Is glycated hemoglobin related to other dysmetabolic variables implicated in the increase of cardiovascular risk in polycystic ovary syndrome? A comparative study.

BACKGROUND: In non-PCOS patients the concentration of glycated hemoglobin (HbA1C) has been employed to identify individuals at higher risk for impaired glucose tolerance (IGT) and diabetes mellitus. A few studies have examined the role of HbA1C in PCOS patients and current results are controversial. AIM: To compare the strength of the association between glycated hemoglobin and other predictors of cardiovascular risk in polycystic ovary syndrome (PCOS). METHODS: This cross-sectional study enrolled 197 PCOS patients and 72 non-PCOS women. Transvaginal ultrasound, biochemical and hormone measurement were performed. Glycated hemoglobin (HbA1C) was correlated with other variables related to dysmetabolic/vascular diseases. RESULTS: The HbA1C levels were 6.0±1.4% and 4.9±0.4% in PCOS patients and non-PCOS controls, respectively (p<0.001). The HbA1C levels were≥5.7% in 46.4% of PCOS and in none of the control subjects (OR=90.8). HbA1C was well-correlated with several anthropometric, metabolic and endocrine parameters. Stepwise multiple regression including HbA1C and other known predictors of cardiovascular risk resulted in a significant model in which body mass index (BMI) and free testosterone exhibited the best correlation with HbA1C (adjusted R(2)=0.530; F=39.8; p<0.001). CONCLUSION: HbA1C was elevated and correlated with anthropometric, biochemical and endocrine variables of metabolic/vascular disease risks in PCOS patients. Combined HbA1C, BMI and free testosterone levels provided a significant model with potential use to evaluate metabolic/vascular disease in PCOS patients.

Analysis of sexual function in kidney transplanted men.

INTRODUCTION: Sexual dysfunction among renal failure and kidney transplant patients remains controversial. The aim of this study was to evaluate sexual functions of men on hemodialysis compared with patients undergoing kidney transplantation. MATERIALS AND METHODS: Our study was based on 36 end-stage renal disease (ESRD) patients undergoing hemodialysis versus 32 kidney transplanted patients. A control group was composed of 23 healthy patients. The patients underwent an anamnesis, a physical examination, and the International Index of Erectile Function about sexual performance. Statistical analysis was performed by Student's t-test or the chi-square test with the level of significance set at P < .05. Data are reported as mean values +/- standard error of the means. RESULTS: The mean scores of the control, ESRD, and transplanted group were, respectively: for erectile function, 27.4 +/- 0.5, 22.4 +/- 1.3, 23.4 +/- 1.3; for orgasmic function, 9.5 +/- 0.1, 7.6 +/- 0.5, 8.9 +/- 0.5; for sexual desire function 9.4 +/- 0.1, 7.1 +/- 0.3, 9.0 +/- 0.5; for intercourse satisfaction 12.8 +/- 0.3, 9.4 +/- 0.7, 11.0 +/- 0.7; and for satisfaction related to sexual life 9.2 +/- 0.2, 7.7 +/- 0.3, 8.6 +/- 0.6, proving that there were significant differences regarding orgasmic function, sexual desire, and intercourse satisfaction. CONCLUSION: It was possible to conclude from our study that kidney transplants do improve sexual function of patients with ESRD on hemodialysis.

A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide

A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM) and for atrial natriuretic peptide (Km = 5 µM) suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones

Specific fluorogenic substrates for neprilysin (neutral endopeptidase, EC 3.4.24.11) which are highly resistant to serine- and metalloproteases

Two intramolecularly quenched fluorogenic peptides containing oaminobenzoyl (Abz) and ethylenediamine 2,4-dinitrophenyl (EDDnp) groups at amino- and carboxyl-terminal amino acid rsidues, Abz-Darg-Arg-Leu-EDDnp (Abz-DRRL-EDDnp) and Abz-DArg-Arg-Phe-EDDnp (Abz-DRRF-EDDnp), were selectively hydrolyzed by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) at the Arg-Leu and Arg-Phe bonds, respectively. The kinetic parameters for the NEP-catalyzed hydrolysis of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp were Km = 2.8muM, Kcat = 5.3 min-1, Kcat/Km = 2 min-1 muM-1 and Km = 5.0 muM, Kcat = 7.0 min-1, Kcat/Km = 1.4 min-1 muM-1, respectively. The high specificity of these substrates was demonstrated by their resistance to hydrolysis by metalloproteases [thermolysin (EC 3.4.24.2), angiotensin-converting enzyme (ACE;EC 3.4.24.15)], serineproteases [trypsin (EC 3.4.21.4), alpha-chymotrypsin (EC 3.4.21.1)] and proteases present in tissue homogenates from kidney, lung, brain and testis. The blocked amino- and carboxyl-terminal amino acids protected these substrates against the action of aminopeptidases, carboxypeptidases and ACE. Furthermore, DR amino acids ensured total protection of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp against the action of thermolysin and trypsin. Leu-EDDnp and Phe-EDDnp were resistant to hydrolysis by alpha-chymotrypsin. The high specifity of these substrates suggests their use for specific NEP assays in crude enzyme preparations.

A new fluorometric assay for neutral endopeptidase (EC 3.4.24.11)

An intramolecularly quenched fluorogenic peptide structurally related to Leu-enkephalin, Abz-GGdFLRRV-EDDnp, was selectively hydrolyzed at the R-V bond by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) with kinetic parameters (Km = 3 µM,Kcat = 127 / min and Kcat / Km = 42 / min µM) similar to those of Leu-enkephalin. The specificity of the assay for NEP was demostrated by incubating Abz-GGdFLRRV-EDDnp with a kidney homogenate and with crude membrane preparations of brain and lung. For all three homogenates the complementary fragments Abz-GGdFLRRnp accounted for more than 95 percent of the products wich were totally inhibited by 1 µM thiorphan, a highly specific NEP inhibitor. A continuous fluorometric assay for only 5 min was sufficient to quantify the NEP activity with a minimum sensitivity of 5 ng of purified NEP or the equivalent enzymatic activity in crude tissue preparations.

A simple method using the light microscope to visualize spermatozoon tail swelling in the hypo-osmotic test

The functional integrity of the sperm (SPTZ) membrane is believed to be an important factor in fertilization. This function was assessed by Jeyendran et al. (Journal of Reproduction and Fertility, 70:219-228, 1984), who concluded that when SPTZ from normal fertile men are exposed to a hypo-osmotic solution with an ionic strength of 0.15 mol/l, 60 percent or more will exhibit tail swelling. Essentially no changes have occurred in the test procedure since it was first published, except that SPTZ could be fixed after exposure to the hypo-osmotic solution and observed at a later time using a phase-contrast microscope. We describe here a simple test which does not require phase-contrast microscopy to a read a stained preparation after the hypo-osmotic test. A drop of semen preincubated in the hypo-osmotic medium of Jeyendran et al. and fixed with 18.5 percent formalin is placed on an albumin-coated slide. A second (spreader) slide is placed on the first as a coverslip and pulled forward at moderate speed until all the sperm has been spread into a moderately thin film. The preparation is then air dried and submitted to Papanicolaou staining. The slide can be read at any time after staining with a light microscope and provides permanent documentation