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1.
RSC Adv ; 14(34): 24928-24941, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39135973

RESUMO

A series of 3-cyano-2(1H)-pyridones 4a-c were efficiently synthesized using an expeditious microwave-assisted multicomponent approach. Single-crystal XRD analysis revealed the presence of six independent molecules in the asymmetric unit cell for all compounds, with the crystal packing stabilized by a network of cyclic dimers formed by N-H⋯O[double bond, length as m-dash]C and C-H⋯O[double bond, length as m-dash]C intermolecular interactions. Additional supramolecular interactions, including C-H⋯π, C-N⋯π, and π⋯π, and C-H⋯X (for halogenated derivatives, i.e., 4b and 4c), appear crucial for crystal stabilization. Density Functional Theory (DFT) calculations were employed to understand the electronic structures and potential binding affinities. Comprehensive spectroscopic characterization by FT-IR, UV-Vis, NMR, and HMRS techniques confirmed the structures of all synthesized compounds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed to evaluate the thermal stability of these compounds. The in vitro anticancer activity was evaluated against a panel of 60 human cancer cell lines, demonstrating promising activity against non-small-cell lung and breast cancer cell lines. Notably, compounds 4a and 4c exhibited the highest anticancer activity against the HOP-92 and MCF7 cell lines, with growth inhibition percentages (GI%) of 54.35 and 40.25, respectively.

2.
Chempluschem ; 89(9): e202400172, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38840415

RESUMO

Herein, a Cs2CO3-promoted N-alkylation of 3-cyano-2(1H)-pyridones containing alkyl groups with diverse alkyl halides to synthesize N-alkyl-2-pyridones over O-alkylpyridines is reported. The use of alkyl dihalides resulted in complex mixtures of N- and O-alkylated products. The primary factor influencing regioselectivity in these reactions is the electronic effects of substituents on the 2(1H)-pyridone ring, as evidenced by the preferential formation of O-alkylpyridines upon the introduction of aryl groups. Remarkably, we efficiently employed CuAAC and Ti(Oi-Pr)4-catalyzed amidation reactions to functionalize N-alkyl-2-pyridones containing propargyl and ester groups, leading to the synthesis of 1,2,3-triazoles and amides, respectively. Moreover, O-alkylpyridines 10 b and 10 d displayed remarkable selectivity toward the A-498 renal cancer cell line with growth inhibition percentages (%GI) of 54.75 and 67.64, respectively. The binding modes of compounds 10 b and 10 d to the PIM-1 kinase enzyme were determined through molecular docking studies.


Assuntos
Antineoplásicos , Simulação de Acoplamento Molecular , Piridonas , Humanos , Piridonas/química , Piridonas/farmacologia , Piridonas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Alquilação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Carbonatos/química , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Estrutura Molecular , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores
3.
RSC Adv ; 12(54): 34965-34983, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36540221

RESUMO

2-Pyridone-containing heterocycles are considered privileged scaffolds in drug discovery due to their behavior as hydrogen bond donors and/or acceptors and nonpeptidic mimics, and remarkable physicochemical properties such as metabolic stability, solubility in water, and lipophilicity. This review provides a comprehensive overview of multicomponent reactions (MCRs) for the synthesis of 2-pyridone-containing heterocycles. In particular, it covers the articles published from 1999 to date related to anticancer, antibacterial, antifungal, anti-inflammatory, α-glucosidase inhibitor, and cardiotonic activities of 2-pyridone-containing heterocycles obtained exclusively by an MCR. The discussion focuses on bioactivity data, synthetic approaches, plausible reaction mechanisms, and molecular docking simulations to facilitate comparison and underscore the applications of the 2-pyridone motif in drug discovery and medicinal chemistry. We also present our conclusions and outlook for the future.

