Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus

Background: The pathogenesis of pruritus in renal disease is not yet understood. Evidence suggests that mast cells play a role; for example, the number of dermal mast cells is increased in patients on hemodialysis. Patients and methods: To investigate a possible role of mast cell tryptase in pruritus of patients undergoing chronic hemodialysis, serum mast cell tryptase concentrations were measured in blood samples taken from 93 such patients, 53 of whom also recorded the severity of their pruritus on a visual analogue scale. Results: Serum mast cell tryptase levels were above 11.4 µg/l (95^th percentile) in 84 of 93 hemodialysis patients (90.3 %). The intensity of pruritus correlated significantly (p = 0.014) with the tryptase levels, an associated not yet shown for other mast cell‐related parameters. Conclusions: Mast cells or even tryptase itself may be involved in the pathogenesis of pruritus of hemodialysis patients.     

Methimazole Slows Hepatocyte Streaming in Rats

Hepatocytes are hypothesized to continuallystream from the portal tract to the terminal hepaticvein. By this model, when a cell divides, one of itsprogeny replaces the dividing ancestor and the other is displaced into a more remote location. Thepresent experiment aims to demonstrate thathypothyroidism affects liver cell turnover. Thirty maleadult rats were divided into two groups. One receivedmethimazole for two weeks and the other served as control.Each rat was injected intraperitoneally with 18.5 KBq[³H]thymidine/g body weight. Rats were killedafter 1 hr and two and four weeks. Autoradiography was done. The distance of the labeled cells fromthe portal tract was measured. The mean TSH levels ofthe methimazole-treated group and controls were 1.45 and0.25 mM/liter, respectively (P < 0.01). Hepatocyte streaming was lower in hypothyroid (1.8m/day) than in untreated rats (2.5 m/day) (P< 0.01). The respective labeling indices 1 hr afterlabeling were 0.9% and 1.24% (P < 0.05). We concludethat hypothyroidism diminishes hepatocyte and littoral cellturnover and slows down their streaming.     

Anticoagulation in patients with atrial fibrillation,thrombocytopenia and hematological malignancy

Journal of Thrombosis and Thrombolysis - Managing anticoagulation in hematological malignancy patients with atrial fibrillation and thrombocytopenia is a clinical challenge with limited data. We...     

Does digoxin sensitize left ventricular mechanoreceptors?

Summary Afferent nerve fibre activity from left ventricular mechanoreceptors was recorded in 10 anaesthetized cats before and after two intravenous injections of 15 g/kg digoxin at 1 hour interval. These receptors are activated by coronary artery occlusion and induce a depressor cardiovascular reflex resulting in bradycardia and hypotension.Neither the spontaneous activity of the receptor's afferent nerve fibres nor their maximum activity during temporary coronary artery occlusion was affected by digoxin. The results show that digoxin in therapeutic doses has no sensitizing effect on left ventricular mechanoreceptors with vagal afferent fibres. The sensitization of cardiopulmonary baroreflexes by digitalis glycosides shown in previous investigations is thus more likely to be mediated by a central nervous effect of the drug.     

Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study

ObjectivesThis study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women.BackgroundTo our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women.MethodsProspective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition.ResultsThe propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476 to 8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation.ConclusionsAmong pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217)     

Intracellular sodium activity and Bretschneider's cardioplegia: Continuous measurement by ionselective microelectrodes at initial equilibration

Summary Intracellular sodium activity (a_Na ⁱ), intracellular pH (pH_i) and membrane potential were directly and continuously measured in sheep cardiac Purkinje fibers using neutral carrier liquid membrane ionselective microelectrodes. Changing the superfusing medium from normal Tyrode's solution to the cardioplegic solution HTK according to Bretschneider (6) a depolarization from –73.7±7.2 mV to –55.0±9.5 mV (n=25), a decrease of a_Na ⁱ from 9.1±1.9 mM to 4.0±1.4 mM (n=25) and an intracellular acidification from pH_i 7.18±0.06 to pH_i 7.01±0.06 (n=11, x±S.D.) occurred at 35°C. The decrease of intracellular sodium activity was not effected by replacement of K, Mg, or histidine by mannitol in the cardioplegic solution. Addition of 4 mM Ca somewhat enhanced a_Na ⁱ decline. Inhibition of the sodium pump with the cardiac steroid dihydroouabain (10^–4 M) lowered the effect of HTK on intracellular sodium by approximately 35% (n=5). Sodium decline was also sensitive to equilibration temperature, giving a Q₁₀ of 1.54 for the initial decrease velocity (temperature range 20 to 35°C), which is less than that found by other investigators for pure sodium pump activity. It is suggested that although the electrochemical sodium gradient remains inward throughout, sodium may leave myocardial cells on induction of Bretschneider's cardioplegia because of a reduction of inward fluxes by simultaneously increasing sodium pump activity, thus increasing Na efflux. Na/Ca exchange is assumed to be of minor importance and the Na/H exchange may be involved. With respect to the clinical application of the low Na and nominally Ca-free cardioplegic solution HTK lowering of intracellular sodium activity is interpreted as a factor minimizing the risk of a calcium paradox on reperfusion with Ca at serum levels, as well as a possible mechanism preventing early development of cellular edema.Supported by the DFG, SFB 330 Organprotektion.Part of this work has already been published in abstract form (Pflüg. Arch. 1987: 408, R11) and comprises unpublished results of E. Krohn's thesis.The technical assistance of Mrs. U. Markmann and Mrs. E. Neumeyer is gratefully acknowledged.     

Targeting the Dopaminergic System in Autoimmunity

Journal of Neuroimmune Pharmacology - Dopamine has emerged as a fundamental regulator of inflammation. In this regard, it has been shown that dopaminergic signalling pathways are key players...