Characterization of Various Titanium-Dioxide-Based Catalysts Regarding Photocatalytic Mineralization of Carbamazepine also Combined with Ozonation.

Titanium-dioxide-based semiconductors proved to be appropriate for photocatalytic application to efficiently degrade emerging organic pollutants such as various herbicides, pesticides, and pharmaceuticals in waters of environmental importance. The characterization of various TiO2 catalysts, both bare and modified (Ag- and/or N-doped), by mechanochemical treatment was carried out in this work, regarding their structure, morphology, and photocatalytic activity. For the latter investigations, carbamazepine, an antidepressant, proved to be applicable and versatile. The photocatalytic behavior of the catalysts was studied under both UV and visible light. Besides the decomposition efficiency, monitoring the intermediates provided information on the degradation mechanisms. Mechanochemical treatment significantly increased the particle size (from 30 nm to 10 µm), causing a considerable (0.14 eV) decrease in the band gap. Depending on the irradiation wavelength and the catalyst, the activity orders differed, indicating that, in the mineralization processes of carbamazepine, the importance of the different oxidizing radicals considerably deviated, e.g., Ag-TiO2 < DP25-TiO2 < ground-DP25-TiO2 < N-TiO2 ≈ N-Ag-TiO2 for O2•− and N-TiO2 ≈ Ag-TiO2 < N-Ag-TiO2 < ground-DP25-TiO2 ≈ DP25-TiO2 for HO• generation under UV irradiation. Toxicity studies have shown that the resulting intermediates are more toxic than the starting drug molecule, so full mineralization is required. This could be realized by a synergistic combination of heterogeneous photocatalysis and ozonation.

Fatal idiopathic pulmonary haemosiderosis in association with pregnancy - medico-legal evaluation.

Idiopathic pulmonary haemosiderosis is a rare disorder characterised by repeated episodes of intra-alveolar bleeding in association with consecutive anaemia, pulmonary fibrosis, pulmonary hypertension and respiratory failure. Pregnancy may exacerbate the symptoms of idiopathic pulmonary haemosiderosis typically worsening in the third trimester. A 32-year-old female after delivery was admitted to hospital with progressive dyspnoea of about 1-month duration. Sudden circulatory collapse caused fatal complication. During the post-mortem investigation, lung haemorrhage and histologically abundant iron deposition in macrophages and interstitial fibrosis were found. Medico-legal post-mortem evaluation of fatal cases may support the clinico-pathological context of the diagnosis of this entity.

Association of PPAR polymorphisms with cytokine levels in allergic rhinitis.

Our aim was to study the association of Pro12Ala and exon6 C161T polymorphisms of PPARgamma and intron7 G/C polymorphisms of PPAR-alpha with clinical symptoms, peak nasal inspiratory flow values, serum soluble TNF-alpha, TNF-R1, Fas, Fas ligand and IgE concentrations in patients with seasonal allergic rhinitis during and after pollen season. We performed a follow-up study of 66 Hungarian patients with seasonal allergic rhinitis and 180 healthy referent subjects. We used PCR-RFLP technique and ELISA. The distribution of mutant alleles of PPAR-gamma and -alpha did not differ in patients and referent subjects. Patients carrying the mutant 12Ala, exon6 161T alleles of PPAR-gamma and intron7 C allele of PPAR-alpha had significantly higher clinical symptom score values, TNF-alpha and IgE levels and lower peak nasal inspiratory flow values during and after pollen season. The results indicated that nuclear receptors PPAR-gamma and PPAR-alpha are involved in the regulation of inflammatory mediator production in patients with seasonal allergic rhinitis and polymorphisms of the receptors are very likely to contribute to the heterogeneity of clinical and immunological parameters of allergic patients.

Synthesis, photochemistry, and photophysics of butadiene derivatives: influence of the methyl group on the molecular structure and photoinduced behavior.

Novel butadiene derivatives display diverse photochemistry and photophysics. Excitation of 2-methyl-1-(o-vinylphenyl)-4-phenylbutadiene leads to the dihydronaphthalene derivative, whereas photolysis of the corresponding model o-methyl analogue results in the formation of the naphthalene-like derivative, deviating from the nonmethylated analogue of the prior starting compound and producing benzobi- and -tricyclic compounds. The effect of the methyl substituents is even more dramatic in the case of the dibutadienes. The parent unsubstituted compound undergoes photoinduced intramolecular cycloaddition giving benzobicyclo[3.2.1]octadiene, whereas the photochemical reaction of the corresponding dimethylated derivative shows only geometrical isomerization due to the steric effect of the substituents. Methyl groups on the butadiene backbones reduce the extent of conjugation, causing a blue-shift of the characteristic absorption band. The fluorescence efficiency is dramatically decreased, as a consequence of nonplanarity and reduced rigidity of the molecules due to the crowding by the methyl and phenyl groups together. Four molecules of very similar structures show dramatically different photoinduced behavior, revealing how changes of the nature and position of the substituents are valuable in understanding the photophysics and photochemistry of these types of compounds.

The effect of the position of methyl substituents on photophysical and photochemical properties of [Ru(x,x'-dmb)(CN)4]2- complexes: experimental confirmation of the theoretical predictions.

The molecular geometry, electronic structure and electronic spectra and the energy levels of the molecular orbitals responsible for the photophysical characteristics of a series of solvent tunable [Ru(x,x'-dmb)(CN)(4)](2-) complexes (where x,x'-dmb = x,x'-dimethyl-2,2'-bipyridine) were calculated by density-functional theory-based quantum chemical methods, with the purpose of proposing for experimental study the best candidate for sensitizing electron- and energy transfer processes or for light induced structural changes in the molecule. The methods applied include geometry optimization using the B3LYP functional combination and various basis sets, time-dependent density functional theory with the B3LYP and PBE0 functionals, with and without explicit inclusion of coordinated solvent H(2)O molecules and the conductor-like polarizable continuum model for solvation. The accuracy of the theoretical predictions was tested by experiments: the model compounds have been synthesized and characterized by various spectroscopic methods, such as (1)H-NMR, UV-Vis absorption and emission spectroscopy and by cyclic voltammetry. Excellent correlation was found between the theoretically calculated and the experimentally determined photophysical and photochemical characteristics. The electronic transition energies measured in water are superbly reproduced by TD-PBE0 and well by TD-B3LYP, but the performance of both functionals is worse if the solvent is acetonitrile.

PPAR-gamma2 pro12Ala polymorphism is associated with post-challenge abnormalities of glucose homeostasis in children and adolescents with obesity.

AIM: The aim of the study was to investigate the association between PPAR-gamma2 Pro12Ala polymorphism and laboratory characteristics of carbohydrate metabolism in children and adolescents with obesity. In addition, serum levels of tumor necrosis factor (TNF)-alpha, and soluble form of its receptors (sTNFR1 and sTNFR2) were assessed. METHODS: In a cross-sectional study, 79 obese children and adolescents of Caucasian origin were investigated. PPAR-gamma2 Pro12Ala polymorphism was determined using polymerase chain reaction--restriction fragment length polymorphism technique. Serum levels of TNF-alpha, sTNFR1 and sTNFR2 were measured by enzyme amplified sensitivity immunoassay. RESULTS: The minor Ala allele frequency was found to be 14.56% in our cohort. No significant differences in age, BMI, waist circumference, blood pressure, serum lipid, uric acid, TNF-alpha, sTNFR1 and sTNFR2 values were found between carriers of the Ala allele (Pro/Ala and Ala/Ala; n=21) vs. homozygous carriers of the Pro allele (Pro/Pro; n=58). However, post-challenge (120 min) plasma glucose and insulin values were significantly lower in Ala allele carriers vs. homozygous Pro allele carriers (6.56 +/- 0.26 vs. 7.36 +/- 0.25 mmol/L and 65.9 +/- 13.8 vs. 111.8 +/- 20.7 microU/mL, respectively; p < 0.05); while no significant differences were found at fasting state. CONCLUSIONS: The association between PPAR-gamma2 Prol2Ala polymorphism and glucose metabolism is already present in children and adolescents with obesity who might be at the very beginning of the natural course of type 2 diabetes. At this stage, higher insulin sensitivity can be detected in Ala allele carriers compared to homozygous Pro subjects at post-challenge but not in fasting state; however, the TNF-system seems not to be involved in the alteration of glucose homeostasis due to PPAR-gamma2 Pro12Ala polymorphism.

