Basics on the use of acid-sensing ion channels' inhibitors as therapeutics

Since the discovery of acid-sensing ion channels in 1997, their importance in the health of neurons and other non-neuronal cells has gained significant importance. Acid-sensing ion channels play important roles in mediating pain sensation during diseases such as stroke, inflammation, arthritis, cancer, and recently migraine. More interestingly, acid-sensing ion channels may explain the sex differences in pain between males and females. Also, the ability of acid-sensing ion channel blockers to exert neuroprotective effects in a number of neurodegenerative diseases has added a new dimension to their therapeutic value. The current failure rate of ～45% of new drugs(due to toxicity issues) and saving of up to 7 years in the life span of drug approval makes drug repurposing a high priority. If acid-sensing ion channels' blockers undergo what is known as "drug repurposing", there is a great potential to bring them as medications with known safety profiles to new patient populations. However, the route of administration remains a big challenge due to their poor penetration of the blood brain and retinal barriers. In this review, the promise of using acid-sensing ion channel blockers as neuroprotective drugs is discussed.     

Comparing the results of Pap smear and Direct Visual Inspection (DVI) with 5% acetic acid in cervical cancer screening

Background:

Cervical cancer is the most second common cancer among Iranian women. This study was carried out to compare the results of Pap smear method and Direct Visual Inspection (DVI) with 5% acetic acid in cervical cancer screening in Tabriz, Iran.

Material and Methods:

This cross-sectional study was carried out in Alzahra Therapeutic-Educational Centre, Tabriz, Iran in 2013 on 1000 women. First, Pap smear was done for all women, and then the cervix exposed with 5% acetic acid by cotton swab for 30 seconds and observed under adequate light. At the end, women with abnormal results in Pap smear or DVI method were referred to colposcopy and biopsy. Test''s sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), LR+, LR- and confidence interval (CI) were determined (P < 0.05).

Results:

Nine-hundred and seventy-four (94.7%) cases were normal and had no abnormal findings and 26 (2.6%) participants had positive results in Pap smear or DVI test. Twelve women had abnormal Pap smear (nine women with atypical squamous cells of undetermined significance, ASCUS, three women with dysplasia, atypical endocervical, and low-grade squamous intraepithelial lesion, LSIL results) and 14 women had positive DVI (four women with human papillomavirus, HPV or koilocyte,) and one women with abnormality in both method had carcinoma in biopsy that referred to oncologist. In this study the sensitivity, specificity, PPV and NPV for DVI were 71.4%, 50%, 35.7%, and 81.8% respectively in comparison with 14.3%, 50%, 10%, and 60% for Pap smear.

Conclusion:

As the DVI method has higher sensitivity and positive predictive value than Pap smear, it could be used as a useful method beside the Pap smear.     

Pure familial 6q21q22.1 duplication in two generations

Familial transmissions of unbalanced chromosomal abnormalities are rare. We report here the first case of a maternally inherited pure partial duplication of the long arm of chromosome 6 [46,XX,dup(6)(q21q22.1)mat]. The proband was referred for karyotyping as she presented intrauterine growth retardation (IUGR), moderate mental retardation and facial dysmorphism. Molecular cytogenetics analysis with various BACs showed a duplication of 5-10 Mb between 6q21 and 6q22.1. The proband's mother was found to have the same chromosome abnormality and a similar phenotype, but less severe dysmorphism. This variability in clinical findings between generations may have several causes, including attenuation with aging, imprinting or mosaicism. Only three other cases of pure partial 6q duplication similar to that of our case have been reported. The available information for all four cases was used to refine the karyotype-phenotype correlations for duplications of the 6q21q22 segment.     

Discriminative and diagnostic value of anti-cyclic citrullinated peptide antibodies in Iranian patients with rheumatoid arthritis

Most studies on the diagnostic utility of the anti-cyclic citrullinated peptide antibody (anti-CCP) test in rheumatoid arthritis (RA) have been performed in developed countries, with only a few done in the developing world. We undertook a cross-sectional study to determine the diagnostic utility of the rheumatoid factor (RF) and anti-CCP tests in urbanized Iranians with early RA. One hundred and ninety-three serum samples were obtained from consecutive patients who were diagnosed with RA. Serum samples of 254 ones without RA, consisting of other inflammatory polyarthritis disorders, were also collected as controls. RF was measured for IgM by latex agglutination test, and titers higher than 1/80 were considered positive. Anti-CCP was also assayed using an ELISA with 6.25 RU/ml as the threshold for a positive result. The anti-CCP had sensitivity, specificity, positive predictive value, and negative predictive value for a diagnosis of RA of 47.2, 92.9, 83.5, and 69.8 %, respectively. Those for RF were 57.0, 83.9, 72.8, and 72.0 %, respectively. For anti-CCP antibodies in combination with RF, they were 38.9, 96.5, 89.3, and 67.5 %, respectively. Anti-CCP has higher specificity and predictive values compared with the RF parameter in diagnosing RA in Iranian patients, but their discriminative values were similar. Anti-CCP and RF in combination further increases the diagnostic value for RA.