Body composition in Egyptian Turner syndrome girls

OBJECTIVE:

This cross-sectional study was undertaken to construct the new body fat % curve and provide body composition reference data for adolescent girls with Turner syndrome (TS). They diagnosed cytogenetically by blood karyotyping and not treated with growth hormone (GH).

MATERIALS AND METHODS:

The study included 70 TS girls from age 13 years to age 17 years. Body composition was measured by bioelectrical impedance. Smoothed centile charts were derived by using the least mean square (LMS) method.

RESULTS:

The new body fat curves reflect the increase of body fat mass (FM) from age 13 years to age 17 years. Body FM % of Egyptian TS girls was lower when compared with age-matched American untreated TS girls.

CONCLUSION:

This study presents the new body fat curves and reference values of body composition for untreated Egyptian TS adolescent girls. The present charts can be used for direct assessment of body FM % for Egyptian TS girls and evaluation for cases on GH treatment or other growth promoting therapy.     

Assessment of the potential iridology for diagnosing kidney disease using wavelet analysis and neural networks

Alternative or complementary medicine emphasizes therapies that are claimed to improve quality of life, prevent disease, and address conditions that conventional medicine has limited success in curing. There are many techniques which are prevalent in many countries and these can cause harm if not scientifically evaluated. The objective of this paper is to validate the use of iridology to diagnose kidney abnormalities. Two subject groups were evaluated: one was 168 subjects free from kidney disease and the other was 172 subjects with chronic renal failure. The procedure to acquire, process and classify the iris images was designed in such a way that avoids any dependency on the iridologists by using wavelet analysis and Adaptive Neuro-Fuzzy Inference System. The results show a correct classification for both subjects with kidney problems and normal subjects of 82% and 93%, respectively. The proposed technique conducted on a systemic disease with ocular manifestations showed encouraging results. However, it is necessary to perform extensive studies with diseases that do not have ocular manifestations according to conventional medicine in order to validate iridology as a valid scientific technique.     

Biochemical studies of the multicopper oxidase (small laccase) from Streptomyces coelicolor using bioactive phytochemicals and site‐directed mutagenesis

Multicopper oxidases can act on a broad spectrum of phenolic and non‐phenolic compounds. These enzymes include laccases, which are widely distributed in plants and fungi, and were more recently identified in bacteria. Here, we present the results of biochemical and mutational studies of small laccase (SLAC), a multicopper oxidase from Streptomyces coelicolor (SCO6712). In addition to typical laccase substrates, SLAC was tested using phenolic compounds that exhibit antioxidant activity. SLAC showed oxidase activity against 12 of 23 substrates tested, including caffeic acid, ferulic acid, resveratrol, quercetin, morin, kaempferol and myricetin. The kinetic parameters of SLAC were determined for 2,2′‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulphonic acid), 2,6‐dimethoxyphenol, quercetin, morin and myricetin, and maximum reaction rates were observed with myricetin, where k_cat and K_m values at 60°C were 8.1 (± 0.8) s^?1 and 0.9 (± 0.3) mM respectively. SLAC had a broad pH optimum for activity (between pH 4 and 8) and temperature optimum at 60–70°C. It demonstrated remarkable thermostability with a half‐life of over 10 h at 80°C and over 7 h at 90°C. Site‐directed mutagenesis revealed 17 amino acid residues important for SLAC activity including the 10 His residues involved in copper coordination. Most notably, the Y229A and Y230A mutant proteins showed over 10‐fold increase in activity compared with the wild‐type SLAC, which was correlated to higher copper incorporation, while kinetic analyses with S929A predicts localization of this residue near the meta‐position of aromatic substrates.     

Exome sequencing discloses <Emphasis Type="Italic">KALRN</Emphasis> homozygous variant as likely cause of intellectual disability and short stature in a consanguineous pedigree

Background

The recent availability of whole-exome sequencing has opened new possibilities for the evaluation of individuals with genetically undiagnosed intellectual disability.

Results

We report two affected siblings, offspring of first-cousin parents, with intellectual disability, hypotonia, short stature, growth hormone deficiency, and delayed bone age. All members of the nuclear family were genotyped, and exome sequencing was performed in one of the affected individuals. We used an in-house algorithm (CATCH v1.1) that combines homozygosity mapping with exome sequencing results and provides a list of candidate variants. One identified novel homozygous missense variant in KALRN (NM_003947.4:c.3644C>A: p.(Thr1215Lys)) was predicted to be pathogenic by all pathogenicity prediction software used (SIFT, PolyPhen, Mutation Taster). KALRN encodes the protein kalirin, which is a GTP-exchange factor protein with a reported role in cytoskeletal remodeling and dendritic spine formation in neurons. It is known that mice with ablation of Kalrn exhibit age-dependent functional deficits and behavioral phenotypes.