4.
Mol Ther Methods Clin Dev ; 27: 391-403, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36381303

RESUMO

The insect cell-based baculovirus expression vector (BEV) system is a leading platform for scalable production of adeno-associated viruses (AAVs). The previously described One-Bac system consists of an insect packaging cell line harboring the AAV Rep and Cap genes and a BEV carrying the transgene and AAV inverted terminal repeats. Here we describe a new system where we successfully translated the molecular design of a double AAV Rep expression cassette to inducible plasmid vectors. These optimized plasmid vectors employ non-canonical late promoters and alternative start codons that alleviate promoter-promoter competition. Because too much Rep expression can be toxic to the host cells, tighter regulation of AAV Rep expression is warranted. This has been achieved by adopting alternate baculovirus homologous region enhancers. Inoculation of the resultant stable insect Rep packaging cell line by a recombinant BEV produced high-titer recombinant AAV (rAAV) preparations (1 × 1011 genome copies/mL). Sequential batch reactor experiments indicate that this system is amenable to large-scale AAV production. We generated an insect packaging cell line that employs an optimized Rep gene control system, ensuring stable and appropriate Rep expression. This platform produces potent and high-yield AAV particles and demonstrates potential for scale up.

5.
Mol Pharm ; 19(2): 414-431, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34967632

RESUMO

Nanoconfinement is a recent strategy to enhance solubility and dissolution of active pharmaceutical ingredients (APIs) with poor biopharmaceutical properties. In this work, we combine the advantage of cocrystals of racemic praziquantel (PZQ) containing a water-soluble coformer (i.e., increased solubility and supersaturation) and its confinement in a mesoporous silica material (i.e., increased dissolution rate). Among various potential cocrystalline phases of PZQ with dicarboxylic acid coformers, the cocrystal with glutaric acid (PZQ-GLU) was selected and successfully loaded by the melting method into nanopores of SBA-15 (experimental pore size of 5.6 nm) as suggested by physical and spectroscopic characterization using various complementary techniques like N2 adsorption, powder X-ray diffraction (PXRD), infrared spectroscopy (IR), solid-state NMR (ss-NMR), differential scanning calorimetry (DSC), and field emission-scanning electron microscopy (FE-SEM) analysis. The PZQ-GLU phase confined in SBA-15 presents more mobility according to ss-NMR studies but still retains its cocrystal-like features in the IR spectra, and it also shows depression of the melting transition temperature in DSC. On the contrary, pristine PZQ loaded into SBA-15 was found only in the amorphous state, according to the aforementioned studies. This dissimilar behavior of the composites was attributed to the larger crystal lattice of PZQ over the PZQ-GLU cocrystal (3320.1 vs 1167.9 Å3) and to stronger intermolecular interactions between PZQ and GLU, facilitating the confinement of a more mobile solid-like phase in the constrained channels. Powder dissolution studies under extremely nonsink conditions (SI = 0.014) of the confined PZQ-GLU and amorphous PZQ phases embedded in mesoporous silica showed transient supersaturation behavior when dissolving in simulated gastric fluid (HCl pH 1.2 at 37 ± 0.5 °C) in a similar fashion to the bare cocrystal PZQ-GLU. A comparison of the area under the curve (AUC0-90 min) of the dissolution profiles afforded a dissolution advantage of 2-fold (p < 0.05) of the new solid phases over pristine racemic PZQ after 90 min; under these conditions, the solubilized API reprecipitated as the recently discovered PZQ hemihydrate (PZQ-HH). In the presence of a cellulosic polymer, sustained solubilization of PZQ from composites SBA-15/PZQ or SBA-15/PZQ-GLU was observed, increasing AUC0-90 min up to 5.1-fold in comparison to pristine PZQ. The combination of a confined solid phase in mesoporous silica and a methylcellulose polymer in the dissolution medium effectively maintained the drug solubilized during times significant to promote absorption. Finally, powder dissolution studies under intermediate nonsink conditions (SI = 1.99) showed a fast release profile from the nanoconfined PZQ-GLU phase in SBA-15, which reached rapid saturation (95% drug dissolved at 30 min); the amorphous PZQ composite and bare PZQ-GLU also displayed an immediate release of the API but at a lower rate (69% drug dissolved at 30 min). In all of these cases, a large dissolution advantage was observed from any of the novel solid phases over PZQ.


