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The inflammasome modulates the release of key proinflammatory cytokines associated with periodontal disease pathogenesis. The aim of this study was to evaluate the expression of proteins that regulate the inflammasome, namely pyrin domain‐only proteins (POPs), caspase activation recruitment domain (CARD)‐only proteins, and tripartite motif‐containing (TRIM) proteins, in periodontal diseases. A total of 68 participants (34 males and 34 females) were divided into four groups, including periodontal health (H), gingivitis (G), chronic periodontitis (CP), and aggressive periodontitis (AgP) based on clinical parameters. Gingival tissue samples were obtained from all participants for reverse transcription polymerase chain reaction (RT‐PCR)‐based gene expression analyses of molecules that regulate the inflammasome, including apoptosis‐associated speck‐like protein (ASC) containing CARD, caspase‐1, interleukin‐1β (IL‐1β), interleukin‐18 (IL‐18), nucleotide‐binding domain, leucine rich family (NLR) pyrin domain containing 3 (NLRP3), NLR family pyrin domain containing 2 (NLRP2), AIM2 (absent in melanoma 2), POP1, POP2, CARD16, CARD18, TRIM16, and TRIM20 by RT‐PCR. NLRP3 and IL‐1β were upregulated in the G, CP, and AgP groups compared with group H (P< 0.05). AIM2 was downregulated in the CP group compared with the H, G, and AgP groups (P< 0.05). TRIM20, TRIM16, and CARD18 were downregulated in the G, CP, and AgP groups compared with the H group (P< 0.05). POP1 and POP2 were downregulated in the CP and AgP, and AgP and G groups, respectively (P< 0.05). Active periodontal disease may result in downregulation of inflammasome regulators that may increase the activity of NLRP3 and IL‐1β in periodontal disease.

The aim of the study was to investigate the effects of colchicine on cytokine production, apoptosis, alveolar bone loss, and oxidative stress in an experimental model of periodontitis in rats. Forty‐eight rats were divided equally into four groups: healthy (H); periodontitis (P); periodontitis+colchicine low dose (CL, 30 μg/kg/day), and periodontitis+colchicine high dose (CH, 100 μg/kg/day). After 11 days, interleukin (IL) ‐1β, IL‐8, and IL‐10 were analyzed in gingival samples using Enzyme‐Linked ImmunoSorbent Assay. Receptor activator of nuclear factor kappa‐B ligand (RANKL), osteoprotegerin (OPG), total oxidative stress (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured in gingiva and serum. Alveolar bone volume was evaluated via micro‐CT. Apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in histological sections. Colchicine treatment significantly reduced IL‐1β, IL‐8, RANKL, RANKL/OPG, TOS, OSI, and bone volume ratio levels, and increased TAS levels compared to group P (p < 0.05). High dose colchicine treatment (CH) significantly decreased TUNEL+ cell counts compared to group P (p < 0.05). These finding suggest that colchicine has a prophylactic potential for the prevention of periodontal tissue destruction through anti‐inflammatory, anti‐oxidative, anti‐apoptotic, and bone‐protective effects.

Hashimoto’s disease is a polygenic disorder with complex etiopathogenesis. Apoptosis is proposed as one of its mechanisms. The Fas/Fas ligand cascade represents a major pathway initiating apoptosis. This study aims to evaluate the influence of Fas and FasL gene polymorphism in Hashimoto’s thyroiditis in Turkish population. A total of 112 patients with Hashimoto’s thyroiditis and 112 cases of healthy control people were included in this study. The evaluation of genotype for Fas -670 A/G and FasL 843 C/T gene polymorphism was performed by using PCR-RFLP method. The FAS genotype and gene allele frequency distribution did differ between the control group (AA 36.6 %, AG 50.0 %, GG 13.4 %, A 61.6 %, G 38.4 %) and the Hashimoto’s thyroiditis patients (AA 21.4 %, AG 50.9 %, GG 27.7 %, A 46.9 %, G 53.1 %) (p< 0.01). The evaluation of FasL genotype and gene allele frequency did not show statistically significant difference between the patient group (CC 27.7 %, CT 45.5 %, TT 26.8 %, C 50.4 %, T 49.6 %) and control group (CC 33.9 %, CT 44.6 %, TT 21,4 %, C 56.3 %, T 43.8 %) (p> 0.05). Gene polymorphism of Fas and G allele frequency may play a role in the regulation of apoptosis in thyroid autoimmune disorders. There is a need for further studies to clarify the genetic role of apoptosis in HT.

