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Background: The management of HIV-positive patients with psoriasis is controversial and limited to individual cases or short series of patients. Objectives: To evaluate the safety and effectiveness of conventional and biologic immunosuppressive drugs in the treatment of patients with psoriasis and concomitant HIV infection. Methods: A retrospective multicenter study was conducted. The study included data from 2008 to 2016. Inclusion criteria were: HIV adult patients with moderate-to-severe psoriasis, HIV viral load determinations at baseline and at least after 6 months of treatment, and systemic immunosuppressive treatment for at least 6 months. A descriptive analysis was performed. Results: Twenty-three patients with plaque-type psoriasis and HIV infection (five with AIDS) were included. Median follow-up time was 3.2 years. The main drugs used were etanercept, methotrexate, and ustekinumab. In most cases, viral load and CD4 cell count not only remained stable but also improved throughout the follow-up. Six patients presented severe adverse events during the follow-up, four of them in the AIDS stage. At the end of the follow-up period, 76.5% of the patients had achieved a PASI 75. Conclusion: Biologic drugs, both anti-TNF alpha agents and ustekinumab, seem to have an acceptable safety profile and high effectiveness in HIV-positive patients.

There is a vast amount of studies which state that sleep is necessary for many functions, such as for encoding and consolidation of memory, for regulation of cognitive and emotional brain processes, for saving energy, for removing free radicals and for regulation of some neurotransmitters. Sleep disorders include a very frequent pathology of diverse origins. These disorders can appear alone or associated with each other, thereby making this pathology even more complex. In the second international classification of sleep disorders (ICSD-2), more than 90 sleep disorders are included divided in eight main categories. The most common sleep disorders include insomnia, sleep apnea, restless legs syndrome, and narcolepsy, with insomnia being the most prevalent among them. The treatment of insomnia for example, involves a great variety of treatments including psychological and behavioral therapies as well as pharmacological therapies. In many cases, combining the behavioral and pharmacological strategies results in the most efficacious treatment. In the past few years, melatonin receptors MT1 and MT2 have become one of the most interesting pharmacological targets for the treatment of many sleep disorders. Ever since the idea arose with regard to melatonin (MLT) acting as a hormonal photoperiodic messenger controlling the biological ¿clocks¿ of the individuals, the hypothesis that MLT administration might be a potential therapy to treat sleep disorders gained more acceptance. MLT exerts too many effects in the body including initiation and maintenance of sleep by the activation of MLT receptors MT1 and MT2. In the last few decades, a multitude of research groups have centered their efforts on the obtainment of new MT1 and MT2 receptor agonists in order to find a new drug for the treatment of diverse sleep disorders. All those compounds contain, without exception, an aliphatic chain substituted on a central aromatic ring and linked to an alkylamide or a derivative. Moreover, in the majority of these cases, the structures also possess an alkoxy group, generally a methoxy, joined to the central core. The principal aim of this work has been to synthesize new molecules as agonists of the melatonin receptors MT1 and MT2 with potential activity for the treatment of sleep disorders. In this sense, after having carried out an extensive bibliographical review, some initial compounds have been designed. Later, after obtaining the biological activity values, a SAR study has been performed and the starting hypothesis has been then redefined, followed by optimization of the initially designed structures. In addition, when enough data has been collected, alternative molecular modeling techniques have been included in this cycle that allows the discrimination of inactive molecules in stages previous to their synthesis. During this project forty-eight final compounds have been synthesized, for which four different synthetic routes have been optimized. Once the new derivatives have been chemically characterized, they have been sent to the ¿Institute de Recherches Servier¿ in France for being biologically evaluated in order to know their affinity for MT1/MT2 receptors first and their agonism/antagonism profile then. With this data a SAR study have been carried out which in combination with new bibliographic reviews performed have permit the redefinition of the starting hypothesis as well as of the initially designed structures. All these approaches have provided significantly promising results that open a new line of research for the development of future MT1/MT2 receptor agonists.

