Association between follicular fluid leptin and serum insulin levels in nonoverweight women with polycystic ovary syndrome.

AIMS: We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF). MATERIALS AND METHODOLOGY: We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17- ß -estradiol (17 ß -E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin). RESULTS: In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. CONCLUSIONS: Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.

Is the catalytic mechanism of bacteria, plant, and mammal copper-TPQ amine oxidases identical?

This short review is mostly concerned with the work carried out in Rome on the copper amine oxidase from bovine serum (BSAO). The first target was the copper oxidation state and its relationship with the organic cofactor. It was found that copper is not reduced on reaction with amines under anaerobic conditions or along the catalytic cycle and that it is not within bonding distance of the quinone cofactor. The copper stability in the oxidised state was supported by BSAO ability to oxidise benzylhydrazine, a slow substrate, in the presence of N,N-diethyldithiocarbamate (DDC) and by the substantial catalytic activity of Co(2+)-substituted BSAO. Parallel work established that only one subunit of the dimeric enzyme readily binds reagents of the carbonyl group. Flexible hydrazides with a long aromatic tail were found to be highly specific inhibitors, suggesting the presence of an extended hydrophobic region at the catalytic site. A study by stopped-flow transient spectroscopy and steady state kinetics led to the formulation of a simplified, yet complete and consistent, catalytic mechanism for BSAO that was compared with that available for lentil seedling amine oxidase (LSAO). As in other copper amine oxidases, BSAO is inactivated by H(2)O(2) produced in the catalytic reaction, while the cofactor is stabilised in its reduced state. A conserved tyrosine hydrogen-bonded to the cofactor might be oxidised.

New perspectives on the role of amine oxidases in physiopathology.

In the paper here presented we summarize some results obtained in our laboratory in the last few years on new structural and functional aspects of some amine oxidases (AOs), which have to be taken into consideration in defining new strategies of controlling the cellular physiopathology. In particular, the ability of Cu-AO purified from vegetal sources or from bovine serum to bind different cellular targets inducing in them conformational as well as chemical modifications are described and the consequences of this interaction on cellular functions are discussed. This is the case of the protective effect of Cu-AO against the damage induced by free radicals, cell enrichment with Cu-AO, induction of cataract and the leukocyte-endothelia interaction. The role of Cu and FAD-amine oxidases related as to the protection or damage of cells is also discussed. In this context the involvement of MAOs in the modulation of the mitochondrial functions and in the induction of apoptosis is described and some aspects of the molecular mechanism of AO inhibition by H(2)O(2) and metronidazole analyzed.

Tyramine and monoamine oxidase inhibitors as modulators of the mitochondrial membrane permeability transition.

Incubation of rat liver mitochondria with 100-500 mM tyramine, a substrate for monoamine oxidases A and B (MAOs), in the presence of 30 mM Ca2+ induces matrix swelling, accompanied by collapse of membrane potential, efflux of endogenous Mg2+ and accumulated Ca2+ and oxidation of endogenous pyridine nucleotides. These effects are completely abolished in the presence of cyclosporin A, ADP, dithioerythritol and N-ethylmaleimide, thus confirming the induction of the mitochondrial membrane permeability transition (MPT). The observed partial protective effect exerted by catalase indicates the involvement of both MAO-derived hydrogen peroxide and aldehyde. Higher concentrations of tyramine (1-2 mM) are less effective or even completely ineffective. At these high concentrations tyramine has an inhibitory effect when the MPT is induced by 100 mM Ca2+. The MAO inhibitors clorgyline (50 mM) and pargyline (500 mM) completely protect against MPT induction by 100 mM tyramine but also inhibit the phenomenon, although with different efficacy, when it is induced by 100 mM Ca2+ in the absence of tyramine. Taken together, our data suggest that tyramine, clorgyline and pargyline act as modulators of the MPT either through a direct inducing/protective effect or by controlling hydrogen peroxide and aldehyde generation.

Modulation of bovine serum amine oxidase activity by hydrogen peroxide.

