Proteasome modulator 9 (PSMD9) gene rs14259 polymorphism in Alzheimer's disease.

IM: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder resulting in degeneration of certain neuronal structures in certain brain regions and severe neuronal loss, characterized by a pathological accumulation of senile amyloid plaques (SP) and neurofibrillary tangles (NFT) within the brain . Alzheimer's disease has been associated with Type 2 diabetes mellitus (T2DM) in recent years. We designed our study on the relationship between AD and T2DM. Genome screening studies in different populations had linked the chromosome 12q24 region to type 2 diabetes. Within this region, there is the PSMD9 gene encoding a transcriptional coactivator of insulin production. METHOD: The effect of PSMD9 gene E197G (rs14259) polymorphism on AD was investigated in29 Alzheimer's patients and 25 healthy controls, who were included in the study. RESULTS: In our study, it was determined that the variant of PSMD9 gene E197G (rs14259) did not cause genetic risk factor for Alzheimer's disease in Turkish population. CONCLUSIONS: Our study was the first to investigate the relationship between PSMD9 gene and Alzheimer's disease. A larger sample group is needed to investigate the contribution of the PSMD9 gene to Alzheimer's disease in further studies (Tab. 5, Ref. 8).

The frequency of MEFV gene mutation in patients admitted to hospital with preliminary diagnosis of familian mediterranean fever who undergone a prior appendectomy.

OBJECTIVES: Familial mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent and self-limiting fever, peritonitis, arthritis, synovitis, pleuritis, carditis, and erysipelas-like lesions. The aim of this study was to investigate the frequency of the MEFV gene mutation in patients who admitted to hospital with preliminary diagnosis FMF and who had undergone a prior appendectomy. PATIENTS AND METHODS: We retrospectively reviewed the files of 52 patients between the ages of 7-18 who admitted to hospital with preliminary diagnosis of FMF and who had undergone a prior appendectomy. Age, gender and the MEFV gene mutations were included in the data. The 12 known, common MEFV gene mutations [E148Q, P369S, F479L, M6801 (G/C), M6801 (G/A), 1692del, M694V, M6941, K695R, V726A, A744S, R761H] were investigated in the patients. RESULTS: Of these 52 cases, 29 (55.8%) were female and 23 (44.2%) were male. Their mean age was 12.1 +/- 3.1 years (range 7-18 yr). MEFV gene mutation was detected in 31/52 cases (59.6%). In this study was found an high frequency of the MEFV gene mutation in patients admitted to hospital with a preliminary diagnosis FMF who had undergone a prior appendectomy. MEFV gene mutations were M694V 16/41 (39%), E148Q 13/41 (31%), M6801 6/41 (15%), V726A 4/41 (10%) and R761H 2/41 (5%). Other genes mutations were F479L, M6801 (G/A), 1692del, M6941, K695R and A744S. CONCLUSION: There are too much indications of unnecessary appendectomy in MEFV gene mutation carriers. In MEFV gene mutation carriers the frequency of appendicitis can be higher than the normal population. A more detailed and extensive study should be done about it.

Type I plasminogen activator inhibitor 4G allele frequency is associated with chronic venous insufficiency.

Chronic venous insufficiency (CVI) is a common disease associated with poor quality of life. Genetic polymorphisms causing coagulation abnormalities may account for some of the CVI pathogenesis. Type I plasminogen activator inhibitor (PAI-1) is responsible for fibrinolytic system regulation, and plasma levels of PAI-1 are strongly correlated with PAI-1 4G/5G gene polymorphism. The association between PAI-1 4G/5G gene polymorphism and CVI was investigated. In 34 consecutive patients with clinically overt CVI, the PAI-1 4G/4G polymorphism was detected in three cases (8.8%); the 4G/5G polymorphism was detected in 28 (82.4%). In 34 age- and sex-matched controls, the PAI-1 4G/4G polymorphism was detected in one case (2.9%) and the 4G/5G polymorphism was detected in 14 cases (41.2%). The PAI-1 4G allele was found significantly more frequently in CVI patients than in controls. The 4G allele was associated with a 3.25-fold increase in CVI risk. Thus, a relationship between CVI and the PAI-1 4G allele is apparent.

Mechanism of Anti-rotavirus Synergistic Activity by Epigallocatechin Gallate and a Proanthocyanidin-Containing Nutraceutical.

Epigallocatechin gallate (EGCG) of green tea and the nutraceutical CystiCran®-40 (containing 40% proanthocyanidins) of the cranberry plant have been associated with antiviral activity. The purpose of this work was to determine the mechanism of antiviral synergy between each compound. Coliphage T4II (phage T4) and the rotavirus strain SA-11(RTV) were used as model virus systems. Individual and combined flavonoids structural and molecular weight analyses were performed by NMR and HPCL/MS, respectively. A suboptimal concentration of EGCG or C-40 alone or in combination reduced phage infectivity by ≤10%. Similarly, EGCG (30 µg/ml) and C-40 (25 µg/ml), respectively, reduced RTV titers by 3 and 13%. However, RTV titers were reduced by 32% (p < .05) with both flavonoids used in combination. RTV was not recognized in host cells by electron microscopy 24-h post-inoculation. NMR and HPLC/MS findings revealed significant structural and potential changes in molecular weight of the flavonoids in complex.

