Poor sleep quality is associated with cardiac autonomic dysfunction in treated hypertensive men

Hypertensives present cardiac autonomic dysfunction. Reduction in sleep quality increases blood pressure (BP) and favors hypertension development. Previous studies suggested a relationship between cardiovascular autonomic dysfunction and sleep quality, but it is unclear whether this association is present in hypertensives. Thus, this study evaluated the relationship between sleep quality and cardiac autonomic modulation in hypertensives. Forty-seven middle-aged hypertensive men under consistent anti-hypertensive treatment were assessed for sleep quality by the Pittsburgh Sleep Quality Index (PSQI—higher score means worse sleep quality). Additionally, their beat-by-beat BP and heart rate (HR) were recorded, and cardiac autonomic modulation was assessed by their variabilities. Mann-Whitney and t tests were used to compare different sleep quality groups: poor (PSQI > 5, n = 24) vs good (PSQI ≤ 5, n = 23), and Spearman’s correlations to investigate associations between sleep quality and autonomic markers. Patients with poor sleep quality presented lower cardiac parasympathetic modulation (HR high-frequency band = 26 ± 13 vs 36 ± 15 nu, P =.03; HR total variance = 951 ± 1373 vs 1608 ± 2272 ms2, P =.05) and cardiac baroreflex sensitivity (4.5 ± 2.3 vs 7.1 ± 3.7 ms/mm Hg, P =.01). Additionally, sleep quality score presented significant positive correlation with HR (r = +0.34, P =.02) and negative correlations with HR high-frequency band (r = −0.34, P =.03), HR total variance (r = −0.35, P =.02), and cardiac baroreflex sensitivity (r = −0.42, P =.01), showing that poor sleep quality is associated with higher HR and lower cardiac parasympathetic modulation and baroreflex sensitivity. In conclusion, in treated hypertensive men, poor sleep quality is associated with cardiac autonomic dysfunction

Morning versus Evening Aerobic Training Effects on Blood Pressure in Treated Hypertension

Introduction The acute blood pressure (BP) decrease is greater after evening than morning exercise, suggesting that evening training (ET) may have a greater hypotensive effect. Objective This study aimed to compare the hypotensive effect of aerobic training performed in the morning versus evening in treated hypertensives. Methods Fifty treated hypertensive men were randomly allocated to three groups: morning training (MT), ET, and control (C). Training groups cycled for 45 min at moderate intensity (progressing from the heart rate of the anaerobic threshold to 10% below the heart rate of the respiratory compensation point), while C stretched for 30 min. Interventions were conducted 3 times per week for 10 wk. Clinic and ambulatory BP and hemodynamic and autonomic mechanisms were evaluated before and after the interventions. Clinic assessments were performed in the morning (7:00-9:00 am) and evening (6:00-8:00 pm). Between-within ANOVA was used (P ≤ 0.05). Results Only ET decreased clinic systolic BP differently from C and MT (morning assessment -5 ± 6 mm Hg and evening assessment -8 ± 7 mm Hg, P < 0.05). Only ET reduced 24 h and asleep diastolic BP differently from C and MT (-3 ± 5 and -3 ± 4 mm Hg, respectively, P < 0.05). Systemic vascular resistance decreased from C only in ET (P = 0.03). Vasomotor sympathetic modulation decreased (P = 0.001) and baroreflex sensitivity (P < 0.02) increased from C in both training groups with greater changes in ET than MT. Conclusions In treated hypertensive men, aerobic training performed in the evening decreased clinic and ambulatory BP due to reductions in systemic vascular resistance and vasomotor sympathetic modulation. Aerobic training conducted at both times of day increases baroreflex sensitivity, but with greater after ET

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

<p>Abstract</p> <p>Background</p> <p>Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome.</p> <p>Methods</p> <p>Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed.</p> <p>Results</p> <p>Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson).</p> <p>Conclusions</p> <p>The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.</p