Platelet Ca2+ handling in essential hypertension: Role of a plasma ouabain-like factor

A humoral ouabain-like plasma factor has been observed in patients with essential hypertension (EHT). In the present study, we hypothesized that this humoral factor might be responsible for the elevated cytosolic free calcium concentrations [Ca²⁺]_i seen in these patients. Patients with mild to moderate EHT and their normotensive first degree blood relatives (NTBR) participated in the study. Platelet Na⁺, K⁺-ATPase activity was assayed in EHT patients and their NT first-degree relatives. To confirm the ouabain-like activity in plasma from EHT patients, control platelets were incubated with EHT and NTBR plasma and their Na⁺, K⁺-ATPase activity was measured. In addition, the effect of EHT plasma on platelet⁴⁵Ca-uptake was studied. Thein vitro effects of ouabain (10 ΜM) on (i)⁴⁵Ca-uptake and (ii) [Ca²⁺]_i response in control platelets were also observed. A decreased Na⁺K⁺-ATPase activity (P< 0.05) was observed in platelet membranes from EHT patients. Incubation of control platelets with EHT plasma decreased their Na⁺, K⁺-ATPase activity (P< 0.01) and increased their⁴⁵Ca-uptake (P< 0.05). C-18 Sep-Pak filtered hypertensive plasma extracts (containing the ouabain-like fraction) also decreased Na⁺, K⁺-ATPase activity (P< 001) in control platelet membranes.In vitro incubation of control platelets with ouabain increased⁴⁵Ca-uptake (P< 005) and [Ca²⁺]_i response (P< 0.05) in these platelets. Thus it appears that an ouabain-like factor in the EHT plasma may contribute to the elevated platelet [Ca²⁺]_i observed in EHT patients.     

Non-dipper treated hypertensive patients do not have increased cardiac structural alterations

Background

Non-dipping pattern in hypertensive patients has been shown to be associated with an excess of target organ damage and with an adverse outcome. The aim of our study was to assess whether a reduced nocturnal fall in blood pressure (BP), established on the basis of a single 24-h BP monitoring, in treated essential hypertensives is related to more prominent cardiac alterations.

Methods

We enrrolled 229 treated hypertensive patients attending the out-patient clinic of our hypertension centre; each patient was subjected to the following procedures : 1) clinic BP measurement; 2) blood and urine sampling for routine blood chemistry and urine examination; 3) standard 12-lead electrocardiogram; 4) echocardiography; 5) ambulatory BP monitoring (ABPM). For the purpose of this study ABPM was carried-out in three subgroups with different clinic BP profile : 1) patients with satisfactory BP control (BP < 140/90 mmHg; group I, n = 58); 2) patients with uncontrolled clinic BP (clinic BP values ≥ 140 and/or 90 mmHg) but lower self-measured BP (< 20 mmHg for systolic BP and/or 10 mmHg for diastolic BP; group II, n = 72); 3) patients with refractory hypertension, selected according to WHO/ISH guidelines definition (group III, n = 99). Left ventricular hypertrophy (LVH) was defined by two gender-specific criteria (LV mass index ≥125/m² in men and 110 g/m² in women, ≥51/gm^2.7 in men and 47/g/m^2.7 in women).

Results

Of the 229 study participants 119 (51.9%) showed a fall in SBP/DBP < 10% during the night (non-dippers). The prevalence of non-dippers was significantly lower in group I (44.8%) and II (41.6%) than in group III (63.9%, p < 0.01 III vs II and I). The prevalence of LVH varied from 10.3 to 24.1% in group I, 31.9 to 43.1% in group II and from 60.6 to 67.7% in group III (p < 0.01, III vs II and I). No differences in cardiac structure, analysed as continuous variable as well as prevalence of LVH, were found in relationship to dipping or non-dipping status in the three groups.

Conclusions

In treated essential hypertensives with or without BP control the extent of nocturnal BP decrease is not associated with an increase in LV mass or LVH prevalence; therefore, the non-dipping profile, diagnosed on the basis of a single ABPM, does not identify hypertensive patients with greater cardiac damage.     

Administration Time‐Dependent Effects of Valsartan on Ambulatory Blood Pressure in Elderly Hypertensive Subjects

Previous results have indicated that valsartan administration at bed‐time, as opposed to upon wakening, improves the diurnal/nocturnal ratio of blood pressure (BP) toward a normal dipping pattern, without loss of 24 h efficacy. This ratio is characterized by a progressive decrease with aging. Accordingly, we investigated the administration time‐dependent antihypertensive efficacy of valsartan, an angiotensin blocking agent, in elderly hypertensive patients. We studied 100 elderly patients with grade 1–2 essential hypertension (34 men and 66 women), 68.2±4.9 years of age, randomly assigned to receive valsartan (160 mg/d) as a monotherapy either upon awakening or at bed‐time. BP was measured for 48 h by ambulatory monitoring, at 20 min intervals between 07∶00 to 23∶00 h and at 30 min intervals at night, before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately determine the duration of sleep and wake spans to enable the accurate calculation of the diurnal and nocturnal means of BP for each subject. There was a highly significant BP reduction after 3 months of valsartan treatment (p<0.001). The reduction was slightly larger with bed‐time dosing (15.3 and 9.2 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively) than with morning dosing (12.3 and 6.3 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively). The diurnal/nocturnal ratio, measured as the nocturnal decline of BP relative to the diurnal mean, was unchanged in the group ingesting valsartan upon awakening (?1.0 and ?0.3 for systolic and diastolic BP; p>0.195). This ratio was significantly increased (6.6 and 5.4 for systolic and diastolic BP; p<0.001) when valsartan was ingested at bed‐time. The reduction of the nocturnal mean was doubled in the group ingesting valsartan at bed‐time, as compared to the group ingesting it in the morning (p<0.001). In elderly hypertensive patients, mainly characterized by a diminished nocturnal decline in BP, bed‐time valsartan dosing is better than morning dosing since it improves efficacy during the nighttime sleep span, with the potential reduction in cardiovascular risk that has been associated with a normalized diurnal/nocturnal BP ratio.     

OSAS对冠心病患者的血糖和血脂水平的影响

目的:探讨阻塞性睡眠呼吸暂停综合征(Obstructive sleep apnea syndrome,OSAS)对冠心病患者血糖和血脂的影响。方法:纳入我科住院的明确诊断冠心病患者共168人,根据呼吸暂停低通气指数(Apnea-hypopnea index,AHI)共分2组:冠心病组133例,冠心病合并OSAS组45例(轻度OSAS组16例;中度OSAS组18例,重度OSAS组12例)。对比分析冠心病组和冠心病合并OSAS组患者血脂及血糖水平及其相关性。结果:BMI、LDL、HDL在四组间差异有统计学意义(P0.05)。冠心病合并OSAS的BMI、LDL、HDL明显高于冠心病组,各组间BMI差异有统计学意义(P0.05)。FPG、HOMA-I、RHb A1、OX-LDL、AHI在冠心病组和冠心病合并轻度OSAS组之间差异无统计学意义(P0.05)。FPG、HOMA-I、RHb A1、OX-LDL、AHI在OSAS轻、中、重各组间差异有统计学意义(P0.05)。冠心病合并OSAS患者AHI和BMI、LDL、FPG、HOMA-I、OX-LDL呈正相关关系(P0.05)。结论:OSAS增加了冠心病患者血脂水平和糖尿病的风险,及机制可能与胰岛素抵抗和OX-LDL水平增高有关。     

Reactivity of isolated toad aortic rings to angiotension II: the role of nitric oxide

