Vasopressin release is enhanced by the Hemocontrol biofeedback system and could contribute to better haemodynamic stability during haemodialysis

Haemodialysis with the Hemocontrol biofeedback system (HHD) is associated with improved haemodynamic stability compared with standard haemodialysis (HD) (SHD). Although the beneficial effect of HHD on haemodynamic stability is generally explained by its effect on blood volume, we questioned whether additional factors could play a role. Since HHD is associated with higher initial dialysate sodium concentrations and ultrafiltration (UF) rate, we studied whether the beneficial effect of HHD on haemodynamic stability may be explained by an increased release of the vasoconstrictor arginine vasopressin (AVP). Fifteen chronic dialysis patients underwent SHD and HHD in random order. All other treatment factors were identical and patients served as their own control. Plasma levels of AVP were measured pre-dialysis, at 30 and 60 min intra-dialysis and, next, hourly until completion of the dialysis session. Plasma AVP levels did not change significantly during SHD, whereas AVP levels rose significantly within 30 min after the start of HHD (P 0.01). AVP levels were significantly higher at 30 and 60 min of HHD in comparison with SHD (P 0.05). Dialysis hypotension occurred significantly less frequent during HHD than during SHD (P 0.05). HHD is associated with higher initial AVP levels compared with SHD. The enhanced release of the vasoconstrictor AVP with HHD could contribute to the lower frequency of dialysis hypotension by facilitating fluid removal during the first part of the dialysis session, permitting lower UF rates during the second half of the dialysis session

Angptl4 Upregulates Cholesterol Synthesis in Liver via Inhibition of LPL- and HL- Dependent Hepatic Cholesterol Uptake

Background¿ Dysregulation of plasma lipoprotein levels may increase the risk for atherosclerosis. Recently, angiopoietin-like protein 4, also known as fasting-induced adipose factor Fiaf, was uncovered as a novel modulator of plasma lipoprotein metabolism. Here we take advantage of the fasting-dependent phenotype of Angptl4-transgenic (Angptl4-Tg) mice to better characterize the metabolic function of Angptl4. Methods and Results¿ In 24-hour fasted mice, Angptl4 overexpression increased plasma triglycerides (TG) by 24-fold, which was attributable to elevated VLDL-, IDL/LDL- and HDL-TG content. Angptl4 overexpression decreased post-heparin LPL activity by stimulating conversion of endothelial-bound LPL dimers to circulating LPL monomers. In fasted but not fed state, Angptl4 overexpression severely impaired LPL-dependent plasma TG and cholesteryl ester clearance and subsequent uptake of fatty acids and cholesterol into tissues. Consequently, hepatic cholesterol content was significantly decreased, leading to universal upregulation of cholesterol and fatty acid synthesis pathways and increased rate of cholesterol synthesis. Conclusions¿ The hypertriglyceridemic effect of Angptl4 is attributable to inhibition of LPL-dependent VLDL lipolysis by converting LPL dimers to monomers, and Angptl4 upregulates cholesterol synthesis in liver secondary to inhibition of LPL- and HL-dependent hepatic cholesterol uptake. The present study exploits the fasting-dependent phenotype of Angptl4-transgenic mice to characterize the function of Angptl4. We conclude that: (1) Angptl4 causes hypertriglyceridemia by inhibiting LPL-dependent VLDL lipolysis by converting LPL dimers to monomers, and (2) Angptl4 upregulates hepatic cholesterol synthesis secondary to inhibition of LPL- and HL-dependent hepatic cholesterol uptake

Correlations of blood and brain biochemistry in phenylketonuria: results from the Pah-enu2 PKU mouse

Background: In phenylketonuria (PKU), treatment monitoring is based on frequent blood phenylalanine (Phe) measurements, as this is the predictor of neurocognitive and behavioural outcome by reflecting brain Phe con-centrations and brain biochemical changes. Despite clinical studies describing the relevance of blood Phe to out-come in PKU patients, blood Phe does not explain the variance in neurocognitive and behavioural outcome completely. Methods: In a PKU mouse model we investigated 1) the relationship between plasma Phe and brain biochemistry (Brain Phe and monoaminergic neurotransmitter concentrations), and 2) whether blood non-Phe Large Neutral Amino Acids (LNAA) would be of additional value to blood Phe concentrations to explain brain biochemistry. To this purpose, we assessed blood amino acid concentrations and brain Phe as well as monoaminergic neuro -transmitter levels in in 114 Pah-Enu2 mice on both B6 and BTBR backgrounds using (multiple) linear regression analyses. Results: Plasma Phe concentrations were strongly correlated to brain Phe concentrations, significantly negatively correlated to brain serotonin and norepinephrine concentrations and only weakly correlated to brain dopamine concentrations. From all blood markers, Phe showed the strongest correlation to brain biochemistry in PKU mice. Including non-Phe LNAA concentrations to the multiple regression model, in addition to plasma Phe, did not help explain brain biochemistry. Conclusion: This study showed that blood Phe is still the best amino acid predictor of brain biochemistry in PKU. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain Phe concen-trations, necessitating a search for other additional parameters. Take-home message: Blood Phe is still the best amino acid predictor of brain biochemistry in PKU. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain Phe concentrations, neces-sitating a search for other additional parameters. (c) 2021 Published by Elsevier Inc.Education and Child Studie

