Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis and rheumatoid related osteoporosis

Objective

To study the role of VDR polymorphisms as risk factor for RA and osteoporosis, and whether osteoporosis complicating RA is due to RA or VDR polymorphisms.

Methods

VDR gene polymorphisms ApaI, TaqI, BsmI and FokI were typed by RFLP for 128 RA patients, 30 postmenopausal osteoporotic females and 150 healthy controls.

Results

Significant differences were found between patients and healthy controls in the frequency of BsmI and TaqI (Pc < 0.05) but no significant associations were found for FokI and ApaI polymorphisms except for aa genotype (Pc < 0.001). Titers of RF were higher with aa and bb genotypes. Anti-CCP and CRP levels were higher with aa genotype and more bone loss was associated with Bb genotype. Ff genotype frequency was higher in RA patients with osteoporosis than those without osteoporosis.

Conclusions

The ApaI, BsmI and TaqI polymorphisms may be a susceptibility risk factors for RA and the Ff genotype may be responsible for development of osteoporosis in RA Egyptian patients. However, the present study needs to be replicated in a large number of patients from allover the Egypt and also in multi-ethnic populations.     

Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.     

Misoprostol decreases oxidative stress and liver injury in bacterial lipopolysaccharide-induced endotoxemia in mice

The effect of misoprostol, a synthetic prostaglandin E1 analog, on the development of oxidative stress induced in mice with lipopolysaccharide (LPS) endotoxin was investigated. Misoprostol was administered by intraperitoneal route (i.p.) at doses of 10, 100, or 1,000 μg/kg at the time of LPS injection (200 μg/kg, i.p.). Mice were euthanized 4 h later. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels as well as paraoxonase activity were measured in brain and liver. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as DNA fragmentation were determined in the liver. The administration of LPS increased oxidative stress both in the brain and liver tissue. There were significantly increased MDA and nitrite and decreased GSH and PON1 activity in the brain and liver, respectively. In addition, LPS was associated with markedly elevated plasma ALT and AST level as well as increased liver DNA fragmentation. The administration of misoprostol at 100 or 1,000 μg/kg decreased brain MDA by 17.6 and 30 %, increased GSH by 29.8 and 33.3 %, and decreased nitric oxide by 21.74 and 42.5 %, respectively, compared with the lipopolysaccharide control group. Liver MDA decreased by 27 %, GSH increased by 47.7 %, and nitric oxide decreased by 37.2 % with misoprostol at 1,000 μg/kg. Paraoxonase activity increased in both the brain and liver by misoprostol administration. The increase in liver AST and ALT and DNA fragmentation after endotoxin administration was normalized by misoprostol. These results indicate that misoprostol can alleviate oxidative stress in the presence of a mild systemic inflammatory illness, indicating a new and potentially important therapeutic application for the drug.     

Teleaudiology practice in COVID-19 pandemic in Egypt and Saudi Arabia

Objective:To evaluate the audiologists’attitudes and practice towards teleaudiology, as well as to assess the audiological services provided in Egypt and Saudi ...     

Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological,Immunohistochemical, and Biochemical Study

Potassium bromate (KBrO₃) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO₃ mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO₃ induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO₃ orally twice weekly for 4 weeks and Group 4: received both KBrO₃ and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO₃ induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO₃. Anat Rec, 299:1256–1269, 2016. © 2016 Wiley Periodicals, Inc.     

New Latex Bead Agglutination Assay for Differential Diagnosis of Cattle Infected with Mycobacterium bovis and Mycobacterium avium subsp. paratuberculosis

