ε2 , ε3 , and ε4 variants of ApoE; rs2228570 (VDR), rs4588 and rs7041 (VDBP) polymorphisms in patients with multiple sclerosis: A case-control study in Turkish population.

AIM OF THE STUDY: Multiple sclerosis (MS) is a degenerative disease characterized by autoimmune demyelination in the central nervous system. Yet, underlined genetics or environmental markers are still controversial. The impact of vitamin D and cholesterol on disease activity has been phrased by many studies; however, the data available for the Turkish population are very limited. This study aimed to investigate the effect of vitamin D-related polymorphisms (VDBP and VDR) and cholesterol-related variants of ApoE on Turkish MS patients. MATERIALS AND METHODS: Total DNAs were extracted from peripheral blood samples of 51 MS patients and 50 healthy volunteers. rs4588 and rs7041 polymorphisms of VDBP, rs2228570 of VDR, as well as ε2, ε3, and ε4 variants of ApoE, were investigated by RT-PCR. Biochemical parameters which thought to be associated with MS were also measured. Results were evaluated statistically. RESULTS: Homozygous mutant genotype and G allele of rs2228570 in VDR, as well as heterozygous genotype of rs4588 in VDBP, were found statistically high in patients. Total cholesterol, triglyceride, and LDL-C levels were found significantly high, whereas HDL-C and vitamin D levels were low in patients. An association was found between rs4588 variation and high triglyceride levels. Similar correlations were found between ε2 genotype and low LDL-C level; ε3 genotype and higher LDL-C. Gender, triglyceride, HDL-C, and AA genotype in rs4588 had a significant effect on MS progression. CONCLUSION: The variations of rs2228570 and rs4588, vitamin D deficiency, and biological parameters related to cholesterol metabolism may be associated with MS risk.

Mitochondrial depletion in CD4+ and CD19+ peripheral lymphocytes in early stage Alzheimer's disease.

Alzheimer's disease (AD) may be associated with mitochondrial defects. The aim of the present study was to investigate changes in mitochondrial abundance in peripheral lymphocytes of early and late stage AD patients. We analysed levels of mitochondrial DNA (mtDNA) and mean fluorescence intensity (MFI) of the mitochondria-specific antibody 113-1 in CD4+, CD8+, CD19+ and CD56+ peripheral lymphocytes of early and late stage AD by quantitative real-time PCR and flow cytometry, respectively. In early stage AD, the levels of mtDNA were significantly decreased in CD4+, CD19+ and CD56+ peripheral lymphocytes while the MFI of 113-1 staining was significantly decreased in CD4+ and CD19+ cells. Thus, CD4+ and CD19+ peripheral lymphocytes of early stage AD patients exhibit mitochondrial depletion, as seen both at the level of DNA and protein.

A Novel Electrophysiological Method in the Diagnosis of Pudendal Neuropathy: Position-related Changes in Pudendal Sensory Evoked Potentials.

OBJECTIVE: To examine the diagnostic value of pudendal somatosensory evoked potentials (SEPs) in pudendal nerve entrapment (PNE) neuropathy by stimulating the 2 sides separately after provocation by a standard sitting position. Routine pudendal SEPs performed in the supine position with bilateral simultaneous stimulation may fail to show the abnormality because the complaints of PNE appear or worsen in the sitting position. METHODS: Forty-nine patients with PNE and 16 controls were included. SEP recordings were performed by stimulating the dorsal nerve of penis or clitoris on either side. The recordings were performed at the initial supine position, at the beginning and end of the provocation by sitting position, and at the second supine position. RESULTS: Amplitude loss in the SEP responses after prolonged sitting was significantly more pronounced on the symptomatic sides of the patients. Approximately 45% decrease in the SEP amplitude or an amplitude value less than 1.5 µV at the end of sitting are the parameters to be used with high selectivity. CONCLUSION: The dynamic pudendal SEP study described herein seems to be more helpful in PNE diagnosis than in conventional SEPs.

Paraoxonase1 192 (PON1 192) gene polymorphism and serum paraoxonase activity in panic disorder patients.