Conclusion

Exome sequencing provided initial evidence linking KALRN to monogenic intellectual disability in man, and we propose that KALRN is the causative gene for the autosomal recessive phenotype in this family.

     

Early onset of cabergoline therapy for prophylaxis from ovarian hyperstimulation syndrome (OHSS): A potentially safer and more effective protocol

Vascular endothelial growth factor (VEGF) is the most important angiogenic mediator in ovarian hyperstimulation syndrome OHSS. Studies proved that cabergoline administration blocks the increase in vascular permeability via dephosphorylation of VEGF receptors and hence can be used as prophylactic agent against OHSS. This study aimed at evaluating the effectiveness of early administration of cabergoline in the prevention of OHSS in high risk cases prepared for ICSI. This case series study was conducted on 126 high risk patients prepared for ICSI using the fixed antagonist protocol. High risk patients were defined as having more than 20 follicles >12 mm in diameter, and/or E2 more than 3000 pg/ml when the size of the leading follicle is more than 15 mm. When the size of the leading follicle reached 15 mm, cabergoline was administered (0.5 mg/day) for 8 days. Patients were followed up clinically, ultrasonographically and hematologically. The final E2 was 6099.5 ± 2730 and the mean number of retrieved oocytes was 19.7 ± 7.8. The clinical pregnancy rate was 62/126 (49.2%). There were no significant changes (p > 0.05) comparing hematological parameters, renal function tests and liver function tests between the day of HCG and the day of blastocyst transfer. The incidence of severe OHSS in this group was 1/126 (0.9%), while moderate OHSS was 12 (9.5%) and there were no cases of critical OHSS. We concluded that early administration of cabergoline is a safe and potentially more effective approach for prophylaxis against OHSS in high risk cases.     

Risk factors associated with E. coli causing neonatal calf diarrhea

Calf diarrhea is one of the major health challenges in cattle herds. The bacteriological examination of fecal samples collected from apparently healthy and diarrheic calves' revealed isolation of 26 E. coli isolates out of 56 calves with an incidence of 46.4%. Serogroups O1, O26, O44, O55, O115, O119, O125, O146, and O151 were identified from the collected fecal samples. Using PCR all isolates was positive for ompA gene species specific for E. coli. While stx1 and eaeA genes detected with incidence of 3.8 and 19.2% respectively from the isolates. The presence of stx2 gene was negative in the fecal isolates. Among colostrum samples 4 E. coli isolates were detected and serogrouped to O26, O55 and O119. They were negative for eaeA, stx1 and stx2 except strain number 4 (O55) was positive for stx1. E. coli strains were sensitive to norfloxacin (80.7%) and resistant to ampicillin and cefotaxime (100% each). Based on our findings, there was no association between occurrence of E. coli and age of calf (2–14 days), while bottle feeding calf colostrum may be a source of E. coli contamination.     

Detoxification of olefinic epoxides and nucleotide excision repair of epoxide-mediated DNA damage: Insights from animal models examining human sensitivity to 1,3-butadiene

1,3-Butadiene (BD) is a well-documented mutagen and carcinogen in rodents and is currently classified as a probable carcinogen in humans. Studies investigating workers exposed to BD indicate that, in some plants, there may be an increased genetic risk, and that polymorphisms in biotransformation and DNA repair proteins may modulate genetic susceptibility. To investigate the role of genetic polymorphisms in microsomal epoxide hydrolase (mEH) or nucleotide excision repair (NER) in contributing to the mutagenicity of BD, we conducted a series of experiments in which mice lacking mEH or NER activity were exposed to BD by inhalation or to the reactive epoxide metabolites of BD (epoxybutene-EB or diepoxybutane-DEB) by i.p. injection. Genetic susceptibility was measured using the Hprt cloning assay. Both deficient strains of mouse were significantly more sensitive to the mutagenic effects of BD and the injected epoxides. These studies provide support for the critical role that mEH plays in the biotransformation of BD, and the role that NER plays in maintaining genomic integrity following exposure to BD. Additional studies are needed to examine the importance of base excision repair (BER) in maintaining genomic integrity, the differential formation of DNA and protein adducts in deficient strains, and the potential for enhanced sensitivity to BD genotoxicity in mice either lacking or deficient in both biotransformation and DNA repair activity.     

A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice

No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals.     

Protein S-guanylation by the biological signal 8-nitroguanosine 3',5'-cyclic monophosphate

The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3',5'-cyclic monophosphate (cGMP). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO.