Intraprocedural Cortisol Measurement Increases Adrenal Vein Cannulation Success Rate in Primary Aldosteronism: A Systematic Review and Meta-analysis.

BACKGROUND: This study aimed to explore the effectiveness of intraprocedural cortisol measurement (IPCM) for the technical success rates of bilateral adrenal vein, right adrenal vein (RAV), and left adrenal vein (LAV) cannulation during adrenal vein sampling (AVS). METHODS: Systematic searches of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were performed from database inception to May 10, 2023, without any restrictions. We estimated the overall effect estimates of outcomes using the Mantel-Haenszel random-effects model. We conducted subgroup analyses, meta-regression, and sensitivity analysis to explore the possible sources of between-study heterogeneity. RESULTS: In total, 3,485 patients from 11 studies (three prospective and eight retrospective) were enrolled. Bilateral selectivity in patients who underwent IPCM during AVS was significantly higher than that in patients who underwent a routine AVS procedure (84% vs. 64%, RR 1.42, 95% confidence interval [CI]: 1.27-1.59, P < 0.01), with significant heterogeneity (I2 = 68%). A 42% relative risk reduction in the failure rate of bilateral adrenal vein cannulation was found in the IPCM group. Moreover, pooled analysis showed a significant increase in the success rates of RAV cannulation (84% vs. 72%, RR 1.21, 95% CI 1.12-1.31, P < 0.01, I2 = 33%) and LAV cannulation (89% vs. 84%, RR 1.05, 95% CI 1.02-1.08, P < 0.01, I2 = 4%) when IPCM was implemented during the AVS procedure compared to the routine AVS procedure. CONCLUSIONS: An IPCM-based strategy during AVS appears to have a significant beneficial effect on improving the success rate of bilateral cannulation, RAV cannulation and LAV cannulation.

Modeling pKa of the Brønsted Bases as an Approach to the Gibbs Energy of the Proton in Acetonitrile.

A simple but efficient computational approach to calculate pKa in acetonitrile for a set of phosphorus, nitrogen, and carbon bases was established. A linear function that describes relations between the calculated ΔG'a.sol(BH+) and pKa values was determined for each group of bases. The best model was obtained through the variations in the basis set, in the level of theory (density functionals or MP2), and in the continuum solvation model (IPCM, CPCM, or SMD). The combination of the IPCM/B3LYP/6-311+G(d,p) solvation approach with MP2/6-311+G(2df,p)//B3LYP/6-31G(d) gas-phase energies provided very good results for all three groups of bases with R2 values close to or above 0.99. Interestingly, the slopes and the intercepts of the obtained linear functions showed significant deviations from the theoretical values. We made a linear plot utilizing all the conducted calculations and all the structural variations and employed methods to prove the systematic nature of the intercept/slope dependence. The interpolation of the intercept to the ideal slope value enabled us to determine the Gibbs energy of the proton in acetonitrile, which amounted to -258.8 kcal mol-1. The obtained value was in excellent agreement with previously published results.

Estimate of the number of urea transport sites in erythrocyte ghosts using a hydrophobic mercurial.

In this paper a variety of mercurials, including a pCMB-nitroxide analogue, were used to study urea transport in human red cell ghosts. It was determined that the rate of inhibition for pCMBS, pCMB, pCMB-nitroxide, and chlormerodrin extended over four orders of magnitude consistent with their measured oil/water partition coefficients. From these results, we concluded that a significant hydrophobic barrier limits access to the urea inhibition site, suggesting that the urea site is buried in the bilayer or in a hydrophobic region of the transporter. In contrast, the rate of water inhibition by the mercurials ranged by only a factor of four and did not correlate with their hydrophobicities. Thus, the water inhibition site may be more directly accessible via the aqueous phase. Under conditions that leave water transport unaffected, we determined that < or = 32,000 labeled sites per cell corresponded to complete inhibition of urea transport. This rules out major transmembrane proteins such as band 3, the glucose carrier, and CHIP28 as candidates for the urea transporter. In contrast, this result is consistent with the Kidd (Jk) antigen being the urea transporter with an estimated 14,000 copies per cell. From the experimental number of urea sites, a turnover number between 2-6 x 10(6) sec-1 at 22 degrees C is calculated suggesting a channel mechanism.

[Functional system of secretion in renal tuberculosis]. / Funktsional'naia sistema vydeleniia pri nefrotuberkuleze.

