War consequences as the potential hazard for the Croatian karst ecosystem

In the recent war in Croatia, the karstic area of the country was endangered by hazardous waste, which calls for particular attention because of its exceptional ecological sensitivity. There are strong indications that various organic pollutants have entered the environment. It is also assumed that oil containing polychlorinated biphenyls (PCBs) was spilled in a number of locations. After the penetration in the environment, these substances are quickly absorbed in soil, sediment or bioaccumulated in the organisms of the aquatic ecosystem. In view of the locations of damaged electric transformer stations in Zadar, Bilice and Dubrovnik, there was some speculation on potential hazard posed by organohalogenated toxicants to Lake Vransko and the coastal area around Zadar, Sibenik and Dubrovnik. Samples of sediments and aquatic organisms were collected and analysed, and the results showed no significant or high levels of contaminants in the areas of Lake Vransko, Sibenik, and Dubrovnik (Petka location), while in the Mikulandra Bay near Sibenik, in Rijeka Dubrovacka, Brodanovo location and Marina near the Vruljica Creek in Zadar, significantly higher levels of PCBs were observed and these toxicants were additionally monitored within the APOPSBAL project from 2002 to 2005. The results of these investigations are presented in this paper.     

From big fat cells to high blood pressure: a pathway to obesity-associated hypertension

PURPOSE OF REVIEW: The environment created by modern industrialized societies has caused an unprecedented rise in the prevalence of obesity and obesity-related disorders, including hypertension. Mechanisms that underlie the development of hypertension in obese individuals are not very well understood; they are thought to involve activation of the sympathetic nervous system, the renin-angiotensin-aldosterone system, and oxidative stress. RECENT FINDINGS: Recent research suggests that obesity-associated hypertension may be causally related to the accumulation of 'dysfunctional' adipose tissue characterized by the presence of 'large' lipid-laden adipocytes. SUMMARY: Excess energy-intake leads to an expansion of adipose tissue, a hallmark of obesity. But morphology of the expanded adipose tissue differs across individuals, including the size of adipocytes. The presence of 'large' rather than 'small' adipocytes is associated with functional and structural abnormalities of adipose tissue. These include increased production of bioactive molecules, such as leptin, angiotensinogen, pro-inflammatory cytokines, and reactive oxygen species; insufficient capacity to accommodate excess energy-intake leading to ectopic fat storage in tissues and in turn insulin resistance and hyperinsulinemia; and augmented macrophage infiltration enhancing the production of pro-inflammatory cytokines and reactive oxygen species. Such a 'dysfunctional' adipose tissue may, in turn, induce activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and oxidative stress and, hence, promote the development of obesity-associated hypertension.     

EFFECTS ON THE COPROPORPHYRIN TEST OF DRUGS USED IN THE TREATMENT OF PARASITIC DISEASE

The effects of the following drugs on urinary coproporphyrin estimations were studied: fouadin, tartar emetic, coramine, emetine hydrochloride, carbon tetrachloride, hexylresorcinol, and atebrin. None of these substances interferes directly with the fluorimetric determination of urinary porphyrin if porphyrin is extracted from urine by ether or ethyl acetate and subsequently re-extracted into the aqueous phase with hydrochloric acid.

Persons under treatment with tartar emetic showed a significantly higher coproporphyrin excretion. For this reason the coproporphyrin test for abnormal lead absorption is likely to be unreliable in persons treated with tartar emetic.

     

An evaluation of calculation parameters in the EGSnrc/BEAMnrc Monte Carlo codes and their effect on surface dose calculation

The Monte Carlo (MC) method has proven invaluable for radiation transport simulations to accurately determine radiation doses and is widely considered a reliable computational measure that can substitute a physical experiment where direct measurements are not possible or feasible. In the EGSnrc/BEAMnrc MC codes, there are several user-specified parameters and customized transport algorithms, which may affect the calculation results. In order to fully utilize the MC methods available in these codes, it is essential to understand all these options and to use them appropriately. In this study, the effects of the electron transport algorithms in EGSnrc/BEAMnrc, which are often a trade-off between calculation accuracy and efficiency, were investigated in the buildup region of a homogeneous water phantom and also in a heterogeneous phantom using the DOSRZnrc user code. The algorithms and parameters investigated include: boundary crossing algorithm (BCA), skin depth, electron step algorithm (ESA), global electron cutoff energy (ECUT) and electron production cutoff energy (AE). The variations in calculated buildup doses were found to be larger than 10% for different user-specified transport parameters. We found that using BCA?= EXACT gave the best results in terms of accuracy and efficiency in calculating buildup doses using DOSRZnrc. In addition, using the ESA?= PRESTA-I option was found to be the best way of reducing the total calculation time without losing accuracy in the results at high energies (few keV ～ MeV). We also found that although choosing a higher ECUT/AE value in the beam modelling can dramatically improve computation efficiency, there is a significant trade-off in surface dose uncertainty. Our study demonstrates that a careful choice of user-specified transport parameters is required when conducting similar MC calculations.     