Assuntos
Praziquantel , Dióxido de Silício , Varredura Diferencial de Calorimetria , Preparações Farmacêuticas , Praziquantel/química , Dióxido de Silício/química , Solubilidade , Difração de Raios X
6.
Rev. colomb. cir ; 36(3): 462-470, 20210000. tab
Artigo em Espanhol | LILACS | ID: biblio-1254292

RESUMO

Introducción. La colecistectomía es uno de los procedimientos quirúrgicos más realizados a nivel mundial, por lo que su aprendizaje es cada vez más necesario para los médicos residentes en entrenamiento, pero sin comprometer la seguridad de los pacientes. El objetivo de este estudio fue determinar el impacto de la participación de los médicos residentes en los principales desenlaces clínicos de la colecistectomía. Métodos. Se realizó un estudio prospectivo de cohortes, donde se incluyeron los pacientes llevados a colecistectomía laparoscópica, desde junio de 2019 hasta julio de 2020. Se llevó a cabo el análisis estadístico para describir medidas de frecuencia, tendencia central, dispersión y análisis bivariados para los desenlaces de interés. Resultados. Se incluyeron 482 pacientes a quienes se les practicó colecistectomía, 475 de ellas por vía laparoscópica. El 62,5 % fueron mujeres y el 76,2 % se realizaron de carácter urgente. En el 96 % de los procedimientos se contó con la participación de un residente. En el análisis bivariado no se encontró una diferencia estadísticamente significativa entre la participación del residente y un impacto negativo en los desenlaces clínicos de las variables relevantes. Discusión. No hay evidencia de que la participación de médicos residentes en la colecistectomía laparoscópica se asocie con desenlaces adversos en los pacientes, lo que sugiere estar en relación con una introducción temprana y responsable a este procedimiento por parte de los docentes, permitiendo que la colecistectomía sea un procedimiento seguro


Introduction. Cholecystectomy is one of the most performed surgical procedures worldwide, so its learning is increasingly necessary for resident physicians in training, but without compromising the safety of patients. The objective of this study was to determine the impact of the participation of resident physicians on the main clinical outcomes of cholecystectomy. Methods. A prospective cohort study was performed, which included patients undergoing laparoscopic cholecys-tectomy from June 2019 to July 2020. Statistical analysis was carried out to describe measures of frequency, central tendency, dispersion, and bivariate analysis for outcomes of interest. Results. 482 patients who underwent cholecystectomy were included, 475 of them laparoscopically; 62.5% were women and 76.2% were performed urgently, and 96% of the procedures involved the participation of a resident. In the bivariate analysis, no statistically significant difference was found between resident participation and a negative impact on the clinical outcomes of the relevant variables. Discussion. There is no evidence that the participation of resident physicians in laparoscopic cholecystectomy is associated with adverse outcomes in patients, which suggests being related to an early and responsible introduction to this procedure by teachers, allowing cholecystectomy to be a safe procedure


Assuntos
Humanos , Cirurgia Geral , Colecistectomia Laparoscópica , Educação Médica , Colelitíase , Programas de Pós-Graduação em Saúde , Complicações Intraoperatórias
7.
Biomédica (Bogotá) ; Biomédica (Bogotá);40(3): 516-527, jul.-set. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1131903

RESUMO

Introduction: Triatoma recurva is a Trypanosoma cruzi vector whose distribution and biological development are determined by factors that may influence the transmission of trypanosomiasis to humans. Objective: To identify the potential spatial distribution of Triatoma recurve, as well as social factors determining its presence. Materials and methods: We used the MaxEnt software to construct ecological niche models while bioclimatic variables (WorldClim) were derived from the monthly values of temperature and precipitation to generate biologically significant variables. The resulting cartography was interpreted as suitable areas for T. recurva presence. Results: Our results showed that the precipitation during the driest month (Bio 14), the maximum temperature during the warmest month (Bio 5), and the altitude (Alt) and mean temperature during the driest quarter (Bio 9) determined T. recurva distribution area at a higher percentage evidencing its strong relationship with domestic and surrounding structures. Conclusions. This methodology can be used in other geographical contexts to locate potential sampling sites where these triatomines occur.


