Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity.

Irreversible hearing loss is a catastrophic complication of treatment with aminoglycoside antibiotics such as streptomycin, gentamycin, and kanamycin. Many kindreds showing a matrilineal pattern of inheritance of this trait have been described in China where the widespread use of aminoglycoside antibiotics accounts for approximately 25% of profound deafness in some districts. Because of the characteristic inheritance pattern, mitochondrial DNA (mtDNA) mutations were postulated to be the cause of the deafness in these pedigrees. In 1993 it was shown that an A to G substitution at base pair 1555 of the mitochondrial 12S ribosomal RNA gene was the only mutation common to all the families with aminoglycoside ototoxicity. We ascertained three Mongolian pedigrees from the School for the Deaf and Blind in Ulaanbaatar, all of which contained multiple affected subjects with streptomycin induced deafness in a pattern consistent with matrilineal transmission. Amplified mtDNA, obtained from transformed lymphoblastoid cell lines using previously described primers, showed the A to G point mutation in the 12S rRNA gene in two of the three families by restriction analysis as well as direct sequencing. No other example of this substitution was found among 400 control samples from Mongolians with normal hearing. We have thus confirmed the clinical relevance of the 1555 A to G mitochondrial mutation in the 12S rRNA gene by identifying it in affected subjects with familial aminoglycoside ototoxicity in another ethnic group. In countries where aminoglycosides are widely used, genetic counselling and screening of high risk families before the use of these drugs could have a dramatic effect on the incidence of deafness.     

Protocol for a national, mixed-methods knowledge, attitudes and practices survey on non-communicable diseases

Background

Iran has one of the highest rates of road traffic crash death rates throughout the world and road traffic injuries are the leading cause of years of life lost in the country. Using child car safety seats is not mandatory by law in Iran. The purpose of this research was to determine the parental willingness to pay (WTP) for child restraints in Mashad, the second most populated city in Iran with one of the highest rates of road traffic-related deaths.

Methods

We surveyed 590 car-owner parents of kindergarten children who were willing to participate in the study in the year 2009. We asked them about the maximum amount of money they were willing to pay for car safety seats using contingent valuation method.

Results

The mean age of children was 33.5 months. The median parental WTP for CSS was about $15. Considering the real price of CSSs in Iran, only 12 percent of responders could be categorized as being willing to pay for it. Family income level was the main predictor of being willing to pay.

Conclusions

The median parental WTP was much lower than the actual price of the safety seats, and those who were of lower socio-economic class were less willing to pay. Interventions to increase low-income families' access to child safety seats such as providing free of charge or subsidized seats, renting or health insurance coverage should be considered.     

Fibrinolytic and antiplatelet aggregation properties of a recombinant Cheonggukjang kinase

This study characterized the efficacy of recombinant Cheonggukjang kinase (CGK) 3-5-rich fraction as a thrombolytic agent, which we overexpressed in Bacillus licheniformis ATCC10716, a strain normally lacking fibrinolytic activity. We found that CGK3-5 is a plasmin-like protease that directly degrades fibrin clots and does not activate plasminogen during fibrin clot lysis and platelet-rich clot lysis assays. We also confirmed antiplatelet and antithrombotic activity by CGK3-5-rich fraction both in vitro and in vivo. CGK3-5-rich fraction inhibited collagen-induced platelet aggregation in platelet-rich plasma in a concentration-dependent manner. The concentration of 1.5?mg/mL CGK3-5-rich fraction completely inhibited collagen-induced platelet aggregation. Furthermore, injection of CGK3-5-rich fraction into tail veins dose-dependently protected mice from death by pulmonary embolism induced by collagen and epinephrine. The survival rates were 30%, 70%, and 100%, respectively, with doses of 130?mg/kg, 260?mg/kg, and 520?mg/kg. These findings suggest that CGK3-5 holds promise as a treatment to mitigate the potentially effects of stroke and heart failure.     

GJB2 Mutations in Mongolia: Complex Alleles,Low Frequency,and Reduced Fitness of the Deaf

We screened the GJB2 gene for mutations in 534 (108 multiplex and 426 simplex) probands with non‐syndromic sensorineural deafness, who were ascertained through the only residential school for the deaf in Mongolia, and in 217 hearing controls. Twenty different alleles, including four novel changes, were identified. Biallelic GJB2 mutations were found in 4.5% of the deaf probands (8.3% in multiplex, 3.5% in simplex). The most common mutations were c.IVS1 + 1G > A (c.‐3201G > A) and c.235delC with allele frequencies of 3.5% and 1.5%, respectively. The c.IVS1 + 1G > A mutation appears to have diverse origins based on associated multiple haplotypes. The p.V27I and p.E114G variants were frequently detected in both deaf probands and hearing controls. The p.E114G variant was always in cis with the p.V27I variant. Although in vitro experiments using Xenopus oocytes have suggested that p.[V27I;E114G] disturbs the gap junction function of Cx26, the equal distribution of this complex allele in both deaf probands and hearing controls makes it a less likely cause of profound congenital deafness. We found a lower frequency of assortative mating (37.5%) and decreased genetic fitness (62%) of the deaf in Mongolia as compared to the western populations, which provides an explanation for lower frequency of GJB2 deafness in Mongolia.     

Comparative effect of genistein and daidzein on the expression of MCP-1, eNOS, and cell adhesion molecules in TNF-��-stimulated HUVECs

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-1 production. The effects of genistein and daidzein on MCP-1 secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-α exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)κB activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-1 and eNOS expression than that of daidzein. Additionally, NFκB transactivation might be partially related to the down-regulation of these mRNAs in TNF-α-stimulated HUVECs.     

Male infertility： risk factors in Mongolian men

Aim: To determine the most common risk factors of male infertility in Mongolian men attending an infertility clinic. Methods: A prospective, case-control study was conducted in which 430 men were enrolled. All the men had sought their first infertility evaluation between 1998-2002 in the State Research Center on Maternal Child Health, Ulaanbaatar, Mongolia. They were divided into two groups depending on the results of their semen analysis:191 with abnormal semen and 239 with normal semen profile. Univariate and multivariate analyses were performed to determine any association between risk factors and semen abnormality. Results: Logistic regression analysis demonstrated that the testicular volume, a history of sexually transmitted infections (STI), epididymitis and testicular damage all have statistically significant associations with semen abnormality, when controlled for multiple risk factors.Adjusted odds ratios of 3.4 for mumps orchitis, 2.3 for other orchitis and 3.9 for testicular injury were found.Gonorrhoea, the most commonly reported STIs in this study, gave an adjusted odds ratio of 1.0 for having one or more sperm abnormality. An adjusted odds ratio for subjects with a history of other STIs was 2.7. However, as a predictor of azoospermia, STIs had very high odds ratio, being 5.6 in patients with gonorrhoea and 7.6 in patients with other STIs. Conclusion: A history of pathology involving testicular damage appeared to have the strongest impact on male infertility in Mongolia. STIs have less impact on semen quality except when complicated by orchitis, epididymitis and vasal obstruction. (Asian J Androl 2004 Dec, 6: 305-311)