Association of TLR-4 and TNF-alpha polymorphisms with clinical symptoms and cytokine levels in patients with allergic rhinitis.

Our objective was to determine the frequency of TNF-alpha -238, -308 G/A promoter and TLR-4 299 D/G and 399 T/I polymorphisms in healthy population and in patients with seasonal allergic rhinitis, and to examine its influences on serum TNF-alpha, TNF receptor-1, Fas, Fas-ligand, IgE levels and on clinical symptoms. A pilot study was performed in 66 patients with seasonal allergic rhinitis to ragweed pollen and 161 non-allergic subjects using PCR-RFLP technique and ELISA. Carriers of the -238A and -308G alleles have significantly higher TNF-alpha and IgE levels, clinical score values and lower peak nasal flow (PNIF) values during and after ragweed pollen season. Patients with the 299G/399I alleles of the TLR-4 gene have significantly lower TNF-alpha, Fas, FasL and IgE levels, clinical scores and higher PNIF values during and after pollen season. The -238A and -308G polymorphisms of the TNF-alpha promoter and 299D/399T polymorphisms of the TLR-4 gene are associated with more pronounced clinical symptoms, higher cytokine and IgE levels, and low PNIF values. These polymorphisms are very likely to contribute to the heterogeneity of clinical and laboratory parameters of patients.

Association between toll-like receptor polymorphisms and serum levels of tumor necrosis factor-alpha and its soluble receptors in obese children.

BACKGROUND: In obesity, increased tumor necrosis factor (TNF)-alpha level is involved in the development of insulin resistance. Toll-like receptor (TLR)-4 and TLR2 are expressed in adipose tissue, and polymorphisms of these receptors may influence TNF-alpha secretion from adipocytes. In our study, TNF-alpha, soluble TNF receptor 1 (sTNFR1), and soluble TNF receptor 2 (sTNFR2) levels were determined, and any association between polymorphisms of TLR4 (D299G, T399I), TLR2 (R753Q, R677W), and cytokine levels was assessed in obese children and non-obese control subjects. MATERIAL/METHODS: In a cross-sectional study, 79 obese children and 42 matched non-obese control children were investigated. Cytokine levels were measured by enzyme amplified sensitivity immunoassay. TLR4 and TLR2 polymorphisms were determined using polymerase chain reaction - restriction fragment length polymorphism technique. RESULTS: TNF-alpha and sTNFR2 levels in obese children were significantly (P<.01) higher than controls. Significant (P<.05), positive, linear correlations were observed between TNF-alpha, sTNFR2 levels, and BMI. Patients carrying the mutant alleles of TLR4 (299G and 399I) had lower TNF-alpha and sTNFR2 levels compared to patients carrying wild-type alleles (299D and 399T) (TNF-alpha 4.4+/-0.7 pg/mL vs 5.5+/-0.9 pg/mL; sTNFR2 2.9+/-1.2 ng/mL vs 4.4+/-1.1 ng/mL; P<.001). The R753Q polymorphism of TLR2 was not associated with altered cytokine levels, and the R677W polymorphism was not detected in the sample population. CONCLUSIONS: Serum levels of TNF-alpha and its soluble receptors are elevated and associated with increasing BMI values in obese children. Serum cytokine levels, as modifying factors of insulin resistance, may be affected by TLR4 polymorphisms in obese children.

Toll-like receptor 4 gene polymorphisms and preeclampsia: lack of association in a Caucasian population.

