Association study of promoter polymorphisms within the NOS3 gene and allergic diseases

BACKGROUND: Nitric oxide (NO) is an important mediator of physiologic and pathologic processes in the airways. On this basis, we hypothesized that polymorphisms in the NOS3 gene could be associated with the disease process. METHODS: Two promoter variants (-786C/T and -691C/T) were examined in a Caucasian Czech population of allergic patients [n = 671, with a subgroup of asthmatics (n = 305)] and healthy controls (n = 334) using PCR-RFLP analyses. RESULTS: NOS3 -786C/T and -691C/T were not associated with allergic diseases or asthma. However, the -786 variant was significantly associated with asthma in men (p < 0.01, p(corr) < 0.05) but not in women. NOS3 -691C/T was found to be in strong linkage disequilibrium with -786C/T, and the distribution of combined genotypes was marginally different between the asthmatic and control men. CONCLUSION: Our results suggest that NOS3 gene variants may be one of the factors that participate in the pathogenesis of asthma in men.     

Time Interval and the Factors Associated with the Development of Asthma in Patients with Allergic Rhinitis

Rhinitis and asthma commonly coexist and studies have shown a positive association between rhinitis and asthma in both atopic and nonatopic adults. Longitudinal studies have shown that in many cases rhinitis precedes the onset of asthma. The aims of this study were to study the time interval for the development of asthma after the onset of rhinitis, to determine the proportion of patients in whom rhinitis precedes asthma, and to study the factors associated with the development of asthma in patients with allergic rhinitis compared to patients who continue to have allergic rhinitis alone. This was a cross-sectional study done at a tertiary care allergy center in Mysore, South India. It included consecutive patients between 2004 and 2006 with allergic rhinitis and/or asthma. We used a structured questionnaire, clinical evaluation, spirometry, and skin-prick testing. A total of 1,141 subjects were included in the study. Among them, 700 had allergic rhinitis for varying intervals before developing asthma and 355 had rhinitis without asthma. In subjects aged 20 years or younger, logistic regression analysis confirmed an independent association with a family history of allergic rhinitis and sensitization to house dust mites as risk factors and ever-used nasal steroids as protective against developing asthma in subjects with allergic rhinitis. In subjects older than 20 years, a family history of allergic rhinitis, atopy, and sensitization to house dust mites and trees were risk factors and ever-user of nasal steroids was protective. Rhinitis often preceded asthma and a high proportion of patients, both children and adults, developed asthma within 2 years after the onset of rhinitis. A family history of allergic rhinitis, atopy, and sensitization to house dust mites and trees are associated with the development of asthma in patients with allergic rhinitis.     

Analysis of the interleukin-6 gene promoter polymorphisms in Czech patients with chronic periodontitis

BACKGROUND: Chronic periodontitis is an inflammatory disease, which is a major cause of tooth loss. The proinflammatory cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) are key regulators of the host response to microbial infection and major modulators of extracellular matrix catabolism and bone resorption. The purpose of this study was to investigate the associations of chronic periodontitis with IL-6 gene polymorphisms (at positions -597 [G/A], -572 [G/C], and -174 [G/C]). METHODS: We analyzed allele, genotype, and haplotype distributions of the IL-6 promoter variants in a case-control study involving 148 patients with chronic periodontitis and 107 unrelated controls. RESULTS: Our results showed significant differences in the distributions of alleles and genotypes of the IL-6 (-572 G/C) polymorphism between patients and the control population (chi2 = 10.393, P= 0.001, P(corr) < 0.01). The difference was due to the underrepresentation of the -572 G/C heterozygotes in patients (6.1%) compared to controls (19.6%). Although no variant "CC" homozygotes were detected in our cases and controls, heterozygosity protected against chronic periodontitis, representing a 73% reduction of risk (odds ratio [OR] = 0.27, 95% confidence interval: 0.12-0.61) compared to wild-type homozygotes. However, there were no significant differences in genotype or allele frequencies between both groups for IL-6 -597 G/A and -174 G/C polymorphisms. CONCLUSION: This study is the first, to our knowledge, suggesting that the -572 G/C polymorphism of the IL-6 gene may be one of the protective factors associated with lower susceptibility to chronic periodontitis.     

