Excito-repellent and Pesticide-Likeness Properties of Essential Oils on Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae).

Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae) are insect pests that cause severe damage in important walnut growing regions in the northwest of Argentina. The current management approaches for these pests involve the use of unsafe phosphorus pesticides whose overuse have led to farmworker poisoning, pest resistance issues, and environmental contamination. Plant extracts, particularly essential oils, are an alternative source of insect control agents. Excito-repellent essential oils can be used to develop ecofriendly tools for managing the pest population without affecting quality and visual appearance of the stored walnuts. Laboratory studies were conducted to assess the excito-repellent effects of C. dimidiatus and O. mercator of 12 essential oils derived from aromatic plants used as food additives and traditional medicine in Argentina: Aloysia citrodora (AC), Aloysia gratissima (AG), Aloysia gratissima var. Gratissima (AGG), Blepharocalyx salicipholius (BS), Hyptis mutabilis (HM), Lippia junelliana (LJ), Lippia turbinata (LT), Mentha x piperita (MP), Minthostachys mollis (MM), Minthostachys verticillata (MV), Origanum vulgare(OV), and Rosmarinus officinalis (RO). The most bioactive EOs (ERijk ≥ 70%) were Aloysia gratissima var. Gratissima (AGG), Minthostachys verticillata, and Lippia junelliana. Their bioactivity profile and chemical space, characterized from GC-MS measures, Generalized Estimating Equations, and Hierarchical Cluster Analysis, revealed that they are mixtures of very functionalized molecules with physicochemical properties similar to those of insecticides with low residual property that enter the insect body through the respiratory system by inhalation. The AGG, MV, and LJ oils are promising as protective agents of walnut products. In our laboratory, studies of their formulations for use in integrated pest management programs are still ongoing.

Cu(II)-acylhydrazone complex, a potent and selective antitumor agent against human osteosarcoma: Mechanism of action studies over in vitro and in vivo models.

Osteosarcoma (OS) is a frequent bone cancer, affecting largely children and young adults. Cisplatin (CDDP) has been efficacious in the treatment of different cancer such us OS but the development of chemoresistance and important side effects leading to therapeutic failure. Novel therapies including copper compounds have shown to be potentially effective as anticancer drugs and one alternative to usually employed platinum compounds. The goal of this work is the evaluation of the in vitro and in vivo antitumoral activity and dilucidate the molecular target of a Cu(II) cationic complex containing a tridentate hydrazone ligand, CuHL for short, H2L=N'-'-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide, against human OS MG-63 cells. Anticancer activity on MG-63 cell line was evaluated in OS monolayer and spheroids. CuHL significantly impaired cell viability in both models (IC50 2D: 2.1 ± 0.3 µM; 3D: 9.1 ± 1.0 µM) (p < 0.001). Additional cell studies demonstrated the copper compound inhibits cell proliferation and conveys cells to apoptosis, determined by flow cytometry. CuHL showed a great genotoxicity, evaluated by comet assay. Proteomic analysis by Orbitrap Mass Spectometry identified 27 differentially expressed proteins: 17 proteins were found overexpressed and 10 underexpressed in MG-63 cells after the CuHL treatment. The response to unfolded protein was the most affected biological process. In addition, in vivo antitumor effects of the compound were evaluated on human OS tumors xenografted in nude mice. CuHL treatment, at a dose of 2 mg/kg i.p., given three times/week for one month, significantly inhibited the progression of OS xenografts and was associated to a reduction in mitotic index and to an increment of tumor necrosis (p < 0.01). Administration of standard-of-care cytotoxic agent CDDP, following the same treatment schedule as CuHL, failed to impair OS growth and progression.

Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics.

Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to the usually employed platinum-derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazone complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in endoplasmic reticulum stress and unfolded protein response, as well as the downregulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of gain-of-function-mutant p53. Moreover, we found a novel and interesting effect for a copper metallodrug, which was the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels.

Chemical composition and insecticidal activity of essential oils from cultivated and native aromatic plants of Argentina against Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae).