Preeclampsia is a multifactorial disorder with genetic and environmental components. As Toll-like receptor 4 (TLR4) has an essential role in innate immune response, which is exaggeratedly activated in preeclampsia, our aim was to investigate whether two single nucleotide polymorphisms (SNPs) of the TLR4 gene--Asp299Gly (A896G) and Thr399Ile (C1196T)--are associated with preeclampsia in a Caucasian population from Hungary. In a case-control study, we analyzed blood samples from 180 preeclamptic patients and 172 normotensive, healthy pregnant women with the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. The linkage disequilibrium (LD) profile of the TLR4 gene was investigated and tag SNPs were identified using data from the International HapMap Project. There were no significant differences in the genotype and allele frequencies of Asp299Gly and Thr399Ile polymorphisms between the two study groups. Additionally, no significant difference was found in the distribution of the estimated haplotypes created by the two polymorphisms between the preeclamptic and the control group. Furthermore, no significant differences were detected in the genotype, allele and haplotype frequencies of Asp299Gly and Thr399Ile TLR4 SNPs between patients with mild and severe preeclampsia, between patients with late and early onset of the disease, or between preeclamptic patients with and without fetal growth restriction. In conclusion, we did not find an association between TLR4 Asp299Gly and Thr399Ile gene polymorphisms and preeclampsia. As the Thr399Ile polymorphism is a highly informative tag SNP of the TLR4 gene, our results suggest that variations in this genomic region are not associated with preeclampsia. Nevertheless, further studies are required with determination of fetal TLR4 genotypes to explore the role of TLR4 gene polymorphisms in the risk of preeclampsia, especially in ethnically different populations.

Association between tumor necrosis factor (TNF)-alpha G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction.

BACKGROUND: Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are multifactorial disorders with genetic and environmental components. Given that the tumor necrosis factor (TNF)-alpha G-308A single nucleotide polymorphism (SNP) affects TNF-alpha gene transcription and that preeclampsia and HELLP syndrome are characterized by a shift towards a Th1-type maternal immune response with increased TNF-alpha production, the aim of the current study was to investigate whether this SNP is associated with preeclampsia and HELLP syndrome in a Caucasian population from Hungary. Additionally, we aimed to examine whether TNF-alpha G-308A polymorphism can influence the risk for fetal growth restriction in preeclamptic patients, which issue none of the earlier studies dealt with. METHODS: In a case-control study, we analyzed blood samples from 140 preeclamptic patients, 69 patients with HELLP syndrome and 144 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. We performed also a meta-analysis with our results and those of 8 previously published studies. RESULTS: There were no significant differences in the genotype and allele frequencies of the TNF-alpha G-308A polymorphism between preeclamptic patients and normotensive, healthy pregnant women. However, the mutant (TNF2 or A) allele occurred significantly more frequently in preeclamptic patients with IUGR than in those without IUGR (18.5% versus 7.1%, p=0.003). In addition, the frequency of the mutant allele carriers was significantly higher among preeclamptic patients with IUGR compared to those without IUGR (30.6% versus 12.8%, p=0.010). The mutant allele carriers were found to have an increased risk of severe IUGR-complicated preeclampsia, which was independent of maternal age, prepregnancy BMI and primiparity (odds ratio (OR): 2.89, 95% confidence interval (CI): 1.16-7.22, p=0.023; adjusted OR: 2.78, 95% CI: 1.04-7.45, p=0.042). Nevertheless, no significant differences were detected in the genotype and allele frequencies of the TNF-alpha G-308A polymorphism between patients with HELLP syndrome and control subjects. In the meta-analysis, no association was observed between this SNP and preeclampsia (summary OR: 0.956, 95% CI: 0.693-1.319). CONCLUSIONS: Although the meta-analysis demonstrated a lack of an overall association between TNF-alpha G-308A polymorphism and preeclampsia, our results suggest a role of this SNP in the risk of severe IUGR-complicated preeclampsia. However, further studies are required with a larger sample size to confirm our findings.

Polymorphisms of TNF-alpha and LT-alpha genes in multiple myeloma.

Allelic distribution of -308 G>A (TNF 1/2) polymorphism of the TNF-alpha, and the +252 A>G promoter polymorphism of the LT-alpha gene, the 1267 A>G polymorphism of the HSP70-2 gene as well as the -429 T>C promoter polymorphism of the RAGE gene were tested in 94 MM cases and 141 controls. Significantly less MM patients than controls carried the TNF2 allele (p=0.018) and the TNF2-LTA 252G haplotype (p=0.025). The difference was, however, restricted to the females, as well as the relatively young (<69 years) subjects. By contrast, we did not find differences with the other SNPs tested.

Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction.

