Voriconazole incorporated nanofiber formulations for topical application: preparation, characterization and antifungal activity studies against Candida species.

In this study, voriconazole (VCZ) incorporated polyvinyl alcohol/sodium alginate electrospun nanofibers were produced and, then crosslinked with glutaraldehyde for topical antifungal treatment. The nanofibers were characterized in terms of fiber size, surface morphology, and compatibility between drug-polymer and polymer-polymer using scanning electron microscopy, atomic force microscopy, attenuated total reflection-Fourier transform infrared spectroscopy, and high pressure liquid chromatography. After optimization studies, in vitro drug release, skin penetration, and deposition studies were performed using Franz diffusion cells. Antifungal activities of the nanofiber formulations against Candida albicans, Candida tropicalis, and Candida parapysilosis strains were evaluated using susceptibility test and subsequently time-kill study was performed against C. albicans. The cytotoxicity study was performed using 4-succinate dehydrogenase viability assay on mouse fibroblast cell line. The release rate of VCZ from crosslinked nanofibers was slower than that of non-crosslinked nanofibers and Higuchi kinetic model best fitted to the in vitro release data of both of formulations. VCZ deposited in deeper skin layers from nanofiber formulations was higher than that of the control formulation (VCZ solution in propylene glycol (1% (w/v)). According to the susceptibility and time-kill studies, all of the nanofiber formulations showed antifungal activity against C. albicans with confirming no cytotoxicity on mouse fibroblast cells.

The role of HMGB1 in liver inflammation in obese rats.

Obesity is a chronic disease that is characterized by increased body fat owing to imbalance between consumed and expended energy. Inflammation generally is accompanied by accumulation of excess lipid in adipose tissue and liver. High mobility group box-1 (HMGB1) participates in the pathogenesis of inflammatory diseases. We investigated the relation of the number of HMGB1 positive cells to body mass index (BMI), liver inflammation and the number of Kupffer cells. We divided 18 female Wistar albino rats into two groups: group 1, untreated control fed normal commercial rat diet and group 2, obese rats fed a special diet containing 40% fat. The plasma concentrations of cholesterol, glucose, superoxide dismutase enzyme (SOD) and catalase activities were measured for all animals. The numbers of hepatocytes, Kupffer cells and HMGB1 positive cells were counted using stereological methods. The mean numbers of Kupffer cells and HMGB1 positive cells were higher for group 2 than for group 1. The concentrations of plasma cholesterol and glucose levels also were higher in group 2. Plasma levels of SOD and catalase were significantly lower in group 2 compared to group 1. The number of HMGB1 cells was related directly to BMI and inflammation. The role of HMGB1 was demonstrated for the liver of the obese group. We demonstrated the relations among HMGB1, BMI, obesity and inflammation.

Effect of EGF on Bax, Bcl-2 and Fas expression in ulcerous disease and N87 cell line.

BACKGROUND: To evaluate the effect of epithelial growth factor (EGF) in primary culture of ulcer patients and N87 cell line on expressions of apoptotic genes. METHODS: Ulcer patients who attended Gastroenterology Clinic of Mersin University Medical Faculty were included in this study. Three different doses of EGF were applied to the primary culture of biopsy samples from ulcer patients and gastric cancer cell-line (ATCC-NCI-N87) . The expression levels of Bax, Bcl-2 and Fas genes were measured with quantitative real-time PCR (qRT-PCR). RESULTS: ΔΔCT analysis with qRT-PCR revealed no significant change in gene expression of Bax, Bcl-2 or Fas within the ulcer, normal tissue and gastric cancer. No significant change was determined between Bax and Bcl-2 gene expression levels and applied EGF doses when groups were compared for each EGF dose. On the other hand, when 50 ng/µl of EGF was administered, Fas mRNA expression level was significantly lower in the gastric cancer cell line compared to patients with ulcer and normal gastroduodenal tissue (p<0.05). CONCLUSION: In this study which was done with a restricted patient group, our results revealed that apoptosis induced by Fas expression in gastroduodenal suppressing carcinogenesis process plays an active role in gaining anti-apoptotic properties of cells (Tab. 4, Fig. 2, Ref. 27).

Relationship between the DAT1 gene and the effects of methylphenidate administration in adult attention deficit hyperactivity disorder: a magnetic resonance spectroscopy study.