Little is known about the vascular actions of angiotensin II (Ang II) and nitric oxide (NO) in Amphibia. This study investigated (1) Ang II contractility, (2) NO concentrations, and (3) correlations between Ang II contractility, NO concentration and mean arterial pressure (MAP) in isolated Bufo arenarum toad aortic rings. Contractility was measured in isometric conditions, NO concentrations were determined by the Griess reaction, and MAP was determined by a direct method. In isolated toad aortic rings, Ang II produced a contractile response (292.7 ± 89.2 mg; n = 20). Furthermore, a contractile response to norepinephrine (NE) was also obtained. A significant correlation between both the Ang II and NE contractile responses was found (r = 0.89; n = 11; P < 0.01). Administration of Ang II increased MAP values (Basal 16.8 ± 1.7; n = 19 vs. Ang II 28.4 ± 1.8 mmHg; n = 19; P < 0.001), and the increase of MAP by Ang II was positively correlated with the Ang II contractile response (P < 0.01). Administration of L-NAME also increased MAP values, and this effect was higher in those toads that presented a lower pressure response to Ang II (Pearson r = −0.68; P < 0.05). NO was present in all aortic rings, and its concentrations were negatively related to the Ang II contractile response (P < 0.036) and pressure response (Pearson r = −7.08; P < 0.001). These findings suggest that, in the B. arenarum toad, the NO system contra-regulates both the contractile and pressure Ang II responses, although its action could be different in each specimen.     

ELISA examining urinary angiotensinogen as a potential indicator of intrarenal renin–angiotensin system (RAS) activity: a clinical study of 128 chronic kidney disease patients

In the current study, we measured urinary angiotensinogen (AGT) through enzyme-linked immunoadsordent assay (ELISA) and analyzed its correlation with intrarenal renin–angiotensin system (RAS) activity in 128 chronic kidney disease (CKD) patients. Urinary and plasma renin activity, AGT, angiotensin II (Ang II) and aldosterone levels were also measured by radioimmunoassay (RIA) or ELISA in these participants. Further, the expression level of intrarenal renin, AGT, Ang II and Ang II receptors were examined by immunohistochemistry staining (IHCS) in 72 CKD patients. Their correlations with urinary AGT were also analyzed. We found that the urinary AGT level was positively correlated with hypertension (ρ = 0.28, P < 0.01), urinary protein (r = 0.38, P < 0.01), urinary Ang II (r = 0.29, P < 0.05), urinary type IV collagen (Col IV) (r = 0.56, P < 0.01), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r = ?0.28, P < 0.01), urinary sodium (r = ?0.22, P < 0.05) and serum AGT (r = ?0.27, P < 0.01). Multiple regression analysis indicated low serum AGT (P < 0.01), high urinary protein (P < 0.01), high urinary Ang II (P < 0.05) and high urinary Col IV (P < 0.01) were correlated significantly with high urinary AGT. Urinary AGT level was positively correlated with intrarenal expression level of AGT (ρ = 0.46, P < 0.01), Ang II (ρ = 0.56, P < 0.01) and Ang II type 1 receptor (ρ = 0.32, P < 0.01), as detected by IHCS. Together, these data suggest that urinary AGT might be a potential biomarker of intrarenal RAS and Ang II activities in CKD patients.     

Influence of daylight and incubation interval on water column respiration in tropical fish ponds

Water column respiration (WCR) was measured in dark BOD bottles for 2, 4 and 8 h intervals during 22 h periods in two 1000 m² ponds stocked withOreochromis niloticus at 1 m^–2, and fertilized weekly with chicken litter at 750 kg total solids ha^–1. Mean WCR ranged from a low of 0.39 mg l^–1 for 8 h nocturnal intervals to a high of 0.62 mg l^–1 for 2-h diurnal intervals. WCR was significantly influenced by daylight and time into the diurnal or nocturnal period when it was determined. Mean WCR was significantly greater during the day than during the night (P<0.01). During the day, 2 h incubation intervals resulted in significantly higher WCR than 4 h or 8 h intervals (P<0.01); length of incubation interval did not significantly influence nocturnal WCR (P>0.05). Higher WCR during the day and during short diurnal incubation intervals was attributed to greater availability of photosynthetic respiration substrate. Diurnal, diel, or nocturnal WCR could be best estimated by a single 2, 4 or 8 h incubation interval, respectively, beginning at 0800 h.     