BACKGROUND AND OBJECTIVES: Some recent data indicate that risk of death after acute coronary syndrome is under genetic control. Previously, we found that the C4B*Q0 genotype (low copy number of the C4B gene that encodes the fourth component of complement) is strongly associated with morbidity and mortality of cardiovascular diseases (CVD). The +252 G allele of the lymphotoxin-alpha (LTA) gene encoded close to the C4B gene was also reported to be related to CVD-related mortality in an Oriental population. METHODS: The relationship between the copy number of the genes encoding the fourth component of complement (C4A and C4B) and LTA 252 single-nucleotide polymorphism (SNP) on the one hand and mortality after acute myocardial infarction (AMI) was studied in 142 Icelandic patients. The number of the C4A and C4B genes was determined in genomic DNA samples by a newly developed real-time PCR-based method; lymphotoxin-alpha (LTA) +252 A>G polymorphism was determined by PCR-restriction fragment length polymorphism analysis. RESULTS: The C4B*Q0 genotype was found to be strongly associated with 1-year mortality, with a hazard ratio of 3.50 (1.38-8.87) (P = 0.008) (adjusted Cox regression analysis). This association was, however, restricted to ever-smoking patients. By contrast, neither C4A gene copy numbers nor LTA 252 SNP did confer increased risk of mortality after AMI. CONCLUSIONS: This observation indicates that low C4B copy number is a strong risk factor for short-term mortality after AMI in smoking Icelandic patients, whereas LTA 252 G allele is not a risk factor in Caucasian population.

Frequency of carriers of 8.1 ancestral haplotype and its fragments in two Caucasian populations.

Within the human MHC region larger stretches of conserved DNA, called conserved ancestral haplotypes exist. However, many MHC haplotypes contain only fragments of an ancestral haplotype. Little is known, however, on relative distribution of the ancestral haplotypes to their fragments. Therefore we determined the frequency of carriers of the whole ancestral haplotype 8.1 (AH8.1) and its fragments in 127 healthy Hungarian people, 101 healthy Ohioian females, and in nine Hungarian families. The HLA-DQ2, HLA-DR3(17), RAGE -429C allele, the mono-S-C4B genotype, the HSP70-2 1267G allele and the TNF -308A (TNF2) allele were used as markers of the AH8.1. Frequency of carriers of the whole AH8.1 and its fragments was similar in the both populations. 18% of the subjects carried the whole AH8.1 in at least one chromosome, while 17-20%, 36-39%, and 24-29%, respectively carried two or three constituents of the haplotype, only one constituent or none of them. Similar results were obtained in the family study. In addition, marked differences were found in the relationship of the constituents' alleles to the whole AH8.1. In both populations, 29%, 50-59%, 52-56% and 76-96%, respectively of the carriers of HSP70-2 1267G, RAGE-429C, TNF2, and mono-S carriers carried the whole 8.1 haplotype. These findings may have important implications for studies of the disease associations with different MHC ancestral haplotypes.

Estrogen receptor alpha (ESR1) PvuII and XbaI gene polymorphisms in ischemic stroke in a Hungarian population.

BACKGROUND: Ischemic stroke is a multifactorial disorder with genetic and environmental components. The aim of our study was to investigate whether two polymorphisms of the estrogen receptor alpha (ESR1) gene (ESR1 c.454-397T>C and c.454-351A>G) are associated with ischemic stroke in a Caucasian population from Hungary. METHODS: One hundred and ninety-eight patients with ischemic stroke and 180 control subjects were enrolled in this case-control study. Ischemic stroke subtypes were categorized according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification as large-artery atherosclerosis, small-artery occlusion, cardioembolism or stroke of other determined etiology. The ESR1 PvuII and XbaI genotypes were determined using the PCR-RFLP method. RESULTS: There were no significant differences in the genotype, allele and haplotype frequencies of PvuII and XbaI polymorphisms between the group of patients with ischemic stroke and the control group. Furthermore, ESR1 PvuII and XbaI genotypes, alleles and haplotypes were not associated with any subtype of ischemic stroke. CONCLUSIONS: We did not observe an association between ESR1 PvuII and XbaI gene polymorphisms and ischemic stroke or any subtype of ischemic stroke. However, further studies are needed to explore the complex interaction between environmental factors and ESR1 gene polymorphisms in the risk of ischemic stroke, particularly in ethnically different populations.

Metal-metal bonding in tetracyanometalates (M=PtII, PdII, NiII) of monovalent thallium. Crystallographic and spectroscopic characterization of the new compounds Tl2Ni(CN)4 and Tl2Pd(CN)4.

