Potentiation of arsenic neurotoxicity by folate deprivation: Protective role of S-adenosyl methionine

Folate deficiency contributes to a variety of age-related neurological and psychological disorders including amyotrophic lateral sclerosis (ALS). The environmental neurotoxin arsenic has recently been linked with decreased neurofilament (NF) content in peripheral nerve. We examined herein, whether or not folate deprivation potentiated the impact of arsenic on NF dynamics. Arsenic inhibited translocation of NFs into axonal neurites in culture and increased perikaryal NF phosphoepitopes. Folate deprivation potentiated the impact of arsenic on these phenomena. Supplementation with S-adenosyl methionine (SAM) attenuated the impact of folate deprivation on arsenic neurotoxicity, consistent with the decrease in SAM following folate deprivation and the requirement for SAM-mediated methylation for arsenic bioelimination. These findings demonstrate how key nutritional deficiencies can potentiate the impact of enrivonmental neurotoxins.     

Differences in Developmental Concerns of Young Children with Autism Spectrum Disorder Across Racial/Ethnic Groups

Purpose: Parents/caregivers of children with autism spectrum disorder (ASD) have varying types of initial concerns regarding their child’s development, which may be culturally bound to parents’ perceptions of their child’s development. This study investigated differences in the types of initial developmental concerns reported by parents or caregivers of different racial/ethnic groups with children in an early intervention program.

Method: This study examined the frequency of endorsement of different types of concerns in African American, Caucasian, and Hispanic families.

Results: No significant differences between racial/ethnic groups were found in the endorsement of concerns related to communication, language/speech, motor, problem behavior, sensory, feeding, prematurity, attention, adaptive functioning, and medical conditions. Racial/ethnic groups differed significantly in their endorsement for social concerns.

Conclusion: Racial/ethnic group differences were confirmed regarding initial developmental concerns related to social behavior, which may be due to cultural beliefs. The implications of these findings on early identification are discussed.     

Compound library development guided by protein structure similarity clustering and natural product structure

To identify biologically relevant and drug-like protein ligands for medicinal chemistry and chemical biology research the grouping of proteins according to evolutionary relationships and conservation of molecular recognition is an established method. We propose to employ structure similarity clustering of the ligand-sensing cores of protein domains (PSSC) in conjunction with natural product guided compound library development as a synergistic approach for the identification of biologically prevalidated ligands with high fidelity. This is supported by the concepts that (i) in nature spatial structure is more conserved than amino acid sequence, (ii) the number of fold types characteristic for all protein domains is limited, and (iii) the underlying frameworks of natural product classes with multiple biological activities provide evolutionarily selected starting points in structural space. On the basis of domain core similarity considerations and irrespective of sequence similarity, Cdc25A phosphatase, acetylcholinesterase, and 11beta-hydroxysteroid dehydrogenases type 1 and type 2 were grouped into a similarity cluster. A 147-member compound collection derived from the naturally occurring Cdc25A inhibitor dysidiolide yielded potent and selective inhibitors of the other members of the similarity cluster with a hit rate of 2-3%. Protein structure similarity clustering may provide an experimental opportunity to identify supersites in proteins.     

The pulmonary bioprosthetic heart valve: its unsuitability for use as an aortic valve replacement

BACKGROUND AND AIM OF THE STUDY: The porcine pulmonary bioprosthetic heart valve represents an alternative means of aortic valve replacement (AVR), though knowledge of its biomechanical function and characteristics is limited. The valve has potential advantages over the aortic bioprosthesis; notably, it lacks the muscular shelf of the right coronary cusp of the latter bioprosthesis. The study aim was to investigate the suitability of the porcine pulmonary bioprosthetic valve for AVR. METHODS: Porcine pulmonary and aortic roots were zero pressure-fixed with 0.5% buffered glutaraldehyde, characterized, and compared with fresh porcine pulmonary and aortic roots. The in-vitro analysis included assessment of mechanical properties, hydrodynamic function, geometry of the pulmonary root, and durability. RESULTS: The fixed pulmonary roots and fresh aortic roots were similar in certain aspects of mechanical response, notably leaflets in the radial direction and the root wall. The fixed pulmonary root was slightly more compliant than the fixed aortic root, and this led to an improvement in forward flow hydrodynamic function. The reverse flow hydrodynamic function of the pulmonary roots was poor; fresh pulmonary roots exhibited a trivial closed valve regurgitant volume. On fixation, this characteristic was aggravated, leading to a gross closed valve regurgitant volume in 50% of all fixed pulmonary roots. The cause of leakage was identified as a prolapsed anterior leaflet. Durability of the fixed pulmonary root was also inferior to that of the fixed aortic root; three fixed pulmonary roots subjected to accelerated fatigue testing showed signs of leaflet macroscopic damage. CONCLUSION: Overall, the performance of the porcine pulmonary bioprosthesis was far inferior to that of the currently used porcine aortic bioprosthesis. Hence, the porcine pulmonary bioprosthetic valve was deemed unsuitable for AVR.     

Treatment of recurrent attacks of supraventricular tachycardia during pregnancy causing complications in both mother and fetus

Cardiac arrhythmias including supraventricular tachycardia are commonly encountered during pregnancy. The case of a young Indian woman with recurrent attacks of supraventricular tachycardia during pregnancy which was managed with adenosine and verapamil is reported. The possible mechanisms of maternal and fetal complications are discussed.