Albuminuria and neck circumference are determinate factors of successful accurate estimation of glomerular filtration rate in high cardiovascular risk patients.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is used for diagnosis of chronic kidney disease (CKD). The eGFR models based on serum creatinine or cystatin C are used more in clinical practice. Albuminuria and neck circumference are associated with CKD and may have correlations with eGFR. AIM: We explored the correlations and modelling formulates among various indicators such as serum creatinine, cystatin C, albuminuria, and neck circumference for eGFR. DESIGN: Cross-sectional study. METHODS: We reviewed the records of patients with high cardiovascular risk from 2010 to 2011 in Taiwan. 24-hour urine creatinine clearance was used as the standard. We utilized a decision tree to select for variables and adopted a stepwise regression method to generate five models. Model 1 was based on only serum creatinine and was adjusted for age and gender. Model 2 added serum cystatin C, models 3 and 4 added albuminuria and neck circumference, respectively. Model 5 simultaneously added both albuminuria and neck circumference. RESULTS: Total 177 patients were recruited in this study. In model 1, the bias was 2.01 and its precision was 14.04. In model 2, the bias was reduced to 1.86 with a precision of 13.48. The bias of model 3 was 1.49 with a precision of 12.89, and the bias for model 4 was 1.74 with a precision of 12.97. In model 5, the bias could be lower to 1.40 with a precision of 12.53. CONCLUSIONS: In this study, the predicting ability of eGFR was improved after the addition of serum cystatin C compared to serum creatinine alone. The bias was more significantly reduced by the calculation of albuminuria. Furthermore, the model generated by combined albuminuria and neck circumference could provide the best eGFR predictions among these five eGFR models. Neck circumference can be investigated potentially in the further studies.

Neck Circumference as a Predictive Indicator of CKD for High Cardiovascular Risk Patients.

BACKGROUND: Neck circumference (NC) is an anthropometric measure of obesity for upper subcutaneous adipose tissue distribution which is associated with cardiometabolic risk. This study investigated whether NC is associated with indicators of chronic kidney disease (CKD) for high cardiometabolic risk patients. METHODS: A total of 177 consecutive patients who underwent the outpatient departments of cardiology were prospectively enrolled in the study. The patients were aged >20 years with normal renal function or with stages 1-4 CKD. A linear regression was performed using the Enter method to present an unadjusted R(2), standardized coefficients, and standard error, and the Durbin-Watson test was used to assess residual independence. RESULTS: Most anthropometric measurements from patients aged ≧ 65 were lower than those from patients aged < 65, except for women's waist circumference (WC) and waist hip ratio. Female NC obtained the highest R(2) values for 24 hr CCR, uric acid, microalbuminuria, hsCRP, triglycerides, and HDL compared to BMI, WC, and hip circumference. The significances of female NC with 24 hr CCR and uric acid were improved after adjusted age and serum creatinine. CONCLUSIONS: NC is associated with indicators of CKD for high cardiometabolic risk patients and can be routinely measured as easy as WC in the future.

Antiplatelet activity of nifedipine is mediated by inhibition of NF-κB activation caused by enhancement of PPAR-ß/-γ activity.