Bovine serum amine oxidase (BSAO), reduced by excess amine under limited turnover conditions, was over 80% inactivated by H(2)O(2) upon oxygen exhaustion. The UV-Vis spectrum and the reduced reactivity with carbonyl reagents showed that the cofactor topaquinone (TPQ) was stabilized in reduced form. The protein large M(r) (170 kDa) prevented the identification of modified residues by amino acid analyses. Minor changes of the Cu(2+) EPR signal and the formation of a radical at g = 2.001, with intensity a few percent of that of the Cu(2+) signal, unaffected by a temperature increase, suggest that Cu(2+)-bound histidines were not oxidized and the radical was not the Cu(+)-semiquinolamine in equilibrium with Cu(2+)-aminoquinol. It may derive from the modification of a conserved residue in proximity of the active site, possibly the tyrosine at hydrogen-bonding distance of TPQ C-4 ionized hydroxyl. The inactivation reaction appears to be a general feature of copper-containing amine oxidases. It may be part of an autoregulatory process in vivo, possibly relevant to cell adhesion and redox signaling.

The demand for health: an empirical test of the Grossman model using panel data.

Grossman derives the demand for health from an optimal control model in which health capital is both a consumption and an investment good. In his approach, the individual chooses his level of health and therefore his life span. Initially an individual is endowed with a certain amount of health capital, which depreciates over time but can be replenished by investments like medical care, diet, exercise, etc. Therefore, the level of health is not treated as exogenous but depends on the amount of resources the individual allocates to the production of health. The production of health capital also depends on variables which modify the efficiency of the production process, therefore changing the shadow price of health capital. For example, more highly educated people are expected to be more efficient producers of health who thus face a lower price of health capital, an effect that should increase their quantity of health demanded. While the Grossman model provides a suitable theoretical framework for explaining the demand for health and the demand for medical services, it has not been too successful empirically. However, empirical tests up to this date have been exclusively based on cross section data, thus failing to take the dynamic nature of the Grossman model into account. By way of contrast, the present paper contains individual time series information not only on the utilization of medical services but also on income, wealth, work, and life style. The data come from two surveys carried out in 1981 and 1993 among members of a Swiss sick fund, with the linkage between the two waves provided by insurance records. In all, this comparatively rich data set holds the promise of permitting the Grossman model to be adequately tested for the first time.

Decreased Tamm-Horsfall protein in lithiasic patients.

OBJECTIVES: Tamm-Horsfall glycoprotein (THP) is the most abundant substance of renal origin appearing in urine. It seems to be one of the major inhibitors of calcium oxalate crystal nucleation and/or aggregation, but its role in the pathogenesis of stone formation has not yet been clarified. The present work was undertaken to quantify THP excretion in lithiasic (L) patients, so as to determine if these levels are different from those of control subjects (C). DESIGN AND METHODS: THP was isolated from human urine by reprecipitation steps, rabbit antiTHP antibody was obtained and its specificity determined, an ELISA was developed and technical conditions standardized, and quantitative measurements of urinary THP were performed on samples from L patients, who had suffered more than one lithiasic episode, and from C subjects. Microtiter plates coated with THP or diluted urine samples were subjected to successive incubation with antiTHP and alkaline phosphatase antirabbit IgG. RESULTS: A good correlation between measured absorbance and THP concentration in standard and urine samples was observed. Data, expressed as Median and Interquartile Range, are 388/209-626 micrograms THP/mmol creatinine for C (n = 85) and 124/82-171 micrograms THP/mmol creatinine for L (n = 23). CONCLUSIONS: We have obtained an antiserum antiTHP that can be used in the ELISA technique to determine reliable urinary THP values. The results show a significant decrease of THP excretion in recurrent stone formers compared to controls (p < 0.001) and may have interesting implications in the pathogenesis of urolithiasis.

[Mesenteric cysts. Clinical case]. / Le cisti del mesenere. Caso clinico

A case of multiple mesentery cysts is presented and the etiopathogenesis, anatomopathology, symptomatology and therapy of this disease discussed.