Introducción. Triatoma recurva es un vector de Trypanosoma cruzi cuya existencia y desarrollo biológico están determinados por factores que pueden influir en la transmisión de la tripanosomiasis a los seres humanos. Objetivo. Determinar una posible distribución espacial de Triatoma recurva y algunos factores sociales que determinan su presencia. Materiales y métodos. El modelado de nicho ecológico se hizo con el programa MaxEnt empleando las variables bioclimáticas (WorldClim) derivadas de los valores mensuales de temperatura y precipitación para generar variables biológicamente significativas. La cartografía resultante evidenció áreas adecuadas para la presencia de T. recurva. Resultados. Los resultados indicaron que la precipitación del mes más seco (Bio 14), la temperatura máxima del mes más cálido (Bio 5), y la altitud (Alt) y la temperatura media del trimestre más seco (Bio 9), determinaron en mayor porcentaje el área de distribución de T. recurva, observándose que es una especie con una acentuada relación con las estructuras domésticas y circundantes. Conclusión. Esta metodología puede emplearse en otros contextos geográficos para localizar posibles sitios de muestreo de estos triatominos.


Assuntos
Triatoma , Triatominae , Clima , Doença de Chagas , Ecossistema , Vetores de Doenças
8.
Angew Chem Int Ed Engl ; 58(16): 5413-5416, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30770618

RESUMO

B←N coordination supports a [2+2] photodimerization in the solid state. The bond is defined by an orthogonal interaction between stilbazole and a phenylboronic ester to enable a stereocontrolled and rapid photoreaction. The cyclobutane photoproduct affords a novel diboron bis-tweezer adduct that is used to separate a mixture of benzene and thiophene upon crystallization.

9.
Clin Biochem ; 55: 63-68, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29518381

RESUMO

BACKGROUND: Intracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the world and these ruptures are associated with a high mortality. Some risk factors, such as age, gender, smoking, alcohol, hypertension and familial history are associated with the number of aneurysms and their size. In addition, inflammatory processes within the blood vessels of the brain can activate matrix metalloproteinase-9 (MMP-9), which degrades various components of the extracellular matrix, such as elastin. Thereby, this work has aimed at evaluating the relationship between plasma MMP-9 levels and the risk factors that are associated with intracranial aneurysm, as well as investigating the aneurysm statuses (ruptured and unruptured) and comparing them with the control volunteers. METHODS: Between August 2014 to June 2016, blood samples were collected from 282 patients (204 ruptured and 78 unruptured saccular intracranial aneurysms) and 286 control volunteers. The MMP-9 plasma levels were measured by ELISA. Statistical analyzes were performed with SPSS software when using parametric or nonparametric tests, after the normality tests. RESULTS: Higher levels of MMP-9 were found in the aneurysm groups as a whole and when they were stratified by rupture status, then compared with the control group (p < 0.0001). When stratifying them by diameter, those smaller than 7 mm presented high levels of MMP-9 (p < 0.0001), especially in the ruptured ones. As for risk factors, hypertension and smoking were the most important. However, hypertension was mostly associated with the ruptured aneurysms (p < 0.0001). CONCLUSIONS: High levels of MMP-9 were found in smaller ruptured and unruptured intracranial aneurysms (<7 mm) with strongest statistical associations than other sizes, especially when associated with smoking and hypertension.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Metaloproteinase 9 da Matriz/sangue , Adulto , Idoso , Aneurisma Roto/sangue , Aneurisma Roto/diagnóstico por imagem , Feminino , Humanos , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
BMC Syst Biol ; 11(1): 49, 2017 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-28412970

