Efficient transmembrane anion transport mediated by a bis(imidazolyl)-functionalized bis(choloyl) conjugate.

A bis(imidazolyl)-functionalized bis(choloyl) conjugate was synthesized and assessed for its transmembrane anionophoric activity by means of chloride ion selective electrode technique and pyranine assays. The results indicate that under the assay conditions, this conjugate was capable of mediating the symport of proton and anions, presumably via a channel mechanism. In addition, this compound was found to exhibit much higher anionophoric activity than the analogue without imidazolyl groups, revealing the significant role of the imidazolyl groups in the anion transport process.

2,6-Bis(benzimidazol-2-yl)pyridine as a potent transmembrane anion transporter.

2,6-Bis(benzimidazol-2-yl)pyridine was shown to exhibit potent anionophoric activity via a process of both Cl(-)/NO3(-) antiport and H(+)/Cl(-) symport. This is in sharp contrast to the finding that its corresponding N-methylated analog exhibited negligible activity and reveals the importance of the imidazolyl-NH fragments in the anion-transport process.

Synthesis and transmembrane anion/cation symport activity of a rigid bis(choloyl) conjugate functionalized with guanidino groups.

A rigid bis(choloyl) conjugate functionalized with guanidino groups was synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Its transmembrane ionophoric activity across egg-yolk l-α-phosphatidylcholine-based liposomal membranes was investigated by means of chloride ion selective electrode technique and pH discharge assay. The data indicate that under the assay conditions, this conjugate was capable of promoting the transport of anions, presumably via a cation/anion symport process. A Hill analysis reveals that two molecules of this compound are assembled into the transport-active species.

Does lipophilicity affect the effectiveness of a transmembrane anion transporter? Insight from squaramido-functionalized bis(choloyl) conjugates.

Six squaramido-functionalized bis(choloyl) conjugates were synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Their transmembrane anionophoric activity was investigated in detail by means of chloride ion selective electrode technique and pyranine assay. The data indicate that this set of compounds is capable of promoting the transmembrane transport of anions presumably via proton/anion symport and anion exchange processes, and that lipophilicity in terms of clog P from 3.90 to 8.32 affects the apparent ion transport rate in a concentration-dependent fashion. Detailed kinetic analysis on the data obtained from both the chloride efflux and pH discharge experiments reveals that there may exist an optimum clog P range for the intrinsic ion transport rate. However, lipophilicity exhibits little effect on the effectiveness of this set of compounds in terms of either k2/Kdiss or EC50 values.

Synthesis and potent ionophoric activity of a squaramide-linked bis(choloyl) conjugate.

A squaramide-linked bis(choloyl) conjugate was synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Fluorescence and chloride ion selective electrode assays indicate that this compound exhibits potent ionophoric activity across egg-yolk L-α-phosphatidylcholine-based liposomal membranes, presumably via an anion-modulating anion-cation co-transport/symport process. A Hill analysis reveals that three molecules of this compound are assembled into the transport-active species.

Synthesis and ionophoric activities of functionalized bis(choloyl) conjugates with a rigid core.

Three bis(choloyl) conjugates bearing a rigid p-phenylenediamine/p-bis(aminomethyl)benzene linker and amino/acetamido groups were synthesized, and fully characterized on the basis of (1)H NMR, ESI-MS and HRMS. Their ionophoric activities were investigated by means of pH discharge assay. The results indicate that these conjugates exhibit potent ionophoric activities across egg-yolk l-α-phosphatidylcholine (EYPC)-based liposomal membranes, via a cation/proton antiport mechanism. They show moderate ion selectivity among alkali metal ions. Of the three conjugates, the ones having amino groups transport alkali metal ions in the order of Na(+)>Li(+)>K(+)≈Rb(+)≈Cs(+), whereas the one having acetamido groups functions in the order of Li(+)>Na(+)>K(+)≈Rb(+)≈Cs(+).

Synthesis and anionophoric activities of dimeric polyamine-sterol conjugates: the impact of rigid vs. flexible linkers.

Two dimeric spermine-choloyl conjugates were synthesized and found to be capable of promoting the transport of anions across egg-yolk L-α-phosphatidylcholine-based liposomal membranes, via an anion-exchange mechanism and with moderate selectivity with respect to monoanionic ions. A Hill analysis indicated that these two conjugates exhibited similar aggregation behaviors. However, the conjugate bearing a rigid p-bis(aminomethyl)benzene moiety functioned more efficiently than the analogue having a flexible putrescine linker.

Early morning home blood pressure control among treated patients with controlled office blood pressure.

Elevated morning blood pressure (BP) has a significantly increased risk of cardiovascular events, so morning BP is of substantial clinical importance for the management of hypertension. This study aimed to evaluate early morning BP control and its determines among treated patients with controlled office BP. From May to October 2018, 600 treated patients with office BP < 140/90 mm Hg were recruited from hypertension clinics. Morning BP was measured at home for 7 days. Morning home systolic blood pressure (SBP) increased by an average of 11.5 mm Hg and that morning home diastolic blood pressure (DBP) increased by an average of 5.6 mm Hg compared with office BP. Morning home SBP, DBP, and their moving average were more likely to be lower among patients with a office SBP < 120 mm Hg than among patients with a office SBP ranging from 120 to 129 mm Hg and from 130 to 139 mm Hg (P < .001). A total of 45% of patients had early morning BP < 135/85 mm Hg. The following factors were significantly correlated with morning BP control: male sex, age of <65 years, absence of habitual snoring, no drinking, adequate physical activity, no habit of high salt intake, office BP < 120/80 mm Hg, and combination of a calcium channel blocker (CCB) and angiotensin receptor blocker or angiotensin-converting enzyme inhibitor (ARB/ACEI). Less than half of patients with controlled office BP had controlled morning BP and that positive changes may be related to an office BP < 120/80 mm Hg, combination of a CCB and ACEI/ARB and a series of lifestyle adjustments.

A risk score for carotid plaque as an assessment risk of cardiovascular risk among patients with hypertension.

This study aimed to describe the status of carotid plaques and develop a simple scoring system to predict the risk of carotid lesions in patients with hypertension. Basic testing for carotid plaques was carried out and used for risk score development (the training dataset, n = 2665) and validation (the test dataset, n = 1333). Independent predictors of carotid plaques from the multivariate model were assigned integer weights based on their coefficients and incorporated into a risk score. The discriminant ability of the score was tested by receiver operating characteristic analysis using the test dataset. A total of 1346 of 2665 patients were examined for carotid plaques, which were more frequent in men than in women, and increased with age. The final model included eight significant variables, and these variables were then used to develop a risk score for the prediction of carotid plaques. Receiver operating characteristic analysis demonstrated good discriminant power with a C-statistic of 0.732 (95% confidence interval: 0.713-0.751) and good calibration across quantiles of observed predicted risk (74.6%). We developed a simple risk score for the prediction of carotid plaques based on eight variables. The prediction model showed good discriminant power and calibration.

Control of cardiovascular disease risk factors among patients with type II diabetes in a primary-care setting in Beijing.

The aim of this study was to assess the control of blood glucose, blood pressure (BP), serum low-density lipoprotein cholesterol (LDL-c), and other cardiovascular disease risk factors among patients with type II diabetes in a primary-care setting in Beijing. We performed a cross-sectional, multi-center survey of 4056 patients with type II diabetes aged ≥40 years. In total, 22.6% were current smokers, 10.8% often drank alcohol, 29.0% were obese, and 67.4% participated in adequate levels of physical activity. About 70% of patients reported comorbid hypertension or dyslipidemia. Of these, 70.8% were being treated for diabetes and 79.3% for hypertension; 20.5% were receiving statins and 28.5% aspirin. The proportions of patients achieving their therapeutic target were 52.6% for fasting plasma glucose, 58.2% for BP, and 33.0% for LDL-c. Only 11.1% achieved all three goals. Among 1960 (48.3%) patients with a record of hemoglobin A1C, 27.8% achieved the hemoglobin A1C target (<6.5%). These data suggest that blood glucose and BP were more likely to be well controlled than LDL-c, the likelihood of control of multiple risk factors is low, and that the statin and aspirin use should be intensified in patients with a substantial risk of cardiovascular disease.

Survivin gene functions and relationships between expression and prognosis in patients with nasopharyngeal carcinoma.

This study aimed to investigate the relationship between prognosis and protein and mRNA expression of an apoptotic inhibitor gene, survivin, in patients with nasopharyngeal carcinoma. Furthermore, functions of the survivin gene in the CNE2 nasopharyngeal carcinoma cell line were assessed. Immunohistochemistry and in situ hybridization were used in detecting the survivin protein and mRNA in 44 nasopharyngeal carcinoma specimens, and 30 chronic nasopharyngitis samples as controls. Survivin gene expression in CNE2 cell line was suppressed with an shRNA (short hairpin RNA). The positive ratios of expression for survivin protein and mRNA in nasopharyngeal carcinoma were 79.5% and 75.0% respectively, obviously higher than in the control group (p<0.01), and there is very good consistency between the two methods. The mean survival time of patients with higher survivin protein or mRNA expression was shorter than in patients with lower levelsv(p<0.01). Proliferation of the CNE2 cell line was distinctly inhibited by the shRNA . The results indicate that overexpression of the survivin gene plays an important role in onset and development of nasopharyngeal carcinoma, and it may be helpful for prognostic appraisal.