Effects of the tetravanadate [V4O12]4- anion on the structural, magnetic, and biological properties of copper/phenanthroline complexes.

The aim to access linked tetravanadate [V4O12]4- anion with mixed copper(II) complexes, using α-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)]2[Cu(dmb)(Gly)]2[V4O12]·9H2O (1) [Cu(dmb)(Lys)]2[V4O12]·8H2O (2), [Cu(dmp)2][V4O12]·C2H5OH·11H2O (3), and [Cu(dmp)(Gly)Cl]·2H2O (4), where dmb = 4,4'-dimethioxy-2,2'-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12]4- anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)]2+ units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cu⋯O/Cu⋯Cu bridges. Stability studies of water-soluble 3 and 4 by UV-Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)2]+ that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 ± 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 µM in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium-copper(II) systems.

Variabilidad climática y su influencia en la aparición del dengue en provincia Guantánamo

Introducción: El dengue es considerada una de las enfermedades más devastadoras a nivel mundial con un 40 % de la población viviendo en zonas de transmisión y de las más relacionadas con el clima. Objetivo: Determinar la incidencia de la variabilidad climática sobre la infestación por mosquito Aedes aegypti y la aparición del dengue en provincia Guantánamo en el periodo 2017-2019. Método: Se realizó una investigación descriptiva longitudinal, retrospectiva, donde el universo estuvo conformado por 9 municipios y 10 221 casos sospechosos de dengue. Se estudiaron las variables: infestación en depósitos por mosquitos Aedes aegypti según temporada climática, tasa de riesgo de arbovirosis según estratos, casos de dengue, temperatura y precipitación. Los datos fueron obtenidos de los registros meteorológicos mensuales y del departamento de Estadística del Centro Provincial de Higiene, Epidemiología y Microbiología. Se utilizaron frecuencias absolutas y relativas, la media, desviación estándar y coeficiente de correlación de Pearson. Resultados: La temperatura media anual varió 1 °C, los valores medios de humedad relativa y precipitación disminuyeron e impactaron en todos los estratos. La infestación ascendió con la mayor tasa de riesgo de dengue en el estrato de clima tropical de sabana, razón de tasa 0,63 (IC 95 %: 0,59-0,67) P=0,000. La temperatura y precipitación guardaron la mayor relación de asociación lineal con infestación y tasa de riesgo de dengue con coeficiente de correlación lineal R2=0,9 y R2=0,8. Conclusiones: La variabilidad climática ejerce efectos favorecedores sobre la infestación por Aedes aegypti y la transmisión de dengue durante la temporada climática húmeda, con correlación significativa en todos los estratos.

Introduction: Dengue virus is considered one of the most devastating diseases worldwide with 40% of the population living in transmission areas and one of the most climate-related diseases. Objective: To determine the incidence rate of climate variability on Aedes aegypti mosquito infestation and dengue virus appearing in Guantanamo province, period time 2017-2019. Method: A retrospective, longitudinal, descriptive research was carried out, in which 9 municipalities and 10,221 suspected cases of dengue fever were selected (as universe). The variables studied were as follows: infestation in reservoirs by Aedes aegypti mosquitoes according to climatic season, arboviroses risk rate according to stratum, dengue cases, temperature and precipitation. Data were obtained from monthly meteorological records and from the Statistics Department of Centro Provincial de Higiene, Epidemiología y Microbiología. It was used the absolute and relative frequencies, mean frequency, the standard deviation and the Pearson correlation coefficient. Results: Mean annual temperature varied by 1 °C, mean values of relative humidity and precipitation decreased and impacted all stratums. Infestation ascended with the highest dengue risk rate in the tropical savanna climate stratum, rate ratio 0.63 (95 % CI: 0.59-0.67) P=0.000. Temperature and precipitation had the strongest linear association with Aedes aegypti mosquito infestation and dengue risk rate with the linear correlation coefficient of R2=0.9 and R2=0.8. Conclusions: Climatic variability has a favorable effect on Aedes aegypti infestation and dengue transmission during the wet season, with a significant correlation in all stratums.