Background:The aim of the present study is to investigate matrix metalloproteinase (MMP)‐8 and tissue inhibitor of MMP‐1 (TIMP‐1) gene polymorphisms in generalized aggressive periodontitis (GAgP) and to assess the effects of MMP‐8 and TIMP‐1 genotypes on the outcomes of non‐surgical periodontal therapy. Methods:Genomic DNA was obtained from peripheral blood of 100 patients with GAgP and 167 periodontally healthy controls. MMP‐8 +17 C/G, −799 C/T, −381 A/G and TIMP‐1 372 T/C, *429 T/G polymorphisms were determined by polymerase chain reaction‐restriction fragment length polymorphism. Patients with GAgP received non‐surgical periodontal therapy and were followed for 6 months. Clinical periodontal parameters and gingival crevicular fluid (GCF) samples were collected at baseline and at follow‐up visits. GCF biomarkers were analyzed by immunofluorescence assay and enzyme‐linked immunosorbent assay. Results:Distribution of the MMP‐8 −799 C/T genotypes was significantly different between the GAgP and control groups (P<0.005). TIMP‐1 372 T/C and *429 T/G genotypes in males were also significantly different between study groups (P<0.004). GCF MMP‐8 levels decreased until 3 months after non‐surgical therapy compared with baseline in T and G alleles, as well as G and C allele carriers (P<0.0125), whereas no significant decreased was observed in non‐carriers (P>0.0125). Conclusion:On the basis of the present findings, it can be suggested that MMP‐8 −799 C/T and TIMP‐1 372 T/C, *429 T/G gene polymorphisms in males may be associated with the susceptibility to GAgP in the Turkish population.

AbstractThe researchers investigated the relationship between intense training, the catechol-Omethyltransferase (COMT) Val108/158Met gene polymorphism, and alexithymia. Eighteen female and 77 male athletes were included. The Toronto Alexithymia Scale (TAS) questionnaire and polymerase chain reaction method were used to evaluate alexithymia and the COMT gene Val108/158Met polymorphism, respectively. Fifteen (15.8%) subjects were evaluated as alexithymic and 80 (84.2%) were non-alexithymic according to the TAS. The COMT Vall08/158 Met gene polymorphism frequencies were as follows: 17.9% Met/Met, 50.5% Val/Met, and 31.6% Val/Val. No difference were observed among training intensity, the COMT Vall08/158 Met gene polymorphism, and alexithymia(p > 0.05). However, 60% of the alexithymic subjects trained intensively and only 6.7% trained lightly. Intensive and light training rates for non-alexithymic athletes were 46.3% and 20%, respectively. The Val/ Val and Met/Met genotyping rates for athletes engaged in intensive training were 32.6% and 29.3%. In conclusion, no significant relationship was observed among TAS scores, the COMT gene polymorphism, and training intensity.

AbstractPatients with DAX-1gene mutations on chromosome Xp21 usually present with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Yet, neither correlation between the type of mutation and the age of onset of the disease nor mechanism of the mutation on puberty is fully understood. Here, we report a novel non-sense p.Gln208X mutation in the amino terminal domain of the DAX-1gene observed in a large family with three boys presenting with adrenal manifestations at different ages. Furthermore, two boys developed spontaneous puberty that failed to progress at similar ages, whereas the other boy developed precocious puberty at 10 month of age. The unique structure of the DAX-1gene may explain this phenotypic variability. However, more studies are needed to understand the role of the DAX-1gene on development of the adrenal gland and hypothalamus-pituitary-gonadal axis.

AbstractBackground/aims:Pseudohypoaldosteronism Type 1 (PHA1) is a rare heterogeneous syndrome characterized by severe salt loss, hyperkalemia, hyponatremia, metabolic acidosis, hyperaldosteronism and hyperreninemia. Multi-system form of PHA1 is caused by mutations in one of the genes encoding the α, β and γ subunits of epithelial sodium channels (ENaC). In this study, we presented a novel splice site mutation in the beta-gene of ENaC in a patient with multi-system PHA.Methods:We performed DNA sequencing analysis of SCNN1A, SCNN1B, SCNN1Gand NR3C2genes.Results:We found a novel c.1266-1G>C homozygous splice site mutation in intron 8 of the SCNN1Bgene. Initially elevated plasma renin activity (PRA) and aldosterone levels of the patient returned to normal with large amounts of dietary salt and serum sodium (Na+) and potassium (K+) levels were within normal range at the end of the first year of life.Conclusion:This improvement may be due to partial activity of mutated ENaC subunits, reduced dependence on aldosterone in salt homeostasis with increasing age, and alternative regulating mechanisms in sodium homeostasis. The results enhance our understanding of the pathophysiology of this disorder and the mechanisms of renal salt conservation.

