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1.
Subst Use Misuse ; 58(8): 1046-1052, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37127921

RESUMO

Background: Alcohol use and the use of social media and other forms of digital communications is characteristic of young adults. The present study prospectively examined the relationship between social drinking motives and positive urgency and the engagement in regretted online social risk behaviors while drunk (having posted on social media, called or texted someone, or been visibly drunk in a photo) among a community sample of young adults. Methods: Using a targeted sampling procedure, we accessed a baseline sample of 360 young adults aged 18-25 years old from the community. Of these, 339 (mean age: 21.1 [SD = 2.21]; female = 50.7%) completed 2-month follow-up measures. Results: Social drinking motives and the tendency to act impulsively under conditions of positive affect (i.e. positive urgency) were measured at baseline, and frequency of regretted online social risk behaviors were measured at follow-up. Results showed that baseline social drinking motives were positively associated with all three regretted online social risk behaviors examined at follow-up. Higher baseline positive urgency scores were associated with a higher frequency of regretted posting on social media and calling or texting someone while drunk at follow-up. Conclusions: Our findings support the inclusion of positive urgency and social drinking motives as key components of preventive interventions aimed at reducing potential negative consequences of using social media and other forms of digital communications while under the effects of alcohol.


Assuntos
Intoxicação Alcoólica , Alcoolismo , Adulto Jovem , Humanos , Feminino , Adolescente , Adulto , Adaptação Psicológica , Comportamento Social , Motivação , Consumo de Bebidas Alcoólicas , Assunção de Riscos
2.
Molecules ; 28(21)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37959872

RESUMO

BACKGROUND: Antimicrobial resistance is one of the most pressing health issues of our time. The increase in the number of antibiotic-resistant bacteria allied to the lack of new antibiotics has contributed to the current crisis. It has been predicted that if this situation is not dealt with, we will be facing 10 million deaths due to multidrug resistant infections per year by 2050, surpassing cancer-related deaths. This alarming scenario has refocused attention into researching alternative drugs to treat multidrug-resistant infections. AIMS: In this study, the antimicrobial activities of four manganese complexes containing 1,2,3,-triazole and clotrimazole ligands have been evaluated. It is known that azole antibiotics coordinated to manganese tricarbonyl complexes display interesting antimicrobial activities against several microbes. In this work, the effect of the introduction of 1,2,3,-triazole-derived ligands in the [Mn(CO)3(clotrimazole)] fragment has been investigated against one Gram-positive bacterium and five Gram-negative bacteria. METHODS: The initial antimicrobial activity of the above-mentioned complexes was assessed by determining the minimum inhibitory and bactericidal concentrations using the broth microdilution method. Growth curves in the presence and absence of the complexes were performed to determine the effects of these complexes on the growth of the selected bacteria. A possible impact on cellular viability was determined by conducting the MTS assay on human monocytes. RESULTS: Three of the Mn complexes investigated (4-6) had good antimicrobial activities against all the bacteria tested, with values ranging from 1.79 to 61.95 µM with minimal toxicity. CONCLUSIONS: Due to the increased problem of antibiotic resistance and a lack of new antibacterial drugs with no toxicity, these results are exciting and show that these types of complexes can be an avenue to pursue in the future.


Assuntos
Manganês , Triazóis , Humanos , Triazóis/farmacologia , Manganês/farmacologia , Clotrimazol/farmacologia , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias , Testes de Sensibilidade Microbiana
3.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677663

RESUMO

Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, partly due to the ineffectiveness of the available antifungal agents. The rampant increase in infections recalcitrant to the current antifungals has worsened this scenario and made the discovery of new and more effective antifungals a pressing health issue. In this study, 65 extracts from marine organisms of the Yucatan Peninsula, Mexico, were screened for antifungal activity against Candida albicans and Candida glabrata, two of the most prevalent fungal species that cause nosocomial invasive fungal infections worldwide. A total of 51 sponges, 13 ascidians and 1 gorgonian were collected from the coral reef and mangrove forest in the Yucatan Peninsula (Mexico) and extracted with organic solvents. Nine crude extracts showed potent antifungal activity, of which four extracts from the sponge species Aiolochroia crassa, Amphimedon compressa, Monanchora arbuscula and Agelas citrina had promising activity against Candida spp. Bioassay-guided fractionation of the M. arbuscula extract revealed the remarkable fungicidal activity of some fractions. Analysis of the chemical composition of one of the most active fractions by UHPLC-HRMS and NMR indicated the presence of mirabilin B and penaresidin B, and their contribution to the observed antifungal activity is discussed. Overall, this work highlights marine organisms of the Yucatan Peninsula as important reservoirs of natural products with promising fungicidal activity, which may greatly advance the treatment of invasive fungal infections, especially those afflicting immunosuppressed patients.


