Mifepristone Prevents Stress-Induced Apoptosis in Newborn Neurons and Increases AMPA Receptor Expression in the Dentate Gyrus of C57/BL6 Mice

Chronic stress produces sustained elevation of corticosteroid levels, which is why it is considered one of the most potent negative regulators of adult hippocampal neurogenesis (AHN). Several mood disorders are accompanied by elevated glucocorticoid levels and have been linked to alterations in AHN, such as major depression (MD). Nevertheless, the mechanism by which acute stress affects the maturation of neural precursors in the dentate gyrus is poorly understood. We analyzed the survival and differentiation of 1 to 8 week-old cells in the dentate gyrus of female C57/BL6 mice following exposure to an acute stressor (the Porsolt or forced swimming test). Furthermore, we evaluated the effects of the glucocorticoid receptor (GR) antagonist mifepristone on the cell death induced by the Porsolt test. Forced swimming induced selective apoptotic cell death in 1 week-old cells, an effect that was abolished by pretreatment with mifepristone. Independent of its antagonism of GR, mifepristone also induced an increase in the percentage of 1 week-old cells that were AMPA+. We propose that the induction of AMPA receptor expression in immature cells may mediate the neuroprotective effects of mifepristone, in line with the proposed antidepressant effects of AMPA receptor potentiators

Crystalline cataract caused by a heterozygous missense mutation in γD-crystallin (CRYGD)

Purpose: To describe phenotypic characteristics of two pedigrees manifesting early onset crystalline cataract with mutations in the γD-crystallin gene (CRYGD). Methods: A detailed medical history was obtained from two Caucasian pedigrees manifesting autosomal dominant congenital cataracts. Genomic DNA was extracted from saliva (DNA Genotek). Single Nucleotide Polymorphism (SNP) based genome analysis of the larger pedigree revealed linkage to an 8.2 MB region on chromosome 2q33-q35 which encompassed the crystallin-gamma gene cluster (CRYG). Exons and flanking introns of CRYGA, CRYGB, CRYGC and CRYGD were amplified and sequenced to identify disease-causing mutations. Results: A morphologically unique cataract with extensive refractile “crystals ” scattered throughout the nucleus and perinuclear cortex was found in the probands from both pedigrees. A heterozygous C→A mutation was identified at position 109 of the coding sequence (R36S of the processed protein) in exon 2 of CRYGD and this missense mutation was found to cosegregate with the disease in the larger family; this mutation was then identified in affected individuals of pedigree 2 as well. Conclusions: The heterozygous 109C→A CRYGD missense mutation is associated with a distinct crystalline cataract in two US Caucasian pedigrees. This confirms crystalline cataract formation with this mutation, as previously reported in sporadic childhood case from the Czech Republic and in members of a Chinese family

Synthesis and evaluation of partially hydrolysed polyacrylamide (PHPA) as viscosifier in water based drilling fluids

83-88<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">High molecular weight (106<span style="font-size:11.0pt; line-height:115%;font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;="" mso-fareast-font-family:"times="" new="" roman";mso-fareast-theme-font:minor-fareast;="" mso-hansi-theme-font:minor-latin;mso-bidi-font-family:arial;mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">) partially hydrolysed polyacrylamide (PHPA) has been prepared and its efficacy as viscosifier in water based drilling mud has been evaluated. When PHPA is added to bentonite mud system, it causes a viscosity hump indicating encapsulating effect. The breakdown point of the hump varies with the concentration of the solid mud and also with the molecular weight of the polymer. The polymer mud system is non-Newtonian in nature. The formulated polymer mud containing PHPA as viscosifier, carboxy methyl cellulose (CMC)/poly anionic cellulose (PAC) as fluid loss reducing agent, Na salt of sulphonated asphaltene as shell stabilizer, bentonite as builder and barite as high density material were evaluated at room temperature and after aging at 80-120°C. Polymer mud system can be used in reservoirs having temperature below 120°C. PAC shows better efficacy as fluid loss reducing agent with PHPA polymer mud than CMC.</span