Altered cardiovascular responses to chronic angiotensin II infusion in aged rats

In this work we determined by telemetry the cardiovascular effects produced by Ang II infusion on blood pressure (BP) and heart rate (HR) in aged rats. Male Wistar aged (48-52 weeks) and young (12 weeks) rats were used. Ang II (6 microg/h, young, n=6; aged, n=6) or vehicle (0.9% NaCl 1 microl/h, young, n=4; aged, n=5) were infused subcutaneously for 7 days, using osmotic mini-pump. The basal diurnal and nocturnal BP values were higher in aged rats (day: 98+/-0.3 mm Hg, night: 104+/-0.4 mm Hg) than in the young rats (day: 92+/-0.2 mm Hg, night: 99+/-0.2 mm Hg). In contrast, the basal diurnal and nocturnal HR values were significantly smaller in the aged rats. Ang II infusion produced a greater increase in the diurnal BP in the aged rats (Delta MAP=37+/-1.8 mm Hg) compared to the young ones (Delta MAP=30+/-3.5 mm Hg). In contrast, the nocturnal MAP increase was similar in both groups (young rats; Delta MAP=22+/-3.0 mm Hg, aged rats; Delta MAP=24+/-2.6 mm Hg). During Ang II infusion HR decreased transiently in the young rats. An opposite trend was observed in the aged rats. Ang II infusion also inverted the BP circadian rhythm, in both groups. No changes in HR circadian rhythm were observed. These differences suggest that the aging process alters in a different way Ang II-sensitive neural pathways involved in the control of autonomic activity.     

Angiogenic and Restorative Abilities of Human Mesenchymal Stem Cells Were Reduced Following Treatment With Serum From Diabetes Mellitus Type 2 Patients

This experiment investigated the impact of serum from patients with type 2 diabetes mellitus on the angiogenic behavior of human mesenchymal stem cells in vitro. Changes in the level of Ang‐1, Ang‐2, cell migration, and trans‐differentiation into pericytes and endothelial lineage were monitored after 7 days. The interaction of mesenchymal stem cells with endothelial cells were evaluated using surface plasmon resonance technique. Paracrine restorative effect of diabetic stem cells was tested on pancreatic β cells. Compared to data from FBS and normal serum, diabetic serum reduced the stem cell survival and chemotaxis toward VEGF and SDF‐1α (P < 0.05). Diabetic condition were found to decline cell migration rate and the activity of MMP‐2 and ‐9 (P < 0.05). The down‐regulation of VEGFR‐2 and CXCR‐4 was observed with an increase in the level of miR‐1‐3p and miR‐15b‐5p at the same time. The paracrine angiogenic potential of diabetic stem cells was disturbed via the changes in the dynamic of Ang‐1, Ang‐2, and VEGF. Surface plasmon resonance analysis showed that diabetes could induce an aberrant increase in the interaction of stem cells with endothelial cells. After treatment with diabetic serum, the expression of VE‐cadherin and NG2 and ability for uptake of Dil‐Ac‐LDL were reduced (P < 0.01). Conditioned media prepared from diabetic stem cells were unable to decrease fatty acid accumulation in β‐cells (P < 0.05). The level of insulin secreted by β‐cells was not affected after exposure to supernatant from diabetic or non‐diabetic mesenchymal stem cells. Data suggest diabetes could decrease angiogenic and restorative effect of stem cells in vitro. J. Cell. Biochem. 119: 524–535, 2018. © 2017 Wiley Periodicals, Inc.     

Prevalence of Sleep Apnea and Electrocardiographic Disturbances in Morbidly Obese Patients

