Adjunctive low-dose doxycycline therapy effect on clinical parameters and gingival crevicular fluid tissue plasminogen activator levels in chronic periodontitis

Objective and design: The present study examined effectiveness of low-dose doxycycline (LDD) in combination with nonsurgical therapy on gingival crevicular fluid (GCF) tissue plasminogen activator (t-PA) levels and clinical parameters in chronic periodontitis (CP) a over 12-month period. Methods: GCF samples were collected, probing depth (PD), clinical attachment level (CAL), gingival index (GI) and plaque index were recorded at baseline, 3, 6, 9 and 12 months. CP patients (n = 65) were randomized to LDD or placebo groups. LDD group received LDD (20 mg) b.i.d for 3-months plus and root planing (SRP), while placebo group was given placebo capsules b.i.d for 3-months plus SRP. GCF t-PA levels were determined by ELISA. Friedman, Wilcoxon and Mann-Whitney test was used for statistical analysis. Results: Significant improvement was observed in all clinical parameters in both groups over 12-month period (p < 0.01). LDD group had lower PD, CAL and GI scores than placebo group at 6, 9 and 12-months (p < 0.05). GCF t-PA levels reduced in both groups over 12-month period (p < 0.01). LDD group had lower GCF t-PA levels than placebo group at 6 and 9-months (p < 0.05). Conclusions: These results provide additional information about usefulness of LDD therapy as an adjunct to nonsurgical therapy in long-term management of periodontitis. Received 8 May 2006; returned for revision 13 June 2006; accepted by J. Di Battista 12 July 2006     

Plasma platelet-activating factor levels in newborn infants with and without perinatal asphyxia: Is it an additional marker of perinatal asphyxia?

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) is still a very important cause of neonatal mortality and morbidity. Recently platelet-activating factor (PAF) has been accused of being responsible for the neuronal damage in hypoxic-ischemic brain.
Methods: Therefore, we conducted a study in newborns with perinatal asphyxia to try to show the relationship between the clinical severity and plasma PAF levels.
Results: Mean plasma levels of 19 asphyxiated infants (997.8 ± 363.5 pg/mL) were significantly higher than that of 20 healthy infants (410.2 ± 148.6 pg/mL, P< 0.0001). Patients with clinically severe HIE had significantly higher levels of PAF (1494.2 ± 386.6 pg/mL) when compared with patients with mild HIE (815 ± 114.5 pg/mL) and with moderate HIE (828.3 ± 61.1 pg/mL). There was a significant correlation between plasma PAF concentration and arterial pH and base deficit, but no correlation with platelet and leukocyte counts.
Conclusions: Plasma PAF levels correlating with the severity of HIE is interpreted to mean that high PAF levels may be an indicator of clinical severity and probably the poorer prognosis of patients with HIE.     

Familial Mediterranean fever gene mutation frequencies and genotype�Cphenotype correlations in the Aegean region of Turkey

Familial Mediterranean fever (FMF) is a disease characterized by recurrent, self-limiting fever and serositis and caused by altered pyrin due to mutated MEFV gene. The aim of this study was to investigate clinical manifestations and MEFV mutations among patients with FMF and healthy controls in the Aegean region of Turkey. This study included 308 patients and 164 healthy controls. Patients were divided into three groups according to Tel-Hashomer criteria; definitive, probable, and suspicious. Among the patients, 146 were women (47.4%) and 162 were men (52.6%). The mean age (±SD) of the patients at the diagnosis was 9.6 ± 3.95 (range 0.5–18). The mean age (±SD) at onset of the symptom was 6.2 ± 3.95 (range 1–18). Symptoms were seen earlier onset in definitive group than the suspicious group in our cohort (4.7 ± 3.9 years, 6.6 ± 3.9 years, respectively; P = 0.001). Clinical features were abdominal pain (83.1%), fever (55%), arthritis (17.1%), myalgia (4.5%), pleuritis (10%), and erysipelas—like erythema (7.7%). Fever, arthralgia, arthritis, chest pain, and amyloidosis were found statistically significant more in definitive group than suspicious group (P < 0.001, P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). MEFV gene mutations were identified in 199 patients (64.6%). The most commonly encountered MEFV mutation among the patients was M694V homozygote (25%). M694V homozygous mutation was found most frequently in definitive FMF group than other groups (49, 9, 8.9%, respectively). To our knowledge that FMF should be suspected in the case of non-specific but recurrent attacks of serositis and high fever, and molecular analysis should be performed in order to make diagnosis of FMF.     