AbstractHomozygous mutations in the glucokinase gene (GCK) result in a complete deficiency of the GCK enzyme, which leads to permanent neonatal diabetes mellitus. Whilst there has been one report of a patient (with a homozygous p.T168A) who was diagnosed with diabetes at the age of 2 months, all other cases were diagnosed with diabetes within the first 2 weeks of life. We now report a second unrelated patient with the same p.T168A GCKmutation who was diagnosed with diabetes at the age of 9 months. We conclude that the specific GCKmutation, as yet unidentified genetic modifiers, and/or environmental factors might have different effects on pancreatic β-cell functions, causing variability in the age at diagnosis of diabetes.

It is difficult to predict outcome in neonates that experience perinatal hypoxic ischaemia. Morbidity and mortality may be affected by genetic factors that augment inflammatory and coagulative responses. This prospective study analysed the effects of proinflammatory cytokine gene polymorphisms (tumour necrosis factor-α [TNFA]308G>A and interleukin-6 [IL6]174G>C) and prothrombotic factor gene mutations (prothrombinG20210A, factor V LeidenG1691A and methylenetetrahydrofolate reductase [MTHFR]C677T) on the early neurological prognosis in 40 term hypoxic ischaemic encephalopathic neonates. There were significant relationships for Sarnat and Sarnat staging with electroencephalographic findings, transfontanelle ultrasound (US) results, early neonatal outcome and neurological morbidity. Genetic mutations in the prothrombotic proteins, the TNFA308G>A polymorphism and the cerebrospinal fluid levels of TNF-α protein were not related to clinical stage, electroencephalography, transfontanelle US or neurological status at discharge or at postnatal months 6 and 12. The IL6174GC genotype demonstrated a protective role, being significantly correlated with normal electroencephalography, transfontanelle US and normal neurological findings at discharge. In conclusion, the IL6174GC gene polymorphism seems to play a role in determining the risk and/or severity of perinatal cerebral injury.

Abstract: Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy (DN). The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene polymorphism in the healthy and patients with and without DN. The MCP-1 genotypes were determined in 43 patients with nephropathy and 43 without nephropathy and a control group of 105 healthy individuals. The genotype MCP-1 (−2518G/A) distribution did differ between the control group and the type 2 diabetic patients (P = 0.004). The frequency of the polymorphic G allele was also no similar for the group with type 2 diabetes as for the control group with 20.9 and 32.4%, respectively (P = 0.012). The AA genotype and A allele at MCP-1 −2518 was an independent risk factor for the progression of type 2 diabetes. In conclusion, MCP-1 AA genotype and A allele may play a specific role(s) in determining diabetic susceptibility, but do not seem to be important in the clinical manifestations of DN.

ABSTRACTObjective: A number of different gene polymorphisms have been found to be involved in the predisposition to development of panic disorder (PD). Previous studies showed that progesterone might play an important role in the psychophysiology of PD. The aim of this study was to investigate the relationship between two different progesterone receptor gene polymorphisms and agoraphobia, nocturnal panic attacks, and respiratory subtype of PD.Methods: Ninety-eight patients diagnosed with PD and 129 healthy controls participated in the study. Patients with PD were divided into two groups on the basis of their symptom profile: respiratory and nonrespiratory subtypes. Seventy-six of 98 patients with PD (79.6%) were in respiratory subtype (RS) of PD.Results: The association between G331A polymorphism and PD in both sexes was significant (p=0.02; OR=2.291; CI=1. 141–4.6). PROGINS Alu gene polymorphism was associated with PD in women (p=0.036; OR=0,46; CI=0, 219- 0.95). It has been also found an assocaition between PROGINS Alu polymorphism and agoraphobia (p=0.002; OR= 3.8; CI=1.65–8.76).Conclusion: Our results suggest that the progesterone receptor gene polymorphism might be a susceptibility factor for PD.