Objective: To determine the prevalence of sleep apnea in morbidly obese patients and its relationship with cardiac arrhythmias. Research Methods and Procedures: Fifty‐two consecutive morbidly obese (body mass index ≥ 40 kg/m²) outpatients from the Obesity Clinic of the National Institute of Nutrition Salvador Zubirán underwent two nights of polysomnography with standard laboratory techniques. Electrocardiographic polysomnography signals (Lead II) were evaluated by two experienced cardiologists, and sleep complaints were measured with a standard sleep questionnaire (Sleep Disorders Questionnaire). In order to make comparisons between groups with different severities of sleep‐disordered breathing, we classified the patients in four groups using the apnea‐hypopnea index (AHI): Group 1, AHI 5 < 15 (n = 10); Group 2, AHI 15 < 30 (n = 10); Group 3, AHI 30 < 65 (n = 14); Group 4, AHI ≥ 65 (n = 17). Results: A wide range of sleep‐disordered breathing, ranging from AHI of 2.5 to 128.9 was found. Ninety‐eight percent of the sample (n = 51) had an AHI ≥ 5 (mean = 51 ± 37), and 33% had severe sleep apnea with AHI ≥ 65 with a mean nocturnal desaturation time of <65% over 135 minutes. Electrocardiographic abnormalities were present in 31% of the patients. Cardiac rhythm alterations showed an association with the level of sleep‐disordered breathing and oxygen desaturation. Discussion: We conclude that there is a high prevalence of sleep apnea in morbidly obese patients and that the risk for cardiac arrhythmias increases in this population in the presence of a severe sleep apnea (AHI ≥ 65) with severe oxygen desaturation (Sao ₂ ≤ 65%).     

Comparison of Ambulatory Blood Pressure Parameters of Hypertensive Patients With and Without Chronic Kidney Disease

There is strong association between chronic kidney disease (CKD) and increased prevalence of hypertension, risk of end-organ damage, and cardiovascular disease (CVD). Non-dipping, as determined by ambulatory blood pressure (BP) monitoring (ABPM), is frequent in CKD and has also been consistently associated with increased CVD risk. The reported prevalence of non-dipping in CKD is highly variable, probably due to relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary fixed clock-hour spans. Accordingly, we assessed the circadian BP pattern of patients with and without CKD by 48-h ABPM to increase reproducibility of the results. This cross-sectional study involved 10 271 hypertensive patients (5506 men/4765 women), 58.0?±?14.2 (mean?±?SD) yrs of age, enrolled in the Hygia Project. Among the participants, 3227 (1925 men/1302 women) had CKD. At the time of recruitment, 568/2234 patients with/without CKD were untreated for hypertension. Patients with than without CKD were more likely to be men and of older age, have diagnoses of obstructive sleep apnea, metabolic syndrome, diabetes, and/or obesity, plus have higher glucose, creatinine, uric acid, and triglyceride, but lower cholesterol, concentrations. In patients with CKD, ambulatory systolic BP (SBP) was significantly elevated (p?<?.001), mainly during the hours of nighttime sleep, independent of presence/absence of BP-lowering treatment. In patients without CKD, ambulatory diastolic BP (DBP), however, was significantly higher (p?<?.001), mainly during the daytime. Differing trends for SBP and DBP between groups resulted in large differences in ambulatory pulse pressure (PP), it being significantly greater (p?<?.001) for the entire 24?h in patients with CKD. Prevalence of non-dipping was significantly higher in patients with than without CKD (60.6% vs. 43.2%; p?<?.001). The largest difference between groups was in the prevalence of the riser BP pattern, i.e., asleep SBP mean?>?awake SBP mean (17.6% vs. 7.1% in patients with and without CKD, respectively; p?<?.001). The riser BP pattern significantly and progressively increased from 8.1% among those with stage 1 CKD to a very high 34.9% of those with stage 5 CKD. Elevated asleep SBP mean was the major basis for the diagnosis of hypertension and/or inadequate BP control among patients with CKD; thus, among the uncontrolled hypertensive patients with CKD, 90.7% had nocturnal hypertension. Our findings document significantly elevated prevalence of a blunted nocturnal BP decline in hypertensive patients with CKD. Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was 2.5-fold more prevalent in CKD, and up to 5-fold more prevalent in end-stage renal disease. Patients with CKD also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. Collectively, these findings indicate that CKD should be included among the clinical conditions for which ABPM is mandatory for proper diagnosis and CVD risk assessment, as well as a means to establish the best therapeutic scheme to increase CVD event-free survival. (Author correspondence: rhermida@uvigo.es)     

Lipopolysaccharide-stimulated activation of murine DC2.4 cells is attenuated by <Emphasis Type="Italic">n</Emphasis>-butylidenephthalide through suppression of the NF-κB pathway