OBJECTIVE: This study investigated the relationship between DAT1 gene polymorphisms and the effects of methylphenidate (MPH) administration on N-acetyl aspartate (NAA), creatine (Cr), and choline (Cho) levels in the anterior cingulate cortex, prefrontal cortex, striatum, and cerebellum in adult patients with attention deficit hyperactivity disorder (ADHD). This was the first study to investigate the relationship between DAT gene variable number tandem repeat (VNTR) polymorphisms and the responses of brain metabolites to MPH. PATIENTS AND METHODS: Samples in this study were collected from 60 patients aged between 18 and 60 years with ADHD according to DSM-IV criteria. Genetic analysis of DAT1 gene polymorphisms was carried out using blood samples obtained after a detailed clinical evaluation. Levels of NAA, Cr, and Cho were measured in the anterior cingulate cortex, prefrontal cortex, striatum, and cerebellum by magnetic resonance spectroscopy. After this evaluation, 10 mg of MPH was given orally to patients, and the levels of the same metabolites were measured 30 min later. RESULTS: No marked difference in NAA, Cr, or Cho levels was detected before and after MPH administration with respect to the DAT1 gene VNTR polymorphisms. A considerable increase in Cr levels in the cerebellum was identified after MPH administration in individuals with the 10/10 repeat genotype as the DAT1 VNTR polymorphism (p=0.008). CONCLUSIONS: An increase in the previously decreased blood flow after MPH therapy may induce an increase in creatine levels in patients with the 10/10 repeat genotype. Our results thus suggest that the 10R allele as the DAT1 gene VNTR polymorphism might be associated with MPH-related changes in brain metabolites in adults with ADHD.

Colloidal nanocarriers for the enhanced cutaneous delivery of naftifine: characterization studies and in vitro and in vivo evaluations.

In topical administration of antifungals, the drugs should pass the stratum corneum to reach lower layers of the skin in effective concentrations. Thus, the formulation of antifungal agents into a suitable delivery system is important for the topical treatment of fungal infections. Nanosized colloidal carriers have gained great interest during the recent years to serve as efficient promoters of drug penetration into the skin. Microemulsions are soft colloidal nanosized drug carriers, which are thermodynamically stable and isotropic systems. They have been extensively explored for the enhancement of skin delivery of drugs. This study was carried out to exploit the feasibility of colloidal carriers as to improve skin transport of naftifine, which is an allylamine antifungal drug. The microemulsions were formulated by construction of pseudoternary phase diagrams and composed of oleic acid (oil phase), Kolliphor(®) EL or Kolliphor(®) RH40 (surfactant), Transcutol(®) (cosurfactant), and water (aqueous phase). The plain and drug-loaded microemulsions were characterized in terms of isotropy, particle size and size distribution, pH value, refractive index, viscosity, and conductivity. The in vitro skin uptake of naftifine from microemulsions was studied using tape stripping technique in pig skin. The drug penetrated significantly into stratum corneum from microemulsions compared to its marketed cream (P<0.05). Moreover, the microemulsion formulations led to highly significant amount of naftifine deposition in deeper layers of skin than that of commercial formulation (P<0.001). Microemulsion-skin interaction was confirmed by attenuated total reflectance - Fourier transformed infrared spectroscopy data, in vitro. The results of the in vivo tape stripping experiment showed similar trends as the in vitro skin penetration study. Topical application of the microemulsion on human forearms in vivo enhanced significantly the distribution and the amount of naftifine penetrated into the stratum corneum as compared to the marketed formulation (P<0.05). The relative safety of the microemulsion formulations was demonstrated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability test. This study indicated that the nanosized colloidal carriers developed could be considered as an effective and safe topical delivery system for naftifine.

Colloidal carriers of isotretinoin for topical acne treatment: skin uptake, ATR-FTIR and in vitro cytotoxicity studies.