Objective: The aim of our study was to demonstrate demographic characteristics, presence of inflammatory markers, distribution of angiotensin-converting enzyme (ACE), tumor necrosis factor (TNF), endothelial nitric oxide synthase (eNOS) genotypes and relations among these parameters in these patients and control subjects. Research design and methods: Study samples were collected from 50 patients with adrenal mass and 30 control groups. The eNOS, ACE, TNF-α, transforming growth factor (TGF)-β genes polymorphisms, TNF-α, adiponectin levels were analysed in 50 unrelated Turkish patients with a diagnosis of adrenal incidentaloma (AI). Results: There was statistically significant difference between TNF-α levels of patient and controls (p=0.048). We have not detected the connection between TGF-β, TNF-α, ACE, eNOS gene polymorphism with serum TNF-α and adiponectin levels. In this study, we demonstrated that there were significant differences for ACE genotypes in the patients when compared to the controls (p<0.05). The percentages of the ID, DD, II genotypes for ACE gene polymorphism in the patients group were 30.0, 13.0, 7.0%, respectively. Conclusions: According to different cases of eNOS, TGF-β, ACE, and TNF-α gene genotypes; no statistical significant difference was found between basal cortisol, ACTH, DHEAS, metanephrine, renin, aldosterone, normetanephrine, 17-hydroxyprogesterone, 1 mg low-dose dexamethasone suppression test-cortisol response and AI size. In this study, I/D genotype was determined to be statistically higher in ACE gene in patients with AI (p=0.014).

Introduction: Interleukins and cytokines play an important role in the pathogenesis of many cancers. We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in patients with papillary thyroid carcinoma (PTC) and control subjects. Material and methods: In this study, 42 patients with PTC and 340 healthy controls were included. Peripheral blood samples were taken from control group and patients, and blood samples were preserved at −80 C in tubes containing Na-EDTA. Results: We also found a statistically significant difference between patients with PTC and the control group with respect to IL-6 genotype (p<0.05). IL-6 gene polymorphism in patients with PTC patients did not reveal statistically significant difference between the 2 groups (size of tumor >1 cm and <1 cm), multicentricity, RET-PTC types and capsule invasion (p>0.05). We also did not find a statistically significant difference between patients with PTC and the control group with respect to IL-6-gene allele frequency (p>0.05). Discussion: Our data suggest that the IL-6 G-174 C polymorphism could play a role in thyroid cancer risk, but there is no effective role as a prognostic factor.

Objective: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. Results: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). Conclusions: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.

Objective: Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular (CD) diseases. Cardiovascular risk factors that have been reported include oxydative stress markers [nitric oxide (NO), malondialdehyde (MDA), disulphite (SH)]. We aimed to evaluate the relation between the IL-6 G/C gene polymorphism and oxidative stress markers in polycystic ovary syndrome (PCOS) patients. Design and patients: We studied 85 PCOS patients and 115 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. Results: The genotype IL-6 distribution did differ between the control group (CC 9.6%, GC 63.4%, GG 27.0%) and the PCOS patients (CC 4.7%, GC 29.4%, GG 65.9%) (p<0.001). The frequency of the polymorphic G allele was also not similar for the group with PCOS as for the control group with 80.6% and 58.7%, respectively (p<0.001). No statistically significant difference was determined for MDA and NO levels in PCOS patients and control group (p>0.05). Only SH levels were found to be high in favor of patient group (p<0.05). No statistically significant difference was determined between IL-6 G/C gene polymorphism and oxidative stress markers in PCOS patients and in the control group. Conclusion: Gene polymorphism of IL-6 −174 G>C is a risk factor for PCOS in Turkish patients. IL-6 gene polymorphisms are not related to NO, MDA, and SH levels in PCOS. Our negative results in risks factors of CV disorders can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short period of time.

Matrix metalloproteinases(MMPs) can affect early events in carcinogenesis and tumor invasion and/or metastasis. In this study we attempt to explain the relationship of the MMP-1, -2, and -9gene polymorphism with prognostic factors in papillary thyroid cancer patients.

