Paschalis-Adam Molyvdas

Cognitive status in Down syndrome individuals with sleep disordered breathing deficits (SDB)

Twelve subjects with Down syndrome underwent polysomnographic studies during night sleep and performed the Mini-Mental state test and the Raven Progressive Matrices (RPM), sets A, B, and B(1). Sleep-disordered breathing (SDB) deficits were observed in Down syndrome individuals and their Mini-Mental and RPM scores were extremely low. Regression analysis of the results revealed that the number of apneas per hour was related with the results of the RPM, set A, which were also related with the orientation of Mini-Mental test, indicating that the more apneas an individual has the more difficulties he has in the kind of visuoperceptual skills, including orientation, associated with normal right hemisphere functioning, which are tested by set A of the RPM.

Non‐genomic effect of testosterone on airway smooth muscle

Recent studies on blood vessels have provided evidence that testosterone may exert direct effects on smooth muscle. However, an acute effect on airway reactivity has not been shown yet. The aim of this study was to assess the direct effect of testosterone on the responsiveness of male adult rabbit airway smooth muscle (ASM), precontracted with 10 μM acetylcholine, 10μM carbachol or 80 mM KCl.

Diabetes mellitus and lung function.

Objectives: To assess the nature of pulmonary dysfunction in type 1 diabetes and the relationship of pulmonary function tests to diabetic factors and complication. Subjects and Methods: Sixteen type 1 diabetic patients and 26 control subjects matched for age and sex were studied. We performed spirometry measurements and measured pulmonary diffusing capacity (DLCO) in sitting and supine position by the single-breath method corrected by alveolar volume (VA). Glycosylated hemoglobin (HbAIc), retinopathy and microalbuminuria were included as parameters of metabolic control and diabetic complications. Results: Diabetic patients showed a significant reduction of the following pulmonary function tests (% predicted value) as compared with control subjects: total lung capacity (TLC, 92.6 ± 14.5 vs. 113.9 ± 17.5, p < 0.001), lung diffusing capacity in sitting position (DLCO, 90.4 ± 21.1 vs. 107.7 ± 15.6, p = 0.004), lung diffusing capacity in supine position (DLCO, 88.3 ± 19.3 vs. 111.9 ± 19.9, p = 0.001). The differences in diffusing capacity corrected by alveolar volume in sitting and supine position (DLCO/VA) were not significant. By changing the posture from sitting to supine position both diabetic patients and control subjects significantly increased DLCO/VA (103.4 ± 17.7 vs. 112.7 ± 22.3, p = 0.046 and 99.5 ± 13.4 vs. 114.4 ± 13, p < 0.001, respectively). There was no correlation between pulmonary function tests and diabetic complications. Conclusion: These data indicate that type 1 diabetic patients showed reduced TLC and DLCO, features of pulmonary restrictive dysfunction. There was no correlation between abnormal pulmonary function and the presence of other diabetic complications.

Ranolazine enhances the antiarrhythmic activity of amiodarone by accelerating conversion of new-onset atrial fibrillation after cardiac surgery.

Ranolazine is a relatively novel antiischemic/antianginal compound with antiarrhythmic properties. We investigated its ability to shorten the time to conversion of postoperative atrial fibrillation (POAF) when added to amiodarone after coronary artery bypass graft (CABG) surgery. In this prospective, randomized, allocation-concealed, single-blind, single-site clinical trial, we enrolled consecutive eligible patients who developed POAF after elective on-pump CABG surgery. Participants were randomized to receive either ranolazine 375 mg twice daily orally plus intravenous amiodarone (active group) or intravenous amiodarone alone (control group). We enrolled 41 patients; 20 in the active and 21 in the control group. There were no significant differences between the groups in terms of age, procedural duration, extracorporeal circulation time, and aortic cross-clamp time. Mean time of conversion was significantly shorter in the active group (19.9 ± 3.2 vs 37.2 ± 3.9 hours, P < .001), suggesting that compared to amiodarone alone, the ranolazine–amiodarone combination had a superior antiarrhythmic effect against POAF.

