Differences between familial and sporadic cases of vitiligo.

BACKGROUND: Most cases of vitiligo are sporadic, but about 10-36% of the patients have positive family history. OBJECTIVE: The aim of our study was to describe differences between familial and sporadic cases of vitiligo. METHODS: A total of 186 adult vitiligo patients were examined, in 173 of whom the level of thyroid peroxidase antibodies, gastric parietal cell antibodies (PCA), antinuclear antibodies (ANA), anti-adrenal cortex antibodies and rheumatoid factor in blood was measured. All patients were divided in two groups: the cases with positive family history of vitiligo (51) and the sporadic cases (135). RESULTS: The risk of onset of the disease up to 20 years of age was higher in the familial group (P=0.008). Patients in familial group showed more widespread depigmentation compared with sporadic cases [body surface area (BSA) over 10%: P=0.004; BSA over 50%: P=0.001]. In familial group, patients had darker skin phototype (P=0.045) and the disease had started more often as a vulgar vitiligo (P=0.008). In sporadic vitiligo group, female gender was a risk factor for more widespread depigmentation (BSA over 10%, P=0.001). Extensive depigmentation was associated with reported triggering factors and mucosal involvement in both groups and with leukotrichia only in familial group. Widespread depigmentation related to the risk of presence of autoantibodies (P=0.03) in sporadic cases of vitiligo (especially of PCA: P=0.04 and ANA: P=0.0002). CONCLUSIONS: In this study, we demonstrated first time that patients with familial vitiligo have a higher risk for vulgar type at the beginning of the disease and female gender increases the risk for more extensive depigmentation in sporadic cases.

Gene expression study of IL10 family genes in vitiligo skin biopsies, peripheral blood mononuclear cells and sera.

BACKGROUND: Vitiligo is a pigmentation disorder, the cause of which is complex and not yet fully understood. There is a significant change of epidermal cytokines in involved skin of patients with vitiligo compared with uninvolved skin and skin of healthy controls, thus suggesting a possible involvement of cytokines in the pathogenesis of vitiligo. OBJECTIVES: To evaluate potential roles of IL10 family cytokines (IL10, IL19, IL20, IL22 and IL24) in vitiligo. Along with the selected cytokines, we investigated subunits of the receptors (IL10RA, IL10RB, IL20RA and IL22RA1) which are involved in the signalling pathway of the cytokines. METHODS: Quantitative real-time polymerase chain reaction was used to detect mRNA expression levels in samples extracted from skin biopsies and peripheral blood mononuclear cells and an enzyme-linked immunosorbent assay was used to measure protein concentrations in serum from patients with vitiligo and healthy controls. RESULTS: IL22 is significantly associated with vitiligo, especially with the active stage of vitiligo, as shown by results of mRNA expression and supported by results of protein level in sera. IL22 may provoke inflammation which leads to destruction of melanocytes. CONCLUSIONS: The actual role of IL22 during pathogenesis of vitiligo remains to be better characterized. Signal transductions of other investigated cytokines seem to be regulated on the expression level of their receptor complex subunits.

Electron impact ionization mass spectrometry and intramolecular cyclization in 2-substituted pyrimidin-4(3H)-ones.

Electron impact ionization mass spectrometry indicates that the behavior of W-unsubstituted pyrirnidin-4-ones with CH2-R type substitution at C-2 differs from homologs that are N-substituted and/or 2-aryl- or 2-methyl-substituted. A dominant intramolecular cycliza-tion was found to occur between 3ZV (in agreement with the predominance of the 3NH tautomers) and the ortho positions of the aryl moiety in compounds with a CH2-aryl substitution at C-2. Theoretical calculations with an AMI SCFR method on 2-, 6-, and 2, 6-disubstituted pyrimidin-4-ones support the mass spectrometric observations.

Whole Transcriptome Analysis (RNA Sequencing) of Peripheral Blood Mononuclear Cells of Vitiligo Patients.