Essential oils from aerial parts of six aromatic plants were analysed by GC-MS. The major compounds identified were γ-terpinene (11.5%), cuminaldehyde (26.6%) and γ-terpinen-7-al (40.6%) in Cuminum cyminum, trans-anethol (95.2%) in Pimpinella anisum, α-pinene (11.6%), limonene (21.0%), ß-caryophyllene (22.3%) and α-humulene (16.7%) in Lippia integrifolia, limonene (40.8%) and artemisia ketone (19.3%) in Lippia junelliana, trans-ß-ocimene (15.6%), 4-ethyl-4-methyl-1-hexene (24.5%), trans-tagetone (20.5%) and verbenone (27.2%) in Tagetes minuta, 1,8-cineole (17.9%),elixene (10.3%) and spathulenol (13.8%) in Aloysia gratissima. Oils with strong insecticidal activity on Carpophilus dimidiatus and Oryzaephilus mercator were from P. anisum (LC50 = 4 µl/L; LC100 = 10 µl/L) and T. minuta (LC50=10.19-12.57 µl/L; LC100=20 µl/L). Scents of C. cyminum and L. junelliana were strong insecticides on O. mercator (LC50=7.02-7.17 µl/L; LC100=10.00-20.00 µl/L). The insecticidal activity was associated to the whole content of C10 molecules and oxygenated constituents. The P. anisum oil is promising as protective agent of nut products.

Anticancer Activity and Mechanism of Action Evaluation of an Acylhydrazone Cu(II) Complex toward Breast Cancer Cells, Spheroids, and Mammospheres.

The purpose of this work was to screen the anticancer activity and mechanisms of action of Cu(II)-acylhydrazone complex [Cu(HL)(H2 O)](NO3 )⋅H2 O, (CuHL), to find a potential novel agent for breast chemotherapies. Cytotoxicity studies on MCF7 cells demonstrated that CuHL has stronger anticancer properties than cisplatin over breast cancer cell models. Computational simulations showed that CuHL could interact in the minor groove of the DNA dodecamer, inducing a significant genotoxic effect on both cancer cells from 0.5 to 1 µM. In this sense, molecular docking and molecular dynamics simulations showed that the compound could interact with 20S proteasome subunits. Also, cell proteasome experiments using breast cancer cells revealed that the complex can inhibit proteasomal activity. Moreover, CuHL induced apoptosis in breast cancer cells at very low micromolar concentrations (0.5-2.5 µM) and displayed relevant anticancer activity over spheroids derived from MCF7 cells. Ultimately, CuHL diminished the number of mammospheres formed, disturbing their morphology and size.

DNA cleavage mechanism by metal complexes of Cu(II), Zn(II) and VO(IV) with a schiff-base ligand.

Metal ions and metal complexes are important components of nucleic acid biochemistry, participating both in regulation of gene expression and as therapeutic agents. Three new transition metal complexes of copper(II), zinc(II) and oxidovanadium(IV) with a ligand derived from o-vanillin and thiophene were previously synthesized and their antitumor properties were studied in our laboratory. To elucidate some molecular mechanisms tending to explain the cytotoxic effects observed over tumor cells, we investigated the interaction of these complexes with DNA by gel electrophoresis, UV-Vis spectroscopy, docking studies and molecular dynamics simulations. Our spectroscopy and computational results have shown that all of them were able to bind to DNA, Cu(II) complex is located in the minor groove while Zn(II) and oxidovanadium(IV) complexes act as major groove binding molecules. Interestingly, only the Cu(II) complex caused double-strand DNA nicks, consistent with its higher cytotoxic activities previously observed in tumor cell lines. We propose that the DNA-complex interaction destabilize the molecule either disrupting the phosphodiester bonds or impairing DNA replication, giving those complexes strong antitumor potential.

Modeling the Listeria innocua micropopulation lag phase and its variability.