Endothelial Progenitor Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis: An Evolving Concept

Background Idiopathic pulmonary fibrosis (IPF) has been associated with abnormal vascular remodeling. Bone marrow derived endothelial progenitor cells (EPCs) are considered to possess lung tissue repair and vascular remodeling properties. Objectives The study aimed to assess early EPCs levels and EPCs endogenous vascular endothelial growth factor (VEGF) expression in IPF. In order to examine alterations in the mobilization of EPCs from the bone marrow we measured plasma VEGF. Main Results Twenty-three patients with IPF and fifteen healthy subjects were included. The number of early EPCs colonies was markedly reduced in IPF patients vs controls (6.00±6.49 vs 49.68±16.73, respectively, p<0.001). EPCs were further decreased in patients presenting systolic pulmonary arterial pressure (sPAP)≥35 mmHg. The number of colonies per well correlated negatively with P(A-a)O2 (r =  −0.750, p<0.001). Additionally, VEGF mRNA levels were significantly increased in IPF patients. There were no differences observed in VEGF plasma levels in IPF patients when compared to controls. Conclusions The current data suggest that inadequate levels of early EPCs may potentially contribute to suppressed repair and recovery of the damaged pulmonary endothelium and thereby may drive the sequence of events in profibrogenic direction. Increased VEGFmRNA levels in the clinical context of IPF may represent a compensatory mechanism to overcome reduced EPCs levels.

Effect of ranolazine in preventing postoperative atrial fibrillation in patients undergoing coronary revascularization surgery.

BACKGROUND/OBJECTIVE Ranolazine is a new anti-ischemic agent approved for chronic angina with additional electrophysiologic properties. The purpose of the present trial was to investigate its effect in preventing postoperative atrial fibrillation (POAF) after on-pump coronary artery bypass graft (CABG) surgery. METHODS In the current prospective, randomized, (1 active: 2 control), single-blind (outcome assessors), single-centre clinical trial we recruited consecutive eligible patients scheduled for elective on-pump CABG. Participants were assigned to receive either oral ranolazine 375 mg twice daily for 3 days prior to surgery and until discharge, or to receive usual care. Patients were monitored for the development of POAF. RESULTS We enrolled 102 patients. Significantly lower incidence of POAF was noted in the ranolazine group compared with the control group (3 out of 34 patients, 8.8%, vs 21 out of 68 patients, 30.8%; p< 0.001). Mean values of left atrial diameter and left ventricular ejection fraction between the control and the ranolazine group were not significantly different. CONCLUSION Our findings suggest a protective role of oral ranolazine when administered in a moderate dose preoperatively in patients undergoing on-pump CABG surgery. Future studies based on a wider sample of patients will eventually support our conclusions.

Azithromycin has an antiproliferative and autophagic effect on airway smooth muscle cells.

Azithromycin is used in long-term, low-dose treatment of airway diseases where airway wall remodelling is present. Since it improves total score symptom and respiratory function of such patients, we hypothesise that azithromycins additional clinical benefits are due to an inhibition of airway smooth muscle cell (SMC) proliferation. Rabbit tracheal SMCs were treated with azithromycin (10−5 to 10−6 M) in the presence or absence of 10% fetal bovine serum (FBS). The proliferation was estimated using the Cell Titer 96® AQueous One Solution Assay (Promega, Madison, WI, USA). Cell viability was assessed with Trypan blue staining and flow cytometry after 7-aminoactinomycin D (7-AAD) staining. Induction of autophagy was studied by indirect immmunofluorescence and/or Western blotting with antibodies against human smooth muscle α-actin, beclin 1, light chain 3 and caspase 3. The involvement of the phosphoinositide 3-kinase pathway was investigated with the inhibitors LY294002 and wortmannin. Incubation with azithromycin for 72 h in the presence of FBS reduced SMC proliferation and viability in a dose-dependent manner. Azithromycin treatment was accompanied by the formation of cytoplasmic vacuoles, characteristic of autophagy. All these effects were reversible after azithromycin removal and prevented by the autophagy inhibitor, 3-methyladenine, or LY294002, but not by wortmannin. In conclusion, azithromycin reduces proliferation and causes autophagy of airway SMCs.

The mitogenic effect of testosterone and 17β-estradiol on airway smooth muscle cells.