Assuntos
Antifúngicos , Infecções Fúngicas Invasivas , Antifúngicos/química , Candida , México , Organismos Aquáticos , Testes de Sensibilidade Microbiana , Infecções Fúngicas Invasivas/tratamento farmacológico
4.
Environ Monit Assess ; 195(6): 796, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37264253

RESUMO

Efficient management of land use/land cover (LULC) features is vital for a balanced sustainable ecosystem. Thus, this work aimed to document the LULC changes in the less studied El Peñol-Guatapé reservoir, Antioquia, Colombia, especially in the reservoir area due to the construction of a hydro-electric power plant. For this study, Landsat images of 1977, 1986, 1997, and 2017 were used and the results indicated an increase in the settlement area and road networks by 0.10 and 0.60%, respectively, while during 1986 to 2017, cropland, plantation, dense forest, and open forest areas presented an increase of 0.52, 1.06, 2.87 and 2.61%, respectively. However, the marshy vegetation, scrub forest and fallow land decreased to - 0.51, - 3.79 and - 4.29%, respectively, in the same period. The water body before and after the completion of reservoir project denoted an increase from 13.1 km2 in 1977 to 45.7 km2 in 1986. This study provides a first-hand report on LULC dynamics in this tourism dominated municipalities that will serve as a reference for ecosystem management to reconcile the conflicts between different LULC classes in ecologically enriched regions.


Assuntos
Ecossistema , Monitoramento Ambiental , Colômbia , Monitoramento Ambiental/métodos , Florestas , Cidades , Conservação dos Recursos Naturais
5.
J Biol Inorg Chem ; 27(1): 49-64, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34713347

RESUMO

The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias Ovarianas , Animais , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Complexos de Coordenação/química , Feminino , Humanos , Manganês , Neoplasias Ovarianas/patologia , Peixe-Zebra
6.
Int J Mol Sci ; 23(21)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36362381

RESUMO

Ruthenium(II) arene complexes exhibit promising chemotherapeutic properties. In this study, the effect of the counter anion in Ru(II) complexes was evaluated by analyzing the biological effect of two Ru(II) p-cymene derivatives with the 1,10-phenanthroline-5,6-dione ligand of general-formula [(η6-arene)Ru(L)Cl][X] X = CF3SO3 (JHOR10) and PF6 (JHOR11). The biological activity of JHOR10 and JHOR11 was examined in the ovarian carcinoma cell line A2780, colorectal carcinoma cell line HCT116, doxorubicin-resistant HCT116 (HCT116-Dox) and in normal human dermal fibroblasts. Both complexes JHOR10 and JHOR11 displayed an antiproliferative effect on A2780 and HCT116 cell lines, and low cytotoxicity in fibroblasts. Interestingly, JHOR11 also showed antiproliferative activity in the HCT116-Dox cancer cell line, while JHOR10 was inactive. Studies in A2780 cells showed that JHOR11 induced the production of reactive oxygen species (ROS) that trigger autophagy and cellular senescence, but no apoptosis induction. Further analysis showed that JHOR11 presented no tumorigenicity, with no effect in the cellular mobility, as evaluated by thye wound scratch assay, and no anti- or pro-angiogenic effect, as evaluated by the ex-ovo chorioallantoic membrane (CAM) assay. Importantly, JHOR11 presented no toxicity in chicken and zebrafish embryos and reduced in vivo the proliferation of HCT116 injected into zebrafish embryos. These results show that these are suitable complexes for clinical applications with improved tumor cell cytotoxicity and low toxicity, and that counter-anion alteration might be a viable clinical strategy for improving chemotherapy outcomes in multidrug-resistant (MDR) tumors.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias Ovarianas , Rutênio , Animais , Humanos , Feminino , Rutênio/farmacologia , Rutênio/uso terapêutico , Peixe-Zebra , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Complexos de Coordenação/farmacologia , Proliferação de Células
7.
Int J Mol Sci ; 23(6)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35328692

RESUMO

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability.


Assuntos
RNA Longo não Codificante , Homeostase do Telômero , Cromatina/genética , Heterocromatina , Metilação , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Telômero/genética , Telômero/metabolismo
8.
Am J Pathol ; 190(9): 1867-1880, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32479821

RESUMO

The most commonly reported symptom of post-Ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent Ebola virus infection is not well characterized in human patients or animal models. Through immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by Ebola virus/Kikwit, Ebola virus/Makona-C05, and Marburg virus/Angola in the rhesus macaque model. Furthermore, histologic analysis, immunohistochemistry, RNAscope in situ hybridization, and transmission electron microscopy showed that synoviocytes of the stifle, shoulder, and hip are a target for mouse-adapted Ebola virus/Yambuku-Mayinga infection during acute disease in rhesus macaques. A time course of infection study with Ebola virus/Kikwit found that the large joint synovium became immunopositive beginning on postinfection day 6. In total, the synovium of 28 of 30 rhesus macaques with terminal filovirus disease had evidence of infection (64 of 96 joints examined). On the basis of immunofluorescence, infected cell types included CD68+ type A (macrophage-like) synoviocytes and CD44+ type B (fibroblast-like) synoviocytes. Cultured primary human fibroblast-like synoviocytes were permissive to infection with Ebola and Marburg viruses in vitro. Because synovial joints include immune privileged sites, these findings are significant for future investigations of filovirus pathogenesis and persistence as well as arthralgias in acute and convalescent filovirus disease.


Assuntos
Infecções por Filoviridae/virologia , Sinoviócitos/virologia , Animais , Células Cultivadas , Filoviridae , Humanos , Macaca mulatta
9.
Inorg Chem ; 60(11): 8011-8026, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-33973771

RESUMO

A new series of half-sandwich ruthenium(II) compounds [(η6-arene)Ru(L)Cl][CF3SO3] bearing 1,2,3-triazole ligands (arene = p-cymene, L = L1 (1); arene = p-cymene, L = L2 (2); arene = benzene, L = L1 (3); arene = benzene, L2 (4); L1 = 2-[1-(p-tolyl)-1H-1,2,3-triazol-4-yl]pyridine and L2 = 1,1'-di-p-tolyl-1H,1'H-4,4'-bi(1,2,3-triazole) have been synthesized and fully characterized by 1H and 13C NMR and IR spectroscopy, mass spectrometry, and elemental analysis. The molecular structures of 1, 2, and 4 have been determined by single-crystal X-ray diffraction. The cytotoxic activity of 1-4 was evaluated using the MTS assay against human tumor cells, namely ovarian carcinoma (A2780), colorectal carcinoma (HCT116), and colorectal carcinoma resistant to doxorubicin (HCT116dox), and against normal primary fibroblasts. Whereas compounds 2 and 4 showed no cytotoxic activity toward tumor cell lines, compounds 1 and 3 were active in A2780, while showing no antiproliferative effect in human normal dermal fibroblasts at the IC50 concentrations of the A2780 cell line. Exposure of ovarian carcinoma cells to IC50 concentrations of compound 1 or 3 led to an accumulation of reactive oxygen species and an increase of apoptotic and autophagic cells. While compound 3 displayed low levels of angiogenesis induction, compound 1 showed an ability to induce cell cycle delay and to interfere with cell migration. When the in vivo toxicity studies using zebrafish and chicken embryos are considered, compounds 1 and 3, which were not lethal, are promising candidates as anticancer agents against ovarian cancer due to their good cytotoxic activity in tumor cells and their low toxicity both in vitro and in vivo.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Rutênio/farmacologia , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Modelos Moleculares , Conformação Molecular , Rutênio/química , Triazóis/química
10.
Inorg Chem ; 60(5): 2914-2930, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33570919

