Although there is tremendous interest in stem cell (SC)–based therapies for cardiomyopathy caused by chronic myocardial infarction, many unanswered questions regarding the best approach remain. The ...TAC-HFT study is a phase I/II randomized, double-blind, placebo-controlled trial designed to address several of these questions, including the optimal cell type, delivery technique, and population. This trial compares autologous mesenchymal SCs (MSCs) and whole bone marrow mononuclear cells (BMCs). In addition, the study will use a novel helical catheter to deliver cells transendocardially. Although most trials have used intracoronary delivery, the optimal method is unknown and data suggest that the transendocardial approach may have important advantages. Several trials support the benefit of SCs in patients with chronic ischemic cardiomyopathy (ICMP), although the sample sizes have been small and the number of trials sparse. After a pilot phase of 8 patients, 60 patients with ICMP (left ventricular ejection fraction 15%-50%) will be randomized to group A (30 patients further randomized to receive MSC injection or placebo in a 2:1 fashion) or group B (30 patients further randomized to BMCs or placebo in a 2:1 fashion). All patients will undergo bone marrow aspiration and transendocardial injection of SCs or placebo. The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy (determined primarily by cardiac magnetic resonance imaging) of BMCs and MSCs administered transendocardially in patients with ICMP.
ABSTRACT
BACKGROUND AND PURPOSE
The spinal subarachnoid space (SSAS) is vital for neurologic function. Although SSAS alterations are known to occur after spinal cord injury (SCI), there is a lack of ...high‐resolution imaging studies of the SSAS after SCI in rodents. Therefore, the aim here was to assess changes in the SSAS of rats subjected to graded SCI, using high‐resolution micro‐CT myelography.
METHODS
Long‐Evans adult rats were subjected to mild or severe spinal cord contusion at T9. Imaging studies of SSAS features were carried out in injured rats at acute (day 1) and subacute (day 15) stages postinjury, as well as in control rats, using high‐resolution micro‐CT myelography with a contrast‐enhanced digital subtraction protocol. We studied a total of 33 rats randomly allocated into five experimental groups. Micro‐CT myelograms were assessed by expert observers using both qualitative and quantitative criteria.
RESULTS
Qualitative and quantitative analyses showed that SCI induces changes in the SSAS that vary as a function of both injury severity and time elapsed after injury. SSAS blockage was the main alteration detected. Moreover, the method used here allowed fine details to be observed in small animals, such as variations in the preferential pathways for contrast medium flow, neuroimaging nerve root enhancement, and leakage of contrast medium due to tearing of the dural sac.
CONCLUSION
Micro‐CT myelography provides high‐resolution images of changes in the SSAS after SCI in rats and is a useful tool for further experimental studies involving rat SCI in vivo.
Aβ(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer’s disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing ...worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent Aβ(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express Aβ(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by Aβ(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by Aβ(1-42) peptide in human erythrocytes and molecular models.
Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of
biovar
, a causal agent of Caseous Lymphadenitis, have been evaluated in a ...murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of
. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of
Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.
La presente investigación presenta un análisis del principio de interpretación conforme a la Constitución (ICC) desde la teoría del derecho, especialmente, desde la escuela genovesa. La hipótesis que ...guía la investigación afirma que la ICC no es un único canon, directiva u operación interpretativa, sino que es un procedimiento o una secuencia de actividades. Contrastamos esta conjetura con el discurso de dogmáticos latinoamericanos para hacer visible cómo es comprendida la ICC en distintos contextos que comparten una tradición jurídica común (civil law) en el marco del paradigma constitucional transformador que caracteriza a la experiencia latinoamericana. Nuestra reconstrucción muestra que la ‹‹interpretación conforme›› incluye varias operaciones de interpretación de la ley y que en ellas los compromisos del intérprete juegan un rol más importante que lo que los juristas latinoamericanos parece admitir.
Peptides constitute an alternative and interesting option to develop treatments, vaccines, and diagnostic tools as they demonstrate their scope in several health aspects; as proof of this, commercial ...peptides for humans and animals are available on the market and used daily. This review aimed to know the role of peptides in the field of veterinary diagnosis, and include peptide-based enzyme-linked immunosorbent assay (pELISA), lateral flow devices, and peptide latex agglutination tests that have been developed to detect several pathogens including viruses and bacteria of health and production relevance in domestic animals. Studies in cattle, small ruminants, dogs, cats, poultry, horses, and even aquatic organisms were reviewed. Different studies showed good levels of sensitivity and specificity against their target, moreover, comparisons with commercial kits and official tests were performed which allowed appraising their performance. Chemical synthesis, recombinant DNA technology, and enzymatic synthesis were reviewed as well as their advantages and drawbacks. In addition, we discussed the intrinsic limitations such as the small size or affinity to polystyrene membrane and mention several strategies to overcome these problems. The use of peptides will increase in the coming years and their utility for diagnostic purposes in animals must be evaluated.
Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99mTc-GA-5, a radiotracer targeting Glial ...Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5’s recognition/specificity ability were observed after the radiolabeling. The GA-5’s radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.
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