Lipid profile and atherogenic indices in patients with stable chronic obstructive pulmonary disease

Background and aimsLimited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy.Methods and resultsThe study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated.HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742–0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases.ConclusionLipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.     

Determination of intracellular K+ activity in rat kidney proximal tubular cells

The intracellular K⁺ activity of rat kidney proximal tubular cells was determined in vivo, using intracellular microelectrodes. In order to minimize damage from the impaling electrodes, separate measurements on separate cells, were performed with single-barrelled KCl-filled non-selective electrodes and single-barrelled, K⁺-sensitive microelectrodes, which were filled with a liquid K⁺-exchanger resin that has also a small sensitivity to Na⁺. Both electrodes had tip diameters of 0.2 m or below. The proper intracellular localization of the electrodes was ascertained by recording the cell potential response to intermittent luminal perfusions with glucose. The membrane potential measured with the non-selective microelectrodes was –76.3±8.1 mV (n=81) and the potential difference measured with the K⁺-sensitive microelectrode was –7.2±5.8 mV (n=32). Based on the activity of K⁺ in the extracellular fluid of 3 mmol/l the intracellular K⁺ activity was estimated to be 82 mmol/l. Assuming equal K⁺-activity coefficients to prevail inside and outside the cell, this figure suggests that the intracellular K⁺ concentration is 113 mmol/l which must be considered as a lower estimate, however. The data indicate that the K⁺-ion distribution between cytoplasm and extracellular fluid is not in equilibrium with the membrane potential, but that K⁺ is actively accumulated inside the cell. This result provides direct evidence for the presence of an active K⁺ pump in the tubular cell membranes, which in view of other observations, must be envisaged as a (not necessarily electroneutral) Na⁺/K⁺-exchange pump which operates in the peritubular cell membrane and is eventually responsible for the major part of the tubular solute and water absorption.     

Incubation in tissue culture media allows isolated rabbit proximal tubules to regain in-vivo-like transport function: response of HCO3 – absorption to norepinephrine

Using a new stop-flow perfusion technique with microspectrofluorometric determination of luminal fluid pH, we have studied which substrates or incubation conditions allow isolated rabbit proximal tubules to attain in-vivo-like rates of HCO3- absorption (J(HCO3)) and maximal responses of J(HCO3) to norepinephrine (NE). Essentially three incubation media were tested: plasma-like HCO(3-)-Ringer solution containing 5 mmol/l D-glucose (G-Ringer sol.), the same solution also containing 10 mmol/l lactate and 5 mmol/l L-alanine, (LAG-Ringer sol.), and two tissue culture media (DMEM and RPMI 1640). Compared to G-Ringer sol., application of LAG-Ringer sol. in the bath and/or lumen, or application of DMEM or RPMI 1640 in the bath either slightly increased or decreased J(HCO3) with borderline significance. However, RPMI 1640 plus 1 mmol/l pyruvate stimulated J(HCO3) by 55%. While NE (10(-5) mol/l), if applied in G-Ringer sol., had no effect, in the presence of LAG-Ringer sol. it increased J(HCO3) by approximately =40%, and in the presence of DMEM or RPMI 1640 it increased J(HCO3) by approximately =100%. This stimulation by NE followed Michaelis-Menten kinetics with an EC50 value of 0.25 micromol/l and was probably mediated by alpha1-adrenergic receptors. Additional cell pH measurements suggest that NE stimulates the basolateral Na+-HCO3- cotransporter which then becomes susceptible to inhibition by cAMP. We conclude that incubation in tissue culture media allows isolated proximal tubules to maintain a better functional state than the commonly used solutions with unphysiologically high substrate concentrations.     

Loss of heterozygosity of DPC4 tumor suppressor gene in human sporadic colon cancer

We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. Thirty-six cases of human sporadic colon carcinoma and corresponding normal tissue samples were examined to evaluate loss of heterozygosity at the DPC4 tumor suppressor locus using variable nucleotide tandem repeat (VNTR) analysis and three polymorphic markers. From 36 analyzed samples 35 (97%) were heterozygous or informative. Loss of heterozygosity at the DPC4 locus was detected in 18 (51%) of informative tumor DNAs. The DPC4 LOH was more frequent in smaller tumors (<5 cm) than in larger ones. There was no correlation between DPC4 LOH and age or sex of patients. There was a negative correlation between DPC4 LOH and histological grade or Dukes' stage of tumors, but without statistic significance. Observed results are in agreement with the view that malignant progression is consequence of many genetic changes. It can be concluded that inactivation of the DPC4 gene plays a role in a multistep process of outgrowth and progression of colon cancer.     