RESUMO

BACKGROUND: Microbial production of nitrogen containing compounds requires a high uptake flux and assimilation of the N-source (commonly ammonium), which is generally coupled with ATP consumption and negatively influences the product yield. In the industrial workhorse Saccharomyces cerevisiae, ammonium (NH4+) uptake is facilitated by ammonium permeases (Mep1, Mep2 and Mep3), which transport the NH4+ ion, resulting in ATP expenditure to maintain the intracellular charge balance and pH by proton export using the plasma membrane-bound H+-ATPase. RESULTS: To decrease the ATP costs for nitrogen assimilation, the Mep genes were removed, resulting in a strain unable to uptake the NH4+ ion. Subsequent analysis revealed that growth of this ∆mep strain was dependent on the extracellular NH3 concentrations. Metabolomic analysis revealed a significantly higher intracellular NHX concentration (3.3-fold) in the ∆mep strain than in the reference strain. Further proteomic analysis revealed significant up-regulation of vacuolar proteases and genes involved in various stress responses. CONCLUSIONS: Our results suggest that the uncharged species, NH3, is able to diffuse into the cell. The measured intracellular/extracellular NHX ratios under aerobic nitrogen-limiting conditions were consistent with this hypothesis when NHx compartmentalization was considered. On the other hand, proteomic analysis indicated a more pronounced N-starvation stress response in the ∆mep strain than in the reference strain, which suggests that the lower biomass yield of the ∆mep strain was related to higher turnover rates of biomass components.


Assuntos
Compostos de Amônio/metabolismo , Proteínas de Transporte de Cátions/genética , Deleção de Genes , Potenciais da Membrana , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Trifosfato de Adenosina/metabolismo , Aerobiose , Transporte Biológico , Proteínas de Transporte de Cátions/deficiência , Proteínas de Transporte de Cátions/metabolismo , Difusão , Espaço Extracelular/metabolismo , Concentração de Íons de Hidrogênio , Espaço Intracelular/metabolismo , Metabolômica , Nitrogênio/metabolismo , Permeabilidade , Proteômica , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
12.
Educ. med. super ; 31(1): 193-202, ene.-mar. 2017.
Artigo em Espanhol | LILACS | ID: biblio-891163

RESUMO

Introducción: el pensamiento educativo de Fidel Castro en la formación de valores de los profesionales de la salud, constituye una herramienta inestimable para quienes desempeñan la noble labor de educar. Objetivos: realizar una aproximación al pensamiento educativo de Fidel Castro Ruz, resaltando las ideas inscritas en su obra como formador de valores internacionalistas en los profesionales de la salud. Métodos: como métodos de mayor protagonismo para la realización de la investigación se resaltan el histórico-lógico, el analítico-sintético y la sistematización. El eje de sistematización establecido fue: las ideas educativas sobre el internacionalismo como valor humano. En esta arista se inscribe el pensamiento educativo de Fidel Castro en el período comprendido entre 1959 hasta el 2009, su estudio como brújula para el posterior análisis constituyó un lineamiento clave en el desarrollo de la investigación. Se identificaron 37 pronunciamientos relacionados con el internacionalismo en salud, los cuales fueron categorizados y jerarquizados atendiendo a su valor educativo; posterior se seleccionaron 19 ideas esenciales y por último se extrajeron 13 núcleos teóricos integradores que conformarían una agenda educativa para la formación de valores internacionalistas en los profesionales de la salud. Conclusiones: el pensamiento educativo de Fidel Castro sobre el internacionalismo ha sido objeto de sistematización y constituye un fundamento metodológico, regulador y normativo en el contexto de la formación de valores en profesionales de la salud(AU)


Introduction: Fidel Castro's educative thinking for building values in health professionals constitutes a priceless tool for those who practice the lovely work of educating. Objectives: To carry out an approach to Fidel Castro Ruz's educative thinking, highlighting the ideas inscribed in his work as a builder of internationalist values in the health professionals. Methods: As methods of greater protagonism to carry out this research we should highlight the logical-historical, the analytic-synthetic and the systematization. The systematization axis established was: the educative ideas about internationalism as a human value. In this area, Fidel Castro's educative thinking is contained in the period from 1959 to 2009, his study as a guide for subsequent analysis was key guidelines in the research development. We identified 37 statements concerning internationalism in health, which were categorized and ranked according to their educative value. Later, 19 essential ideas were selected. Finally, 13 integrating theoretical nucleuses were drawn up to form an educative agenda for building internationalist values in the health professionals. Conclusions: Fidel Castro's educative thinking on internationalism has been systematized and constitutes a methodological, regulatory and normative foundation in the context of building values in the health professionals(AU)