Prevalence and significance of MEFV gene mutations in patients with gouty arthritis

Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.     

Alpha 2 integrin gene (ITGA2) polymorphism in renal transplant recipients with and without drug induced gingival overgrowth

Background

Variances in fibroblasts’ α2β1 integrin intensity may lead to altered adhesion to type I collagen and consequently to suppression of phagocytosis which may be one of the mechanisms for drug induced gingival overgrowth. The present study aimed to evaluate the genotype and allele frequencies of α2 integrin +807 gene in renal transplant patients with and without gingival overgrowth.

Material and methods

Seventy renal transplant patients with cyclosporine A (CsA)-induced gingival overgrowth (CsA GO+) were enrolled. Renal transplant patients without GO medicated with CsA (CsA GO−; n = 79) and tacrolimus (Tac; n = 52) served as controls. DNA was obtained from peripheral blood and ITGA2 +807C/T polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism method. Clinical parameters including probing depth and plaque, papilla bleeding and hyperplasia indexes were recorded. Chi-square, Kruskal–Wallis and Mann–Whitney tests were used in statistical analysis.

Results

Clinical parameters of CsA GO+ group were significantly higher than those of the CsA GO− and Tac groups (p < 0.05). ITGA2 807C/T genotype and allele frequencies of study groups were similar (p > 0.05).

Conclusion

Within the limits of the present study it can be concluded that ITGA2 +807 gene polymorphism is not associated with susceptibility to CsA-induced GO.     

FcγRIIIa-V/F 158 polymorphism in Turkish children with asthma bronchiale and allergic rhinitis

Fc receptors (FcR) play an important role in immune regulation. This might be linked to the variability in immune response, therefore relating to the pathogenesis of atopic diseases. The aim of the present study was to evaluate the Fc γ RIIIa gene polymorphism in Turkish children with asthma and allergic rhinitis. The study included 364 atopic children (184 bronchial asthma, 180 allergic rhinitis) and 234 healthy subjects as the control group, aged between 5 to 16 years. Patients were recruited from outpatient clinics of allergy and general pediatric care. Plasma IgE concentrations were measured by immunoassays and skin prick test was done in children with atopic diseases. The Fc γ RIIIa gene polymorphism was determined using the polymerase chain reaction method. Distribution of V158V genotype was significantly different among patient groups compared to controls (for asthmatic children OR: 5.33, 95% CI: 2.80–10.23, p < 0.001; for allergic rhinitis OR: 3.25, 95% CI: 1.75–6.07, p = 0.001). Distribution of 158 V allele was significantly different among asthmatic children (OR: 2.20, 95% CI: 1.65–2.92, p < 0.001) and allergic rhinitis patients (OR: 1.77, 95% CI: 1.32–2.35, p < 0.001) compared to healthy controls. Our study shows that the V158V genotype in Fc γ RIIIa gene polymorphism may be a genetic risk factor for the development of atopic diseases.     

ACE gene insertion/deletion polymorphism in childhood idiopathic nephrotic syndrome