Airway disease distribution and/or severity exhibit sex differences suggesting that sex hormones are involved in the respiratory system physiology and pathophysiology. The implication of airway smooth muscle cells (ASMCs) in the physiology of the airways and the pathogenetic mechanism of airway remodeling is of great interest. Therefore, we studied the effect of testosterone and 17β-estradiol on ASMC proliferation and the mechanisms involved. Cell proliferation was estimated using the methyl-[³H]thymidine incorporation and Cell Titer 96® AQueous One Solution Assay methods. ASMC isolated from adult male or female rabbit trachea were incubated with testosterone (1 pM-1 μM) or 17β-estradiol (1 pM-1 μM), in the presence or absence of the androgen receptor antagonist flutamide (10 nM) or estrogen receptor antagonist ICI182780 (10 nM), as well as of the PI3K inhibitors LY294002 (20 μM) or wortmannin (1 μM), or the MAPK inhibitors PD98059 (100 μM) or U0126 (1 μM). After 24 h of incubation, testosterone and 17β-estradiol increased methyl-[³H]thymidine incorporation and cell number, in ASMC isolated from male or female animals. The induction of ASMC proliferation by testosterone or 17β-estradiol was inhibited by flutamide or ICI182780 respectively, as well as by LY294002, wortmannin, PD98059 or U0126. In conclusion, testosterone and 17β-estradiol have a mitogenic effect on ASMC, which is receptor-mediated and involves the MAPK and PI3K signaling pathways. Moreover, their effect is the same for ASMC from male and female animals. It is possible that gender-related differences in ASMC remodeling, may be influenced by the different patterns of sex steroid hormone secretion in males and females.

Amiloride-sensitive Sodium Channels on the Parietal Human Peritoneum: Evidence by Ussing-type Chamber Experiments

The mesothelium is part of the peritoneal water and ion transport barrier essential for peritoneal dialysis (PD) treatment and has a central role in the pathogenesis of peritoneal fibrosis and ultrafiltration failure observed in many PD patients. We investigated the effect of amiloride on the transmesothelial electrical resistance (RTM) of isolated parietal human peritoneum. Intact sheets were obtained from seven patients (three men, four women; mean age, 64 ± 8 years). Fourteen peritoneal planar sheets were transferred to the laboratory in oxygenated Krebs-Ringer bicarbonate solution at 4°C within 30 minutes after removal and mounted in an Ussing-type chamber. Amiloride (10−3 mol/L) added apically (n = 8) caused a rapid rise of the RTM to 24.15 ± 0.76 &OHgr;H cm2 and a subsequent value persistence (p < 0.05); added basolaterally (n = 6), it increased the RTM to 22.66 ± 0.59 &OHgr;H cm2 within 1 minute, which persisted throughout the experiment. RTM was measured before and serially for 30 minutes after addition of amiloride. Control RTM was 20.29 ± 0.86 &OHgr;H cm2. These results indicate a rapid inhibitory effect of amiloride on the ionic permeability of parietal human peritoneum. The increase in the RTM observed after addition of amiloride clearly indicates the existence of amiloride-sensitive sodium channels on the human parietal peritoneal membrane, which may play some role in the ultrafiltration process and sodium removal during PD.

Comparison of the electrophysiological properties of the sheep isolated costal and diaphragmatic parietal pleura

1 Pleural permeability may contribute to pleural fluid turnover. The transmesothelial resistance (RTM), is an established surrogate of mesothelial permeability. The aim of the present study was to compare the electrophysiological properties of costal and diaphragmatic parietal pleura. 2 Specimens of the parietal pleura were isolated from 12 adult sheep from the chest wall and the diaphragm. Electrophysiological measurements were conducted with the Ussing system. Specimens of the parietal pleura of both types (diaphragmatic and costal) were compared histologically and total protein content measurements were also made. 3 The RTM of the diaphragmatic parietal pleura was significantly higher than that of the costal parietal pleura throughout the experiment. The diaphragmatic parietal pleura contains more cuboidal cells than the costal parietal pleura and its protein content was higher, however this difference was not statistically significant. 4 The costal parietal pleura consists of a more ‘leaky’ mesothelium than the diaphragmatic pleura. The morphological differences between the two types of parietal pleura may underline the electrophysiological findings.