Introdução: A dengue é considerada uma das doenças mais devastadoras em todo o mundo com 40% da população vivendo em áreas de transmissão e uma das mais relacionadas ao clima. Objetivo: Determinar a incidência da variabilidade climática na infestação pelo mosquito Aedes aegypti e o aparecimento da dengue na província de Guantánamo no período 2017-2019. Método: Realizou-se uma investigação descritiva retrospectiva longitudinal, onde o universo foi constituído por 9 municípios e 10.221 casos suspeitos de dengue. As variáveis estudadas foram: infestação em armazéns por mosquitos Aedes aegypti de acordo com a estação climática, taxa de risco de arbovirose de acordo com estratos, casos de dengue, temperatura e precipitação. Os dados foram obtidos dos registos meteorológicos mensais e do Departamento de Estatística do Centro Provincial de Higiene, Epidemiología y Microbiología. Foram utilizadas frequências absolutas e relativas, média, desvio padrão e coeficiente de correlação de Pearson. Resultados: A temperatura média anual variou 1°C, os valores médios de umidade relativa e precipitação diminuíram e impactaram todos os estratos. A infestação aumentou com a maior taxa de risco de dengue no estrato climático de savana tropical, razão de taxa 0,63 (IC 95%: 0,59-0,67) P=0,000. Temperatura e precipitação tiveram a maior relação de associação linear com infestação de dengue e taxa de risco com coeficiente de correlação linear R2=0,9 e R2=0,8. Conclusões: A variabilidade climática exerce efeitos favoráveis na infestação por Aedes aegypti e na transmissão da dengue durante a estação chuvosa, com correlação significativa em todos os estratos.

Cyclo-tetravanadate bridged copper complexes as potential double bullet pro-metallodrugs for cancer treatment.

Over the last decade, copper and vanadium complexes have shown promising properties for the treatment of several types of cancer. In particular, Casiopeinas®, a group of copper-based complexes, has received specific attention, and their mechanism of action has been extensively studied since their structure is simple and their synthesis may be affordable. Similarly, vanadium-containing compounds in the form of complexes and simple polyoxovanadates have also been studied as antitumor agents. Here, potential prodrugs that would release the two metals, V and Cu, in usable form to act in conjunction against cancer cells are reported. The new series of Casiopeinas-like compounds are bridged by a cyclotetravanadate ion with the generic formula [Cu(N,N')(AA)]2•(V4O12), where (N,N') represent 1,10-phenanthroline and 2,2'-bipyridine, and (AA) are aminoacidate ions (Lysine and Ornithine). The compounds were characterized by elemental analysis, single-crystal X-ray diffraction and Visible, FTIR, and Raman spectroscopies, as well as 51V NMR, EPR, and Thermogravimetric Analysis. Additionally, theoretical calculations based on the Density Functional Theory (DFT) were carried out to model the compounds. Optimized structures, theoretical IR, and Raman spectra were also obtained, as well as docking analysis to test DNA interactions with the casiopeina-like complexes. The compounds may act as prodrugs by providing acting molecules that have showed potential pharmacological properties for the treatment of several types of cancer.

Vanadium in Biological Action: Chemical, Pharmacological Aspects, and Metabolic Implications in Diabetes Mellitus.

Vanadium compounds have been primarily investigated as potential therapeutic agents for the treatment of various major health issues, including cancer, atherosclerosis, and diabetes. The translation of vanadium-based compounds into clinical trials and ultimately into disease treatments remains hampered by the absence of a basic pharmacological and metabolic comprehension of such compounds. In this review, we examine the development of vanadium-containing compounds in biological systems regarding the role of the physiological environment, dosage, intracellular interactions, metabolic transformations, modulation of signaling pathways, toxicology, and transport and tissue distribution as well as therapeutic implications. From our point of view, the toxicological and pharmacological aspects in animal models and humans are not understood completely, and thus, we introduced them in a physiological environment and dosage context. Different transport proteins in blood plasma and mechanistic transport determinants are discussed. Furthermore, an overview of different vanadium species and the role of physiological factors (i.e., pH, redox conditions, concentration, and so on) are considered. Mechanistic specifications about different signaling pathways are discussed, particularly the phosphatases and kinases that are modulated dynamically by vanadium compounds because until now, the focus only has been on protein tyrosine phosphatase 1B as a vanadium target. Particular emphasis is laid on the therapeutic ability of vanadium-based compounds and their role for the treatment of diabetes mellitus, specifically on that of vanadate- and polioxovanadate-containing compounds. We aim at shedding light on the prevailing gaps between primary scientific data and information from animal models and human studies.