Synthesis and antimicrobial studies on novel chloro-fluorine containing hydroxy pyrazolines

A series of chloro-fluorine containing chalcones (3) were prepared by Claisen-Schmidt condensation. Chalcone dibromides (4) were obtained by the bromination of chalcones at room temperature. Treatment of chalcone dibromides (4) with aryloxy acid hydrazides (5) in the presence of triethylamine gave chloro-fluorine containing hydroxy pyrazolines (7) rather than the expected 1-aryloxy-3-aryl-5-aryl pyrazoles (6). The structures of the newly synthesized compounds were confirmed by IR, NMR, mass and elemental analysis. All the compounds were tested for their antibacterial and antifungal activities. Some compounds showed very good antibacterial activity and antifungal activity.     

Synthesis and antimicrobial activities of some new triazolothiadiazoles bearing 4-methylthiobenzyl moiety

A series of substituted triazolothiadiazoles have been synthesized by condensing 4-amino-3-[4-methylthiobenzyl]-4H-1,2,4-triazole-5-thiol (5) with substituted aryl furoic acids/aromatic acids in the presence of POCl3. The triazole (5) was obtained by the fusion of 4-methylthiophenyl acetic acid with thiocarbohydrazide. The structures of newly synthesized compounds are characterized by elemental analysis, IR, 1H NMR and mass spectroscopic studies and were screened for their antimicrobial activities. The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities.     

Low-density lipoprotein receptor activity in Epstein-Barr virus-transformed lymphocytes from heterozygotes for the D374Y mutation in the PCSK9 gene

OBJECTIVE: Missense mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have been found to cause autosomal dominant hypercholesterolemia. The objective of this study was to investigate possible mechanisms by which mutation D374Y in the PCSK9 gene causes hypercholesterolemia. MATERIAL AND METHODS: Binding and internalization of low-density lipoprotein LDL in Epstein-Barr virus (EBV)-transformed lymphocytes from D374Y heterozygotes were examined. The autocatalytic activity of the D374Y mutant was studied in transiently transfected HEK293 cells. RESULTS: As determined by Western blot analysis of transiently transfected HEK293 cells, the autocatalytic activity of the D374Y mutant was approximately 95% of the wild-type. Levels of PCSK9 mRNA in EBV-transformed lymphocytes from D374Y heterozygotes and normal controls were similar and less than 1/1000 of the level in HepG2 cells. The amount of cell surface LDL receptors (LDLRs) in EBV-transformed lymphocytes from five D374Y heterozygotes was non-significantly increased by 17% compared with the amount in normal controls. LDLR-dependent binding and internalization of LDL in EBV-transformed lymphocytes from D374Y heterozygotes were non-significantly reduced by 11% and 12%, respectively, compared to the corresponding values in normal controls. CONCLUSIONS: LDLR-mediated endocytosis of LDL is not reduced in EBV-transformed lymphocytes from D374Y heterozygotes. Because of the extremely low levels of PCSK9 mRNA in EBV-transformed lymphocytes, it is possible that the LDLR-dependent endocytosis of LDL could be more severely affected in hepatocytes from D374Y heterozygotes than in EBV-transformed lymphocytes.     

Dimensional change over time of extended-storage alginate impression materials

Objectives:To evaluate the dimensional change over time of two extended-storage alginate impression materials.Methods:Impressions were made of stainless steel dies in accordance with ADA Specification No. 18 using three alginates: two extended-storage alginates and one conventional alginate. The impressions were stored for 30 minutes, 48 hours, or 100 hours (n  =  10 impressions/material/storage time). Following the respective storage times, dimensional change was measured by comparing the length of the middle horizontal line in the impression with the same line on the die and computing percent difference.Results:Significant differences in dimensional change were noted between materials across time (P < .05). All materials exhibited shrinkage after 30 minutes, with the conventional alginate continuing to shrink over time and the extended-storage alginates expanding with increased storage time. The conventional alginate was most accurate after 30 minutes. In contrast, one extended-storage alginate demonstrated minimal dimensional change at all storage times, and another was most accurate after 100-hour storage.Conclusions:Evidence suggests that delayed pouring with dental gypsum should not adversely affect dimensional accuracy of the generated casts with both extended-storage alginates. However, only one of the extended-storage materials appears suitable for both short-term and extended-storage applications.