Modulation of dendritic cell (DC) fate and function may be one approach for the treatment of inflammatory and autoimmune diseases. n-Butylidenephthalide (BP), derived from Angelica sinensis, at 40 μg/ml significantly decreased the secretion of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide (LPS)-stimulated activation of cultured murine DC2.4 cells (P < 0.01). LPS-induced major histocompatibility complex class II (P < 0.05), CD86 (P < 0.01) and CD40 (P < 0.01) expression on DC2.4 cells was also inhibited by BP. The endocytic capacity of LPS-stimulated DC2.4 cells was increased by BP (P < 0.01). The antigen-presenting capacity of LPS-stimulated DC2.4 cells was decreased by BP (P < 0.05). Moreover, we confirmed BP attenuates the responses of LPS-stimulated activation of DCs via suppression of NF-κB-dependent pathways.     

Raised Interleukin‐6 Levels in Obese Patients

Objective: Obese patients demonstrate a variety of biochemical, metabolic, and pulmonary abnormalities. Inflammatory mediators such as tumor necrosis factor‐α and interleukin‐6 (IL‐6) may have a direct effect on glucose and lipid metabolism. Hypoxemia in itself induces release of IL‐6. The aim of this study was to examine the relationship between IL‐6 levels in healthy volunteers (control group) and three different groups of obese patients: patients without obstructive sleep apnea syndrome (OSAS), patients with OSAS, and patients with obesity hypoventilation syndrome (OHS) (daytime baseline oxygen saturation of <93%). Research Methods and Procedures: We measured serum IL‐6 levels in 25 obese patients (body mass index of >35 kg/m²) and 12 healthy women. Results: The results demonstrate statistically significant differences in serum IL‐6 levels between the control group (1.28 ± 0.85 pg/mL) and obese patients without OSAS (7.69 ± 5.06 pg/mL, p < 0.05) and with OSAS (5.58 ± 0.37 pg/mL, p < 0.0005). In the patients with OHS, IL‐6 concentrations were highest (43.13 ± 24.27 pg/mL). Discussion: We conclude that serum IL‐6 is increased in obese patients. The highest IL‐6 levels were found in the patients with OHS.     

Sleep quality in adult patients with sleep related bruxism

Sleep related bruxism (SB) is the grinding of teeth during sleep and may also be associated with various sleep disorders. However, little is known about sleep structures and disturbances of SB. This study aims to further understand sleep architectures using overnight polysomnography (PSG) in patients with SB. We analyze sleep parameters and architectures in 33 healthy subjects and 25 patients with SB. PSG and sleep questionnaires measured sleep variables including proportions of rapid eye movement (REM) sleep, non-REM sleep (N1, N2 and N3), latency to sleep onset, sleep efficiency, wake after sleep onset (WASO), apnea hypopnea index (AHI), respiratory disturbance index (RDI), and periodic limb movement index (PLMI) during sleep for both groups. Sleep efficiency and the proportion of N3 in the SB group were significantly lower than in the control group (P < 0.05). In addition latency to onset of sleep and WASO were markedly increased in the SB group (P < 0.05). AHI, RDI, and PLMI showed no differences between the groups. Epworth Sleepiness Scale was significantly higher in the SB group than in the control group (P < 0.05). In contrast to previous studies, we conclude that patients with SB are not good sleepers based on PSG study. Further studies are required to assess the relationship between sleep quality and the severity of SB.

     

Relationship among levels of leptin and zinc,copper, and zinc/copper ratio in plasma of patients with essential hypertension and healthy normotensive subjects

Obesity is among the main contributing factors in the etiology of essential hypertension (EHT). Leptin, the product of the ob gene, is expressed mainly in adipose tissue. We examined the relationship between two trace elements, zinc (Zn) and copper (Cu), and leptin in patients with EHT (n=35) and normotensive (NT) controls (n=50) because leptin as well as Zn and Cu were reported to be associated with the pathophysiology of EHT. Plasma leptin levels were determined with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Atomic absorption spectrophotometry was utilized to determine plasma Zn and Cu levels. There was a negative correlation between leptin and Zn, and the Zn/Cu ratio (r=−0.359, p<0.05; r=0.361, p<0.05, respectively) in pooled subjects. When subjects were divided based on the presence or absence of hypertension, there was a negative correlation between leptin and Zn (r=−0.375, p<0.05) as well as leptin and Zn/Cu ratio (r=−0.398, p<0.05) in NT subjects. Similar trends were observed when leptin/BMI (body mass index) levels were utilized. There was no significant correlations between levels of Cu and leptin or leptin/BMI. In conclusion, in addition to high leptin levels, Zn and the Zn/Cu ratio were lower in patients with EHT compared to NT controls.     