Listeria innocua micropopulation lag phase and its variability have been modeled as a function of growth temperature, intensity of heat stress, and the number of surviving cells initiating growth. Micropopulation lag phases were found to correlate negatively with inoculum size and growth temperature and positively with heat shock intensity. Validation of the models using experimental milk samples indicated that the average lag phase duration predicted is shorter and more variable than the observed, meaning that they should be considered safe for risk assessment. Our results suggest that the effect of inoculum size on the population lag phase has both stochastic and physiological components.

Effects of electron beam irradiation on the variability in survivor number and duration of lag phase of four food-borne organisms.

The effect of electron beam irradiation on microbial inactivation and duration of lag time of individual surviving cells of Listeria innocua, Enterococcus faecalis, Pseudomonas fluorescens and Salmonella Enteritidis has been studied. In addition, the data on variability in microbial inactivation and duration of lag phase for surviving microbes have been fitted by normal and gamma distributions, respectively. The standard deviations of survivor number and lag phase duration of individual cells were higher in irradiated batches than in non-irradiated ones. Furthermore, the more intense the irradiation treatment was, the higher the variability in both survivor number and duration of lag phase of survivors. These findings should be considered in predictive models of microbial inactivation, in risk assessment, and in adjusting preserving and/or storage conditions in the food industry.

Pesquisaje de Alcoholismo en un Área de Salud / Screening of alcoholism in a health area

Se realizó un estudio prospectivo y descriptivo de 261 pacientes consumidores de alcohol correspondiente a un consultorio del área del Policlínico Docente "Bayamo Oeste" del municipio Bayamo, provincia Granma, en el período comprendido desde el 1ro de enero hasta el 31 de diciembre de 1995. Para determinar el tipo de consumo de cada uno de ellos y definir la proporción de alcohólicos en la población se realizó un pesquisaje en dicho consultorio y se encontraron los siguientes resultados: la mayoría de las personas que ingerían bebidas alcohólicas se encontraban comprendidas entre los 15 y 44 años de edad, el mayor porcentaje mantenía vínculo marital tanto en el sexo masculino como en el femenino. La ingestión de alcohol comenzó en edades muy tempranas en más de las dos terceras partes de los casos. El 44,5porciento comenzó a ingerir el tóxico entre los 16 y 20 años de edad, el 35,6 porciento entre los 21 y 25 años de edad, y el 7,3porciento entre los 10 y 15 años. El consumo social prevaleció en los cuestionarios aplicados; sin embargo, se encontró que los consumidores de riesgo fueron 43,3 porciento en el cuestionario de identificaciones diagnósticas (CID) y 44,1 porciento en el CAGE; el consumo dañino fue 9,6 porciento en el CID y 9,2 porciento en el CAGE, y la dependencia alcohólica 0,4 porciento en el CID y 0,8 CAGE. La mayoría de los bebedores moderados se encontraban comprendidos entre los 16 y 24 años de edad, y los de consumo dañino entre los 25 y 42 años

[A patient with gastrointestinal manifestations and the common variable immunodeficiency syndrome]. / Paciente con manifestaciones gastrointestinales y síndrome de inmunodeficiencia variable común.

A case of 26-year-old male patient is presented. He developed a "sprue-like" syndrome, giardiasis and nodular lymphoid hyperplasia of the gastrointestinal tract. After the immunological study, the common variable immunodeficiency diagnosis was established. Pathogenic and diagnosis aspects were analyzed. Therapeutic response was excellent.

[Analysis of early carcinoma of the stomach]. / Análisis del carcinoma gástrico precoz.

A review was made of 110 cases of early gastric cancer detected in our endoscopy unit over 13 years, confirming an incidence of about 10% with respect to all gastric cancers. On establishing statistical correlations between the diverse parameters studied, it was observed that cases with lymph node metastases should be considered a separate category of early gastric carcinoma as regards prognosis. Likewise, undifferentiated forms tend more to metastasize when located in the submucosa, although they are less invasive than the intestinal type. Finally, submucous location of the tumor clearly predisposes to the occurrence of metastases.