RESUMO

Ruthenium(II) complexes are currently considered attractive alternatives to the widely used platinum-based drugs. We present herein the synthesis and characterization of half-sandwich ruthenium compounds formulated as [Ru(p-cymene)(L)Cl][CF3SO3] (L = 1,1-bis(methylenediphenylphosphano)ethylene, 1; L = 1,1-bis(diphenylphosphano)ethylene, 2), which were characterized by elemental analysis, mass spectrometry, 1H and 31P{1H} NMR, UV-vis and IR spectroscopy, conductivity measurements and cyclic voltammetry. The molecular structures for both complexes were determined by single-crystal X-ray diffraction. Their cytotoxic activity was evaluated using the MTT assay against human tumor cells, namely ovarian (A2780) and breast (MCF7 and MDA-MB-231). Both complexes were active against breast adenocarcinoma cells, with complex 1 exhibiting a quite remarkable cytotoxicity in the submicromolar range. Interestingly, at concentrations equivalent to the IC50 values in the MCF7 cancer cells, complexes 1 and 2 presented lower cytotoxicity in normal human primary fibroblasts. The antiproliferative effects of 1 and 2 in MCF7 cells might be associated with the induction of reactive oxygen species (ROS), leading to a combined cell death mechanism via apoptosis and autophagy. Despite the fact that in vitro a partial intercalation between complexes and DNA was observed, no MCF7 cell cycle delay or arrest was observed, indicating that DNA might not be a direct target. Complexes 1 and 2 both exhibited a moderate to strong interaction with human serum albumin, suggesting that protein targets may be involved in their mode of action. Their acute toxicity was evaluated in the zebrafish model. Complex 1 (the most toxic of the two) exhibited a lethal toxicity LC50 value about 1 order of magnitude higher than any IC50 concentrations found for the cancer cell models used, highlighting its therapeutic relevance as a drug candidate in cancer chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fosfinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Humanos , Fosfinas/síntese química , Fosfinas/metabolismo , Fosfinas/toxicidade , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química , Albumina Sérica Humana/metabolismo , Peixe-Zebra
11.
Int J Mol Sci ; 22(23)2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34884955

RESUMO

Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.


Assuntos
Aptâmeros de Nucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/administração & dosagem , Oxigênio/efeitos adversos , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neovascularização Retiniana/tratamento farmacológico , Animais , Aptâmeros de Nucleotídeos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Injeções Intravítreas , Camundongos , MicroRNAs/genética , Oligodesoxirribonucleotídeos/farmacologia , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/genética , Fosforilação/efeitos dos fármacos , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Neovascularização Retiniana/induzido quimicamente , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Nucleolina
12.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445620

RESUMO

The clinical success of cisplatin, carboplatin, and oxaliplatin has sparked the interest of medicinal inorganic chemistry to synthesize and study compounds with non-platinum metal centers. Despite Ru(II)-polypyridyl complexes being widely studied and well established for their antitumor properties, there are not enough in vivo studies to establish the potentiality of this type of compound. Therefore, we report to the best of our knowledge the first in vivo study of Ru(II)-polypyridyl complexes against breast cancer with promising results. In order to conduct our study, we used MCF7 zebrafish xenografts and ruthenium complexes [Ru(bipy)2(C12H8N6-N,N)][CF3SO3]2Ru1 and [{Ru(bipy)2}2(µ-C12H8N6-N,N)][CF3SO3]4Ru2, which were recently developed by our group. Ru1 and Ru2 reduced the tumor size by an average of 30% without causing significant signs of lethality when administered at low doses of 1.25 mg·L-1. Moreover, the in vitro selectivity results were confirmed in vivo against MCF7 breast cancer cells. Surprisingly, this work suggests that both the mono- and the dinuclear Ru(II)-polypyridyl compounds have in vivo potential against breast cancer, since there were no significant differences between both treatments, highlighting Ru1 and Ru2 as promising chemotherapy agents in breast cancer therapy.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Compostos de Rutênio/química , Compostos de Rutênio/farmacologia , Animais , Apoptose , Neoplasias da Mama/patologia , Proliferação de Células , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Técnicas In Vitro , Estrutura Molecular , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
13.
Molecules ; 26(18)2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34577006

RESUMO

Cisplatin and its derivatives are commonly used in chemotherapeutic treatments of cancer, even though they suffer from many toxic side effects. The problems that emerge from the use of these metal compounds led to the search for new complexes capable to overcome the toxic side effects. Here, we report the evaluation of the antiproliferative activity of Fe(II) cyclopentadienyl complexes bearing n-heterocyclic carbene ligands in tumour cells and their in vivo toxicological profile. The in vitro antiproliferative assays demonstrated that complex Fe1 displays the highest cytotoxic activity both in human colorectal carcinoma cells (HCT116) and ovarian carcinoma cells (A2780) with IC50 values in the low micromolar range. The antiproliferative effect of Fe1 was even higher than cisplatin. Interestingly, Fe1 showed low in vivo toxicity, and in vivo analyses of Fe1 and Fe2 compounds using colorectal HCT116 zebrafish xenograft showed that both reduce the proliferation of human HCT116 colorectal cancer cells in vivo.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos de Ferro/química , Compostos de Ferro/farmacologia , Metano/análogos & derivados , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Compostos Heterocíclicos/uso terapêutico , Compostos Heterocíclicos/toxicidade , Humanos , Concentração Inibidora 50 , Compostos de Ferro/uso terapêutico , Compostos de Ferro/toxicidade , Metano/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
14.
Actas Esp Psiquiatr ; 49(2): 71-80, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33686639

RESUMO

Dual pathology is often found in addiction and mental health centers. Although there are integrated services for these patients, most countries have developed joint action protocols between addiction and mental health centers. The objective is to analyze the progress of patients diagnosed with dual pathology, comparing the therapeutic outcomes of those who exclusively attend either addiction or mental health centers with those patients who follow a program in which the two services are coordinated. It is hypothesized that patients assisted in coordinate manner will present a better evolution on psychopathological symptomatology, drug use and functional impairment.


