Reduced natriuretic response to acute sodium loading in COMT Gene deleted mice

BACKGROUND: The intrarenal natriuretic hormone dopamine (DA) is metabolised by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Inhibition of COMT, as opposed to MAO, results in a potent natriuretic response in the rat. The present study in anaesthetized homozygous and heterozygous COMT gene deleted mice attempted to further elucidate the importance of COMT in renal DA and sodium handling. After acute intravenous isotonic sodium loading, renal function was followed. RESULTS: COMT activity in heterozygous mice was about half of that in wild type mice and was zero in the homozygous mice. MAO activity did not differ between the genotypes. Urinary sodium excretion increased 10-fold after sodium loading in wild type mice. In heterozygous and homozygous mice, the natriuretic effects of sodium loading were only 29 % and 39 %, respectively, of that in wild type mice. Arterial pressure and glomerular filtration rate did not differ between genotypes. Baseline norepinephrine and DA excretions in urine were elevated in the homozygous, but not in heterozygous, COMT gene deleted mice. Urinary DA excretion increased after isotonic sodium loading in the wild type mice but not in the COMT gene deleted mice. CONCLUSIONS: Mice with reduced or absent COMT activity have altered metabolism of catecholamines and are unable to increase renal DA activity and produce normal natriuresis in response to acute sodium loading. The results support the hypothesis that COMT has an important role in the DA-mediated regulation of renal sodium excretion

The impact of different GFR estimating equations on the prevalence of CKD and risk groups in a Southeast Asian cohort using the new KDIGO guidelines

<p>Abstract</p> <p>Background</p> <p>Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with CKD should be assigned to stages and composite relative risk groups according to GFR (G) and proteinuria (A) criteria. Asians have among the highest rates of ESRD in the world, but establishing the prevalence and prognosis CKD is a problem for Asian populations since there is no consensus on the best GFR estimating (eGFR) equation. We studied the effects of the choice of new Asian and Caucasian eGFR equations on CKD prevalence, stage distribution, and risk categorization using the new KDIGO classification.</p> <p>Methods</p> <p>The prevalence of CKD and composite relative risk groups defined by eGFR from with Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI); standard (S) or Chinese(C) MDRD; Japanese CKD-EPI (J-EPI), Thai GFR (T-GFR) equations were compared in a Thai cohort (n = 5526)</p> <p>Results</p> <p>There was a 7 fold difference in CKD_3-5prevalence between J-EPI and the other Asian eGFR formulae. CKD_3-5prevalence with S-MDRD and CKD-EPI were 2 - 3 folds higher than T-GFR or C-MDRD. The concordance with CKD-EPI to diagnose CKD_3-5was over 90% for T-GFR or C-MDRD, but they only assigned the same CKD stage in 50% of the time. The choice of equation also caused large variations in each composite risk groups especially those with mildly increased risks. Different equations can lead to a reversal of male: female ratios. The variability of different equations is most apparent in older subjects. Stage G3aA1 increased with age and accounted for a large proportion of the differences in CKD_3-5between CKD-EPI, S-MDRD and C-MDRD.</p> <p>Conclusions</p> <p>CKD prevalence, sex ratios, and KDIGO composite risk groupings varied widely depending on the equation used. More studies are needed to define the best equation for Asian populations.</p

LEVONORGESTREL PLASMA-LEVELS DURING CONTINUOUS ADMINISTRATION WITH DIFFERENT MODELS OF SUBDERMAL IMPLANTS

27212313

Levonorgestrel Plasma Levels During Continuous Administration With Different Models Of Subdermal Implants

Plasma concentrations of levonorgestrel were determined in women using subdermal levonorgestrel implants. One group had 6 Silastic ® capsules† † Silastic® supplied by Leiras Pharmaceutical, Turku, Finland. (NORPLANT), one group had 4 and one group had 6 covered Silastic® rods for variable lengths of time. Levonorgestrel concentrations remained constant around 0.4 ng/ml up until 6 years of use in the Norplant group. The observation period was shorter for the covered rods; plasma concentrations were, however, constant around 0.55 ng/ml and 0.70 ng/ml for 3.5 years with the 4 rods and 6 covered rods, respectively. The difference in mean levonorgestrel concentrations between the three groups were statistically significant (p &lt; 0.0005). Plasma levels of levonorgestrel were twice to three times higher in blood obtained from the arm with the implants compared to the levels found in the other arm. The application of a tourniquet for variable periods before blood sampling did not influence the plasma concentrations of levonorgestrel. © 1983.272123130Segal, Croxatto, Single administration of hormones for long-term control of reproductive function (1967) Presentation at the XXIII Meeting of the American Fertility Society, , April 14–16, Washington DCAlvarez, Robertson, Montes de Oca, Sivin, Brache, Faundes, Comparative clinical trial of the progestins R-2323 and levonorgestrel administered by subdermal implants (1978) Contraception, 18, pp. 151-162Coutinho, da Silva, Mattos, Nielsen, Osler, Wiese, Holma, Sivin, Contraception with long acting subdermal implants. I. An effective and acceptable modality in international clinical trials (1978) Contraception, 18, pp. 315-333Coutinho, da Silva, Mattos, Nielsen, Osler, Wiese, Holma, Sivin, Contraception with long acting subdermal implants. II. Measured and perceived effects in international clinical trials (1978) Contraception, 18, pp. 335-353Faundes, Brache de Mejias, Leon, Robertson, Alvarez, First year clinical experience with six levonorgestrel rods as subdermal contraception (1979) Contraception, 20, pp. 167-175Croxatto, Diaz, Miranda, Elamsson, Johansson, Plasma levels of levonorgestrel in women during long-term use of NORPLANT (1980) Contraception, 22, pp. 583-596Weiner, Victor, Johansson, Plasma levels of d-norgestrel after oral administration (1976) Contraception, 14, pp. 563-57