Rivista interdisciplinare di ricerca e intervento familiare

Since melatonin (MLT) was discovered, several physio-pathological functions have been associated with this hormone. One of the most important functions of this natural ligand is the regulation of sleep-wake cycles and its implication in insomnia and other sleep disorders. MLT exerts its actions through two GPCRs receptors, MT1 and MT2, which have been suggested as key targets in this area. Currently, numerous researches have focused their research on new melatoninergic ligands. We have reported design, synthesis and characterization of novel pyridazino[4,5-b]indole (PI) and indole (In) derivatives. In addition, these compounds have been evaluated biologically to melatonin receptors. Based on PI and In biological results, we designed a new pharmacophore to synthesize future leader ligands with potent affinity and activity to melatoninergic receptors with the following characteristics: an indole ring as central core, methoxy group substituted in the 6 position of indole ring, six-atom length distance between methoxy group and the first nitrogen atom of the side chain and two-methylene linker over the indole ring and attached to different nitrogenous chains such as N-acetamide, N-methylurea, N-ethylurea and N-methylsulfonamide.

As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-Noxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi. Compound 17, which was substituted with fluoro groups at the 6- and 7-positions of the quinoxaline ring, was the most active and selective in the cytotoxicity assay. The electrochemical study showed that the most active compounds, which were substituted by electron-withdrawing groups,possessed a greater ease of reduction of the N-oxide groups

Ever since the idea arose that melatonin might promote sleep and resynchronize circadian rhythms, many research groups have centered their efforts on obtaining new melatonin receptor ligands whose pharmacophores include an aliphatic chain of variable length united to an N-alkylamide and a methoxy group (or a bioisostere), linked to a central ring. Substitution of the indole ring found in melatonin with a naphthalene or quinoline ring leads to compounds of similar affinity. The next step in this structural approximation is to introduce a quinoxaline ring (a bioisostere of the quinoline and naphthalene rings) as the central nucleus of future melatoninergic ligands

Continuing with the efforts to identify new active compounds against malaria and leishmaniasis, fourteen new 3-amino-1,4-di-N-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies to analyze graphic SAR and ADME properties were undertaken. Results indicate that compounds with one halogenous group substituted in position 6 and 7 provide an efficient approach for further development of antimalarial and antileishmanial agents. In addition, interesting ADME properties were found

Se estudió el complejo de cambio en suelos aluviales recientes, terrazas medias y terrazas altas del Municipio de Marinilla por el método rápido de Brown. El grado de saturación, bajo en todos ellos, se acentúa en los suelos de las terrazas más antiguas y nos indica el bajo nivel de fertilidad de estos suelos. La extracción del hidrógeno de cambio con acetato cálcico coincide con la que efectúa el acetato amónico, excepto para los suelos más ricos en materia orgánica con los que proporciona resultados más altos la solución extractora de acetato cálcico.

The electrophoretic difference between normal glucose-6-phosphate dehydrogenase (G6PD) and two common variants (G6PD A and G6PD A-) has made the G6PD enzyme system very useful for genetic studies and for investigation on the clonal origin of tumors. This approach has not been possible for another common variant, G6PD mediterranean, which has a normal electrophoretic pattern. The different utilization of 2-deoxy-glucose-6-phosphate (2dG6P), an analog of the normal substrate, by the normal enzyme and the Mediterranean variant, allows a convenient determination of the degree of mosaicism in mononuclear cells from heterozygotes.

Se estudió el complejo de cambio en suelos aluviales recientes, terrazas medias y terrazas altas del Municipio de Marinilla por el método rápido de Brown. El grado de saturación, bajo en todos ellos, se acentúa en los suelos de las terrazas más antiguas y nos indica el bajo nivel de fertilidad de estos suelos. La extracción del hidrógeno de cambio con acetato cálcico coincide con la que efectúa el acetato amónico, excepto para los suelos más ricos en materia orgánica con los que proporciona resultados más altos la solución extractora de acetato cálcico.