The new crystalline compounds Tl2Ni(CN)4 and Tl2Pd(CN)4 were synthesized by several procedures. The structures of the compounds were determined by single-crystal X-ray diffraction. The compounds are isostructural with the previously reported platinum analogue, Tl2Pt(CN)4. A new synthetic route to the latter compound is also suggested. In contrast to the usual infinite columnar stacking of [M(CN)4]2- ions with short intrachain M-M separations, characteristic of salts of tetracyanometalates of NiII, PdII, and PtII, the structure of the thallium compounds is noncolumnar with the two TlI ions occupying axial vertices of a distorted pseudo-octahedron of the transition metal, [MTl2C4]. The Tl-M distances in the compounds are 3.0560(6), 3.1733(7), and 3.140(1) A for NiII, PdII, and PtII, respectively. The short Tl-Ni distance in Tl2Ni(CN)4 is the first example of metal-metal bonding between these two metals. The strength of the metal-metal bonds in this series of compounds was assessed by means of vibrational spectroscopy. Rigorous calculations, performed on the molecules in D4h point group symmetry, provide force constants for the Tl-M stretching vibration constants of 146.2, 139.6, and 156.2 N/m for the NiII, PdII, and PtII compounds, respectively, showing the strongest metal-metal bonding in the case of the Tl-Pt compound. Amsterdam density-functional calculations for isolated Tl2M(CN)4 molecules give Tl-M geometry-optimized distances of 2.67, 2.80, and 2.84 A for M = NiII, PdII, and PtII, respectively. These distances are all substantially shorter than the experimental values, most likely because of intermolecular Tl-N interactions in the solid compounds. Time-dependent density-functional theory calculations reveal a low-energy, allowed transition in all three compounds that involves excitation from an a1g orbital of mixed Tl 6pz-M ndz2 character to an a2u orbital of dominant Tl 6pz character.

The effects of ligand substitution and deuteriation on the spectroscopic and photophysical properties of [Ru(LL)(CN)4]2- complexes.

The spectroscopic characterisation of a series of [Ru(LL)(CN)(4)](2-) complexes, where LL = 1,10-phenanthroline (phen) and its methyl- and phenyl-substituted derivatives and several deuteriated isotopologues are reported. The optical and vibrational properties of these complexes are compared with that of the series of 2,2'-bipyridine (bipy) derivatives and analogous [Ru(LL)(3)](2+) complexes. It has been demonstrated that substitution at the 4,4' positions of bipy and 4,7-positions of phen by electron donating (CH(3)) and withdrawing (C(6)H(5), COO(-)) groups induces a pronounced blue and red shift, respectively, in the lowest energy (1)MLCT absorption band of [Ru(LL)(CN)(4)](2-). The energy of the emission originating from the (3)MLCT excited state is found to be dependant on the nature of the vibrational modes of the aromatic rings and the electron donating and/or withdrawing properties of the substituents. Single-mode Franck-Condon analysis indicates that methyl substitution leads to a significant increase in the Huang-Rhys factor (S(M)), while phenyl substitution results in a decrease in S(M) for both series (bipy and phen) of complexes. The rate of non-radiative (k(nr)) and radiative decay (k(ph)) to the ground state and the parameters of thermally activated deactivation pathways (A(4th), DeltaE(4th) and A(dd), DeltaE(dd)) were estimated from the temperature dependence of luminescence quantum yields and lifetimes. It has been demonstrated that the non-radiative decay rate and the temperature dependent decay processes are more efficient for bipy complexes than for phen derivatives due to the rigidity of the latter ligand.

Lipid, haemostatic and inflammatory variables in relation to the estrogen receptor alpha (ESR1) PvuII and XbaI gene polymorphisms.