Surgical influence of pancreatectomy on the function and count of circulating dendritic cells in patients with pancreatic cancer

Background: Dendritic cells (DCs) are important for an immune surveillance. Myeloid DCs (DC1) are important for an effective antitumor immune system. The function and count of circulating DC1 (cDC1) in hosts with a malignant tumor would be defective. This study focused on analyzing the immunological features of cDC1 in patients with pancreatic cancer during the perioperative period. Materials and methods: Thirty-two pancreatic cancer patients who underwent pancreatectomy and 18 age-matched healthy individuals as controls were enrolled in this study. The perioperative cDC count, the stimulatory capacity of cDC1 against allogeneic T cells and TGF-β1 level in the serum were measured. The cDC count was measured at 12 months after the operation. Results: The preoperative cDC1/cDC2 ratio, cDC1 count, and stimulatory capacity of cDC1 were impaired in patients in comparison to controls (P<0.05). The serum TGF-β1 level was significantly higher in patients than controls (P<0.001). The stimulatory capacity of cDC1 recovered after pancreatectomy (P<0.05). The serum TGF-β1 level significantly decreased after the operation (P<0.05); however, they were still significantly higher than controls (P<0.05). Although the cDC1/cDC2 ratio and the cDC1 count did not increase after the pancreatectomy, they recovered as the controls’ level at 12 months after the pancreatectomy in disease-free patients (P<0.05) and the serum TGF-β1 level in those patients at 12 months after the operation significantly decreased compared with those at the postoperative period (P<0.05). Conclusion: Surgical resection of pancreatic cancer could be associated with improved cDC1 function. When a patient remained disease free, the recovery of cDC1 counts was observed approximately 12 months after pancreatectomy. Further strategy will be needed to improve immune function in patients with pancreatic cancer.     

Insertion/Deletion Polymorphism and Serum Activity of the Angiotensin-Converting Enzyme in Turkish Patients with Obstructive Sleep Apnea Syndrome

This study determined the allelic frequency and genotypic distribution of an angiotensin-converting enzyme (ACE) polymorphism and serum ACE activity in Turkish patients with obstructive sleep apnea syndrome (OSAS). A colorimetric assay measured serum ACE activity in 73 of 97 subjects. Frequencies for II, ID, and DD genotypes were 19.6, 53.6, and 26.8% in the OSAS group and 15, 38, and 47% in the control group, respectively (P = 0.02). The I allele frequency was higher in the OSAS group than in the healthy control group (P = 0.02). Carrying the I allele (II or ID genotypes) increased OSAS risk 2.41 times in the Turkish population. Mean ACE activity was significantly lower in patients with the II genotype than in the DD genotype (P = 0.011), and ACE activity was significantly lower in patients with severe OSAS than in those with mild OSAS (P = 0.006). Our results suggest that II and ID genotypes of the ACE gene increase the risk of developing OSAS in the Turkish population.     

Ambulatory Blood Pressure Monitoring in Individuals with HIV: A Systematic Review and Meta-Analysis

Introduction

Abnormal diurnal blood pressure (BP) rhythms may contribute to the high cardiovascular disease risk in HIV-positive (HIV⁺) individuals. To synthesize the current literature on ambulatory BP monitoring (ABPM) in HIV⁺ individuals, a systematic literature review and meta-analysis were performed.

Methods

Medical databases were searched through November 11, 2015 for studies that reported ABPM results in HIV⁺ individuals. Data were extracted by 2 reviewers and pooled differences between HIV⁺ and HIV-negative (HIV^-) individuals in clinic BP and ABPM measures were calculated using random-effects inverse variance weighted models.