The aim of this study was to determine the distribution of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its effects on clinical, laboratory, histological findings, treatment responses and progression to end-stage renal disease in childhood idiopathic nephrotic syndrome (NS). 227 children diagnosed with idiopathic NS were included in the study. Eighty-three of patients were steroid resistant and 77 of patients were focal segmental glomerulosclerosis. The control group was consisted of 287 unrelated healthy adult volunteers. ACE gene I/D polymorphism were analyzed by using PCR based method. In the entire group of children with NS, the frequencies of the II, ID, and DD genotypes of ACE gene were 13.7%, 38.3% and 48%, respectively. D allele frequency was higher in NS group than control group (0.67 vs. 0.56, p=0.001). Percentage of frequent relapser patients was found more frequently in ID or DD genotype (38.7%) than II genotype (15%) when only steroid sensitive patients were evaluated (p=0.045). The D-allele frequency was 0.65, 0.69 and 0.68 respectively in focal segmental glomerulosclerosis, biopsy proven minimal change and entire minimal change group (p>0.05) and 0.69 and 0.64 respectively in steroid sensitive and resistant groups (p>0.05). D allele frequency was not significantly different in patients with or without end-stage renal disease (0.64 vs. 0.67 respectively, p>0.005) when 115 patients who were at least five year follow-up were evaluated. The D allele frequency was higher in NS patients than healthy controls and DD or ID genotype was related with frequent relapses. ACE gene I/D polymorphism was not important in laboratory and histological findings and progression of the disease in children with NS.     

TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children

The recently described family of toll-like receptors (TLRs) is a key player in host immunity by mediating inflammatory reactions against a wide range of pathogens. Mutations and polymorphisms in TLRs have revealed the importance of TLRs in human defence against diseases. TLR-2 is reported to interact with different bacterial structures, including lipoproteins, peptidoglycan and lipoteichoic acid. To assess the role of TLR-2 gene polymorphism in acute rheumatic fever (ARF) etiopathology, 61 independent Caucasian Turkish patients and 91 child and 116 adult controls were studied. Antistreptolycin O, C-reactive protein, sedimentation and white blood cell counts were studied to evaluate the clinical characteristics of the patients. Genomic DNA was extracted from peripheral blood using a standard column extraction technique. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. The PCR products for the TLR-2 gene were analysed on 1.5% agarose gel pre-stained with ethidium bromide. Compared with healthy adult controls, the Arg753Arg genotype was significantly decreased in the entire group of ARF cases [odds ratio (OR) 0.01, 95% confidence interval (95% CI) 0.0034–0.031, p<0.0001]. Significantly, ARF patients were just 16 times more frequent with Gln allele (OR 15.6, 95% CI 7.87–30.8, p<0.0001). Moreover, evidence for an intensifying effect of the Gln allele was noteworthy when patients with Arg753Gln genotype were compared with healthy controls (OR 97.1, 95% CI 32.5–290, p<0.0001). However, no Arg677Trp polymorphism was detected in either patients or controls. Our data suggest that there is strong evidence for the biological role of TLR-2 in ARF. The common TLR-2 Arg to Gln polymorphism at position 753 significantly contributes to the pathogenesis of ARF. These results will allow the construction of a profile of individuals prone to ARF and may assist in developing new therapies.     

Renin–angiotensin gene polymorphisms in relation to severe chronic periodontitis

Aim: Evidence suggests that the ultimate product of the renin–angiotensin system (RAS), angiotensin II, exerts inflammatory actions. The present study aimed to evaluate the inter‐relation between gene polymorphisms of the RAS components; angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type‐I receptor (AT1R), and severe chronic periodontitis (CP). Material and Methods: DNA was obtained from peripheral blood of 90 CP patients and 126 periodontally healthy subjects, and the clinical parameters were recorded. ACE I/D, AGT M235T and AT1R A1166C polymorphisms were genotyped by the PCR–RFLP method. Chi‐square, anova and logistic regression methods were used in statistical analyses. Results: The frequency of the ACE D allele was significantly lower in the CP group than the healthy group (p_corr=0.015). CP subjects exhibited increased C allele carriage and C allele frequency of the AT1R gene (p_corr=0.03 and p_corr=0.03, respectively). All clinical parameters of CP patients were found to be similar in variant allele‐carrying and non‐carrying subjects (p>0.05). Conclusions: The present findings suggest that ACE I/D and AT1R polymorphisms might be associated with susceptibility to CP but not with disease severity. The D allele of ACE I/D might be associated with decreased, whereas the C variant of AT1R A1166C might be associated with an elevated risk for CP in Turkish population.