Identification by array-Comparative Genomic Hybridization (array-CGH) of a large deletion of luteinizing hormone receptor gene combined with a missense mutation in a patient diagnosed with a 46,XY disorder of sex development and application to prenatal diagnosis

This paper reports the case of an infant presenting with sexual ambiguity at birth. The child presented with labia majora synechia, thready genital tubercle and perineal hypospadias. The karyotype was 46,XY. Low testosterone levels with no response to hCG administration, associated with high LH level for her age, high FSH level, high inhibin B levels and normal AMH indicated a lack of LH receptivity and prompted us to screen the LHCGR gene for mutations. A previously described missense mutation (p.Cys131Arg) was identified at homozygous state in the propositus and at heterozygous state in the mother. This variation, however, was not found in the father. Our attention was drawn by the presence of several single nucleotide polymorphisms (SNPs), identified at homozygous state without any paternal contribution from exon 1 to exon 10 of LHCGR, suggesting a paternal deletion. Array DNA analysis was performed revealing a large deletion extending from 61,493 to 135,344 bp and including the LHCGR gene. Adequate genetic counselling was provided. This paper describes the first application of prenatal diagnosis in LHCGR deficiency for 46,XY disorders of sex development with the subsequent delivery of a normal baby.     

High-pressure study of lithium amidoborane using Raman spectroscopy and insight into dihydrogen bonding absence

One of the major obstacles to the use of hydrogen as an energy carrier is the lack of proper hydrogen storage material. Lithium amidoborane has attracted significant attention as hydrogen storage material. It releases ∼10.9 wt% hydrogen, which is beyond the Department of Energy target, at remarkably low temperature (∼90 °C) without borazine emission. It is essential to study the bonding behavior of this potential material to improve its dehydrogenation behavior further and also to make rehydrogenation possible. We have studied the high-pressure behavior of lithium amidoborane in a diamond anvil cell using in situ Raman spectroscopy. We have discovered that there is no dihydrogen bonding in this material, as the N—H stretching modes do not show redshift with pressure. The absence of the dihydrogen bonding in this material is an interesting phenomenon, as the dihydrogen bonding is the dominant bonding feature in its parent compound ammonia borane. This observation may provide guidance to the improvement of the hydrogen storage properties of this potential material and to design new material for hydrogen storage application. Also two phase transitions were found at high pressure at 3.9 and 12.7 GPa, which are characterized by sequential changes of Raman modes.Hydrogen economy has been considered as potentially efficient and environmental friendly alternative energy solution (1). However, one of the most important scientific and technical challenges facing the “hydrogen economy” is the development of safe and economically viable on-board hydrogen storage for fuel cell applications, especially to the transportation sector. Ammonia borane (BH₃NH₃), a solid state hydrogen storage material, possesses exceptionally high hydrogen content (19.6 wt%) and in particular, it contains a unique combination of protonic and hydridic hydrogen, and on this basis, offers new opportunities for developing a practical source for generating molecular dihydrogen (2–5). Stepwise release of H₂ takes place through thermolysis of ammonia borane, yielding one-third of its total hydrogen content (6.5 wt%) in each heating step, along with emission of toxic borazine (6–8). Recently, research interests are focusing on how to improve discharge of H₂ from ammonia borane, including lowering the dehydrogenation temperature and enhancing hydrogen release rate using different techniques, e.g., nanoscaffolds (9), ionic liquids (10), acid catalysis (11), base metal catalyst (12), or transition metal catalysts (13, 14). More recently, significant attention is given to chemical modification of ammonia borane through substitution of one of the protonic hydrogen atoms with an alkali or alkaline–earth element (15–21). Lithium amidoborane (LiNH₂BH₃) has been successfully synthesized by ball milling LiH with NH₃BH₃ (15–18). One of the driving forces suggested for the formation of LiNH₂BH₃ is the chemical potential of the protonic H^δ+ in NH₃ and the hydridic H^δ− in alkali metal hydrides making them tend to combine, producing H₂ + LiNH₂BH₃. LiNH₂BH₃ exhibits significantly different and improved dehydrogenation characteristics from its parent compound ammonia borane. It releases more than 10 wt% of hydrogen at around 90 °C without borazine emission. Also, the dehydrogenation process of lithium amidoborane is much less exothermic (∼3–5 kJmole⁻¹ H₂) (15–17) than that of NH₃BH₃ (∼22.5 kJmole⁻¹ H₂) (6–8), which greatly enhances the search for suitable regeneration routes (prerequisite for a hydrogen storage material). Although the rationale behind the improved dehydrogenation behavior is still unclear, these improved property modifications evidently originate from the substitution of one H in the NH₃ group by the more electron-donating Li, which exerts influences on the bonding characteristics, especially on the dihydrogen bonding, which is one of the characteristic bonds of ammonia borane (15). So, it is essential to understand details about the bonding behavior of this potential material.High-pressure study of molecular crystals can provide unique insight into the intermolecular bonding forces, such as hydrogen bonding and phase stability in hydrogen storage materials and thus provides insight into the improvement of design (22–30). For instance, Raman spectroscopic study of ammonia borane at high pressure provided insight about its phase transition behavior and the presence of dihydrogen bonding in its structure (25–30). We have investigated LiNH₂BH₃ at high pressure using Raman spectroscopy. We have found that, other than in NH₃BH₃, dihydrogen bonding is absent in lithium amidoborane structure and LiNH₂BH₃ shows two phase transitions at high pressure.     

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl₂ in drinking water; group 3 received 350 ppm CoCl₂ in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity.Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.     

Artemisia campestris leaf extract alleviates early diabetic nephropathy in rats by inhibiting protein oxidation and nitric oxide end products

Chronic hyperglycemia in diabetes leads to free radicals overproduction, which contributes to the development of diabetic nephropathy. The present study investigated the effects of Artemisia campestris (Ac), a plant of the Asteraceae family, on renal impairment and oxidative stress in alloxan-induced diabetic rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg kg(-1)) in rats. Ac (200 mg kg(-1)) was administered to diabetic rats for 3 weeks. Diabetic renal injury was associated with hyperglycemia, increased serum creatinine, urea and uric acid levels. This nephropathophysiology was associated with a surproduction of nitric oxide (NO), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels and a decrease in glutathione (GSH) levels. In addition, hyperglycemia increased the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in the kidney of diabetic rats. Treatment with Ac effectively ameliorated diabetic renal dysfunction by reducing oxidative and nitrosative stress. Histological studies also supported the experimental findings. The results suggested that Ac might act as a beneficial agent against renal dysfunctions developed in alloxan-induced diabetes.     

Antibody response for L1, E6 and E7 HPV 16 and HPV 18 antigens in Tunisian women with cervical cancer and controls

Results obtained in the present work indicated that the Luminex assay is more sensitive than ELISA. The reactivity to the early antigens E6 and E7 was 37% versus 42% for HPV 16 and 21% versus 20% for HPV 18 among cervical cancer cases using ELISA. However, these ratios were 44% and 61%, respectively, for E6 and E7 HPV 16 versus 28% and 21% for E6 and E7 HPV 18 when using the Luminex technique. Data also indicated that HPV 16 and HPV 18 showed distinct profiles for the different antigens tested. Finally, the differences in antibody responses between cervical cancer cases and benign cases toward the different antigens were significant.     

Induction and reversibility of thyroid proliferative changes in suckling rats given thiocyanate

Potassium thiocyanate given in the drinking water of pregnant rats led to decreased body weight in their 14-day-old offspring (27%) without altering thyroid weight. Reduction of the suckling rat's body weight could be explained be defective thyroxinemia (38). Plasma FT3 and TSH were unchanged after thiocyanate treatment. The biochemical changes were in agreement with the histological aspects of the hypothyroid animals. The typical pattern was hyperplastic goiter. Colloid volume was reduced compared with controls. Presence of resorbed peripheral vacuoles, a sign of thyroid hyperactivity, was disclosed by a three-fold increase in radioiodide (131I) uptake compared with controls. When the antithyroid drug was removed from the mother's milk, the pups'weight increased but did not reach control values. Plasma thyroid hormone levels returned to normal and even exceeded control values in spite of partial recovery of thyroid iodine content when thiocyanate treatment was stopped for ten days.     

Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer's disease

Background

Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). In this case-control study, we examined the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and their correlation with this pathology.

Objective

To verify the association between MTHFR C677T and A1298C polymorphisms and Alzheimer's disease.

Method

This work was conducted as a case–control study. Cases consisted of thirty-eight patients and 100 individuals without dementia constituted the control group. Genotyping of MTHFR polymorphisms was performed on patients and controls.

Result

Genetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p = 0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p < 10⁻³). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD.

Conclusion

The MTHFR A1298C polymorphism is a possible risk factor for Alzheimer's disease.