Data are given on the study of functional correlations of the pairs of organs (kidneys-liver and kidneys-lungs) that participate in provision of the functional system of secretion. The correlation of these pairs of organs contribution to the total secretion of metabolites as renal insufficiency grows is characterized by the S-shaped dependence, i.e. by a compensatory increase of the conjoined functions at the early stages and its depression at the graver stages of renal insufficiency. This approach makes it possible to determine the character, terms and significance of the participation of various organs in provision of metabolic homeostasis maintenance long before its failure and to reveal the main links in the pathogenesis of functional disorders of secretion.

Mercury compounds: lipophilicity and toxic effects on isolated myocardial tissue.

Lipophilicity is suggested to modulate the diffusion and the cytotoxic effects of mercury compounds. To investigate this, the positive inotropic effect of four Hg compounds (HgCl2, CH3HgCl, chlormerodrin, bromomercurihydroxypropane) was studied in catecholamine-depleted isolated heart muscle preparations. The rate of development of the positive effect was inversely correlated to the concentration in the case of HgCl2 and chlormerodrin, i.e. the product of concentration (c) and time to half-maximal effect (t50) remained constant. This was in accordance with the assumption of a permeation-controlled rate of action, as was shown earlier for p-chloromercuriphenyl-sulfonic acid. In addition, the c X t50 values of the individual mercurials decreased hyperbolically with the increase in lipophilicity as measured by the octanol/water partition. The results support the view that the toxicity of mercurials increases with their lipid solubility. In conjunction with the previously reported negative inotropic effect of Hg compounds, a model is proposed allocating thiol groups responsible for the negative inotropic action to lipid compartments within the cell membrane, while SH groups conveying the increase in contraction force are thought to be situated at the internal surface of the sarcolemma.

The action of organic mercury compounds on the function of isolated mammalian heart muscle.

The effects of four organic mercury compounds (methylmercuric chloride; bromomercurihydroypropane, BMHP; chlormerodrin; p-chloromercuribenzoic acid, PCMB) on mechanical and electrical functions of guinea-pig papillary muscles were investigated. An initial decline in contraction force was followed by a transient positive inotropic response. The first was accompanied by a shortening of the action-potential duration and by a reduction of the depolarization velocity and the duration of the Ca2+-dependent slow response. The latter was characterized by an indirect component (release of noradrenaline) and by a direct component, which was dependent on the stimulation rate and on the extracellular concentration of Na+ and K+. The direct positive effect, therefore, was likely to have resulted from inhibition of the sarcolemmal Na+ + K+-ATPase. This notion was confirmed by experiments with isolated membrane particles. The prevalence of the negative or positive inotropic action of these compounds could be ascribed to their lipophilic or hydrophilic properties, respectively.

Contraluminal transport of hexoses in the proximal convolution of the rat kidney in situ.

In order to study contraluminal hexose transport, concentration and time-dependent influx of 3H-2-deoxy-D-glucose from the interstitium into cortical tubular cells has been measured. The influx curves fit to a two parameter kinetics (Km 1.3 +/- 0.2 mmol/l, Jmax 0.67 +/- 0.16 pmol/s X cm) plus an additional diffusion term (with P = 6 X 10(-8) cm2/s) and a distribution ratio extracellular to intracellular amount of 2-deoxy-D-glucose of 1:0.6. Since the extracellular to intracellular free water space as estimated from morphological data was 1:2, one must conclude that glucose has only free access to 1/3 of the cell water. The intracellularly accessible space was augmented when the tubules were preperfused for 10 s with hypotonic saline. Thereby an increase of the compartment into which diffusion occurs was revealed and a final rupture of this intracellular compartment at 1/4 isotonic solutions was observed. Total replacement of ions in the peritubular perfusate by mannitol did not change 2-deoxy-D-glucose influx, indicating that it is Na+-independent. By adding isotonic concentrations of the respective sugars to the capillary perfusate, three degrees of inhibition of 2-deoxy-D-glucose influx could be revealed: strong inhibition by D-glucose, methyl-beta-D-glucoside, D-mannose, 3-O-methyl-D-glucose, 2-deoxy-D-galactose, methyl-beta-D-galactoside and 6-deoxy-D-glucose, moderate inhibition by D-galactose, L-glucose, L-mannose and D-fructose, no or borderline inhibition by methyl alpha-D-glucoside, 2-deoxy-methyl-alpha-D-galactoside, 1-thio-beta-D-glucose, 1-thio-beta-D-galactose, 5-thio-alpha-D-glucose, myo-inositol and mannitol.(ABSTRACT TRUNCATED AT 250 WORDS)

[Determination of the amount of functioning renal parenchyma based on multipositional scintigraphy data]. / Opredelenie kolichestva funktsioniruiushchei parenkhimy pochek po dannym polipozitsionnoi stsintigrafii.