Plasma chromogranin A levels are increased in a small portion of patients with hereditary head and neck paragangliomas

P>Context The majority of patients with head and neck paragangliomas (HNPGL) have biochemically silent tumours. Chromogranin A (CgA) is a tumour marker for neuroendocrine tumours. Objective To assess the role of CgA as a tumour marker in patients with hereditary HNPGL. Patients and Methods We included 95 consecutive patients with hereditary HNPGL for screening of plasma CgA levels and catecholamine excess by measurement of 24-h urinary excretion of (nor)metanephrine, (nor)adrenaline, VMA, dopamine and 3-methoxytyramine. In all patients with catecholamine excess, abdominal/intrathoracic paragangliomas were excluded by 123I-MIBG scintigraphy, MRI and/or CT. Results Plasma CgA levels were increased in only 15 of 95 patients (16%). Thirty-three of the 95 patients (35%) had increased urinary excretion rates of catecholamines. Six of these 33 patients (18%) had increased plasma CgA levels. Nine of the 62 patients (15%) with a biochemically silent tumour, i.e. no increased urinary excretion of catecholamines or their metabolites, had increased CgA levels. Increased plasma CgA levels were positively correlated with urinary excretion rates of noradrenaline (r = 0 center dot 68, P = 0 center dot 005) and normetanephrine (r = 0 center dot 68, P = 0 center dot 005). There was a positive correlation between maximal HNPGL diameter and plasma CgA levels in the 57 patients with a single HNPGL (r = 0 center dot 57, P = 0 center dot 001). Conclusions Plasma CgA levels are increased in only a small portion of patients with hereditary HNPGL and have limited additional value to the combination of radiological and routine biochemical assessment of patients with HNPGL. Increased plasma CgA levels are associated with increased noradrenergic activity and tumour size in patients with a single HNPGL.Diabetes mellitus: pathophysiological changes and therap

Evaluation of specific high-performance liquid-chromatographic determinations of urinary adrenaline and noradrenaline by comparison with isotope dilution mass spectrometry

A method for the determination of metadrenaline (MA). normetadrenaline (NMA) and 3-methoxytyramine (3-MT) in human urine using high-performance liquid chromatography followed by electrochemical detection (ECD) was validated primarily by comparing the results with those obtained by a gas chromatography mass spectrometry (GC MS) reference method. Correlation coefficients of 0.93, 0.94 and 0.91 were obtained for MA, NMA and 3-MT. respectively, in a group of healthy controls consisting of 30 women and 30 men. A systematic difference wits detected only for 3-MT (-16%). Further tests Of accuracy (linearity and recovery) and precision demonstrated that the described method must be considered to be a reliable approach to assess urinary metadrenalities in the diagnosis of phaeochromocytoma. At lower concentrations (MA, 248 nmol L; NMA. 434 nmol, L; 3-MT, 402 nmol/L), within-assay coefficients of variation were close to 5%, or less (5(.)3, 4(.)6 and 2(.)2%, respectively) and between-assay, Coefficients Of Variation were 8(.)9. 11(.)2 and 12(.)3%, respectively, for the same low levels. This raises the possibility that this method can also be applied to assess urinary free, unconjugated metanephrines. Sex differences were detected for MA and NMA excretion Mien expressed in nmol per 24h and nmol/mmol creatinine, respectively, by both ECD and GC MS methods

Diagnostic Value of Urinary Steroid Profiling in the Evaluation of Adrenal Tumors

Radiological examination may unexpectedly reveal an adrenal mass. Current algorithms for differentiating between benign and malignant lesions mainly rely on size and densitometry on unenhanced CT, which have limited specificity. We examined the diagnostic value of urinary steroid profiling by gas chromatography/mass-spectrometry (GC/MS) in differentiating between benign and malignant adrenal tumors. A retrospective study in two referral centers for patients with adrenal disease was performed. All urinary steroid profiles ordered for evaluation of an adrenal tumor between January 2000 and November 2011 were examined. Patients were diagnosed with adrenal cortical carcinoma (ACC), adrenal cortical adenoma (ACA), or other adrenal mass. Results of hormonal measurements, imaging studies, pathology reports, and clinical outcome were retrieved from medical records. The diagnostic value of individual urinary steroid metabolites was determined by receiver operating characteristics analysis. Cut-off values were compared to reference values from an age and gender-standardized population of healthy controls. Eighteen steroid metabolites were excreted in significantly higher concentrations in patients with ACC (n = 27) compared to patients with ACA (n = 107) or other adrenal conditions (n = 18). Tetrahydro-11-deoxycortisol (THS) at a cut-off value of 2.35 mu mol/24 h differentiated ACC from other adrenal disorders with 100 % sensitivity and 99 % specificity. Elevated urinary excretion of THS was associated with a very high sensitivity and specificity to differentiate between an ACC and a benign adrenal mass. Urinary steroid profiling might be a useful diagnostic test for the evaluation of patients with an adrenal incidentaloma