Late-onset endothelin-A receptor blockade reduces podocyte injury in homozygous Ren-2 rats despite severe hypertension

We have recently found in male homozygous hypertensive Ren-2 transgenic rats (TGRs) fed a high-salt diet that early onset selective endothelin (ET) A (ET(A)) or nonselective ET(A)/ET B (ET(B)) receptor blockade improved survival rate and reduced proteinuria, glomerulosclerosis, and cardiac hypertrophy, whereas selective ET(A) receptor blockade also significantly attenuated the rise in blood pressure. Because antihypertensive therapy in general is known to be more efficient when started at early age, our study was performed to determine whether onset of ET receptor blockade at a later age in animals with established hypertension will have similar protective effects as does early-onset therapy. Male homozygous TGRs and age-matched normotensive Hannover Sprague-Dawley rats were fed a high-salt diet between days 51 and 90 of age. TGRs received vehicle (untreated), the selective ET(A) receptor blocker atrasentan (ABT-627), or the nonselective ET(A)/ET(B) receptor blocker bosentan. Survival rates in untreated and bosentan-treated TGRs were 50% and 64%, respectively, whereas with atrasentan, survival rate of TGR was 96%, thus, similar to 93% in Hannover Sprague-Dawley rats. From day 60 on, systolic blood pressure in atrasentan-treated TGRs was transiently lower (P<0.05) than in untreated or bosentan-treated TGRs. Glomerular podocyte injury was substantially reduced with atrasentan treatment independent of severe hypertension and strongly correlated with survival (P<0.001). Our data indicate that in homozygous TGR ET receptors play an important role also in established hypertension. Selective ET(A) receptor blockade not only reduces podocyte injury and end-organ damage but also improves growth and survival independently of hypertension.     

2,3,7,8-TCDD exposure, endothelial dysfunction and impaired microvascular reactivity

Vascular function was examined in subjects with long-term high level of serum 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) during their follow-up visits. Their earlier mean peak TCDD level at the time of exposure in 1965-1968 was estimated in the range of 3300-74 000 pg/g lipids. Ten former pesticide production workers heavily exposed to TCDD (age 57 +/- 2 years, TCDD about 170 pg/g lipids) were examined in 2001. Extended group of 15 TCDD-exposed men (age 59 +/- 3 years, TCDD about 130 pg/g lipids) underwent the same examination in 2004. Findings were compared with a control group of 14 healthy men (age 54 +/- 2 years). Skin microvascular reactivity (MVR) was measured by laser Doppler perfusion monitoring in the forearm during post-occlusive reactive hyperemia (PORH) and thermal hyperemia (TH). Several parameters of MVR in men exposed to TCDD were significantly impaired, compared with the control group and further progression of the impairment of MVR has been observed between years 2001 and 2004. Serum concentration of E-selectin and inhibitor of tissue plasminogen activator 1 (PAI-1) was significantly higher in exposed subjects (56.0 +/- 18.4 ng/mL versus 40.0 +/- 12.0 ng/mL, P = 0.022 and 90.9 +/- 33.3 ng/mL versus 45.0 +/- 18.0, P = 0.002, respectively). In addition, PORH in the forearm was significantly negatively associated with SOD activity (r = -0.77, P = 0.009) as well as the velocity of perfusion increase during TH (r = -0.68, P = 0.03) and TH% (r = -0.78, P = 0.008). Our data document the presence of endothelial dysfunction in TCDD-exposed men.     

