licorice intoxication or in the congenital syndrome of apparent mineralocorticoid excess (AME), there is marked sodium retention, hypokalemia, and hypertension. The first proof that this enzyme was defective in AME came from the identification of the R337C mutation in a number of siblings with the syndrome. Subsequent expression studies showed that the mutant had a Km one order of magnitude higher than the wild-type enzyme while in the cell-free system it was without detectable activity. In the present work we have extended our studies on this mutant and provide evidence that the mutant protein may also partially inhibit the wild-type enzyme in heterozygotes. Furthermore, experiments incorporating the protein synthesis inhibitor cycloheximide show that the mutant enzyme is less stable than the wild-type activity in intact cells. These results suggest that mutations in the 11 beta HSD2 enzyme may have multiple consequences for the mineralocorticoid target cell.

11-beta-Hydroxysteroid Dehydrogenases↗