Influence of Genetic Variation in the C-Reactive Protein Gene on the Inflammatory Response During and After Acute Coronary Ischemia

The aim of this research was to assess whether common genetic variants within the C-reactive protein gene ( CRP ) are related to the degree of acute rise in plasma C-reactive protein (CRP) levels following an acute coronary syndrome (ACS). While polymorphisms within CRP are associated with basal CRP levels in healthy men and women, less is known about the relationship of such genetic variants and the degree of CRP rise during and after acute ischemia. Plasma CRP is associated with increased rates of recurrent coronary events. We evaluated seven common genetic variants within CRP and assessed their relationship to the degree of rise in CRP levels immediately following an acute coronary syndrome in 1827 European American patients. Variants in the putative promoter region, −757T > C and −286C > T > A, were associated with the highest CRP elevations after ACS. Patients with two copies of the A allele of SNP −286C > T > A had median CRP values of 76.6 mg/L, compared to 11.1 mg/L in patients with no copies of the rare variant (p-value <0.0001), post ACS. The lowest CRP values were found for patients with minor alleles of the exonic 1059G > C and the 3'untranslated region 1846G > A SNPs. For example, patients homozygous for the minor allele of 1059G > C had 71% lower median CRP values than those homozygous for the major allele [3.5 vs 12.0 mg/L, p < 0.0001]. These trends persisted in the chronic stable phase after ischemia had resolved, and after adjustment for infarct size by peak creatinine kinase levels and clinical status by Killip class. Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome.     

Differences in the Course of Alcohol Withdrawal in Women and Men: A Polish Sample

A retrospective study compared the course of alcohol withdrawal, including delirium tremens, in women and men hospitalized in the Nowowiejski Hospital in Warsaw from 1973 to 1987. Medical records pertaining to 1179 patients were analyzed; 13.8% of these patients were women and 86.2% were men. The study showed that women began intensive alcohol drinking later than men ( p < 0.0001), but the period between the onset of alcohol abuse and the first occurrence of alcohol withdrawal was shorter in women than in men ( p < 0.0001). In the period of heavy drinking before hospitalization, women consumed significantly less alcohol then men ( p < 0.0001); moreover, women drank nonbeverage alcohol less frequently than men ( p < 0.05). Women were hospitalized substantially longer than men ( p < 0.0001), whereas the duration of alcohol withdrawal symptoms at the time of hospitalization was comparable in both groups. Withdrawal seizures were significantly more frequent among men than among women ( p < 0.001). Significant differences in the patients'somatic conditions were not noted between the groups, with the exception of anemia and decreased potassium concentration, which were more frequently observed in women (both p < 0.0001), and of increased concentration of ALT and hypoproteinemia, which were more frequent in men (respectively, p < 0.05 and p < 0.01). Co-existing personality disorders, depressive disorders, and anxiety disorders—as well as abuse of benzodiazepines and barbiturates—were more frequently observed in women ( p < 0.0001). The period between the first hospitalization due to alcohol withdrawal and the time of death was significantly shorter in men than in women ( p < 0.05). The results point to differences in the conditions and the course of alcohol dependence and alcohol withdrawal between women and men.     

The activity of erythrocyte sodium-proton exchanger in women with pregnancy- induced hypertension.

BACKGROUND: Hypertension that develops after 20 gestational weeks and is defined as pregnancy-induced hypertension (PIH). The main cause of PIH is vasoconstriction and the thickening of vascular media, which decreases vascular capacity and increases peripheral resistance. One of the theories postulated to explain this phenomenon is that a transmembrane sodium transport disorder causes an increase in intracellular sodium concentration. In the latest literature, special attention is paid to the role of the increased intracellular sodium concentration in the pathogenesis of essential hypertension (EH). One of the best documented phenotypes for EH is the increased activity of the sodium-proton exchanger (NHE). The aim of this study was to assess if increased NHE activity could be the mechanism responsible for the development of PIH. SUBJECTS AND METHODS: The study included 30 women: 10 pregnant women with PIH after gestational week 30, 10 women with physiological pregnancy after 30 gestational weeks, and 10 healthy non-pregnant women. NHE activity was determined according to Orlov's method as amiloride-sensitive H(+) efflux from acid-loaded cells. RESULTS: The NHE activity in the group of women with PIH was significantly higher than that in women with physiological pregnancy: 10.09 +/- 1.65 vs. 6.81 +/- 2.3 mmol/L RBC/h (p < 0.049) and in the group of non-pregnant women: 10.09 +/- 1.65 vs. 7.56 +/- 1.66 mmol/L RBC/h (p < 0.029). Erythrocyte NHE activity did not differ in the group of women with physiological pregnancy and in the group of non-pregnant women. CONCLUSION: These results seem to suggest that erythrocyte NHE activity is elevated in PIH pregnancies.     

Transient demineralization of the hip--case report]

Transient osteoporosis of the hip is an uncommon disorder of unclear etiology. It is often confused with other diagnosis including osteonecrosis of the femoral head. Authors describe a case of transient osteoporosis of the hip of 32 years woman. The symptoms occurred in third trimester of pregnancy. The primary symptoms were right hip pain and decreased range of motion of the right hip. In diagnostic process helpful were clinical examination, X-ray, ultrasonography, MRI and microscopic examination. As a treatment authors used walking on crutches, calcitonin and calcium preparate. After a few months remission of symptoms and normalization in accessory investigations were obtained.     