Results

Of 597 abstracts reviewed, 8 studies with HIV⁺ cohorts met the inclusion criteria. The 420 HIV⁺ and 714 HIV^- individuals in 7 studies with HIV^- comparison groups were pooled for analyses. The pooled absolute nocturnal systolic and diastolic BP declines were 3.16% (95% confidence interval [CI]: 1.13%, 5.20%) and 2.92% (95% CI: 1.64%, 4.19%) less, respectively, in HIV⁺ versus HIV^- individuals. The pooled odds ratio for non-dipping systolic BP (nocturnal systolic BP decline <10%) in HIV⁺ versus HIV^- individuals was 2.72 (95% CI: 1.92, 3.85). Differences in mean clinic, 24-hour, daytime, or nighttime BP were not statistically significant. I² and heterogeneity chi-squared statistics indicated the presence of high heterogeneity for all outcomes except percent DBP dipping and non-dipping SBP pattern.

Conclusions

An abnormal diurnal BP pattern may be more common among HIV⁺ versus HIV^- individuals. However, results were heterogeneous for most BP measures, suggesting more research in this area is needed.     

Arousal and ventilatory responses during sleep in children with obstructive sleep apnea

Abnormal centralregulation of upper airway muscles may contribute to thepathophysiology of the childhood obstructive sleep apnea syndrome(OSAS). We hypothesized that this was secondary to global abnormalitiesof ventilatory control during sleep. We therefore compared the responseto chemical stimuli during sleep between prepubertal children with OSASand controls. Patients with OSAS aroused at a higherPCO₂ (58 ± 2 vs. 60 ± 5 Torr,P < 0.05); those with the highestapnea index had the highest arousal threshold(r = 0.52, P < 0.05). The hypercapnic arousal threshold decreased after treatment. For all subjects, hypoxia was apoor stimulus to arousal, whereas hypercapnia and, particularly, hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in decreased airway obstruction in OSAS. Ventilatory responseswere similar between patients with OSAS and controls; however, thesample size was small. We conclude that children with OSAS haveslightly blunted arousal responses to hypercapnia. However, the overallventilatory and arousal responses are normal in children with OSAS,indicating that a global deficit in respiratory drive is not a majorfactor in the etiology of childhood OSAS. Nevertheless, subtleabnormalities in ventilatory control may exist.

     

Sympathovagal Balance,Nighttime Blood Pressure,and QT Intervals in Normotensive Obese Women

Objective : We describe associations among the heart‐rate‐corrected QT (QTc) interval, QTc dispersion (QTc‐d), circadian BP variation, and autonomic function in obese normotensive women and the effect of sustained weight loss. Research Methods and Procedures : In 71 obese (BMI = 37.14 ± 2.6 kg/m²) women, 25 to 44 years of age, circadian BP variations (24‐hour ambulatory BP monitoring), autonomic function (power spectral analysis of RR interval oscillations), and cardiac repolarization times (QTc‐d and QTc interval) were recorded at baseline and after 1 year of a multidisciplinary program of weight reduction. Results : Compared with nonobese age‐matched women (n = 28, BMI = 23 ± 2.0 kg/m²), obese women had higher values of QTc‐d (p < 0.05) and QTc (p < 0.05), an altered sympathovagal balance (ratio of low‐frequency/high‐frequency power, p < 0.01), and a blunted nocturnal drop in BP (p < 0.01). In obese women, QTc‐d and the QTc interval correlated with diastolic nighttime BP (p < 0.01) and sympathovagal balance (p < 0.01). Waist‐to‐hip ratio, free fatty acids, and plasma insulin levels correlated with QT intervals and reduced nocturnal drops in both systolic and diastolic BP and sympathovagal balance (p < 0.01). After 1 year, obese women lost at least 10% of their original weight, which was associated with decrements of QTc‐d (p < 0.02), the QTc interval (p < 0.05), nighttime BP (p < 0.01), and sympathovagal balance (p < 0.02). Discussion : Sustained weight loss is a safe method to ameliorate diastolic nighttime BP drop and sympathetic overactivity, which may reduce the cardiovascular risk in obese women.