Decavanadate Salts of Cytosine and Metformin: A Combined Experimental-Theoretical Study of Potential Metallodrugs Against Diabetes and Cancer.

Cytosine, a DNA and RNA building-block, and Metformin, the most widely prescribed drug for the treatment of Type 2 Diabetes mellitus were made to react separately with ammonium or sodium metavanadates in acidic aqueous solutions to obtain two polyoxovanadate salts with a 6:1 ratio of cation-anion. Thus, compounds [HCyt]6[V10O28]·4H2O, 1 and [HMetf]6[V10O28]·6H2O, 2 (where HCyt = Cytosinium cation, [C4H6N3O]+ and HMetf = Metforminium cation, [C4H12N5]+) were obtained and characterized by elemental analysis, single crystal X-ray diffraction, vibrational spectroscopy (IR and Raman), solution 51V-NMR, thermogravimetric analysis (TGA-DTGA), as well as, theoretical methods. Both compounds crystallized in P 1 ¯   space group with Z' = 1/2, where the anionic charge of the centrosymmetric ion [V10O28]6- is balanced by six Cytosinium and six Metforminium counterions, respectively. Compound 1 is stabilized by π-π stacking interactions coming from the aromatic rings of HCyt cations, as denoted by close contacts of 3.63 Å. On the other hand, guanidinium moieties from the non-planar HMetf in Compound 2 interact with decavanadate µ2-O atoms via N-H···O hydrogen bonds. The vibrational spectroscopic data of both IR and Raman spectra show that the dominant bands in the 1000-450 cm-1 range are due to the symmetric and asymmetric ν(V-O) vibrational modes. In solution, 51V-NMR experiments of both compounds show that polyoxovanadate species are progressively transformed into the monomeric, dimeric and tetrameric oxovanadates. The thermal stability behavior suggests a similar molecular mechanism regarding the loss of water molecules and the decomposition of the organic counterions. Yet, no changes were observed in the TGA range of 540-580°C due to the stability of the [V10O28]6- fragment. Dispersion-corrected density functional theory (DFT-D) calculations were carried out to model the compounds in aqueous phase using a polarized continuum model calculation. Optimized structures were obtained and the main non-covalent interactions were characterized. Biological activities of these compounds are also under investigation. The combination of two therapeutic agents opens up a window toward the generation of potential metalopharmaceuticals with new and exciting pharmacological properties.

Pharmacological and Toxicological Threshold of Bisammonium Tetrakis 4-(N,N-Dimethylamino)pyridinium Decavanadate in a Rat Model of Metabolic Syndrome and Insulin Resistance.

Vanadium(IV/V) compounds have been studied as possible metallopharmaceutical drugs against diabetes mellitus. However, mechanisms of action and toxicological threshold have been tackled poorly so far. In this paper, our purposes were to evaluate the metabolic activity on dyslipidemia and dysglycemia, insulin signaling in liver and adipose tissue, and toxicology of the title compound. To do so, the previously reported bisammonium tetrakis 4-(N,N-dimethylamino)pyridinium decavanadate, the formula of which is [DMAPH]4(NH4)2[V10O28]·8H2O (where DMAPH is 4-dimethylaminopyridinium ion), was synthesized, and its dose-response curve on hyperglycemic rats was evaluated. A Long-Evans rat model showing dyslipidemia and dysglycemia with parameters that reproduce metabolic syndrome and severe insulin resistance was generated. Two different dosages, 5 µmol and 10 µmol twice a week of the title compound (equivalent to 2.43 mg·V/kg/day and 4.86 mg·V/kg/day, resp.), were administered intraperitoneal (i.p.) for two months. Then, an improvement on each of the following parameters was observed at a 5 µmol dose: weight reduction, abdominal perimeter, fatty index, body mass index, oral glucose tolerance test, lipid profile, and adipokine and insulin resistance indexes. Nevertheless, when the toxicological profile was evaluated at a 10 µmol dose, it did not show complete improvement, tested by the liver and adipose histology, as well as by insulin receptor phosphorylation and GLUT-4 expression. In conclusion, the title compound administration produces regulation on lipids and carbohydrates, regardless of dose, but the pharmacological and toxicological threshold for cell regulation are suggested to be up to 5 µmol (2.43 mg·V/kg/day) dose twice per week.

