La política criminal implementada por el estado y el hacinamiento penitenciario como fenómeno estructural en la zona oriental 2004-2006. Causas y propuestas de solución

El objetivo de este trabajo es analizar los factores que influyen en la ineficacia de la Política Criminal en materia penitenciaria en El Salvador. Profundizar en el estudio del hacinamiento como fenómeno estructural en los Centros Penitenciarios, y así dar propuestas que ayuden a minimizarlo. En la presente investigación se utilizará el Método Científico; por ser éste el que servirá de guía para obtener resultados más fieles y exactos porque la aplicación de este método implica la realización de un procedimiento sistemático en forma ordenada para realizar una investigación científica la cual se inicia lógicamente con el planteamiento del problema que se quiere solucionar; luego con la información obtenida se realizará el abordaje investigativo del problema y la utilización de las técnicas que éste ofrece permitirá lograr y obtener las metas y objetivos trazados con respecto a la situación de la Política Criminal y el Hacinamiento en los Centros Penitenciarios. Conclusión: Las personas privadas de libertad, además de restringírseles la libertad ambulatoria por haber cometido un hecho ilícito, tienen que padecer la vulneración a sus derechos fundamentales al ser sometidas a condiciones de hacinamiento carcelario, e insalubridad, bajo un clima de violencia e irrespeto a sus derechos, aumentando aun más, la crueldad de la pena de prisión. Las cárceles, lejos de ser lugares donde los reclusos y reclusas reparan el daño causado y se resocializan o readaptan para volver a la sociedad, se han convertido en simples resguardos de seres humanos reducidos a cosas y en verdaderas escuelas del delito, porque en nuestro sistema penitenciario, la cárcel mas que rehabilitar destruye, en vez de ser un lugar donde se cumpla una pena y se reintegre al ciudadano a la sociedad como un ser positivo para ésta, se han convertido en centros en donde se planea la comisión de delitos, incluso dentro de los mismos reclusorios se da la comisión de ilícitos y es el lugar donde los de ya por sí, infractores de la ley, perfeccionan sus técnicas; invirtiéndose así los fines de la pena previstos en la Constitución y en el Derecho Internacional de los Derechos Humano

NeuroBoricuas: a novel approach for incorporating neuroscience education in schools of Puerto Rico

[EN] Puerto Rico is in dire need of transforming its education system to counter the current economic recession and ensure a future with talented Puerto Ricans at the forefront of scientific research and technology development.  Here we present a group of neuroscientists and educators, the NeuroBoricuas, committed to revolutionize the scientific culture of Puerto Rico by incorporating neuroscience research training and inquiry-based activities in public and private schools. We carry out our vision through diverse methods, such as community outreach activities, where we promote neuroscience literacy using diverse learning activities. In parallel, we are designing a neuroscience course and textbook with educators to be implemented in schools. We also established neuroscience laboratories in K-12 schools and trained science teachers to manage such laboratories, using equipment from the company “Backyard Brains”. These laboratory experiences are integrated into the academic curriculum in high schools and the equipment is also available for students interested in designing their independent research projects. Lastly, we are expanding a network of committed scientists who partner with educators to help nurture future neuroscientists early in their academic endeavors. Here, we describe our trajectory and our approach to transform scientific education in Puerto Rico.We thank Dr. Gregory J. Quirk, Dr. Daniel Colon-Ramos and Dr. Mark Miller for their support. We thank Tim Marzullo, from Backyard Brains, for supporting NeuroBoricuas. We also thank Palabreria, Digi-Serv and Puerto Rico 4.0 for their constant support. We thank all the NeuroBoricuas that selflessly work hard for a better Puerto Rico. This work has been supported by generous donations from the Puerto Rican people, a grant from the University of Puerto Rico Medical Sciences Campus’ Chancellor’s office, and the Grass Foundation.http://ocs.editorial.upv.es/index.php/HEAD/HEAD18Bravo-Rivera, C.; Díaz-Ríos, M.; Aldarondo-Hernández, A.; Santos-Vera, B.; Ramos-Medina, L.; De Jesús-Burgos, M.; Bravo-Rivera, H.... (2018). NeuroBoricuas: a novel approach for incorporating neuroscience education in schools of Puerto Rico. Editorial Universitat Politècnica de València. 1447-1455. https://doi.org/10.4995/HEAD18.2018.8223OCS1447145

