DFNB40, a recessive form of sensorineural hearing loss, maps to chromosome 22q11.21-12.1

We report on a novel localization for a recessive form of deafness (DFNB), by linkage analysis in an Iranian consanguineous family. Affected individuals suffer from prelingual profound sensorineural hearing loss. Genome-wide analysis led to the characterization of a new locus, DFNB40, which maps to an approximately 9 Mb interval between markers D22S427 and D22S1144 at chromosome 22q11.21-12.1. Maximum lod score of 3.09 was obtained with D22S1174. Since the Bronx waltzer (bv) mouse mutant, characterized by waltzing behavior, deafness, and degeneration of cochlear inner hair cells, has been mapped to the syntenic region on murine chromosome 5, we suggest that DFNB40 and bv may result from orthologous gene defects.     

Relationship between effort sense and ventilatory response to intense exercise performed with reduced muscle glycogen

The purpose of the present study was to examine the effects of muscle glycogen reduction on surface electromyogram (EMG) activity and effort sense and ventilatory responses to intense exercise (IE). Eight subjects performed an IE test in which IE [100-105% of peak O(2) uptake ([Formula: see text]), 2 min] was repeated three times (IE(1st), IE(2nd) and IE(3rd)) at 100-120-min intervals. Each interval consisted of 20-min passive recovery, 40-min submaximal exercise at ventilatory threshold intensity (51.5 ± 2.7% of [Formula: see text]), and a further resting recovery for 40-60 min. Blood pH during IE and subsequent 20-min recovery was significantly higher in the IE(3rd) than in the IE(1st) (P < 0.05). Effort sense of legs during IE was significantly higher in the IE(3rd) than in the IE(1st) and IE(2nd). Integrated EMG (IEMG) measured in the vastus lateralis during IE was significantly lower in the IE(3rd) than in the IE(1st). In contrast, mean power frequency of the EMG was significantly higher in the IE(2nd) and the IE(3rd) than in the IE(1st). Ventilation ([Formula: see text]) in the IE(3rd) was significantly higher than that in the IE(1st) during IE and the first 60 s after the end of IE. These results suggest that ventilatory response to IE is independent of metabolic acidosis and at least partly associated with effort sense elicited by recruitment of type II fibers.     

Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664

The deficits characteristic of Alzheimer's disease (AD) are believed to result, at least in part, from the neurotoxic effects of beta-amyloid peptides, a set of 39-43 amino acid fragments derived proteolytically from beta-amyloid precursor protein (APP). APP also is cleaved intracytoplasmically at Asp-664 to generate a second cytotoxic peptide, APP-C31, but whether this C-terminal processing of APP plays a role in the pathogenesis of AD is unknown. Therefore, we compared elements of the Alzheimer's phenotype in transgenic mice modeling AD with vs. without a functional Asp-664 caspase cleavage site. Surprisingly, whereas beta-amyloid production and plaque formation were unaltered, synaptic loss, astrogliosis, dentate gyral atrophy, increased neuronal precursor proliferation, and behavioral abnormalities were completely prevented by a mutation at Asp-664. These results suggest that Asp-664 plays a critical role in the generation of Alzheimer-related pathophysiological and behavioral changes in human APP transgenic mice, possibly as a cleavage site or via protein-protein interactions.     

Curcumin has Neuroprotection Effect on Homocysteine Rat Model of Parkinson

Parkinson's disease (PD) is a progressive neurological disorder which is emanated by dopaminergic death cell and depletion. Curcumin as a nontoxic matter has antioxidant, anti-inflammatory, and antiproliferative activities, and it involves antioxidant property same to vitamins C and E. In this study, we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (50 mg/kg) was injected intraperitoneally (i.p.) once daily for a period of 10 days beginning 5 days prior to Hcy (2 μmol/μl) intracerebroventricular (i.c.v.) injection in rats. The studies included immunohistological and locomotor activity tests. These results suggest that homocysteine intracerebroventricular administration (2 μmol/μl i.c.v.) may induce changes in rat brain, and subsequently, polyphenol treatment curcumin 50 mg/kg (i.p.) was capable in improving locomotor function in insulted animal by protecting the nervous system against homocysteine toxicity.     

Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients

Purpose  

To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.     

Treatment of oral lichen planus with photodynamic therapy mediated methylene blue: a case report

Oral lichen planus (OLP) is a common chronic disease of uncertain origin. Many patients with OLP are refractory to all available therapies. The photodynamic therapy (PDT) was used as a possible alternative method in the treatment of lichen planus. Two patients with five oral lichen planus lesions were treated using topical PDT mediated by methylene blue (MB-PDT). The patients were followed up on sessions 3, 7, 15 days and 1 to 9 months after PDT. Clinical improvement was achieved in four lesions. Two lesions showed complete remission, and another two lesions had about 50% clinically improvement 3-9 months after a single session of PDT. No response detected in one lesion. MB-PDT blue seems to be an effective alternative treatment for control of OLP. In our opinion, this preliminary result warrant further studies in order to show the efficacy of MB-PDT in control of OLP for a longer period of time.     

Effect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine

OBJECTIVE: To investigate the long-term effects of continuous methimazole (MMI) therapy. DESIGN AND METHODS: Five hundred and four patients over 40 years of age with diffuse toxic goiter were treated with MMI for 18 months. Within one year after discontinuation of MMI, hyperthyroidism recurred in 104 patients. They were randomized into 2 groups for continuous antithyroid and radioiodine treatment. Numbers of occurrences of thyroid dysfunction and total costs of management were assessed during 10 years of follow-up. At the end of the study, 26 patients were still on continuous MMI (group 1), and of 41 radioiodine-treated patients (group 2), 16 were euthyroid and 25 became hypothyroid. Serum thyroid and lipid profiles, bone mineral density, and echocardiography data were obtained. RESULTS: There was no significant difference in age, sex, duration of symptoms and thyroid function between the two groups. No serious complications occurred in any of the patients. The cost of treatment was lower in group 1 than in group 2. At the end of 10 years, goiter rate was greater and antithyroperoxidase antibody concentration was higher in group 1 than in group 2. Serum cholesterol and low density lipoprotein-cholesterol concentrations were increased in group 2 as compared with group 1; relative risks were 1.8 (1.12-2.95, P<0.02) and 1.6 (1.09-2.34, P<0.02) respectively. Bone mineral density and echocardiographic measurements were not different between the two groups. CONCLUSION: Long-term continuous treatment of hyperthyroidism with MMI is safe. The complications and the expense of the treatment do not exceed those of radioactive iodine therapy.     

Association between Exudative Age-related Macular Degeneration and the G6721T Polymorphism of XRCC7 in Outdoor Subjects

Purpose

To investigate whether the G6721T polymorphism (rs.7003908) of the non-homologous end-joining DNA repair XRCC7 gene contributes to the development of exudative age-related macular degeneration (ARMD).

Methods

The present case-control study consisted of 111 patients with exudative ARMD and 112 sex frequency-matched healthy controls that were randomly selected from unrelated volunteers in the same clinic. Genotypes were determined by the Restriction Fragment Length Polymorphism (PCR-RFLP) based method. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ARMD risk associated with polymorphism of XRCC7. In all analysis the GG genotype was considered to be the reference genotype.

Results

There was no significant association between genotypes of XRCC7 and susceptibility to ARMD. Considering the significant difference in age distribution between cases and controls, age was used as a covariate in further analysis. After ORs were adjusted for age, the same result was observed. In the next step we stratified our subjects into outdoor and indoor groups according to their job titles. The outdoor and indoor patients were occupationally exposed to sunlight and not exposed to sunlight, respectively. Our present study showed that among indoor subjects there was no association between XRCC7 polymorphism and susceptibility to ARMD. However, among outdoor subjects, the GT + TT genotypes compared to the GG genotype increased the risk of ARMD (OR, 3.13; 95% CI, 1.04-9.39; p = 0.042).

Conclusions

Our study revealed that the T allele of the G6721T polymorphism of XRCC7 increased the risk of ARMD among outdoor subjects.