Family-based suppressive intermittent therapy of hyperendemic trachoma with topical oxytetracycline or oral doxycycline.

A controlled double-blind stratified trial was carried out in a village in Southern Iran to assess the efficacy of family-based intermittent therapy of hyperendemic trachoma with topical oxytetracycline oily suspension twice daily for 7 days each month, or oral doxycycline 5 mg per kilogram of body weight once a month, in comparison with a control group which received vitamin pills once a month. In addition all other members of the selected children's families were also treated with the same regimen of therapy. The treatment was given for a period of 1 year by 3 field technicians, each responsible for one regimen of therapy. Examining the whole conjunctiva 4 months after the start of therapy, we observed no marked difference in the cure rate or the number of patients with moderate to severe trachoma between the groups treated with antibiotics and the control group. When treatment was continued for 12 months, a marked decrease in the prevalence of trachoma and in the grades of intensity of inflammatory responses as well as the positivity rate for Chlamydia trachomatis was observed in the groups treated with the topical oxytetracycline or oral doxycycline compared with the control group. While there was no marked difference between the efficacy of these 2 regimens of mass chemotherapy, the monthly intermittent therapy with a single dose of doxycycline offers the advantage of being more practical and less expensive for mass control of trachoma by requiring approximately one-tenth of the staff, transport, and other facilities required for the intermittent topical therapy with tetracycline eye ointment.     

The Effect of Orexin Receptor Antagonism on Quinpirole-Induced Compulsive-Like Checking Behavior in Rats

The orexinergic system supposedly plays a role in stress circuits for arousing behaviors during anxiety, suggesting that it may play a role also in neural circuits mediating the compulsive behavior characteristic of obsessive-compulsive disorder (OCD). This study aims to investigate the roles of the orexinergic system in the development of OCD behaviors, using as preparation the induction of compulsive checking by chronic treatment with the D2/D3 agonist, quinpirole. Repeated injections of quinpirole (0.5 mg/kg, twice per week for a total of 10 injections) were used to induce compulsive checking. In separate groups of rats, OX1R (SB334867-A; 10 μg i.c.v) and OX2R (TCS-OX2-29; 10 μg i.c.v) receptor antagonists were co-administered together with quinpirole. Checking behavior in a large open field was measured after the first, fifth, and tenth injections of the drugs. SB334867-A attenuated checking behavior and the level of anxiety. TCS-OX2-29 administration ameliorated anxiety but did not block the development of compulsive checking. Orexin 1 receptors seem to play a more critical role than orexin 2 receptors in the induction of compulsive checking. Considering that the quinpirole sensitization model of OCD involves activation of dopamine systems and sensitization to quinpirole, it is suggested that neural interaction between orexigenic and dopamine systems may be important in the pathogenesis of OCD.     

Genetic Analysis of Patients with Two Different Types of Hyper IgM Syndrome

ABSTRACT

Background: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections.

Objectives: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients.

Methods: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies. Sanger sequencing was applied to detect pathogenic mutations in CD40L and AID genes causing two most common forms of HIGM, which known as HIGM type 1 and 2, respectively.

Results: All patients who entered the study were males from unrelated families with a median age of 3.8 years. The most frequent clinical manifestation was recurrent pneumonia. Genetic studies of the patients revealed six different mutations, including five mutations in CD40L besides one mutation in AID. Two mutations in CD40L (p.F31fsX5 and p.C84S) were novel and three mutations (p. G219R, p.D62fsX18, and p.Q186X) have been previously reported. The mutation found in AID (p.E122X) was also previously described.

Conclusion: The study results may provide valuable information for prenatal diagnosis and also for genetic counseling especially for those who have a history of primary immunodeficiency in their family.     

BAX pro-apoptotic gene alterations in repeated pregnancy loss

Introduction

Recurrent pregnancy loss (RPL) is a critical medical problem in about 0.5-2% of women. The molecular genetic background for spontaneous abortion is being increasingly understood, and some polymorphisms associated with it have been reported. This study investigates alterations of the Bax gene as a pro-apoptotic gene in women with idiopathic RPL.

Material and methods

The frequency of mutations in the Bax gene of 67 idiopathic RPL women was studied in comparison to a sample of 70 healthy women. The promoter and the entire coding regions (exons 1-7) were amplified using polymerase chain reaction (PCR). The purity of the PCR product was first verified by electrophoresis on a 2% agarose gel. The amplified fragment was then sequenced by automated DNA sequencing.

Results

A statistically significant difference was observed between patients and the control group regarding the frequency of alleles A(-179)G in the Bax promoter region (p= 0.013). Also among patients, G90C and G95A transitions were found in the coding region of exon 1 that change amino acid glutamine (Q) to histidine (H) and arginine (R) to lysine (K), respectively. A statistically significant association was observed between H allele (p = 0.0001) and K allele (p< 0.0001) and the occurrence of RPL.

Conclusions

Our results indicate an association between A(-179)G mutation in the Bax promoter and RPL. Moreover, two polymorphisms, G90C and G95A in exon 1, found among our patients, could be considered as genetic factors making people susceptible to miscarriages. According to our findings, the Bax gene has an important role in pregnancy loss and the variations of this gene could help in the assessment of RPL.     

MTHFR polymorphisms and breast cancer risk

Introduction

Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumour cells.

Material and methods

We evaluated these two common polymorphisms and breast cancer risk association in an Iranian sporadic breast cancer population-based case-control study of 294 breast cancer cases and 306 controls using a PCR-RFLP-based assay.

Results

Analyses of affected and controls show that homozygote genotype MTHFR 677CC has the highest frequency in both groups (28.3% in patients and 25.3% in control group). Genotype MTHFR 677CT and genotype MTHFR 1298AC were found to be statistically significant risk factors in our population (odds ratio: 1.6, 95% CI: 1.019-2.513, p = 0.041; and odds ratio: 2.575, 95% CI: 1.590-4.158, p = 0.001 respectively).

Conclusions

We can conclude based on the results of our study that a significant association between breast cancer and C677T and A1298C polymorphism might exist.     

An A8296G mutation in the MT-TK gene of a patient with epilepsy - a disease-causing mutation or rare polymorphism?

Mitochondrial DNA (mtDNA) mutations are an important cause of human diseases. mtDNA could be considered a candidate modifying factor in neurodegenerative disorders. A homoplasmic A8296G mutation was detected in a 24-year-old patient with idiopathic generalized epilepsy. The A8296G mutation in the mitochondrial DNA MT-TK gene has been associated with severe mitochondrial diseases. The pathogenicity of this mutation or its association with a specific disease is unclear. This mutation has already been reported exclusively as well as together with other mutations during trials of mtDNA. As in this case, the mutation was homoplasmic and there were no clinical findings in other family members. We suggest that this mutation is a rare polymorphism or may be a pathogenic mutation in combination with other mutations outside of the MT-TK gene.