BACKGROUND/AIM: Reactive oxygen species (ROS) are involved in the development of certain neuropsychiatric disorders. Paraoxonase 1 (PON1) activity has been suggested to be adversely related to oxidative stress in plasma. The purpose of the present study was to demonstrate the relationship between serum PON1 activity and PON1 192 polymorphism in panic disorder (PD). MATERIALS AND METHODS: Fourty-two patients with PD and 46 healthy controls were included in this study. PON1 192 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following the addition of paraoxon. RESULTS: PON1 192 AA genotype and A allele in PD were significantly higher than in the control group, whereas the B allele was found to be significantly higher in the control group. Patients with panic disorder have lower PON1 activity than the control group. CONCLUSION: The PON1 192 AA genotype may increase the risk of PD depending on lipid peroxidation.

Utilization of the multiple sclerosis functional composite in follow-up: relationship to disease phenotype, disability and treatment strategies.

As multiple sclerosis (MS) has a dynamic process, monitoring of the disability is important in the remission period. The main aim of the present study was to investigate the usefulness of MSFC instead of EDSS in the follow-up period of MS. In addition, evaluation of the effect of immunomodulatory therapy, and the difference among the type of MS in follow-up was purposed. One hundred and eighty-three patients with definite MS were enrolled in the present study. Patients were diagnosed as having relapsing-remitting (RR) MS (n=149) or secondary progressive (SP) MS (n=34). Fifty-eight out of 149 RRMS patients who had at least two relapses in the last 2 years have received any of the immunomodulator agents. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were performed at baseline and after 2 years to assess disability. Patients who were under disease modifying therapy were assessed before the treatment and 2 years after starting the treatment. Cross-sectional correlations between MSFC and EDSS score at baseline and follow-up were studied. Patients were divided into three subgroups: (1) RRMS patients who did not receive disease modifying therapy (DMT)--non-DMT group, (2) RRMS patients who received DMT--DMT group, (3) SPMS patients who did not receive DMT--SPMS group. EDSS and MSFC scores got worsened significantly at the end of the second year. Decreases in either EDSS or MSFC scores were more prominent in SPMS group. The most significant worsening was found in T25WT. The most prominent and significant decrease was in PASAT of SPMS group. Moderately strong cross-sectional correlations were found between MSFC and EDSS scores at baseline and follow-up. The most prominent correlation was between EDSS and T25WT scores with an excellent correlation. We concluded that the MSFC assesses aspects of neurological function not measured by the EDSS, suggesting that it is more sensitive to detect change over time and better able to demonstrate a therapeutic effect. The pattern of correlations among the MSFC, its components, and the EDSS supported the validity of MSFC.

Correlations between multiple sclerosis functional composite, expanded disability status scale and health-related quality of life during and after treatment of relapses in patients with multiple sclerosis.

The measurement of the clinical manifestations of multiple sclerosis (MS) is difficult. In the present study, we examined the changes in measurement of functions during and after pulse methylprednisolon (MP) treatment of MS exacerbations using the MSFC and EDSS. Correlation between multiple sclerosis quality of life (MSQoL)-54, EDSS and MSFC were studied. Thirty-six clinically definite MS patients were included in this study. Because of MSFC's repeating feature, we administered the tests to a control group to exclude practise effects. All patients received 1000-mg intravenous MP for 5 days, followed by tappering dose of 100-mg oral prednisolone. All three scales were assessed on day 0. EDSS and two components of MSFC (nine HPT and T25WT) were administered on the other days of pulse MP treatment. PASAT was not applied before the day 5 to exclude the practise effect. MSQoL-54 was assessed again on day 30. Mean EDSS values significantly decreased after the day 2. MSFC score improved from 0.03 +/- 1.71 on day 0 to 0.79 +/- 1.51 on day 5. Improvement continued on day 30. The mean physical health composite score increased from 66.50 +/- 9.3 on day 0 to 74.34 +/- 8.9 on day 30. Mental health composite had also a significant improvement on day 30. Correlation between the baseline overall MSFC and the EDSS was moderately strong. T25WT correlated most strongly with EDSS. Significant positive correlation was found between MSFC and both components of MSQoL-54. It is more prominent for the MSFC and physical health composite correlation. The same correlation was found for the EDSS and MSQoL-54 composites. Changes in EDSS and MSFC scores and MSQoL-54 were found significantly correlated for the overall score on day 30 compared with day 0. In conclusion, MSFC seems to be more sensitive in detecting changes in function than the EDSS. Hence, EDSS is still useful for daily routine practise. When these results combined with the significant correlation between MSFC and MSQoL-54 measures, which indicated the MSFC reflects the severity of MS as perceived by patients, MSFC seems to be the most useful scale for clinical trials.