Background:Matrix metalloproteinases (MMPs) are involved in periodontal tissue remodeling and degradation. Polymorphisms in the promoter region of the MMP‐2 and ‐9 genes and in the coding region of the MMP‐12 gene could affect transcription and the function of these enzymes. The aim of the present study was to determine the association between the aforementioned MMP polymorphisms and generalized aggressive periodontitis (GAgP). Methods:Genomic DNA was obtained from the peripheral blood of 92 subjects with GAgP and 157 periodontally healthy subjects. MMP‐2 −735C/T, MMP‐9 −1562C/T, and MMP‐12 357Asn/Ser polymorphisms were genotyped by polymerase chain reaction and restriction fragment length polymorphism. Probing depth, clinical attachment loss, supragingival plaque accumulation, and bleeding on probing were recorded. The data were analyzed by χ2, logistic regression, and Mann‐Whitney U tests. Results:The genotype distributions, allele frequencies, and rare allele carriage of MMP‐2 and MMP‐12 genes were similar in GAgP and healthy subjects (P>0.05). T allele frequency and T allele carriage of the MMP‐9 −1562 C/T polymorphism were significantly lower in the GAgP group than in the healthy group (P<0.05). In addition, logistic regression analysis revealed a protective effect for MMP‐9 −1562 T allele carriers (odds ratio = 0.52; P= 0.04). Conclusions:MMP‐2 −735C/T and MMP‐12 357Asn/Ser polymorphisms are not related to GAgP. Conversely, the MMP‐9 −1562 gene T allele might be associated with a decreased risk for GAgP in the Turkish population.

Background:Toll‐like receptors (TLRs) recognize exogenous ligands such as lipopolysaccharide and bacterial lipoprotein during the immune responses to pathogens. The aim of the present study was to investigate whether TLR2 and TLR4 gene polymorphisms are related to susceptibility to generalized aggressive periodontitis (GAgP). Methods:A total of 245 subjects were included in the present study. Genomic DNA was obtained from the peripheral blood of 90 patients with GAgP and 155 periodontally healthy subjects. Probing depth, clinical attachment loss, plaque accumulation, and bleeding on probing were recorded. The TLR2 gene Arg753Gln and Arg677Trp polymorphisms and TLR4 gene Asp299Gly and Thr399Ile polymorphisms were genotyped by the polymerase chain reaction–restriction fragment length polymorphism method. The data were analyzed by χ2and Mann‐Whitney U tests and logistic regression analysis. Results:There was no significant difference in the distribution of TLR2 and TLR4 genotypes and allele frequencies between GAgP patients and healthy subjects (P>0.05). The TLR2 753Gln allele was found in 3.9% of the GAgP patients compared to 6.1% in the healthy group. The GAgP patients and healthy subjects did not show homozygosity for the TLR2 mutant alleles. The TLR2 677Trp mutant allele was not found in any of the subjects; 2.2% of the GAgP patients and 2.9% of the periodontally healthy subjects were identified as having the TLR4 299Gly polymorphic allele. With regard to the TLR4 399Ile polymorphic allele, 1.1% of the GAgP patients and 2.3% of the periodontally healthy subjects had this allele. Conclusions:The present study failed to find any significant association between the TLR polymorphisms and GAgP, potentially because of the small sample size. To the best of our knowledge, this was the first study to examine the prevalence of these polymorphisms in a Turkish population with aggressive periodontitis.

An allele‐specific voltammetric genoassay for the detection of allele‐specific toll‐like receptor‐2 gene arg753gln polymorphism (TLR‐2) from polymerase chain reaction (PCR) amplified real samples was described in this study. Meldola blue (MDB), an intercalator molecule, was used as hybridization label. The wild‐type and mutant type oligonucleotide probes were immobilized onto disposable graphite electrode surfaces by covalent attachment method. The extent of hybridization between probe and target sequences was determined by using differential pulse voltammetry (DPV). As a result of the interaction between MDB and DNA at electrode surface, the MDB signal observed from probe sequence before hybridization and after hybridization with MM sequence is lower than that observed after hybridization with complementary sequence. The differences between the MDB reduction peaks obtained from probe modified, hybrid modified and MM modified electrode were used to detect TLR‐2 from PCR amplified real samples. The discrimination of homozygous and heterozygous alleles was also established by comparing the peak currents of MDB reduction signals. Numerous factors affecting the target hybridization and indicator binding reactions are optimized to maximize the sensitivity.

Background:Tissue plasminogen activator (t‐PA) and plasminogen activator inhibitor type 1 (PAI‐1) are involved in the pathogenesis of periodontitis by controlling proteolytic events in the extracellular matrix. This study was designed to investigate the association of t‐PA and PAI‐1 gene polymorphisms with chronic periodontitis (CP). Methods:One hundred eighty‐nine subjects were included. Genomic DNA was obtained from the peripheral blood of 84 patients with CP and 105 periodontally healthy subjects. Polymerase chain reaction and endonuclease digestion was used to genotype the 4G/5G polymorphism in the promoter region of the PAI‐1 gene and the Alu‐repeat insertion (I)/deletion (D) polymorphism in intron 8 of the t‐PA gene. Results:The genotype distributions and allele frequencies of t‐PA polymorphism were not different between patients with CP and healthy subjects (24.7% I/I, 45.7% I/D, and 29.6% D/D and 30.3% I/I, 45.5% I/D, and 24.2% D/D, respectively; P>0.05). The t‐PA D allele frequency was similar in patients with CP (52.4%) and healthy subjects (46.5%). PAI‐1 genotype distribution in patients with CP (30.9% 4G/4G, 35.8% 4G/5G, and 33.3% 5G/5G) and healthy subjects (36.2% 4G/4G, 41.9% 4G/5G, and 21.9% 5G/5G) was also similar. The 4G allele frequency was not different between patients with CP (48.8%) and healthy subjects (57.1%) (P>0.05). The 4G allele frequency in non‐smoking CP patients was significantly lower than in non‐smoking, healthy subjects (χ2= 4.201; P= 0.040). Non‐smoking CP patients also had a significantly lower percentage of 4G‐positive genotypes compared to non‐smoking healthy subjects (χ2= 5.046; P= 0.025). Conclusions:t‐PA or PAI‐1 genotypes are not associated with susceptibility to CP in Turkish subjects. Conversely, the 4G allele of the PAI‐1 gene could be related to a decreased susceptibility to CP in non‐smokers.

Objective: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. Results: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. Conclusions: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Abstract.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?

Background:Endothelial nitric oxide synthase (eNOS) is involved in key steps of immune response. The aim of the present study was to evaluate genotype distribution and genotype‐phenotype association in periodontal disease regarding Glu298Asp polymorphism of the eNOS gene. Methods:A total of 272 subjects were included into the study. Genomic DNA was obtained from the peripheral blood of 51 chronic periodontitis (CP) patients, 48 generalized aggressive periodontitis (GAgP), and 173 reference controls. Polymerase chain reaction (PCR) amplification and subsequent BanII restriction fragment length polymorphism (RFLP) analysis were used to detect eNOS Glu298Asp polymorphism. Probing depth, clinical attachment loss, plaque accumulation, and bleeding on probing (BOP) were recorded. The data were analyzed by the χ2test, logistic regression, and Mann‐Whitney U test. Results:The distributions of eNOS Glu298Asp genotypes and alleles were similar among study groups. Subjects with the Asp allele (Asp+) were statistically higher in the CP group compared to the control group (odds ratio [OR] = 1.957; 95% confidence interval [95% CI] = 1.038 to 3.689). In the GAgP group, BOP (%) was significantly higher in patients with the 298Asp allele (Asp+) compared to patients without the Asp allele (Asp−) (P =0.015). Conclusions:The present study showed that eNOS Glu298Asp polymorphism is associated with BOP in GAgP patients. Moreover, the 298Asp allele of the eNOS gene might be related to CP in the Turkish population.

Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and macrophage cytokine; it is likely to play an important role in innate immunity. Its expression was increased in several inflammatory diseases, and MIF gene polymorphisms have an effect on disease outcome and response to glucocorticoid treatment. To investigate the role of the 173G/C polymorphism of the MIF gene for susceptibility to biliary atresia (BA). Between February 2002 and November 2004, 18 patients (mean age 1 ± 0.4 years) diagnosed as having BA were studied. After informed consent, blood was collected, and DNA was obtained. MIF 173C/G polymorphism was detected using the polymerase chain reaction‐restriction fragment length polymorphism based method. BA patients were compared with a group of chronic liver disease patients (CLD) (n = 36) and a group of unrelated healthy controls (n = 103). MIF‐173C allele frequency was significantly higher than both the CLD and healthy control groups (P= 0.03, odds ratio [OR] 4.4, 95% confidence interval [CI] 1.3‐15.1; P= 0.000, OR 4.1, 95% CI 2.3‐7.6, respectively). Univariate analysis showed that MIF‐173G/C polymorphism was significantly associated with BA (for GC genotype, OR = 6, 95 % CI 2.8‐11.5, P= 0.000). There was no significant correlation between pediatric end stage liver disease score and MIF genotypes both in BA and CLD groups. Our results suggest that the ‐173C allele of the MIF gene might be associated with the susceptibility to BA.

Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and macrophage cytokine; it is likely to play an important role in innate immunity. Its expression was increased in several inflammatory diseases, and MIF gene polymorphisms have an effect on disease outcome and response to glucocorticoid treatment.

Background:The present study was planned to evaluate the individual and combined effects of selective cyclooxygenase‐2 (COX‐2) inhibitor, celecoxib, and omega‐3 fatty acid on the gingival tissue levels of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α), leukotriene B4 (LTB4), and platelet activating factor (PAF) in endotoxin‐induced periodontitis in rats. Methods:Experimental periodontitis was induced by repeated injection of Escherichia coliendotoxin (LPS). Forty‐four adult male Sprague‐Dawley rats were divided into five study groups: saline control, LPS, celecoxib, omega‐3 fatty acid, and combination celecoxib and omega‐3 fatty acid. Celecoxib and omega‐3 fatty acid were given either as a single agent or as a combination therapy during 14 days of the study period. At the end of the 2‐week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2α, and LTB4levels by enzyme immunoassay and for PAF levels by radioimmunoassay. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. Results:LPS injection resulted in significantly more bone loss than the saline controls (P<0.05) and significant elevations in the gingival tissue levels of all the analyzed mediators except PGF2α. Individual administration of celecoxib revealed significant reductions in PGE2and PAF levels (P<0.05), while omega‐3 fatty acid provided significant reduction in PGE2, PGF2α, and LTB4levels compared to the LPS group (P<0.05). Combined administration of celecoxib and omega‐3 fatty acid exhibited significantly lower values than those of the LPS group in all the analyzed membrane phospholipid mediators (P<0.05), which approximated the levels in the saline control group (P>0.05). Conclusions:The results of the present study indicate that celecoxib and omega‐3 fatty acid, when used individually, show a rather partial effect on the control of the analyzed mediators, but when combined they show a synergic effect and provide significant reductions in the gingival tissue levels of PGE2, PGF2α, LTB4, and PAF in LPS‐induced experimental periodontitis. These findings may pioneer further clinical human studies investigating the possible place of celecoxib and omega‐3 fatty acid in periodontal treatment. J Periodontol 2005;76:99‐106.

Background:The aim of the present study was 1) to evaluate the possible effects of therapeutic usage of omega‐3 fatty acid on the gingival tissue levels of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α), platelet activating factor (PAF), and leukotriene B4(LTB4) in endotoxin‐induced periodontitis in rats and 2) to investigate whether prophylactic usage provides any additional benefits to therapeutic doses of omega‐3 fatty acid. Methods:Experimental periodontitis was induced by repeated injection of Escherichia coli lipopolysaccharide (LPS). Thirty‐six adult male Sprague‐Dawley rats were divided into four study groups: 1) saline controls; 2) LPS; 3) therapeutic omega‐3 fatty acid (TO3); and 4) prophylactic plus therapeutic omega‐3 fatty acid (P + TO3) groups. In TO3 group, omega‐3 fatty acid was given for 15 days following induction of experimental periodontitis. In P + TO3 group, omega‐3 fatty acid was started 15 days before baseline, and then periodontitis was induced at baseline and omega‐3 fatty acid was continued for 15 days after baseline. On day 15 after baseline, all rats were anesthetized and sacrificed. PGE2, PGF2α, and LTB4levels in gingival tissue samples were analyzed by enzyme immunoassay and PAF levels were analyzed by radioimmonoassay. Data were evaluated statistically by using parametric tests. Results:LPS injection resulted in significant amount of bone loss (P<0.05). Neither therapeutic nor prophylactic plus therapeutic administration of omega‐3 fatty acid with the doses and duration of therapy used in the present study was effective in preventing endotoxin‐induced alveolar bone loss. TO3 group exhibited significant decreases in the gingival tissue levels of PGE2, PGF2α, LTB4, and PAF compared to the LPS group (P<0.05). PGE2and PGF2αlevels in TO3 group were similar to those of the saline group (P>0.05), while LTB4and PAF levels were statistically higher than the saline group (P<0.05). Prophylactic plus therapeutic usage of omega‐3 fatty acid provided similar levels of all these mediators to those of the saline controls (P>0.05). Conclusions:Therapeutic omega‐3 fatty acid significantly reduced the gingival tissue levels of PGE2, PGF2α, LTB4, and PAF in experimental periodontitis. Furthermore, prophylactic usage of omega‐3 fatty acid provided additional beneficial effects to the therapeutic administration by decreasing the gingival tissue levels of these mediators to levels of healthy tissue. These findings should be verified by longitudinal clinical trials investigating clinical and biochemical periodontal parameters to better define the possible role of omega‐3 fatty acids in periodontal treatment. J Periodontol 2004;75:1640‐1646.