Pharmacokinetics of phenazone after bilateral ovariectomy in female rabbits]

The aim of this study was to evaluate the influence of female sex hormones on phenazone pharmacokinetics using as an experimental model female rabbits after a bilateral ovariectomy. Eighteen female rabbits divided into two groups: control animals and experimental rabbits, that underwent ovariectomy, were used in the study. Pharmacokinetic assays were performed in all animals: prior to the study, after 1 month and after 2 months. Blood was sampled within 24 hours after intragastric administration of phenazone at a dose 50 mg/kg b.w. Two compartment open model was used for calculations. Significant increase in AUC and prolongation of phenazone halflife as well as a decrease in the total body clearance were noted. The study demonstrated the possible inhibition of the microsomal mixed-function oxidase system by oestrogens.     

Development of a multiplex ARMS test for mutations in the HFE gene associated with hereditary haemochromatosis.

Genetic testing for hereditary haemochromatosis is likely to be a significant workload for diagnostic laboratories. The C282Y and H63D mutations in the HFE gene associated with hereditary haemochromatosis have previously been detected using a number of methods including alterations in the restriction digest pattern of polymerase chain reaction (PCR) amplified products. An amplification refractory mutation system (ARMS) has been developed that will simultaneously detect both hereditary haemochromatosis mutations. Comparison of the results obtained from the analysis of 46 samples referred for hereditary haemochromatosis testing showed no discrepancies between ARMS and restriction enzyme digestion. Furthermore, consistent results were obtained by ARMS from both blood and buccal mouthwash samples. The ARMS test is quicker and less expensive in terms of consumables and scientist time than restriction enzyme analysis, and is therefore suited to the routine diagnostic analysis of hereditary haemochromatosis.     

Application of the Minnesota Code in evaluating electrocardiographic features of ischemic heart disease in patients exposed to carbon disulphide

Summary We examined 81 men exposed for a long time to carbon disulphide (CS₂) and tested the possible electrocardiographic (ECG) changes of ischemic heart disease (I.H.D.). The subjects were examined twice in two years. In order to make the ECG evaluation more objective, the Minnesota Code was applied. Two obligatory ECG examinations and only one submaximal effort test were carried out. For comparative evaluation, the control group was examined once. We proved that, in spite of the accepted opinion concerning the atheromatous action of CS₂, this compound does not cause ECG symptoms of I.H.D. in a higher percentage of exposed persons. It also does not cause any significant increase in I.H.D. symptoms in dynamic ECG observations.     

Characterization of human hepatocytes isolated from non-transplantable livers

INTRODUCTION: The successful use of hepatocytes depends on a reliable demonstration of the functional and morphological integrity of isolated cells. Herein we investigated whether the isolation and cryopreservation of primary human hepatocytes can compromise cell viability and liver-specific characteristics. MATERIAL/METHODS: Hepatocytes were isolated from encapsulated human liver segments by a modified 2-step perfusion technique. Isolated cells were Percoll-purified, cryopreserved, and stored in liquid nitrogen for 1-12 months. For rapid assessment of fresh and cryopreserve/thawed hepatocyte yield and viability, the cells were stained with trypan blue or labeled with fluorochromes. For immunocytochemical analysis, the cells were labeled with monoclonal antibodies for the presence of the following antigens and chemokines: CD3, CD45Ro, CD45Ra, CD34, CD68, CD90, CD95, CD20, HLA-DR, Ki67, PCNA, Bcl-2, p53, CXCR3, CXCR4, and SDF-1. The cells were tested for several specific functions, such as ureagenesis, energy status, MTT activity, lactate dehydrogenase leakage, and total CYP450 content. RESULTS: Assessment of both freshly isolated (Percoll-purified) and cryopreserved/thawed hepatocytes revealed a low constitutive level of contamination by non-parenchymal cells compared with crude (unpurified) preparations and tissue sections. All viable hepatocytes showed intact morphology and retained CYP450 protein, energy status, and urea synthesis. CONCLUSIONS: Modifications in hepatocyte preparations, such as depletion of dead, damaged, and nonparenchymal cells, improves cell purity, which can be adapted to further evaluation of hepatocyte immunogenicity. These data illustrate the importance and feasibility of human hepatocyte banking.     

VEGF (vascular endothelial growth factor) concentration in serum and pleural fluid of patients with pleural malignancy and pleural tuberculosis

The purpose of this study was comparison of VEGF (vascular endothelial growth factor) levels in serum and pleural fluid and estimation of this test usefulness in diagnosis of pleural effusions. VEGF levels were measured by ELISA method in 68 patients (45 males and 23 females) aged 19-81 years. By Light's criteria in 16 cases transudate and in 52 cases exudate was recognized. By means of fluid cytology, pleural biopsy, microbiology or thoracoscopy in 10 cases pleural metastases from distant organs, in 15 cases coexisting pulmonary neoplasm, in 11 cases mesothelioma and in 16 cases tuberculosis were determined as a cause of fluid accumulation in pleural space. The mean VEGF levels were significantly higher (p < 0.001) in patients with exudates than in patients with transudates (3833 pg/ml and 325 pg/ml respectively). Based on likelihood ratios analysis, as a cut off value in differentiation of exudates and transudates a value 700 pg/ml was accepted. The sensitivity of this test was 75% and the specificity 93% and likelihood ratio (LR) 12.5. The mean VEGF level in exudates was seven times higher than mean VEGF level in serum (3833 pg/ml and 573 pg/ml respectively). Mean VEGF levels in malignant exudates (4615 pg/ml) were significantly higher than in tuberculous exudates (2073 pg/ml). As a cut off value in differentiation between malignant and tuberculous exudates a value of 4500 pg/ml was accepted. We conclude that our results suggests the local VEGF production in pleural cavity and the significant role of this cytokine in pleural exudates accumulations and also suggests the usefulness of VEGF estimation in pleural fluid in differentiation transudates from exudates and malignant from tuberculous pleural fluids.