Folate-Decorated Cross-Linked Cytochrome c Nanoparticles for Active Targeting of Non-Small Cell Lung Carcinoma (NSCLC)

The folate receptor alpha (FR), which is overexpressed in solid tumors including NSCLC, can be utilized for active tumor targeting to afford more effective cancer therapies. In this context, cytochrome c (Cyt c) has drawn attention to cancer research because it is non-toxic, yet, when delivered to the cytoplasm of cancer cells, can kill them by inducing apoptosis. Cyt c nanoparticles (NPs, 169 ± 9 nm) were obtained by solvent precipitation with acetonitrile, and stabilized by reversible homo-bifunctional crosslinking to accomplish a Cyt-c-based drug delivery system that combines stimulus-responsive release and active targeting. Cyt c was released under intracellular redox conditions, due to an S–S bond in the NPs linker, while NPs remained intact without any release under extracellular conditions. The NP surface was decorated with a hydrophilic folic acid–polyethylene glycol (FA–PEG) polymer for active targeting. The FA-decorated NPs specifically recognized and killed cancer cells (IC50 = 47.46 µg/mL) that overexpressed FR, but showed no toxicity against FR-negative cells. Confocal microscopy confirmed the preferential uptake and apoptosis induction of our NPs by FR-positive cancer cells. In vivo experiments using a Lewis lung carcinoma (LLC) mouse model showed visible NP accumulation within the tumor and inhibited the growth of LLC tumors

In Vivo Evaluation of the Acute Systemic Toxicity of (1S,2E,4R,6R,7E,11E)-Cembratriene-4,6-diol (4R) in Sprague Dawley Rats

The tobacco cembranoid (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (4R) interacts with nicotinic acetylcholine receptors, which results in neuroprotection against organophosphate toxicity, brain ischemia, and Parkinson’s disease. The present study is a continuation of our previous research in which we applied a single dose of 4R 1 h before or 24 h after exposure to diisopropylfluorophosphate (DFP) (analog of the nerve agent sarin). The 4R dose robustly decreased neuroinflammation and neuronal death at both timepoints. Here, we investigated the toxicity of a single dose of 4R in male and female Sprague Dawley (SD) rats after a subcutaneous (s.c.) injection of 6, 24, or 98 mg/kg. Body weight was not affected by 4R during the 7-day observation period. No histopathologic changes in the organs were attributed to 4R. Minor hematological and blood composition variations were detected on Day 3 in the mid- and the high-dose males, but these were resolved by Day 8. At the area of the s.c. injection site, alopecia and dry skin were detected in both the 4R-treated males and females and in the female controls

Theoretical Prediction of Gastrointestinal Absorption of Phytochemicals

The discovery of bioactive compounds for non-invasive therapy has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals. Still, it is challenging to determine which components show high biomedical activity and bioavailability after administration. However, based on the chemical structure of these phytochemicals, their physicochemical properties can be calculated to predict the probability of gastrointestinal (GI) absorption after oral administration. Indeed, different researchers have proposed several rules (e.g., Lipinski’s, Veber’s, Ghose’s, and Muegge’s rules) to attain these predictions, but only for synthetic compounds. Most phytochemicals do not fully comply with these rules even though they show high bioactivity and high GI absorption experimentally. Here, we propose a detailed methodology using scientifically validated web-based platforms to determine the physicochemical properties of five phytochemicals found in ginger, echinacea, and tobacco. Furthermore, we analyzed the calculated data and established a protocol based on the integration of these classical rules, plus other extended parameters, that we called the Phytochemical Rule, to obtain a more reliable prediction of the GI absorption of natural compounds. This methodology can help evaluate bioactive phytochemicals as potential drug candidates and predict their oral bioavailability in patients

Accumulation of Amyloid Beta (Aβ) Peptide on Blood Vessel Walls in the Damaged Brain after Transient Middle Cerebral Artery Occlusion

It is well known that amyloid beta (Aβ) peptides are generated in blood vessels, released into the brain during thrombosis, and temporarily accumulate in this organ after injury. Here we demonstrate that 24 h after transient middle cerebral artery occlusion (tMCAO), one of the standard models of focal ischemic stroke, Aβ peptide accumulates in the brain, concentrating on the blood vessel walls. Because Aβ oligomers are known to induce significant damage to brain cells, they act as an additional damaging factor during ischemic stroke. Considering that they have been shown to form ion channels in cells, affecting osmotic balance, we used an Aβ peptide channel blocker, tromethamine (2-amino-2-(hydroxymethyl) propane-1,3-diol), to prevent this additional injury. Tromethamine injected 0.1 g/100 g body weight intraperitoneally at 5 min before tMCAO decreased water content in the damaged hemisphere, as measured by dry brain weight. Congo red staining, which binds only to Aβ oligomer plaques (amyloid), showed that there was no significant presence of plaques. Therefore, we suggest that Aβ peptide oligomers are responsible for some of the brain damage during stroke and that blockage of the ion channels that they form could be beneficial in treating this complex neurological syndrome

Key genes and drug delivery systems to improve the efficiency of chemotherapy

Cancer cells can develop resistance to anticancer drugs, thereby becoming tolerant to treatment through different mechanisms. The biological mechanisms leading to the generation of anticancer treatment resistance include alterations in transmembrane proteins, DNA damage and repair mechanisms, alterations in target molecules, and genetic responses, among others. The most common anti-cancer drugs reported to develop resistance to cancer cells include cisplatin, doxorubicin, paclitaxel, and fluorouracil. These anticancer drugs have different mechanisms of action, and specific cancer types can be affected by different genes. The development of drug resistance is a cellular response which uses differential gene expression, to enable adaptation and survival of the cell to diverse threatening environmental agents. In this review, we briefly look at the key regulatory genes, their expression, as well as the responses and regulation of cancer cells when exposed to anticancer drugs, along with the incorporation of alternative nanocarriers as treatments to overcome anticancer drug resistance

Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells where its release from mitochondria and apoptotic induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and tested their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA. The internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) in LLC cells was confirmed by confocal microscopy. NP caspase activation was more efficient than the NP-free formulation. Caspase activity assays showed NPs retained 88–96% Cyt c activity. The NP formulations were more effective in decreasing LLC cell viability than NP-free formulation, with IC50 49.2 to 70.1 μg/mL versus 129.5 μg/mL, respectively. Our NP system proved to be thrice as selective towards cancerous than normal cells. In vivo studies using near infrared-tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model

The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude Mouse Model

Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies to inhibit metastatic cancer. The Rho family GTPase Rac is an ideal target for anti-metastatic cancer therapy, because Rac is a key molecular switch that is activated by a myriad of cell surface receptors to promote cancer cell migration/invasion and survival. Previously, we reported the design and development of EHop-016, a small molecule compound, which inhibits Rac activity of metastatic cancer cells with an IC50 of 1 μM. EHop-016 also inhibits the activity of the Rac downstream effector p21-activated kinase (PAK), lamellipodia extension, and cell migration in metastatic cancer cells. Herein, we tested the efficacy of EHop-016 in a nude mouse model of experimental metastasis, where EHop-016 administration at 25 mg/kg body weight (BW) significantly reduced mammary fat pad tumor growth, metastasis, and angiogenesis. As quantified by UPLC MS/MS, EHop-016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016. The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by immunohistochemistry of excised tumors and by In Vitro tube formation assays of endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells. In conclusion, EHop-016 has potential as an anticancer compound to block cancer progression via multiple Rac-directed mechanisms