Acne vulgaris is the chronical, multifactorial and complex disease of the pilosebaceous unit in the skin. The main goal of the topical therapy in acne is to target the drug to epidermal and deep dermal regions by minimizing systemic absorption . Isotretinoin, a retinoic acid derivative, is the most effective drug in acne pathogenesis. Because systemic treatment may cause many side effects, topical isotretinoin treatment is an option in the management of acne. However, due to its high lipophilic character, isotretinoin tends to accumulate in the upper stratum corneum, thus its penetration into the lower layers is limited, which restricts the efficiency of topical treatment. Microemulsions are fluid, isotropic, colloidal drug carriers that have been widely studied as drug delivery systems. The percutaneous transport of active agents can be enhanced by microemulsions when compared with their conventional formulations. The purpose of this study was to evaluate microemulsions as alternative topical carriers for isotretinoin with an objective to improve its skin uptake. After in vitro permeation studies, the dermal penetration of isotretinoin from microemulsions was investigated by tape stripping procedure. Confocal laser scanning microscopy provided insight about the localization of the drug in the skin. The interaction between the microemulsion components and stratum corneum lipids is studied by ATR-FTIR spectroscopy. The relative safety of the microemulsions was assessed in mouse embryonic fibroblasts using MTT viability test. The results indicate that microemulsion-based novel colloidal carriers have a potential for enhanced skin delivery and localization of isotretinoin.

Alpha fetoprotein levels and its relationship with histopathological findings in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver disorders ranging from simple steatosis (SS) to cirrhosis. In addition, increasing evidence indicates that hepatocellular carcinoma (HCC) may represent a late complication of NAFLD. Alpha-fetoprotein (AFP) serum levels can rise in adults with HCC. AIM: In the present study, we aimed to investigate circulating AFP concentrations in subjects with histologically proven NAFLD. In addition, the relationship of AFP with liver histology was also searched. PATIENTS AND METHODS: One hundred and three male NAFLD patients and 57 healthy male controls were enrolled in the study. In addition, patients with NAFLD grouped as nonalcoholic steatohepatitis (NASH) (n = 72) and SS (n = 31). AFP serum levels were measured in duplicate by the chemiluminescence's method. RESULTS: Age and gender were similar in subjects with NAFLD and controls. AFP serum levels were not different between two groups. In subgroup analysis, AFP levels were also found to be similar in patients with NASH and SS. Moreover, no significant relationship was found between AFP and histopathological findings in patients with NAFLD. CONCLUSIONS: The results of this preliminary study suggest that AFP is not involved in the pathogenesis of NAFLD.

[Determination of the cytokine gene polymorphism and genetic susceptibility in tuberculosis patients]. / Tüberküloz hastalarinda sitokin gen polimorfizmi ve genetik yatkinligin belirlenmesi.

Tuberculosis (TB) is a complicated disease in which biological, socioeconomical and environmental factors play role. Since only 10% of the individuals infected with Mycobacterium tuberculosis develop active disease, it has been suggested that host genetic factors may influence the risk for the development of TB. In this study, we aimed to investigate the presence and role of single nucleotide polymorphisms in the gene regions responsible for cytokine production, since these factors are considered to be associated with susceptibility or resistance to disease development. Single nucleotide polymorphisms were investigated by Amplification Refractory Mutational System (ARMS) Polymerase Chain Reaction (PCR) and PCR-Restriction Fragment Length Polymorphism (RFLP) methods. The presence of single nucleotide polymorphisms were analyzed in tumor necrosis factor alpha (TNF-α) gene promoter -308 G>A (rs1800629) region, interferon gamma (IFN-γ) gene +874 T>A (rs61923114) region, interleukin (IL)-12B p40 gene 1188 A>C (rs3212227) region, IL-10 gene promoter -1082 G>A (rs1800896) region and IL-4 gene promoter -590 C>T (rs2243250) region. A total of 84 patients (71 male, 13 female; mean age: 32.57 ± 15.94 years) whose clinical samples yielded M.tuberculosis complex growth, and 110 healthy blood donors (93 male, 17 female; mean age: 29.40 ± 11.56 years) as control group were included in this study. Of the patients, 76 (90.5%) were diagnosed as pulmonary and 8 (9.5%) as extrapulmonary TB. While 79 (94.1%) patients were newly diagnosed as TB, 5 (5.9%) patients had a TB history (relapsed TB). It was detected that acid-fast bacilli (AFB) were positive in 58 (69%) patients. According to the single nucleotide polymorphism results, gene frequencies could not be compared for TNF-a gene promoter -308 G>A region since healthy controls were in Hardy-Weinberg equilibrium while the patients were not. There were no statistically significant differences in allele and genotype distribution between the patients and healthy controls in IFN-γ gene +874 T>A region, IL-12B p40 gene 1188 A>C region, IL-10 gene promoter -1082 G>A region and IL-4 gene promoter -590 C>T region (p> 0.05). There were also no statistically significant differences between AFB positive (n= 58) and negative (n= 26) patients, and AFB positive (n= 56) and negative (n= 20) pulmonary TB patients (p> 0.05). In conclusion, no statistically significant differences were found associated with the susceptibility or resistance to TB with single nucleotide polymorphisms in the gene regions responsible for cytokine production in the study population. Only some of the single nucleotide polymorphisms of the gene regions responsible for cytokine release were investigated in our study. Therefore further detailed studies to investigate the polymorphisms in the genes that control the cytokine release and receptors specific for these cytokines, should be conducted. Although this study was performed in a relatively small sized population, these findings might provide a significant contribution to the epidemiologic data about the molecular immunology of TB in Turkey.

Design and in vivo evaluation of emulgel formulations including green tea extract and rose oil.

Prevention of skin aging and its treatment is an emerging field for development of new formulations in cosmetics. Accordingly, plant extracts with antioxidant properties are beneficial cosmetic ingredients for this purpose. This study was aimed at developing a stable and easily manufactured emulgel including green tea extract and rose oil that is effective on the barrier function and hydration of the skin. An emulgel formulation containing 20 % green tea extract and 5 % rose oil was designed as a result of pre-formulation studies. Physicochemical characterization, in vitro stability studies, in vivo water content of the stratum corneum and transepidermal water loss studies were carried out afterwards. In vivo studies on ten female subjects were evaluated by using non-invasive skin bioengineering techniques. Finally, a cosmetically acceptable, stable and effective emulgel formulation for skin barrier function with good hydrating properties was obtained for skin hydration, protection and anti-aging purposes.

Lack of association between the C276T polymorphism of the neuronal nitric oxide synthase gene and migraine.

A migraine attack is a spectacularly complex brain event that can produce a wide array of neurological and systemic symptoms. The molecular mechanisms and genetics of migraine have not yet been clarified. The objective of this study was to analyze the genotype distributions and allele frequencies for the C276T polymorphism of the neuronal nitric oxide synthase (nNOS) gene among the patients with migraine. The diagnosis of migraine was made clinically based on questionnaires. One hundred and twenty patients with migraine were genotyped for the C276T polymorphism of the nNOS gene and compared with 185 age-matched healthy controls. Genomic DNA from migraine patients and controls was analyzed by polymerase chain reaction (PCR). A PCR-restriction fragment-length polymorphism analysis of nNOS gene polymorphism was performed, and the results were compared. Neither genotype distributions nor the allele frequencies for the C276T polymorphism showed a significant difference between the groups. Additionally, there was no marked differences in genotype distribution or allele frequencies for the migraine without aura and migraine with aura subgroups when compared to control group. These results suggested that migraine of the Turkish population seemed to develop without any alterations in nNOS C276T polymorphism. Our data showed that there is no marked association between the C276T polymorphism of the nNOS gene and migraine.

The relationship between the carrying angle and the distal extent of the 2nd and 4th fingertips.

The angle towards the lateral side between the arm and forearm when the forearm is in full extension and supination is defined as the carrying angle. It is well known that the 2nd finger is longer in women whereas the 4th finger is longer in men, due to in-utero hormonal effects. In the present study, the relationship between the carrying angle and the distal extent of the 2nd and 4th fingertips is studied. The findings reveal that the carrying angle was greater both in left and right sides in women than in men. In addition, while the distal extent of the 2nd fingertips was longer in women, the 4th fingertip was longer in men. There was a moderately positive correlation between the carrying angle and the distal fingertip lengths. Therefore, it could be suggested that the morphometric factors play role on the distal extent of the fingertips other than the hormonal effects.

Association between dopamine beta hydroxylase gene polymorphism and age at onset in male schizophrenia.

OBJECTIVES: The heterogeneity of schizophrenia mainly results from variations in clinical expressions of the disease, such as age at onset, gender differences in onset of illness, symptoms and response to antipsychotic treatment. Enhanced sensitisation of dopamine pathways in males, having consistently an earlier onset, might be implicated as disease modifiers for schizophrenia in males. METHODS: In this study, we performed a case (n = 87)-control (n = 100) association study between the DBH5'-ins/del and DBH-444g/a polymorphisms of the DBH gene and also compared the level of psychotic symptoms between patients with different DBH genotypes/haplotypes with respect to antipsychotic therapeutic response and gender difference. RESULTS: No significant differences between allele and genotype and haplotype frequencies at either groups (p < 0.05). When the age is considered in patient group, a significant difference was observed between patients with ID genotype and with II genotype (p = 0.018). Patients with ID genotype have been diagnosed as schizophrenics in early ages when compared to II genotype carriers. We also found a significant difference between II and ID genotype (p = 0.007) when the gender had taken into account, showing that the ID genotype carriers had an early onset to schizophrenia. CONCLUSIONS: This association was more significant in male schizophrenia patients than females. Thus, this finding may constitute a novel biological support for the prior finding that onset of schizophrenia varies with gender. The results also showed that critical genetic vulnerability may be associated with the presence or absence of the ID genotype of DBH5'-ins/del.

