Stem Cell Therapy for Autism

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism

Hypochlorous acid and hydrogen peroxide-induced negative regulation of Salmonella enterica serovar Typhimurium ompW by the response regulator ArcA

<p>Abstract</p> <p>Background</p> <p>Hydrogen peroxide (H₂O₂) and hypochlorous acid (HOCl) are reactive oxygen species that are part of the oxidative burst encountered by <it>Salmonella enterica</it> serovar Typhimurium (<it>S</it>. Typhimurium) upon internalization by phagocytic cells. In order to survive, bacteria must sense these signals and modulate gene expression. Growing evidence indicates that the ArcAB two component system plays a role in the resistance to reactive oxygen species. We investigated the influx of H₂O₂ and HOCl through OmpW and the role of ArcAB in modulating its expression after exposure to both toxic compounds in <it>S.</it> Typhimurium.</p> <p>Results</p> <p>H₂O₂ and HOCl influx was determined both <it>in vitro</it> and <it>in vivo</it>. A <it>S</it>. Typhimurium <it>ompW</it> mutant strain (∆<it>ompW</it>) exposed to sub-lethal levels of H₂O₂ and HOCl showed a decreased influx of both compounds as compared to a wild type strain. Further evidence of H₂O₂ and HOCl diffusion through OmpW was obtained by using reconstituted proteoliposomes. We hypothesized that <it>ompW</it> expression should be negatively regulated upon exposure to H₂O₂ and HOCl to better exclude these compounds from the cell. As expected, qRT-PCR showed a negative regulation in a wild type strain treated with sub-lethal concentrations of these compounds. A bioinformatic analysis in search for potential negative regulators predicted the presence of three ArcA binding sites at the <it>ompW</it> promoter region. By electrophoretic mobility shift assay (EMSA) and using transcriptional fusions we demonstrated an interaction between ArcA and one site at the <it>ompW</it> promoter region. Moreover, qRT-PCR showed that the negative regulation observed in the wild type strain was lost in an <it>arcA</it> and in <it>arcB</it> mutant strains.</p> <p>Conclusions</p> <p>OmpW allows the influx of H₂O₂ and HOCl and is negatively regulated by ArcA by direct interaction with the <it>ompW</it> promoter region upon exposure to both toxic compounds.</p

Effects of a long-term adapted judo program on the health-related physical fitness of children with ASD

[Abstract] Physical fitness is one of the most important physical and mental health aspects for children with Autism Spectrum Disorder (ASD). This study aimed to test the effects of a long-term adapted judo program on the health-related physical fitness of children with ASD. The participants were recruited from various associations of families and schools for children with special needs. Twenty-one children were assigned to an experimental group and nineteen to a control group. The experimental group participated in a six-month adapted judo program consisting of 90 min of practice each week. Health-related physical fitness was measured using the indicators obtained from the ALPHA-fitness battery, the estimated VO2max and the waist/height ratio0.5. Changes within and between groups were analyzed using linear mixed models for repeated measures designs and test-retest reliability of tests requiring a maximum score using the Intraclass Correlation Coefficient (ICC). A judo program tailored for children with ASD can improve the cardio-metabolic health and cardiorespiratory fitness of its participants. The problems involved with administering physical aptitude tests that involve maximum effort or performance in children with ASD cast serious doubts on the reproducibility of their results

Improving motor skills and psychosocial behaviors in children with autism spectrum disorder through an adapted judo program

[Abstract] Introduction: This study aimed to investigate the long-term effects of an adapted judo program on the motor skills and psychosocial abilities of children with Autism Spectrum Disorder (ASD). Methods: All participants had been diagnosed with ASD and were assessed twice, one time at the start of the intervention and again 6 months later, with the Test of Gross Motor Development (TGMD-3) and the Gilliam Autism Rating Scale-Third Edition (GARS-3). A one-way repeated measures MANOVA was carried out in order to evaluate these assessments, and a mediation analysis was done to determine the relationship between them. Results: The experimental group significantly improved (p < 0.05) from the pre-test to the post-test for several subtests of the TGMD-3 and the GARS-3. Conclusion: The study shows that participation in an adapted judo program clearly helps to improve the motor skills and psychosocial behaviors of children with ASD

Modelo de formación de los yacimientos estratoligados de Cu en lechos rojos de Las Vigas (Chihuahua, México)

Peer ReviewedPostprint (published version

Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na+/H+ exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg-1 day-1) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na+/H+ exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg-1 day-1) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Antibodies for β2-Microglobulin and the Heavy Chains of HLA-E, HLA-F, and HLA-G Reflect the HLA-Variants on Activated Immune Cells and Phases of Disease Progression in Rheumatoid Arthritis Patients under Treatment

Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune, symmetrical polyarticular arthritis. It is characterized by synovial infiltration and activation of several types of immune cells, culminating in their apoptosis and antibody generation against altered autoantigens. β2-microglobulin (β2m)-associated heavy chains (HCs) of HLA antigens, also known as closed conformers (Face-1), undergo alteration during activation of immune cells, resulting in β2m-free structural variants, including monomeric open conformers (Face-2) that are capable of dimerizing as either homodimers (Face-3) or as heterodimers (Face-4). β2m-free HCs uncover the cryptic epitopes that can elicit antibodies (Abs). We report here the levels of IgM and IgG Abs against both β2m and HCs of HLA-E, HLA-F, and HLA-G in 74 RA patients receiving immunosuppressive drugs. Anti-β2m IgM was present in 20 of 74 patients, whereas anti-β2m IgG was found in only 8 patients. Abs against β2m would be expected if Abs were generated against β2m-associated HLA HCs. The majority of patients were devoid of either anti-β2m IgM or IgG but had Abs against HCs of different HLA-Ib molecules. The paucity of anti-β2m Abs in this cohort of patients suggests that Abs were developed against β2m-free HLA HCs, such as Face-2, Face-3, and Face-4. While 63 of 68 patients had IgG Abs against anti-HLA-F HCs, 36 and 50 patients showed IgG Ab reactivity against HLA-E and anti-HLA-G HCs, respectively. Evidently, anti-HLA-F HC Abs are the most predominant anti-HLA-Ib HC IgG Abs in RA patients. The incidence and intensity of Abs against HLA-E, HLA-F, and HLA-G in the normal control group were much higher than those observed in RA patients. Evidently, the lower level of Abs in RA patients points to the impact of the immunosuppressive drugs on these patients. These results underscore the need for further studies to unravel the nature of HLA-F variants on activated immune cells and synoviocytes of RA patients

Engineering of III-Nitride Semiconductors on Low Temperature Co-fired Ceramics

This work presents results in the feld of advanced substrate solutions in order to achieve high crystalline quality group-III nitrides based heterostructures for high frequency and power devices or for sensor applications. With that objective, Low Temperature Co-fred Ceramics has been used, as a noncrystalline substrate. Structures like these have never been developed before, and for economic reasons will represent a groundbreaking material in these felds of Electronic. In this sense, the report presents the characterization through various techniques of three series of specimens where GaN was deposited on this ceramic composite, using diferent bufer layers, and a singular metal-organic chemical vapor deposition related technique for low temperature deposition. Other single crystalline ceramic-based templates were also utilized as substrate materials, for comparison purposes

Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na+/H+ exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg-1 day-1) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare