How specific molecules can lead to overeating.

A molecular pathway involving compounds found in processed foods and biogenic amines increases food intake and aging in the roundworm C. elegans.

1-Mesityl-3-(3-Sulfonatopropyl) Imidazolium Protects Against Oxidative Stress and Delays Proteotoxicity in C. elegans.

Due to the increase in life expectancy worldwide, age-related disorders such as neurodegenerative diseases (NDs) have become more prevalent. Conventional treatments comprise drugs that only attenuate some of the symptoms, but fail to arrest or delay neuronal proteotoxicity that characterizes these diseases. Due to their diverse biological activities, imidazole rings are intensively explored as powerful scaffolds for the development of new bioactive molecules. By using C. elegans, our work aims to explore novel biological roles for these compounds. To this end, we have tested the in vivo anti-proteotoxic effects of imidazolium salts. Since NDs have been largely linked to impaired antioxidant defense mechanisms, we focused on 1-Mesityl-3-(3-sulfonatopropyl) imidazolium (MSI), one of the imidazolium salts that we identified as capable of improving iron-induced oxidative stress resistance in wild-type animals. By combining mutant and gene expression analysis we have determined that this protective effect depends on the activation of the Heat Shock Transcription Factor (HSF-1), whereas it is independent of other canonical cytoprotective molecules such as abnormal Dauer Formation-16 (DAF-16/FOXO) and Skinhead-1 (SKN-1/Nrf2). To delve deeper into the biological roles of MSI, we analyzed the impact of this compound on previously established C. elegans models of protein aggregation. We found that MSI ameliorates ß-amyloid-induced paralysis in worms expressing the pathological protein involved in Alzheimer's Disease. Moreover, this compound also delays age-related locomotion decline in other proteotoxic C. elegans models, suggesting a broad protective effect. Taken together, our results point to MSI as a promising anti-proteotoxic compound and provide proof of concept of the potential of imidazole derivatives in the development of novel therapies to retard age-related proteotoxic diseases.

ß-cyclodextrin coating: improving biocompatibility of magnetic nanocomposites for biomedical applications.

The role Beta-cyclodextrin (ßCD) on improving biocompatibility on healthy cellular and animal models was studied upon a formulation obtained from the development of a simple coating procedure. The obtained nanosystems were thoroughly characterized by FTIR, TGA, atomic absorption spectroscopy, dynamic light scattering and zeta potential, TEM/HR-TEM and magnetic properties. ßCD might interact with the magnetic core through hosting OA. It is feasible that the nanocomposite is formed by nanoparticles of MG@OA dispersed in a ßCD matrix. The evaluation of ßCD role on biocompatibility was performed on two healthy models. To this end, in vivo studies were carried out on Caenorhabditis elegans. Locomotion and progeny were evaluated after exposure animals to MG, MG@OA, and MG@OA-ßCD (10 to 500 µg/mL). The influence of ßCD on cytotoxicity was explored in vitro on healthy rat aortic endothelial cells, avoiding alteration in the results derived from the use of transformed cell lines. Biological studies demonstrated that ßCD attaching improves MG biocompatibility.

The flight response impairs cytoprotective mechanisms by activating the insulin pathway.

An animal's stress response requires different adaptive strategies depending on the nature and duration of the stressor. Whereas acute stressors, such as predation, induce a rapid and energy-demanding fight-or-flight response, long-term environmental stressors induce the gradual and long-lasting activation of highly conserved cytoprotective processes1-3. In animals across the evolutionary spectrum, continued activation of the fight-or-flight response weakens the animal's resistance to environmental challenges4,5. However, the molecular and cellular mechanisms that regulate the trade-off between the flight response and long-term stressors are poorly understood. Here we show that repeated induction of the flight response in Caenorhabditis elegans shortens lifespan and inhibits conserved cytoprotective mechanisms. The flight response activates neurons that release tyramine, an invertebrate analogue of adrenaline and noradrenaline. Tyramine stimulates the insulin-IGF-1 signalling (IIS) pathway and precludes the induction of stress response genes by activating an adrenergic-like receptor in the intestine. By contrast, long-term environmental stressors, such as heat or oxidative stress, reduce tyramine release and thereby allow the induction of cytoprotective genes. These findings demonstrate that a neural stress hormone supplies a state-dependent neural switch between acute flight and long-term environmental stress responses and provides mechanistic insights into how the flight response impairs cellular defence systems and accelerates ageing.