Does the imbalance between agonistic and antagonistic IL-1 play a role in progression of febrile convulsions?

OBJECTIVE: Inflammation may play an important role in the etiopathology of febrile convulsions (FC). IL-1ß is an important mediator of inflammation and fever is also important information of FCs. It is suggested that there may be a relationship between polymorphisms of IL-1ß and FC. The aim of the present study is to investigate the polymorphic situation of promoter region of IL-1ß in two sites (-31 and -511) and assess the IL-1 RA VNTR polymorphisms in FC patients in comparison with healthy control groups. MATERIALS AND METHODS: Fifty FC patients and 50 healthy controls (HC) were included in the study. DNA extraction was performed by QIAamp DNA Mini Kit from peripheral blood lymphocytes of all subjects. IL-1ß promoter polymorphisms were analyzed by PCR-RFLP, IL-1 RA VNTR polymorphisms were analyzed by PCR-agarose gel electrophoresis. RESULTS: Genotype distribution of IL-1ß promoter region in position -31 was statistically different between FC patients and control groups. Allele I and allele II of IL-1 RA distribution were also statistically different in FC patients and healthy controls. CONCLUSIONS: We have found a significant association between IL-1 RA allele distribution and FC and a poor correlation of T/C substitution at the -31 position of IL-1ß promoter in FC. Further studies are needed to investigate the gene expression levels and polymorphic situation in same samples.

Investigation of telomerase activity and apoptosis on invasive ductal carcinoma of the breast using immunohistochemical and Western blot methods.

OBJECTIVE: Invasive ductal carcinoma (IDC) comprises the largest group of breast cancers. This study aimed to investigate telomerase activity and apoptosis using immunohistochemical and Western blot methods. PATIENTS AND METHODS: In total, 75 cases that had been diagnosed as IDC and 20 cases that had undergone a freezing procedure were included. The histological sections were stained with Bax, Bcl-2, hTERT and BNIP3. The ages of the patients, as well as their hormonal status and tumour sizes and grades were evaluated, as well as the staining characteristics of the antibodies in question. RESULTS: A decrease in Bcl-2 positivity and an increase in Bax positivity were found immunohistochemically with increasing tumour grades. The data obtained by western blot method showed that Bcl-2 was highest in grade 1 tumours although these results were not statistically significant. The relationship between estrogen and progesterone receptor positivity and Bcl-2 was statistically significant, suggesting there is hormonal control through apoptosis. BNIP3 was found to be decreased with increasing tumour grades. Similarly, BNIP3 was found to be having the lowest value in grade 3 tumours by western blot method. Furthermore, hTERT was found to be increased with increasing tumour grades. In the western blot method, hTERT increased nearly four-fold compared to the control. In addition, hTERT, which was seen in very high levels in tumours, may be a helpful cancer marker. Both hTERT and BNIP3 are important markers that can provide information about prognosis. CONCLUSIONS: Big improvements can be achieved in tumour progression control with new treatment modalities that stop telomerase activity and hypoxic cell death.

The prevalence of Familial Mediterranean Fever common gene mutations in patients with simple febrile seizures.

BACKGROUND: Febrile seizures (FS) represent the most common form of childhood seizures that occurs in 2-5 % of the children younger than 6 years. There have been many recent reports on the molecular genetic and pathogenesis of FC. It has been recognized that there is significant genetic component for susceptibility of FC with different reported mutation. FEB1, FEB2, FEB4, SCNA1, SCNA2, GABRG2 and IL-1ß are related to with febrile convulsions (FCs). Interleukin 1ß (IL-1ß) is a cytokine that contributes to febrile inflammatory responses. There are conflicting results on increasing this cytokine in serum during FC. AIM: The determine the association between mutations of MEFV gene product pyrine and febrile seizures. PATIENTS AND METHODS: The study was carried out on 104 children that were diagnosed as FS and 96 healthy children. MEFV gene mutations were detected and analyzed with PyroMark Q24. PCR was performed using the PyroMark PCR Kit and pyrosequencing reaction was conducted on instrument instructions. RESULTS: M694V is the most common mutation in our patient group and we found a significant association between MEFV gene mutations and FSs. Of 104 patients, 68 were heterozygotes for any mutation and 10 patients were compound. 17.7% of control group were heterozygotes for any studied mutation.Statistical analyses showed that there was strongly significant statistical difference between results obtained from FS and control group (X = 46.20, p < 0.0001). CONCLUSIONS: MEFV gene mutations, especially M694V mutation, are positively associated with FSs.