BACKGROUND: Estrogen is known to affect lipoprotein metabolism, the haemostatic system and inflammatory markers. Our aim was to determine whether estrogen receptor alpha (ESR1) PvuII and XbaI gene polymorphisms can influence lipid, haemostatic and inflammatory variables in healthy Caucasian women and men of reproductive age. METHODS: 58 healthy women (aged between 18 and 45 years) and 55 healthy men (aged between 21 and 45 years) of reproductive age were enrolled in our study. FSH levels, lipid (total cholesterol, triglyceride, HDL cholesterol, lipoprotein(a), apo A-I, apo B), haemostatic (prothrombin time, activated partial thromboplastin time (aPTT), thrombin time, fibrinogen, factor V, VII, VIII, protein C, protein S, antithrombin III) and inflammatory (CRP) variables were measured on autoanalyzers using commercially available kits. Serum VLDL and LDL cholesterol concentrations were calculated with the equation of Friedewald. The ESR1 PvuII and XbaI genotypes were determined with PCR-RFLP method. RESULTS: In the total group, the ESR1 XbaI GG genotype carriers had significantly higher serum lipoprotein(a) concentrations than the AA or AG genotype carriers. Serum total cholesterol concentrations were significantly higher in healthy women with the PvuII CC genotype than in those with the TT or TC genotypes, whereas healthy women with the GG genotype of the ESR1 XbaI polymorphism had significantly higher serum total cholesterol and LDL cholesterol levels compared to those with the AA or AG genotypes. No other effects of the ESR1 PvuII and XbaI polymorphisms were found on the investigated lipid, haemostatic and inflammatory variables either in the total group or in women and men separately. CONCLUSIONS: The ESR1 PvuII and XbaI gene polymorphisms seem to affect lipoprotein metabolism in healthy subjects of peak reproductive age. However, further studies are needed to determine the molecular mechanisms by which the two polymorphisms could influence serum lipid levels.

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients.

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.

Distinction of tris(diimine)ruthenium(II) enantiomers chiral by virtue of helical chirality: temperature-dependent deuterium NMR spectroscopy in partially oriented phases.

2H NMR spectra of perdeuterated tris(diimine)ruthenium(II) complexes have been recorded in lyotropic liquid crystalline phase formed by the chiral polypeptide, poly-gamma-benzyl-L-glutamate (PBLG) and co-solvents. It is demonstrated that the left- and right-rotation isomers of these octahedral metal complexes with D3 symmetry can be distinguished. The effects of temperature and ligand size on spectral resolution were also studied. Although in the case of free bipyridine ligands excellent optical resolution could be obtained at room temperature in the complexes studied, the increase in ligand size has a detrimental effect on the resolution. This can be compensated to some extent by elevating the sample temperature and decreasing the deuterium relaxation rates, but the available temperature range and therefore the applicability of the technique are limited.

Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma.

Claudins (CLDNs), a family of transmembrane proteins, are major constituents of tight junctions (TJs). They have been shown to be differentially regulated in malignant tumors and play a role in carcinogenesis and progression. We aimed to explain the molecular mechanism underlying the main epithelial components of hepatoblastomas (HBs) based on the composition of TJs. Fourteen formalin-fixed, paraffin-embedded surgical resection specimens were analyzed by immunohistochemistry for CLDN-1, -2, -3, -4, -7; proliferating cell nuclear antigen (PCNA); Ki-67; beta-catenin; cytokeratin-7 (CK-7); and hepatocyte-specific antigen; messenger RNA was isolated for real-time reverse transcriptase polymerase chain reaction analysis of the CLDNs from dissected fetal and embryonal cell types. Significantly increased protein and messenger RNA expression of CLDN-1 and -2 was detected in the fetal compared with the embryonal component. Both cell types displayed negative or weak immunostainings for CLDN-3, -4, and -7. Hepatocyte-specific antigen was dominantly expressed in the fetal component. PCNA and Ki-67 labeling indices were significantly higher in embryonal compared with fetal cells. beta-catenin cytoplasmic/nuclear immunoreaction was frequent, although not showing significant differences between fetal and embryonal cells. Mutational analysis of beta-catenin detected mutation in two cases. Our results suggest that increased expression of CLDN-1 and -2 characterizes the more differentiated fetal component in HBs and is a reliable marker for differentiating fetal and embryonal cell types in HBs. The results proved that the embryonal and fetal components of HBs differ in such important feature as the protein composition of TJs. The expression of CLDN-1 and -2 is inversely correlated with cell proliferation. The more aggressive, rapidly proliferating embryonal phenotype is associated with the decrease/loss of CLDN-1 and -2. However, there are no data indicating association with the nuclear translocation of beta-catenin.