Assuntos
Transtornos Mentais/terapia , Serviços de Saúde Mental/organização & administração , Centros de Tratamento de Abuso de Substâncias/organização & administração , Transtornos Relacionados ao Uso de Substâncias/terapia , Diagnóstico Duplo (Psiquiatria) , Feminino , Humanos , Estudos Longitudinais , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/psicologia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Recidiva , Índice de Gravidade de Doença , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/psicologia
15.
J Infect Dis ; 221(Suppl 4): S419-S430, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-31687756

RESUMO

Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 µm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.


Assuntos
Infecções do Sistema Nervoso Central/virologia , Chlorocebus aethiops , Modelos Animais de Doenças , Infecções por Henipavirus/virologia , Vírus Nipah/fisiologia , Aerossóis , Animais , Infecções do Sistema Nervoso Central/patologia , Feminino , Infecções por Henipavirus/patologia , Masculino , Carga Viral
16.
Exp Eye Res ; 193: 107977, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32081668

RESUMO

Corneal neovascularization (CNV) is a common sight-threatening pathology that can be induced by a variety of inflammatory and angiogenic stimuli. Current CNV treatments include anti-inflammatory drugs and antibody-based inhibitors of vascular endothelial growth factor (VEGF). However, these are not always effective and novel therapeutic approaches are needed. Previous work has indicated a role for nucleolin (NCL) in VEGF-mediated neoangiogenesis in a suture-induced CNV model. The major goal for this current study is to test the effect of AS1411, a NCL-binding DNA aptamer that has reached human clinical trials, on neovascularization in a murine model of VEGF-mediated CNV. Our results show that topical administration of AS1411 can significantly inhibit corneal neovascularization in this model. Mechanistic studies indicate that AS1411 reduces the VEGF-stimulated proliferation, migration, and tube formation of primary cells obtained from human limbus stroma (HLSC). AS1411 treatment also significantly reduced VEGF-stimulated induction of miR-21 and miR-221 in HLSC, suggesting a role for these pro-angiogenic miRNAs in mediating the effects of AS1411 in this system. In sum, this new research further supports a role for NCL in the molecular etiology of CNV and identifies AS1411 as a potential anti-angiogenic CNV treatment that works by a novel mechanism of action.


Assuntos
Córnea/patologia , Neovascularização da Córnea/tratamento farmacológico , Oligodesoxirribonucleotídeos/farmacologia , Animais , Aptâmeros de Nucleotídeos , Movimento Celular , Proliferação de Células , Células Cultivadas , Córnea/efeitos dos fármacos , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/patologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
17.
Mar Drugs ; 18(1)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963310

RESUMO

Mexico is one of the three areas of the world with the greatest terrestrial and cultural biological diversity. The diversity of Mexican medicinal flora has been studied for a long time and several bioactive compounds have been isolated. The investigation of marine resources, and particularly the potential of Mexican marine resources, has not been intensively investigated, even though the Yucatan Peninsula occupies 17.4% of the total of the Mexican coast, with great biological diversity in its coasts and the ocean. There are very few studies on the chemistry of natural products from marine organisms that were collected along the coasts of the Yucatan Peninsula and most of them are limited to the evaluation of the biological activity of their organic extracts. The investigations carried out on marine species from the Yucatan Peninsula resulted in the identification of a wide structural variety of natural products that include polyketides, terpenoids, nitrogen compounds, and biopolymers with cytotoxic, antibacterial, antifouling, and neurotoxic activities. This review describes the literature of bioprospecting and the exploration of the natural product diversity of marine organisms from the coasts of the Yucatan Peninsula up to mid-2019.