Extensive studies have shown that the current assays used to identify cattle infected with Mycobacterium bovis or Mycobacterium avium subsp. paratuberculosis are not sufficiently sensitive and specific to detect all infected animals, especially animals recently infected with the pathogens. In the present report we show that these limitations might be overcome with a latex bead agglutination assay (LBAA). With the specific immunodominant epitope (ESAT6-p) of M. bovis, we developed an LBAA and enzyme immunoassay (EIA) for that purpose and compared them with the “gold standard” culture method and skin test for their efficacy in detecting bovine tuberculosis. When sera from control healthy cows (n = 10), M. avium subsp. paratuberculosis-positive cattle (naturally infected, n = 16; experimentally infected, n = 8), and M. bovis-positive cattle (naturally infected, n = 49;experimentally infected, n = 20) were applied to an EIA and an LBAA developed with ESAT6-p, the two tests showed similar sensitivity (97.1% by EIA, 95.7% by LBAA), high specificity (94.2% by EIA, 100% by LBAA), and a positive correlation (kappa value, 0.85; correlation rate, 93.2%; correlation coefficient, 0.64). Receiver operating characteristic analysis of EIA results and comparison with the culture method determined a suitable cutoff value at 0.469, with an area under the curve of 0.991 (95% confidence interval, 0.977 to 1.0). As LBAA didn't show any positive reactions with sera from uninfected control cows or M. avium subsp. paratuberculosis-infected cattle, which were confirmed to be free of M. bovis by culture or PCR, LBAA using the ESAT6-p can be a rapid and useful M. bovis diagnostic assay. The data suggest that rapid, sensitive, and specific assays can be developed with peptides containing immunodominant epitopes present in proteins uniquely expressed in M. bovis or M. avium subsp. paratuberculosis for differential diagnosis of cattle infected with M. bovis or M. avium subsp. paratuberculosis.     

Analysis of UV-induced damage and repair in young and senescent human dermal fibroblasts using the comet assay

A major cause of ageing is thought to be the accumulation of damage to macromolecules. Accumulation to DNA damage in cells therefore presupposes that aged cells are unable to repair this damage. We have used the in vitro model of cellular ageing to test the idea that senescent cells are deficient in some aspect of DNA repair. Using the alkaline single cell gel electrophoresis assay (comet assay), we have determined the responses of young and senescent human dermal fibroblasts to DNA damage caused by exposure to UVC light. At low doses of UVC, senescent cells generate smaller comets than young cells whilst at medium doses the situation is reversed. At high doses, young and senescent cells respond similarly to one another. Time course experiments revealing repair of DNA damage show that senescent cells generate larger comets than young cells at early stages of repair suggesting that either senescent cells bear more damage per genome than do young cells or that senescent cells are more efficient at excising bulky adducts from DNA. Cells maintained in low levels of serum irrespective of age are less able to repair DNA damage compared with cells maintained in high levels of serum, and furthermore young and senescent cells maintained in high levels of serum are equally able to repair DNA damage. Our data, therefore, reveal both age-dependent and age-independent responses to UV-induced DNA damage. Use of the comet assay highlights the heterogeneity of cellular responses to genotoxic stress.     

Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan

This article describes the pathological studies of fatal severe acute respiratory syndrome (SARS) in a 73-year-old man during an outbreak of SARS in Taiwan, 2003. Eight days before onset of symptoms, he visited a municipal hospital that was later identified as the epicenter of a large outbreak of SARS. On admission to National Taiwan University Hospital in Taipei, the patient experienced chest tightness, progressive dyspnea, and low-grade fever. His condition rapidly deteriorated with increasing respiratory difficulty, and he died 7 days after admission. The most prominent histopathologic finding was diffuse alveolar damage of the lung. Immunohistochemical and in situ hybridization assays demonstrated evidence of SARS-associated coronavirus (SARS-CoV) infection in various respiratory epithelial cells, predominantly type II pneumocytes, and in alveolar macrophages in the lung. Electron microscopic examination also revealed coronavirus particles in the pneumocytes, and their identity was confirmed as SARS-CoV by immunogold labeling electron microscopy. This report is the first to describe the cellular localization of SARS-CoV in human lung tissue by using a combination of immunohistochemistry, double-stain immunohistochemistry, in situ hybridization, electron microscopy, and immunogold labeling electron microscopy. These techniques represent valuable laboratory diagnostic modalities and provide insights into the pathogenesis of this emerging infection.