Color Doppler ultrasonography is reliable in assessing the risk of esophageal variceal bleeding in patients with liver cirrhosis

PURPOSE: The aim of the study was to examine the role of Doppler ultrasonography of the portal vein in predicting esophageal variceal bleeding in patients with liver cirrhosis and portal hypertension by comparing the ultrasound data to the endoscopic findings. PATIENTS AND METHODS: 99 patients with liver cirrhosis and esophageal varices underwent color Doppler ultrasonography and esophagogastroduodenoscopy. The following portal hemodynamic parameters were analyzed: diameter and cross-sectional area, mean blood flow velocity, blood flow volume, perfusion pressure gradient, congestion index, and platelet count-to-spleen diameter ratio. Variceal characteristics, the size and the presence of red signs, were determined by endoscopic examination. RESULTS: Patients with variceal red signs had significantly higher values of portal diameter (1.538 +/- 0.246 vs. 1.243 +/- 0.167), cross-sectional area (1.286 +/- 0.448 vs. 0.945 +/- 0.256), blood flow volume (965.520 +/- 432.728 vs. 625.117 +/- 320.999) and congestion index (0.165 +/- 0.068 vs. 0.126 +/- 0.051) than patients without red signs, while the perfusion pressure gradient (0.260 +/- 0.087 vs. 0.447 +/- 0.271) and the platelet-to-spleen ratio (522.424 +/- 222.823 vs. 708.921 +/- 230.769) were lower. The same pattern of differences between the ultrasound parameters was found in patients with large varices comparing ones with red signs to the ones without them (diameter, 1.567 +/- 0.234 vs. 1.258 +/- 0.175; cross-section, 1.313 +/- 0.455 vs. 1.061 +/- 0.264; flow volume, 988.195 +/- 443.353 vs. 739.423 +/- 414.281; congestion index, 0.171 +/- 0.067 vs. 0.130 +/- 0.058; perfusion pressure gradient 0.247 +/- 0.078 vs. 0.501 +/- 0.379 and platelet-to-spleen ratio 479.930 +/- 184.302 vs. 699.094 +/- 316.171). Differences in values of ultrasonographic parameters were less obvious among groups of patients with different variceal sizes: only the diameter, cross-sectional area and blood flow volume were significantly different. The mean blood flow velocity did not depend on the variceal size or on the presence of red signs. The sensitivities and specificities of the analyzed parameters were 60-80% and 48.6-78.4%, respectively. CONCLUSIONS: Results suggest that color Doppler ultrasonography is a useful noninvasive method for evaluating the risk of esophageal variceal bleeding in patients with liver cirrhosis.     

Electrophysiological analysis of rat renal sugar and amino acid transport

Transepithelial and cellular electrical potential changes were measured in response to luminal perfusion ofd-glucose and related substrates in micropuncture experiments on rat kidney in vivo. By studying the dependence of the potential response on various experimental parameters, some insight was obtained into the mechanism of Na⁺ coupled glucose absorption. The experiments confirm the driving forces for glucose absorption in the living cell to be: a) the Na concentration gradient, b) the electrical potential gradient and c) the glucose concentration gradient across the brushborder membrane. Furthermore they describe the substrate specificity of the cotransport mechanism and the mechanism of inhibition ofd-glucose transport by various inhibitors, such as phlorizin, harmaline and oubain. The latter experiments suggest that the active Na⁺ pump in the peritubular cell membrane, which establishes the Na⁺ ion gradient and the electrical potential gradient across the brushborder, contributes a measurable partial conductance to the overall electrical conductance of the peritubular cell membrane.     

Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo

Background

Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). The COX-2 polymorphism rs2745557 (+202 C/T) has been extensively investigated as a potential risk factor for PCa, but the results have thus far been inconclusive. This meta-analysis was performed to derive a more precise estimation of the association.

Methods

A comprehensive search was conducted to identify all case-control studies of COX-2 rs2745557 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Statistical analyses were performed by Review Manage, version 5.0 and Stata 10.0.

Results

A total of 8 available studies were considered in the present meta-analysis, with 11356 patients and 11641 controls for rs2745557. When all groups were pooled, there was no evidence that rs2745557 had significant association with PCa under co-dominant, recessive, over-dominant, and allelic models. However, our analysis suggested that rs2745557 was associated with a lower PCa risk under dominant model in overall population (OR = 0.85, 95%CI = 0.74-0.97, P = 0.02). When stratifying for race, there was a significant association between rs2745557 polymorphism and lower PCa risk in dominant model comparison in the subgroup of Caucasians (OR = 0.86, 95%CI = 0.75-0.99, P = 0.04), but not in co-dominant, recessive, over-dominant and allelic comparisons.

Conclusion

Based on our meta-analysis, COX-2 rs2745557 was associated with a lower PCa risk under dominant model in Caucasians.     

Rare variations in WNT3A and DKK1 may predispose carriers to primary osteoporosis

Childhood-onset primary osteoporosis is manifested as reduced bone mineral density, peripheral fractures and/or vertebral compression fractures. Until now, only mutations in LRP5 have been shown to cause the disorder. Candidate gene analyses were performed on 15 patients with primary osteoporosis and 80 healthy controls using CSGE and sequencing. The genes studied included DKK1, DKK2, WNT3A, WNT10B, AXIN1, SOST, TPH1 and 5-HTR1B. Two rare variants in WNT3A (c.152A > G, p.K51R) and DKK1 (c.359G > T, p.R120L) were identified in two patients and their affected family members, but not in control subjects, suggesting a significance for the skeletal phenotype. The in vitro studies of variants showed reduced signaling activity in p.K51R-Wnt3a, while no differences were observed between the WT and variant forms of DKK1. This study addresses the role of other components of the canonical Wnt signaling pathway besides LRP5 in primary osteoporosis, and putatively associates WNT3A and DKK1 variants with the disorder. Future functional studies are needed to elucidate the functional effects of the variants.