Assuntos
Organismos Aquáticos/química , Produtos Biológicos/química , Animais , Biodiversidade , Humanos , México
18.
Am J Drug Alcohol Abuse ; 45(1): 108-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183371

RESUMO

BACKGROUND: Individuals with cocaine use disorder (CUD) often display behaviours that are paradoxically misaligned with their situation. Typical examples include poor treatment motivation and inconsistent self-reported craving. These behaviours may reflect impairments in the awareness of one's own behaviour. OBJECTIVES: We examined whether impaired self-awareness of addiction-related frontostriatal dysfunction (i.e., symptoms of apathy, disinhibition, and executive dysfunction) was associated with treatment motivation and craving. METHODS: Sixty-five outpatients with CUD (57 male) and their informants (those who knew the patient well) completed parallel self and informant versions of the Frontal Systems Behaviour Scale. Self-awareness was indexed through the discrepancy between self and informant scores in the three sub-scales; apathy, disinhibition and executive dysfunction. The University Rhode Island Change Assessment Scale assessed treatment motivation. Self-reported craving was assessed using a visual analogue scale. Multiple linear regression models examined associations between self-awareness and treatment motivation and craving, adjusting for sociodemographic factors and lifetime drug use. RESULTS: We found an inverse relationship between self-awareness of symptoms of disinhibition and treatment motivation maintenance. Although impaired awareness of disinhibition was also correlated with craving, this association was not significant after adjusting for sociodemographic factors and drug use. The apathy and executive dysfunction awareness scores were not associated with treatment motivation or craving. CONCLUSION: We show that people with lower insight into their disinhibition problems (e.g., impulsivity, mood instability) have more problems maintaining motivation when initiating treatment. Findings suggest that self-awareness interventions could be useful to prevent premature treatment dropout and improve addiction treatment outcomes.


Assuntos
Comportamento Aditivo/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Motivação , Autoimagem , Adulto , Transtornos Relacionados ao Uso de Cocaína/terapia , Fissura , Função Executiva , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Autorrelato
19.
J Environ Manage ; 250: 109453, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31551200

RESUMO

The aim of the article is to evaluate the national adaptation to climate change in the energy generation sector in Colombia via a composite index. To build an index, a framework by stages is used, which includes the definition of the main concepts that supports the measurements; the selection of the relevant indicators using a subject matter experts; standardization of the indicators using a mathematic formula regarding the relationship between the variables that represent the adaptation to climate change; and establishment of the weights using an analytic hierarchical process of paired comparisons and the aggregation of indicators to obtain the following three sub-indexes: reactive adaptation, wherein the replacement of hydraulic energy by thermal energy is evaluated; anticipatory adaptation, which measures the gap between the generation of total energy and the demand of the national energy system; and planned adaptation, which considers indicators such as the sectoral plan for adapting to climate change, the law of alternative energies, and the generation of alternative energies as a percentage of generation capacity. By adding these sub-indices, the climate change adaptation index (CCAI) is obtained. The results of CCAI show that progress was made from a reactive adaptation scenario in which the system vulnerability was high to an anticipatory adaptation scenario wherein the vulnerability was average, indicating that the foundations for this sector to build a planned adaptation are currently being laid.


Assuntos
Aclimatação , Mudança Climática , Colômbia , Fontes Geradoras de Energia , Governo
20.
Fish Shellfish Immunol ; 77: 131-138, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29605503

RESUMO

In crustaceans, lectins and hemocytes of the innate immune system provide the first line of defense. Although evidence points to the potential role of lectins in regulating hemocyte activity, the processes underlying the lectin activation have not been evaluated. In the present study, the receptor for CqL, a humoral lectin from Cherax quadricarinatus specific for galactose/sialic acid, was identified in a granular subset of hemocytes. The CqL receptor (CqLR) is a 490-kDa glycoprotein, composed of four identical 120-kDa subunits. As shown by immunohistochemistry, CqL at 7.5 µg/mL as optimal dose, after 2 min, induced, specifically on granular hemocytes, increased phosphorylation of serine (152%), threonine (192%), and tyrosine (242%) as compared with non-treated hemocytes; moreover, CqL induced increased generation of reactive oxygen species (ROS). Specific kinase inhibitors showed inhibition (P < 0.001) of ROS production induced by CqL. These results strongly suggest that CqL actively participated in the generation of ROS through kinases induced by a CqLR in a subset of granular hemocytes of the crayfish C. quadricarinatus. The results provide strong evidence that CqL activates, through specific granular hemocytes, receptors that modulate cellular functions in C. quadricarinatus.


Assuntos
Astacoidea/genética , Astacoidea/imunologia , Imunidade Inata , Lectinas/genética , Lectinas/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/sangue , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Hemócitos/imunologia , Lectinas/sangue , Alinhamento de Sequência , Transdução de Sinais
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