Is the dopamine D3 receptor mRNA on blood lymphocytes help to for identification and subtyping of schizophrenia?

Schizophrenia is one of the neuropathological disorders, which are associated with dopamine and its receptors. In recent years, it has been shown that mRNA of D3, D4 and D5 dopamine receptor (DRD3, DRD4, DRD5) subtypes is expressed in human peripheral blood lymphocytes (PBL). A total 55 schizophrenic patients and 51 healthy subjects were included in the study to investigate the levels of DRD3 mRNA in PBL of schizophrenic patients and whether DRD3 mRNA level in PBL can serve as peripheral marker for schizophrenia. RNA was isolated from lymphocytes of both groups and reverse transcriptase polymerase chain reaction (RT-PCR) was performed for DRD3 mRNA. We found a significant difference in PBL DRD3 mRNA levels among schizophrenia subtypes (P=0.030) while no difference was detected between control subjects and schizophrenics. We concluded that the levels of DRD3 mRNA can help understanding and severity of clinical manifestations in schizophrenia.

FSHR single nucleotide polymorphism frequencies in proven fathers and infertile men in Southeast Turkey.

The influence of FSH receptor (FSHR) variants on male infertility is not completely understood. The present investigation is the first screening study for SNP at nucleotide position -29 in the core promoter region and codon 680 in exon 10 of the FSHR and the effect of the serum levels of FSH on male infertility in Southeast Turkey. The SNPs in codon 680 and at position -29 of the FSHR gene were analyzed by PCR-RFLP technique in 240 men with proven fathers, and 270 infertile men (150 nonobstructive azoospermic and 120 severe oligozoospermic). The separate analysis for SNP at nucleotide position -29 did not show any difference in genotypic frequencies and serum FSH levels. The genotype distribution of SNP at position 680 was different but does not influence serum FSH levels. Together the two SNPs form four discrete haplotypes (A-Thr-Asn, G-Thr-Asn, A-Ala-Ser, and G-Ala-Ser) occurring in 10 combinations. A statistically significant difference in the allelic distribution of G-Asn/G-Ser and G-Ser/G-Ser genotype between proven fathers and infertile men but there were not any statistically significant difference in the overall frequency of the four FSHR haplotypes. We conclude that the FSHR haplotype does not associate with different serum FSH levels but it is differently distributed in proven fathers and infertile men.

Surgical removal of spinal mass lesions with open door laminoplasty.

OBJECTIVE: The open door laminoplasty technique has been previously used to treat cervical spondylotic myelopathy. We adapted this technique for the removal of spinal tumors all along the spinal axis. METHODS: Between January 2002 and January 2003, 17 patients with various intraspinal lesions underwent open door laminoplasty. The thoracal level was involved in 10 cases, the cervical level in 3 patients and the lumbar level in 4. Location of the tumor was intradural-intramedullary in 7, intradural-extramedullary in 6 and extradural in 4 patients. The histological diagnoses were 4 astrocytomas, 2 meningiomas, 3 neurinomas, 2 ependymomas and one case each with Ewing's sarcoma, metastasis, abcess, hemangioblastoma, arachnoid cyst and lipoma. RESULTS: All lesions were exposed using the open door laminoplasty technique and were successfully removed for intraspinal mass lesions. An average of 3.7 level laminoplasty was performed. Neither spinal malalignment on the coronal plane nor displacement of bone flap (laminoplasty flap) were observed on postoperative CT and MR examinations. No complications due to laminoplasty were encountered. The mean follow-up was 30 months (range 22-48 months). CONCLUSION: Open door laminoplasty is a simple procedure and has two main advantages over the classical laminectomy procedure; a lower incidence of spinal deformities with or without neurological deficits and an absence of epidural scar tissue. This procedure can be used in all spinal cases with intraspinal mass lesions.

Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients.

It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist.

Association of (-1,607) 1G/2G polymorphism of matrix metalloproteinase-1 gene with knee osteoarthritis in the Turkish population (knee osteoarthritis and MMPs gene polymorphisms).

The aim of this study was to investigate whether functional polymorphisms in the promoter of matrix metalloproteinase-1 (MMP-1), MMP-2 and MMP-9 genes were associated with susceptibility to knee osteoarthritis in the Turkish population. The MMP-1 -1,607 1G/2G (rs1799750), MMP-2 -1,306 C/T (rs243865), and MMP-9 -1,562 C/T (rs3918242) polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism assay in 157 patients diagnosed with knee osteoarthritis based on the criteria of American College of Rheumatology and in 84 controls in Mersin, Turkey. Genotype distributions and allele frequencies of MMP-1, MMP-2, and MMP-9 gene polymorphisms were compared between the patients and controls. There were significant differences between the groups regarding the genotype distribution of MMP-1 polymorphism (P = 0.001). The frequencies of 1G/1G and 1G/2G genotypes were significantly higher in the knee osteoarthritis than in the controls (P = 0.002, and P = 0.006, respectively). In addition, 1G allele frequency of MMP-1 gene was higher in the patients than in the control group (P = 0.0001). The genotype distributions and allele frequencies of MMP-2 and MMP-9 gene polymorphisms did not differ between the osteoarthritis and the control groups (P > 0.05). These findings suggest that the -1,607 1G/2G polymorphism in the MMP-1 gene may contribute to susceptibility to knee osteoarthritis in the Turkish population.

Tumour necrosis factor alpha -308G/A gene polymorphism: lack of association with knee osteoarthritis in a Turkish population.

OBJECTIVE: To study the association between TNFalpha-308 G/A polymorphism and susceptibility to and severity of knee osteoarthritis in a Turkish population. METHODS: Genomic DNA was obtained from 151 patients with knee osteoarthritis and 84 ethnically matched healthy controls. Polymerase chain reaction-restriction fragment length analysis was used to identify G/A polymorphism at position -308 in the promoter region. Genotype distributions and allelic frequencies of TNFalpha-308 G/A polymorphism were compared between osteoarthritis patients and controls. Thereafter, this association was investigated between patients and controls of the same sex. In addition, the standard Kellgren-Lawrence grading score and the Turkish version of the Western Ontario and McMaster Universities Osteoarthritis Index were used to assess the radiological and functional severity of the disease and their relationship with the TNFalpha-308 gene polymorphism was investigated. RESULTS: Genotype distribution and allelic frequencies of -308 G/A polymorphism in the TNFalpha gene did not differ significantly between patients with knee osteoarthritis and controls (p>0.05). Moreover, there were no significant differences between patients and controls of the same sex (p>0.05). In addition, no association was observed between the radiological and functional severity of the disease and TNFalpha-308 G/A polymorphism (p>0.05). CONCLUSION: These findings suggest that the examined polymorphism in the TNFalpha gene does not contribute to susceptibility to or severity of knee osteoarthritis in the Turkish population.

Association between tumor necrosis factor-alpha gene promoter polymorphism at position -308 and acne in Turkish patients.

Acne is a multifactorial, chronic inflammatory disease of pilosebaceous unit in which cytokines have been implicated in the pathogenesis. Although it is thought to be an inherited disease, there are limited data supporting the relevant genetic elements. Tumor necrosis factor-alpha (TNF-alpha) is one of the proinflammatory cytokines involved in the acne pathogenesis. Several single-nucleotide polymorphisms (SNPs) have been identified in the human TNF-alpha gene promoter. The polymorphism at position -308, which involves substituting guanine (G) for adenine (A) (TNFA-308 G/A) has been linked to increased susceptibility to several chronic inflammatory diseases. The aim of this study was to determine the TNFA-308 G/A polymorphism in acne and to examine whether there is a relationship between this polymorphism and disease susceptibility. Exactly, 113 patients with acne and 114 healthy control subjects were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used for analysis of the TNFA-308 G/A polymorphism. We found that the frequency of the TNFA-308 GA genotype was statistically significantly increased in patients compared with healthy controls (P < 0.001). There was no association between TNFA genotypes and severity of acne (P > 0.05). There was also no significant difference between male and female patients. Our results suggest that TNFA-308 G/A polymorphism may contribute to a predisposition to acne in Turkish population.