Optimization of Regression Equation for Prediction of Viscosity of Aqueous Solutions of the Cellulose Derivatives

Commercially, cellulose products are designated with viscosity grade measured at 2% w/v concentration in water at 20°C using an Ubbelohde viscometer. To represent viscosity/concentration curves, linear function of the eighth root of dynamic viscosity and the concentration is generally used. In this work, the influence on viscosity of aqueous solutions of methylcellulose 400 and hypromellose 4000 by temperature and polymer concentration was modelled using an empirically proposed multiple linear regression in which the transformation of viscosity by logarithm, the reciprocal value of the absolute temperature, and the concentration by square root was recommended. Due to this, the viscosity of both cellulose derivatives investigated could be predicted simultaneously with the mean difference between the observed data and the ones estimated equal to 16.2%. Expanding the linear regression with the linear interaction between logarithm of the polymer viscosity grade and square root of the polymer concentration, the precision of the viscosity prediction increased to the acceptable level of 4.1%. Other interactions between the studied variables did not provide significantly better results. The optimized regression equation enabled the prediction of kinematic, dynamic, relative, and specific viscosity of the aqueous solutions of cellulose derivatives. The dimensionless relative viscosity could be recommended because it takes into account the water viscosity at the same experimental temperature. Selecting viscosity grade of the cellulose derivative and temperature of measurement, the partial regression equations were obtained from which the relative viscosity could be determined as the function of the polymer concentration with the precision in range of 1.3–4.7%.     

Recurrent pregnancy loss and frequency of eight antiphospholipid antibodies and genetic thrombophilic factors in Czech women

PROBLEM: The aim of this study was to investigate frequencies of eight antiphospholipid antibodies (aPLs) in serum, four genetic thrombophilic factors and their mutual relation in 206 patients with repeated pregnancy loss (RPL). METHOD OF STUDY: Enzyme-linked immunosorbent assay was used for detection of aPLs against ph-serine, ph-ethanolamine, ph-inositol, DL-glycerol, phosphatidic acid, anti-annexin V, cardiolipin, and beta2-GPI. FV 1691G>A (Leiden mutation), FII 20210G>A mutation, MTHFR 677C>T and MTHFR 1298A>C variant genotypes were determined using a melting curve analysis of the PCR amplification product detected by the fluorescence resonance energy transfer. Genotypic distribution and allelic frequencies were calculated. Correlation between aPLs and thrombophilic factors was tested by chi-square and Fisher exact test. RESULTS: Our results show significantly increased prevalence of aPLs against ph-inositol (17-19.6% dependent on number of spontaneous miscarriages) and against ph-serine (18-25%). aPLs in IgG prevail. In 96% of the studied group, at least one risk factor was found (either aPLs positivity or thrombophilic factor). Both aPLs and thrombophilic factors were present in 43%. In the group of women with three or more RPLs, strong positive correlation of aPLs positivity and thrombophilic risk factors was observed. CONCLUSION: Antiphospholipide antibodies and genetic thrombophilic factors are important risk factors in the pathogenesis of RPL. Both autoantibodies against various kinds of phospholipides and genetic thrombophilic factors must be studied together in diagnosis of RPL for appropriate treatment.     

B-lymphocyte Subpopulations in Patients with Selective IgA Deficiency

Introduction

Selective deficiency IgA (IgAD) is the most common primary abnormality of immunoglobulin production with unknown pathophysiology. It is genetically related to common variable immunodeficiency (CVID), where besides IgA also IgG and frequently IgM serum levels are decreased. In this study we focused on determination of B-lymphocyte developmental stages and searching for similarities between CVID and IgAD.

Materials and Methods

Using flow cytometry we determined major lymphocyte subpopulations and B-lymphocyte subsets: na?ve (CD27^-IgD⁺), marginal zone cells (CD27⁺IgD⁺), class-switched memory cells (CD27⁺IgD^-), ??double-negative?? B cells (CD27^-IgD^-), transitional cells (IgM⁺⁺CD38⁺⁺), plasmablasts (CD38⁺⁺⁺IgM⁺ or IgM^-), and CD21^lowCD38^low cells in 80 patients with IgAD, 48 patients with CVID, and 80 control persons.

Results

Compared to healthy controls, a decrease in the absolute number and frequency of CD4+ cells (both?P?P?=?0.035) as well as plasmablasts (P?lowCD38^low subset (P?=?0.007) was observed in IgAD patients compared to control persons. No significant differences were observed in the remaining B-cell developmental subsets. A decrease in CD27⁺IgD^- (<0.4% of peripheral blood lymphocytes), frequently observed in CVID patients and also previously reported in IgAD, was found in only five patients (6%) with IgAD, two of them being first-degree relatives of CVID patients.

Conclusion

Our results show a decrease of terminally differentiated B-lymphocyte subsets in patients with IgAD, similar as previously found in patients with CVID, but these results are less expressed than in CVID patients.