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  • Author: Sudawadee Kongkhum x
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P-glycoprotein expression in human cerebral malaria: a preliminary study

Abstract

Background: P-glycoprotein is an efflux protein, which is expressed on several cell types, including vascular endothelial cells lining brain capillaries. The expression and activity of P-glycoprotein can be modulated under conditions, including inflammatory process. Cerebral malaria (CM), a complication caused by infections of Plasmodium falciparum, is considered an inflammatory disease.

Objective: We determined P-glycoprotein expression at protein levels in human CM brain capillaries.

Methods: Four brains, three CM and one control, were subjected to a postmortem study. The brain capillaries were isolated from cerebellum, cerebral cortex, striatum, and brainstem and analyzed for expression of P-glycoprotein using SDS-PAGE and western blot techniques. The expression levels in CM brain capillaries were assessed by comparing with that in control brain capillaries.

Results: P-glycoprotein decreased in all CM brain capillaries isolated from striatum, while two of three cerebellums showed the reduction, compared with the control. For cerebral cortex and brainstem brain capillaries, the expression decreased only in one of three CM subjects.

Conclusion: P-glycoprotein expression levels were modulated in CM brain capillaries, suggesting an involvement of P-glycoprotein in CM.

Open access
Elevation of serum adiponectin in mildly decreased glomerular filtration rate

Abstract

Background

Adiponectin secreted by adipocytes plays a key role in insulin sensitivity, anti-inflammation, and antiatherosclerosis. It is involved in several conditions including obesity, type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease (CKD). Glomerular filtration rate is monitored to indicate the kidney function and CKD progression.

Objective

To assess the serum adiponectin levels in individuals with normal and mildly decreased glomerular filtration rate, analyze the association of serum adiponectin with various physical and biological parameters, and test whether serum adiponectin is the risk factor of mildly decreased glomerular filtration rate.

Methods

This cross-sectional study was conducted in 172 individuals with 35–60 years of age. Serum samples were collected and divided into two groups, based on estimated glomerular filtration rate (eGFR): 90 with normal eGFR (G1, eGFR ≥90 mL/min/1.73 m2) and 82 with mildly decreased eGFR (G2, eGFR = 60–89 mL/min/1.73 m2). Anthropometric data were recorded. Serum adiponectin was measured by enzyme-linked immunosorbent assay.

Results

Serum adiponectin levels were significantly increased in individuals with mildly decreased eGFR (G2), compared to G1 (8.23 ± 3.26 µg/mL and 6.57 ± 3.24 µg/mL, respectively; P = 0.001). Serum adiponectin was positively associated with age and high-density lipoprotein cholesterol but negatively associated with weight, body mass index, triglyceride, and waist and hip circumferences. Univariate analysis showed that serum adiponectin was significantly correlated with mildly decreased eGFR; however, when adjusting for confounding factors, there were no correlations. Furthermore, multivariate regression analysis showed that individuals at the age of 46–55 years (4.0; 95% CI: 1.9–8.3) and > 55 years (11.4; 95% CI: 3.7–35.5) were significantly correlated with mildly decreased eGFR.

Conclusions

Serum adiponectin was significantly elevated in individuals with mildly decreased eGFR and may be a modulation factor, but was not an independent risk factor for mildly kidney damage. Further study is needed to clarify its potential benefits as monitoring biomarker for CKD progression.

Open access
High glucose enhances CD39 expression in vascular endothelial cells

Abstract

Background: Diabetes mellitus (DM) patients lose their ability to control normal blood glucose levels, resulting in high blood glucose levels (hyperglycemia). Hyperglycemia causes DM complications. This involves responses of vascular endothelial cells (VECs) to hyperglycemia, affecting inflammatory process and platelet activity. Ecto-enzyme CD39 is expressed on VECs, catalyzing the hydrolysis of ATP and ADP to AMP and, consequently, regulating inflammatory process and platelet activation.

Objective: We studied whether high glucose concentration has an effect on CD39 expression on VECs.

Methods: Cultured human umbilical vein endothelial cells (HUVEC) were used as a model of study. HUVEC were cultured in different glucose conditions (4, 9, 24, and 34 mM) for 24 hours. Cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based assay and expression of CD39 was examined by using SDS-PAGE and western blot techniques.

Results: HUVEC were cultured in normal (4 and 9 mM) or high (24 and 34 mM) glucose concentrations for short term (24 hours). The results showed that high glucose (24 and 34 mM) reduced cell viability to 89.5 ± 11.3 and 86.3 ± 13.5 (mean ± SD), compared with control (4 mM), respectively. High glucose also induced increases in CD39 expression in HUVEC.

Conclusion: High glucose decreases cell viability and increases CD39 expression in HUVEC, suggesting involvement of CD39 in cell responses to high glucose.

Open access