Metforminium Decavanadate as a Potential Metallopharmaceutical Drug for the Treatment of Diabetes Mellitus.

New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM) and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca), a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatments with 3.7 µg (2.5 µM)/300 g/twice a week for DM2 and 7.18 µg (4.8 µM)/300 g/twice a week for DM1 of MetfDeca, respectively, were administered. The resulting pharmacological data showed nontoxicological effects on liver and kidney. At the same time, MetfDeca showed an improvement of carbohydrates and lipids in tissues and serum. MetfDeca treatment was better than the monotherapies with metformin for DM2 and insulin for DM1. Additionally, MetfDeca showed a protective effect on pancreatic beta cells of DM1 rats, suggesting a possible regeneration of these cells, since they recovered their insulin levels. Therefore, MetfDeca could be considered not only as an insulin-mimetic agent, but also as an insulin-enhancing agent. Efforts to elucidate the mechanism of action of this compound are now in progress.

Hypoglycemic, lipid-lowering and metabolic regulation activities of metforminium decavanadate (H2Metf)3 [V10O28]·8H2O using hypercaloric-induced carbohydrate and lipid deregulation in Wistar rats as biological model.

Because of the increasing global spread of type 2 diabetes mellitus, there is a need to develop new antidiabetic agents. Recently we have synthesized new decavanadates using metformin as counterion. In particular, the compound containing three metforminium dications has been obtained in high yield and has been completely characterized. Biological studies using Wistar rats that have been fed with a high caloric diet inducing insulin resistance and metabolic syndrome were carried out. Results of the impact on key biochemical parameters mediated by metformin alone and the new compound are here presented. The metforminium decavanadate (H2Metf)3[V10O28]·8H2O, abbreviated as Metf-V10O28, was shown to have pharmacological potential as a hypoglycemic, lipid-lowering and metabolic regulator, since the resulting compound made of the two components with antidiabetic activities, reduces both dosage and time of administration (twice a week). Hence, due to the beneficial effects induced by the metforminium decavanadate we recommend to continue the exploration into the mechanism and toxicology of this new compound.

Riesgo de aparición de eventos de enfermedad diarreica aguda en provincia Guantánamo: estratificación epidemiológica / Event risk of acute diarrheal disease in Guantanamo province: epidemiological stratification

Las enfermedades diarreicas agudas constituyen un problema de salud preocupante en el individuo, la familia y en entornos sociales. Se realiza un estudio en el período de octubre de 2012 a febrero de 2013 en la provincia Guantánamo, con la finalidad de estimar el orden desfavorable de los municipios respecto al riesgo de aparición de dicha enfermedad en la provincia Guantánamo. Se utiliza el método de estratificación epidemiológica a través del cálculo de un índice resumido, lo que implicó trabajar con los municipios como grupos poblacionales y como indicadores, la morbilidad de enfermedades diarreicas agudas, los resultados microbiológicos de muestras de agua y alimentos con aislamiento de gérmenes patógenos, la población no beneficiada con acueducto, la población en riesgo por estar expuesta a fosas y a enfermar de cólera. Los resultados indicaron a los municipios de Niceto Pérez y Guantánamo como el estrato muy desfavorable. Finalmente se emiten conclusiones y recomendaciones(AU)

Acute diarrheal diseases are a pressing health problem in the individual, the family and social environments. A study was conducted from October 2012 to February 2013 in the province Guantánamo, in order to estimate the unfavorable order of the municipalities regarding the risk of that disease in Guantanamo. Epidemiological stratification method is used through the calculation of a summary index, which involved working with municipalities and population groups and as indicators, the morbidity of acute diarrheal diseases, microbiological results from water samples and insulated food germs pathogens, the population benefited aqueduct, the population at risk for being exposed to sick pits and cholera. The results indicated the municipalities of Niceto Perez and Guantanamo as very unfavorable stratum. Finally conclusions and recommendations are issued(AU)

Desafíos ambientales para la prevención de cólera en la provincia Guantánamo / Environmental Challenges for the prevention of cholera in the province of Guantanamo