Diisopropylphenyl-imidazole (DII): A new compound that exerts anthelmintic activity through novel molecular mechanisms.

Nematode parasites cause substantial morbidity to billions of people and considerable losses in livestock and food crops. The repertoire of effective anthelmintic compounds for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance has become a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system, we here screened the nematicidal potential of novel imidazolium and imidazole derivatives. One of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. This lethal effect appears to be specific because DII concentrations which prove to be toxic to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster, and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 has been largely reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously unidentified UNC-29-containing muscle AChR, different from the classical L-AChR. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. Its lethality on C. elegans, its harmlessness in non-nematode species and its novel and dual mechanism of action make DII a promising candidate compound for anthelmintic therapy.

Eficácia do ultrassom de 3 Mhz em pacientes pediátricos comcicatrizes, sequelas de queimaduras de 2° a 3 º grau. Área deCirurgia Plástica Reabilitadora do Hospital Infantil, Córdoba,Argentina: 2006-2012 / Effectiveness of 3 Mhz ultrasound in pediatric patients with scars, sequels of 2nd to 3rd degree burns. Plastic Surgery Rehabilitation Area of Children Hospital, Cordoba, Argentina: 2006-2012

Introdução: As queimaduras são lesões produzidas por agentes físicos, químicos ou biológicos que podem afetar uma ou várias camadas da pele. A reabilitação pediátrica de pacientes queimados cresce dia a dia, devido a muitas razões: avanços da tecnologia aplicada na pele, aumento da taxa de sobrevida em pacientes queimados, os avanços no projeto de protocolos de reabilitação e cooperação interdisciplinar para conseguir a recuperação máxima possível nestes pacientes. Objetivo: O objetivo deste estudo é demonstrar a eficácia do ultrassom de 3 MHz na reabilitação de pacientes queimados com o Scar Scale1 Vancouver, estudos ecográficos de tecidos moles e Escala de Dor Facial - Revisada (FPS-R). Método: Os pacientes foram divididos em dois grupos: Grupo A, que receberam a terapia de EUA, de 3 MHz e Grupo B não receberam terapia. Resultados: A avaliação foi feita por meio da Vancouver Scar Scale (VSS). Uma evolução favorável de 75% foi observada no grupo A, ao passo que uma evolução desfavorável 8% foi observada no grupo B que não recebeu terapia de ultrassom de 3 MHz. No relatório de cada ecografia, a média de melhora nos tecidos moles é de 33,6%. A dor diminui a 42,4%. Além disso, no grupo B, a dor aumenta de 15,5%, de acordo com a FPS-R. Esta é a razão pela qual sugere-se que esta terapia melhora a evolução de cicatrizes na sua flexibilidade, a altura, a vascularização e a dor. Conclusão: O uso do ultrassom de 3 MHz é considerado uma terapia alternativa segura e eficaz para pacientes pediátricos com cicatrizes de queimaduras, que estão à procura de reinserção física, funcional, psicológica e social.

Introduction: Burns are lesions produced by physical, chemical or biological agents that can affect one or various layers of the skin. Pediatric rehabilitation of burnt patients grows day by day, due to many reasons: advances of technology applied to the skin, increase of survival rates in burnt patients, advances in the design of protocols in rehabilitation and interdisciplinary cooperation to achieve the maximum possible recovery in these patients. Objective: The objective of this study is to demonstrate the effectiveness of 3 MHz Ultrasound (US) in the rehabilitation of burnt patients with the Vancouver Scar Scale1, echographics studies of soft tissue and Face Pain Scale – Revised (FPS-R). Method: The patients were divided into two groups: Group A that received therapy of US of 3 MHz and Group B did not receive therapy. Results: Evaluation was done using the Vancouver Scare Scale (VSS). A 75% favorable evolution was observed in the group A, while an 8% unfavorable evolution was observed in the group B that did not receive US therapy of 3 MHz. In the report from each echography, the average of improvement in soft tissues is 33.6%. The pain decreases a 42.4% furthermore in group B the pain increases a 15.5%, according to Face Pain Scale– Revised (FPS-R). This is the reason it is suggested that this therapy improves the evolution of scars in their pliability, height, vascularity and the pain. Conclusion: The use of the 3 MHz ultrasound is considered an effective and safe alternative therapy for pediatric patients with burn scars, who are looking for physical, functional, psychological and social reinsertion.