BACKGROUND AND PURPOSE: The transcription factor NF-κB, stimulates platelet aggregation through a non-genomic mechanism. Nifedipine, a voltage-gated L-type calcium channel blocker, is widely used to treat hypertension. Nifedipine also displays antiplatelet activity, but the underlying mechanisms involved remain unclear. This study was designed to investigate whether the antiplatelet effects of nifedipine are mediated by regulating NF-κB-dependent responses. EXPERIMENTAL APPROACH: Platelet aggregation was measured turbidimetrically using an aggregometer. NF-κB and PPAR activation, intracellular Ca2+ mobilization, PKCα activity, surface glycoprotein IIb/IIIa (GPIIb/IIIa) expression and platelet activation-related signalling pathways were determined in control and nifedipine-treated platelets in the presence or absence of PPAR antagonists or betulinic acid, a NF-κB activator. KEY RESULTS: Exposure of platelets to nifedipine significantly increased the PPAR-ß/-γ activity in activated human platelets. Treatment with nifedipine reduced collagen-induced NF-κB events, including the phosphorylation of IκB kinase-ß, IκBα and p65NF-κB, which were markedly attenuated by GSK0660, a PPAR-ß antagonist, or GW9662, a PPAR-γ antagonist. Furthermore, the interaction of PPAR-ß/-γ with NF-κB and the PPAR-ß/-γ-up-regulated NO/cGMP/PKG1 cascade may contribute to inhibition of NF-κB activation by nifedipine. Suppressing PPAR-ß/-γ activity or increasing NF-κB activation greatly reversed the inhibitory effect of nifedipine on collagen-induced platelet aggregation, intracellular Ca2+ mobilization, PKCα activity and surface GPIIb/IIIa expression.CONCLUSIONS AND IMPLICATIONSPPAR-ß/-γ-dependent inhibition of NF-κB activation contributes to the antiplatelet activity of nifedipine. These findings provide a novel mechanism underlying the beneficial effects of nifedipine on platelet hyperactivity-related vascular and inflammatory diseases.

Mechanisms of antiplatelet activity of nifedipine: role of peroxisome proliferator-activated receptor-ß-γ-dependent processes.

OBJECTIVE: Nifedipine, an L-type calcium channel blocker, is widely used in the treatment of hypertension and coronary heart diseases, and also exhibits an antiplatelet activity. Activation of peroxisome proliferator-activated receptors (PPARs; α, ß/δ, and γ) inhibits the platelet aggregation. Therefore, the purpose of this study was to evaluate the contribution of PPAR-mediated processes to the antiplatelet activity of nifedipine. METHODS AND RESULTS: We assessed human platelet aggregation by using an aggregometer and measured several platelet activating markers and related signaling pathways in platelets treated with nifedipine in the presence or absence of PPAR agonists. Nifedipine treatment (1, 5  µmol/l) dose-dependently increased the activity and intracellular expression of PPAR-ß/-γ by inhibiting the release of PPAR-ß/-γ from activated platelets. Nifedipine treatment also upregulated cyclic 3',5'-cyclic monophosphate (GMP)/protein kinase G (PKG) expression, and increased PI(3)K/Akt pathway, endothelial nitric oxide synthase, and soluble guanylyl cyclase activities. In the presence of a selective PPAR-ß antagonist (GSK0660) or PPAR-γ antagonist (GW9662), the inhibitory effects of nifedipine on collagen-induced platelet aggregation, intracellular Ca mobilization, and protein kinase C (PKC-α) activation were abrogated. Similarly, PPAR-ß-γ antagonists markedly attenuated nifedipine-mediated upregulation of nitric oxide/cyclic GMP/PKG cascade. In a mouse model of thrombosis, the administration of nifedipine substantially inhibited fluorescein sodium-induced vessel thrombus formation; however, the antithrombotic effect was considerably reduced in the presence of PPAR-ß/-γ antagonists. CONCLUSION: This study is the first to show that the PPAR-ß/-γ-dependent upregulation of PI(3)K/Akt/nitric oxide/cyclic GMP/PKG pathway and the inhibition of PKC-α activity and intracellular Ca(+) mobilization in platelets may be the mechanisms underlying the antiplatelet and antithrombotic activities of nifedipine.

Antitubercular constituents from the stem wood of Cinnamomum kotoense.

Five new compounds, kotolactone A (1), kotolactone B (2), secokotomolide (3), kotodiol (4), and 2-acetyl-5-dodecylfuran (5), and 36 known compounds have been isolated from the stem wood of Cinnamomum kotoense. The structures of these new compounds were determined by means of spectroscopic analysis. The known butanolides, isoobtusilactone A (6) and lincomolide B (7), showed in vitro antitubercular activities with MIC values of 22.48 and 10.16 microM, respectively, against Mycobacterium tuberculosis 90-221387.