Se realiza un estudio para identificar aspectos ambientales relacionados con el cólera en los municipios de la provincia Guantánamo. Actualmente, se viene estudiando la compleja relación entre las condiciones ecológicas del medio y la dinámica poblacional de este, con el fin de poder conocer qué variables son las críticas en el surgimiento de un proceso infectivo o una epidemia de ahí que las acciones intencionadas sobre el medio ambiente para prevenir el cólera siempre deberán ser prioritarias en las estrategias de reordenamiento ambiental. Las variables estudiadas fueron la población no beneficiada por acueductos, indicadores de interés sobre los residuales líquidos, el número de fosas existentes, datos relacionados con el manejo de residuales sólidos, así como los resultados relacionados con el aislamiento y tipificación de gérmenes en las muestras de agua y alimentos estudiadas. Finalmente se emiten conclusiones y recomendaciones(AU)

A study was conducted to identify environmental aspects of cholera in the towns of Guantanamo. Currently, two aspects are studied such as: the complex relationship between the ecological conditions of the environment and population dynamics, in order to know which variables are critical in the emergence of an infectious process or an epidemic hence, intentional actions on environment to prevent cholera should always be a priority in environmental reorganization strategies. The variables were studied as: the population with no benefit from waterworks, indicators of interest on liquid waste, the number of existing tanks, data related to the management of solid waste and results related to the isolation and characterization of bacteria in samples of water and foods. Finally conclusions and recommendations are issued

Prevalencia de asma ocupacional en trabajadores expuestos pertenecientes al municipio Guantánamo / Occupational asthama prevalence in exposed workers belonging to Guantánamo Municipality

Se realizó un estudio de corte transversal para estimar la prevalencia de asma ocupacional en la población laboral expuesta del municipio Guantánamo durante el período de julio del 2000 a febrero del 2001. El universo de estudio estuvo integrado por 838 trabajadores pertenecientes a la industria sideromecánica y a la construcción; se trabajó con una muestra de 189 trabajadores, quienes fueron seleccionados a través de un muestreo estratificado polietápico. Se encontró que el mayor numero de trabajadores corresponden al sexo masculino, siendo la exposición ocupacional a polvos, y el tiempo de exposición elementos significativos de predicción de asma. Los síntomas y signos encontrados en la serie de estudio, en orden de frecuencia corresponden a la hiperreactividad bronquial con 58.3 (por ciento), tos 25.0 (por ciento), disnea 14.2 (por ciento) y sibilancia 2.3 (por ciento), asociándose la disfunción ventilatoria obstructiva reversible en 52.3 (por ciento) y los resultados positivos del prick- test en 66.7 (por ciento) de los individuos estudiados. Esta última constituye un elemento significativo de predicción de asma. Se detectan, según criterios de Brook, 17 trabajadores con diagnóstico de asma ocupacional, lo que representa una tasa general de 2 (por ciento)(AU)

Prevalencia de asma ocupacional en trabajadores expuestos pertenecientes al municipio Guantánamo / Occupational asthama prevalence in exposed workers belonging to Guantánamo Municipality

Se realizó un estudio de corte transversal para estimar la prevalencia de asma ocupacional en la población laboral expuesta del municipio Guantánamo durante el período de julio del 2000 a febrero del 2001. El universo de estudio estuvo integrado por 838 trabajadores pertenecientes a la industria sideromecánica y a la construcción; se trabajó con una muestra de 189 trabajadores, quienes fueron seleccionados a través de un muestreo estratificado polietápico. Se encontró que el mayor numero de trabajadores corresponden al sexo masculino, siendo la exposición ocupacional a polvos, y el tiempo de exposición elementos significativos de predicción de asma. Los síntomas y signos encontrados en la serie de estudio, en orden de frecuencia corresponden a la hiperreactividad bronquial con 58.3 (por ciento), tos 25.0 (por ciento), disnea 14.2 (por ciento) y sibilancia 2.3 (por ciento), asociándose la disfunción ventilatoria obstructiva reversible en 52.3 (por ciento) y los resultados positivos del prick- test en 66.7 (por ciento) de los individuos estudiados. Esta última constituye un elemento significativo de predicción de asma. Se detectan, según criterios de Brook, 17 trabajadores con diagnóstico de asma ocupacional, lo que representa una tasa general de 2 (por ciento)(AU)