Background:Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti‐enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α), leukotriene B4(LTB4), and platelet‐activating factor (PAF) in endotoxin‐induced periodontal breakdown in rats. Methods:Experimental periodontitis was induced by repeated injection of Escherichia coliendotoxin (LPS) and 44 adult male Sprague‐ Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7‐day study period. At the end of the 1‐week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2α, LTB4, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. Results:Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P<0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2and PGF2α(P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB4and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P<0.05). Conclusions:Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice. J Periodontol 2004;75:1516‐1523.

Mutations of NPHS2, ie, the gene coding for podocin, are associated with nephrotic syndrome (NS) in children, with a clinical phenotype characterized by variable age at onset (from 1 to 10 years) and steroid/cyclosporine resistance. The authors describe an infantile variant in 2 families (3 patients) from Turkey, characterized by homozygosity of a complex haplotype, in which 2 podocin mutations (P20L-R168H) are present in cis. It results from the insertion of a new mutation (R168H), only found in Turkey, on a more ancient haplotype containing the P20L mutation observed in the European population. All patients described had presented with NS within the first 6 months of life with strict resistance to drugs and a histologic background of focal segmental glomerulosclerosis. This is the first description of double homozygous mutations in an autosomal recessive renal disease reported in the literature. The association with infantile NS widens the panel of clinical presentation related to NPHS2mutations.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autoinflammatory disease common in eastern Mediterranean populations. The most severe complication is the development of secondary amyloidosis. Toll-like receptor (TLR-2) plays a critical role in linking the recognition of microbes to immune activation. We investigated whether the Arg753Gln TLR2 polymorphism affected the development of secondary amyloidosis in patients with FMF. METHODS: We studied 75 patients with FMF, 40 patients with FMF who developed secondary amyloidosis, and 116 healthy controls. TLR2 gene Arg753Gln mutations were analyzed with a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequency of the Arg753Gln TLR2 polymorphism among the Turkish population was 6%, whereas it was 25.2% among patients with FMF (p < 0.01). The difference of the frequency of the polymorphism between FMF patients with and without amyloidosis was significant: 15/40 (37.5%) and 14/75 (18.6%), respectively (p = 0.02). CONCLUSION: The Arg753Gln polymorphism may affect the severity of this monogenic disease by influencing the innate immune response to pathogens. The presence of the polymorphism may influence the phenotype of FMF in geographic areas where bacterial insult is more common.

Objective: The aim of present study was to investigate whether hypoxia-reoxygenation (H/R)-induced necrotizing enterocolitis (NEC) was due to increased apoptosis of the intestinal mucosa in the young mice and whether pre-treatment of the animals with recombinant human Insulin-like growth factor-I (IGF-I), known anti-apoptotic factor, could protect the intestinal cells from H/R-induced apoptosis or intestinal injury.Study design: Young mice were divided into three groups; Group 1 mice (H/R) were hypoxia-reoxygenation; Group 2 mice (H/R + IGF-I) were treated with recombinant human IGF-I by intraperitoneal injection (1 µg/g BW; once daily) for 7 days; Group 3 mice were served as control. Hypoxia was induced by placing young mice in Plexiglas chamber, consisting 10% oxygen for 60 min. After hypoxia, the young mice were reoxygenated for 10 min with 100% oxygen. Intestinal generation of substances reactive to thiobarbituric acid (TBARS) and active caspase-3 were measured in H/R-induced intestinal injury.Results: Increased numbers of apoptotic cells (apoptotic index) across the villi in young mice subjected to H/R were observed with the TUNEL reaction whereas few apoptotic cells existed in the control animals. In addition, H/R-induced intestinal damage in H/R + IGF-I group was greatly attenuated, with necrosis limited partially to the mucosa. Tissue active caspase-3 levels in H/R group were found to be significantly higher when compared with that of H/R + IGF-I group of mice and control. However, TBARS concentrations in the intestine were similar in H/R groups when compared to the intestine of control animals.Conclusion: The present study suggests that both necrosis and apoptosis via mechanisms occurring oxygen-derived free radicals and activation of caspase-3 play a role in the pathogenesis of H/R-induced NEC. We also show that IGF-I protect intestinal mucosa from necrosis and apoptosis from intestinal H/R injury.