The paper is concerned with mathematical calculations of two methods to determine the amount of the functioning renal parenchyma using the polyposition statistic scintigraphy data. These methods are used to determine the depth of kidney location from the body surface in the lumbar region. An analysis of polyposition scintigraphy of 122 patients without tumor lesion has shown that in 41.7% of the cases the difference in the depth of location was over 1 cm. in 13.1% over 2 cm and in 5.7% over 3 cm. If one of the kidneys is shifted forward by 3 cm, in scintigraphy gamma-irradiation from this kidney for 99mTc will be weakened more than 1.5 times, and for 197Hg more than 1.75 times. It is only in renal insufficiency and in obese patients that the method of estimated RPD accumulation in the kidneys with regard to lateral projections is the best as compared to that using the results of scintigraphy of front and back projections.

In vivo localization of chlormerodrin-203Hg in rat kidney as determined by cell fractionation method.

Subcellular distribution of chlormerodrin-203Hg in the rat kidney has been studied. Two hours after i.v. injection of the radiopharmaceutical, kidney tissue homogenate was submitted to differential centrifugation to obtain cell organelles. Radioactivity distribution in relation to total radioactivity of kidney homogenate obtained in nine repeated experiments was as it follows (+/- SD): nuclei 3.5% (+/- 0.5); mitochondria 6.7% (+/- 0.6); microsomes 9.3% (+/- 0.8) and cytosol 38% (+/- 3.9). Specific activities expressed as counts/min/mg of protein were 915 (+/- 13%), 1232 (+/- 14%) and 1097 (+/- 14%) for mitochondria, microsomes and cytosol, respectively. Specific activity of the nuclei was 1445 (+/- 16%) counts/min/mg DNA. These results demonstrate that this imaging agent penetrates into the kidney cells where it remains mostly in the cytosol. A fraction of chlormerodrin-203Hg binds to microsomes, mitochondria and nuclei.

Renal radiopharmaceuticals--an update.

Noninvasive radionuclide procedures in the evaluation of renal disease have been accepted increasingly as effective and valuable alternatives to older clinical methods. The development of suitable radiopharmaceuticals labeled with high photon intensity radionuclides and with 99mTc in particular has stimulated this modality during the last few years. Currently several nearly ideal agents are available for anatomical and functional studies of kidney imparting very low absorbed radiation doses. These include 99mTc-GHA and 99mTc-DMSA for renal morphology and differential function evaluation, 99mTc-DTPA for GFR and 123I orthoiodohippurate for ERPF measurements. A suitable agent as a replacement for the latter labeled with 99mTc is actively being sought. Computer-assisted processing of dynamic renal function studies enables the observer to obtain a wealth of information related to the renal extraction, uptake, parenchymal transit and pelvic transit parameters of the agent administered into the bloodstream. Each of these parameters either globally or differentially contributes to a detailed evaluation of renal disease states. Several of these procedures have been validated against classical techniques clinically but more detailed information is being sought with the recently introduced radiopharmaceuticals. With the detailed validation and increasing recognition of the clinical utility of several of the radionuclidic procedures at many centers, it is hoped that radionuclide assessment of renal disorders ultimately will be made available routinely at all medical facilities.

Selective effects of organic mercurials on the GTP-regulatory proteins of adenylate cyclase systems.

Treatment of membranes from HeLa cells, rat adipocytes, and rat liver with organic mercurials results in complex effects on adenylate cyclase activity that are not mimicked by the reversible sulfhydryl reagent, tetrathionate. At low concentrations (0.1 mM or less 1 mercurials inactivate the enzyme; inactivation is reversed by the thiol-reducing agent, dithiothreitol. Treatment with higher concentrations of organic mercurials (1 mM and above) results in a time-dependent, irreversible change in the ability of guanine nucleotides and fluoride ion to stimulate adenylate cyclase activity. The irreversible changes are blocked by treatment of membranes with cholera toxin and NAD, suggesting that the GTP-regulatory component is the site of mercurial action. This is further suggested by the lack of irreversible effects of mercurials on adenylate cyclase activity in membranes from mouse lymphoma cells that lack this component. Irreversible effects of mercurials on the adipocyte cyclase system also include enhancement of basal activity and potentiation of the inhibitory effects of GTP on cyclase activity; the latter effects of GTP are mediated through a process independent from that mediating stimulation of activity by GTP. It is concluded that the GTP-regulatory proteins responsible for the modulation of adenylate cyclase activity by hormones and neurotransmitters contain the sites of action of organic mercurials. Their possible mode of action is discussed.