Vitiligo is an idiopathic disorder characterized by depigmented patches on the skin due to a loss of melanocytes. The cause of melanocyte destruction is not fully understood. The aim of this study was to detect the potential pathways involved in the vitiligo pathogenesis to further understand the causes and entity of vitiligo. For that the transcriptome of peripheral blood mononuclear cells of 4 vitiligo patients and 4 control subjects was analyzed using the SOLiD System platform and whole transcriptome RNA sequencing application. Altogether 2,470 genes were expressed differently and GRID2IP showed the highest deviation in patients compared to controls. Using functional analysis, altogether 993 associations between the gene groups and diseases were found. The analysis revealed associations between vitiligo and diseases such as lichen planus, limb-girdle muscular dystrophy type 2B, and facioscapulohumeral muscular dystrophy. Additionally, the gene groups with an altered expression pattern are participating in processes such as cell death, survival and signaling, inflammation, and oxidative stress. In conclusion, vitiligo is rather a systemic than a local skin disease; the findings from an enormous amount of RNA sequencing data support the previous findings about vitiligo and should be further analyzed.

Possible relations between the polymorphisms of the cytokines IL-19, IL-20 and IL-24 and plaque-type psoriasis.

The aim of present study was to elucidate the role of the interleukin (IL)-24 gene in predicting risk for plaque-type psoriasis and to describe the linkage disequilibrium (LD) pattern emerging from the genes of IL-19, IL-20 and IL-24. Genes encoding IL-19, IL-20 and IL-24 locate in the region q32 of chromosome 1. The association between the single-nucleotide polymorphisms (SNPs) or haplotypes of the IL-24 gene and the susceptibility of psoriasis was not found. However, a significant protective effect of the combined haplotype CAAAC of IL-20 and IL-24 genes against plaque-type psoriasis was established (OR 0.154). Protective effect against psoriasis was also observed with haplotype TGGGT (OR 0.591) and haplotype CGAGT (OR 0.457). Performing a comprehensive analysis using the data regarding SNPs of IL-24 gene together with the previously published data regarding IL-19 and IL-20 SNPs, we identified two haplotype blocks within the region q32 of chromosome 1. The main result of the present study is that while the IL-19/IL-20 extended haplotype CACCGGAA is a significant susceptibility factor for psoriasis (previous study), IL-20/IL-24 haplotypes CAAAC, TGGGT and CGAGT have a significant protective effect. Nevertheless, family-based studies are required to confirm the impact of IL-19, IL-20 and IL-24 genes in the genetic predisposition for psoriasis.

A QSPR model for the prediction of the gas-phase free energies of activation of rotation around the N-C(O) bond.

A novel approach to predict the gas-phase rotational activation energies of amides is presented. The quantitative structure property relationship (QSPR) treatment, using the statistical package, comprehensive descriptors for structural and statistical analysis (CODESSA), resulted in a three-parameter equation with R2 = 0.982 for the deltaG(double dagger)gas, of a set of 24 N,N-dialkylamides.

Terbinafine: efficacy and tolerability in young children with tinea capitis due to Microsporum canis.

AIMS: We carried out an open, prospective, uncontrolled study to evaluate the efficacy and tolerability of terbinafine in the treatment of young children with tinea capitis due to Microsporum canis. METHODS: A total of 83 healthy, immunocompetent children (age range 2-13 years) were enrolled in eight centres in Estonia, Latvia and Lithuania. Patients received oral terbinafine in dosages based on weight, 62.5 mg for those weighing 10-20 kg, 125 mg for 20-40 kg, plus application of topical 1% terbinafine cream twice daily to affected areas. Treatment lasted for 4 weeks, followed by an 8-week observation (treatment-free) period. All the subjects were assessed for efficacy and tolerability at 12 weeks. RESULTS: Eighty-one subjects were available for assessment at 12 weeks: 32 had completely recovered, with no evidence of relapse during the observation period, and 21 showed mycological cure, but presented residual physical signs of infection. Thus the effective cure rate was 65.4% in an infection known to be more difficult to cure than other causes of tinea capitis. Terbinafine was well tolerated by these children. CONCLUSIONS: This study showed effective cure of two-thirds of 81 cases of tinea capitis caused by M. canis with a 4-week course of treatment. As one-third of the cases did not respond to treatment, we suggest using combined oral and topical treatment with terbinafine in children with tinea capitis caused by M. canis.

Theoretical descriptors in quantitative structure-affinity and selectivity relationship study of potent N4-substituted arylpiperazine 5-HT1A receptor antagonists.

The ability of ad hoc defined size and shape descriptors and theoretical descriptors derived on a single structure to give powerful interpretative and predictive QSAR models has been compared and evaluated with respect to the quality of the pharmacological data available for a series of structurally diverse 5-HT1A receptor antagonists, displaying selectivity towards the alpha 1-adrenergic receptor.

QSPR analysis of flash points.

A quantitative structure property relationship study of the flash point of a diverse set of 271 compounds provided a general three-parameter QSPR model (R(2) = 0.9020, R(2)(cv) = 0.8985, s = 16.1). Use of the experimental boiling point as a descriptor gives a three-descriptor equation with R(2) = 0.9529. Use of the boiling point predicted by a four-parameter reported relationship gives a three-parameter flash point equation with a R(2) value of 0.9247.

Quantitative relationship between rate constants of the gas-phase homolysis of C-X bonds and molecular descriptors

A quantitative structure-property relationship (QSPR) study on the kinetic parameters of the gas-phase homolysis for 287 different C-X bonds was carried out using the CODESSA program. Successful five-, four-, and three-parameter models were developed for the prediction of the log k (891 K) values. These respective multiple linear correlations were obtained by automatic selection of appropriate molecular descriptors for reagents and products, using only the information encoded in the chemical structure.

Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to plaque-type psoriasis.

There is increasing evidence to suggest that the newly discovered cytokines interleukin (IL)-19 and -20 have a role in the function of epidermis and in psoriasis. The genes encoding these cytokines locate into the genomic IL-10 region on human chromosome 1. The aim of the present study was to analyze whether single-nucleotide polymorphisms (SNPs) in these genes have an impact on the susceptibility for psoriasis. From pairwise linkage disequilibrium (LD) matrix of the IL-19 and -20 gene polymorphisms, what reflects the nonrandom association of alleles at these markers, it was apparent that IL-19 and -20 genes form one block of LD. We found that the HT3 CACCGGAA haplotype of the IL-19 and -20 genes was associated with an increased risk of psoriasis, reflecting its role in determining susceptibility to plaque-type psoriasis. Although association analysis of the IL-19 gene indicated that minor alleles of the IL-19 gene SNPs (rs2243188, rs2243169 and rs2243158) revealed protective effect to psoriasis and haplotype analysis of the IL-19 gene proved significant protective effect of the TGATA haplotype in case of late-onset disease, combined haplotype analysis of the IL-19 and -20 genes demonstrated that protective effect of the IL-19 gene is secondary to the susceptibility effect of the IL-20 gene.

Relevance of theoretical molecular descriptors in quantitative structure-activity relationship analysis of alpha1-adrenergic receptor antagonists.

A quantitative structure-activity relationship (QSAR) study of a wide series of structurally diverse alpha1-adrenergic receptor antagonists was performed using the CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) technique. Theoretical descriptors derived on a single structure and ad hoc defined size and shape descriptors were considered in the attempt of describing information relevant to receptor interaction. The relative effectiveness of these two classes of parameters in developing QSAR models for native (alpha1A and alpha1B) and cloned (alpha1a, alpha1b, and alpha1d) adrenergic receptor binding affinity, functional activity of vascular and lower urinary tract tissues, and in vitro and in vivo selectivity was evaluated.

QSRR correlation of free-radical polymerization chain-transfer constants for styrene.

Quantitative structure-reactivity relationships (QSRR) are deduced for kinetic chain-transfer constants for 90 agents on styrene polymerization at 60 degrees C. Three- and five-parameter correlations were obtained with R2 of 0.725 and 0.818, respectively. The descriptors involved in the correlations are consistent with the proposed mechanism of the chain-transfer reactions.

Interpretation of quantitative structure-property and -activity relationships.

The potential utility of data reduction methods (e.g. principal component analysis) for the analysis of matrices assembled from the related properties of large sets of compounds is discussed by reference to results obtained from solvent polarity scales, ongoing work on solubilities and sweetness properties, and proposed general treatments of toxicities and gas chromatographic retention indices.

Prediction of Critical Micelle Concentration Using a Quantitative Structure-Property Relationship Approach

Relationships between the molecular structure and the critical micelle concentration (cmc) of anionic surfactants were investigated using a quantitative structure-property relationship approach. Measured cmc values for 119 anionic structures, representing sodium alkyl sulfates and sodium sulfonates with a wide variety of hydrophobic and hydrophilic structures, were considered. The best multiple linear regression model involved three terms (descriptors) and had a correlation coefficient of R2 = 0.940. Very good correlations (R2 = 0.988) were obtained using three descriptors for a subset of 68 structures, with structural variation only in the hydrophobic domain. From the descriptors used in these regressions, one can conclude that the cmc is primarily dependent on the size (volume or surface area) of the hydrophobic domain and to a lesser extent on the structural complexity of the surfactant molecule.