Assuntos
Humanos , Pessoas Famosas , Pessoal de Saúde/educação , Cooperação Internacional
13.
Eur Radiol ; 27(6): 2619-2628, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27718080

RESUMO

OBJECTIVE: To assess performance of TIRADS classification on a prospective surgical cohort, demonstrating its clinical usefulness. METHODS: Between June 2009 and October 2012, patients assessed with pre-operative ultrasound (US) were included in this IRB-approved study. Nodules were categorised according to our previously described TIRADS classification. Final pathological diagnosis was obtained from the thyroidectomy specimen. Sensitivity, specificity, positive/negative predictive values and likelihood ratios were calculated. RESULTS: The study included 210 patients with 502 nodules (average: 2.39 (±1.64) nodules/patient). Median size was 7 mm (3-60 mm). Malignancy was 0 % (0/116) in TIRADS 2, 1.79 % (1/56) in TIRADS 3, 76.13 % (185/243) in TIRADS 4 [subgroups: TIRADS 4A 5.88 % (1/17), TIRADS 4B 62.82 % (49/78), TIRADS 4C 91.22 % (135/148)], and 98.85 % (86/87) in TIRADS 5. With a cut-off point at TIRADS 4-5 to perform FNAB, we obtained: sensitivity 99.6 % (95 % CI: 98.9-100.0), specificity 74.35 % (95 % CI: 68.7-80.0), PPV 82.1 % (95 % CI: 78.0-86.3), NPV 99.4 % (95 % CI: 98.3-100.0), PLR 3.9 (95 % CI: 3.6-4.2) and an NLR 0.005 (95 % CI: 0.003-0.04) for malignancy. CONCLUSION: US-based TIRADS classification allows selection of nodules requiring FNAB and recognition of those with a low malignancy risk. KEY POINTS: • TIRADS classification allows accurate selection of thyroid nodules requiring biopsy (TIRADS 4-5). • The recognition of benign/possibly benign patterns can avoid unnecessary procedures. • This classification and its sonographic patterns are validated using surgical specimens.


Assuntos
Doença de Hashimoto/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Tireoidite/diagnóstico por imagem , Adulto , Idoso , Biópsia/métodos , Biópsia por Agulha Fina/métodos , Feminino , Doença de Hashimoto/patologia , Doença de Hashimoto/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Tireoidite/patologia , Tireoidite/cirurgia , Ultrassonografia , Procedimentos Desnecessários
16.
Front Physiol ; 4: 198, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23908634

RESUMO

TASK-2 (K2P5.1) is a two-pore domain K(+) channel belonging to the TALK subgroup of the K2P family of proteins. TASK-2 has been shown to be activated by extra- and intracellular alkalinization. Extra- and intracellular pH-sensors reside at arginine 224 and lysine 245 and might affect separate selectivity filter and inner gates respectively. TASK-2 is modulated by changes in cell volume and a regulation by direct G-protein interaction has also been proposed. Activation by extracellular alkalinization has been associated with a role of TASK-2 in kidney proximal tubule bicarbonate reabsorption, whilst intracellular pH-sensitivity might be the mechanism for its participation in central chemosensitive neurons. In addition to these functions TASK-2 has been proposed to play a part in apoptotic volume decrease in kidney cells and in volume regulation of glial cells and T-lymphocytes. TASK-2 is present in chondrocytes of hyaline cartilage, where it is proposed to play a central role in stabilizing the membrane potential. Additional sites of expression are dorsal root ganglion neurons, endocrine and exocrine pancreas and intestinal smooth muscle cells. TASK-2 has been associated with the regulation of proliferation of breast cancer cells and could become target for breast cancer therapeutics. Further work in native tissues and cells together with genetic modification will no doubt reveal the details of TASK-2 functions that we are only starting to suspect.

17.
Nephrol Dial Transplant ; 27(8): 3136-40, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22273669

RESUMO

BACKGROUND: Contrast-induced nephropathy (CIN) is associated with a combination of hypoxic and toxic renal tubular damage, renal endothelial dysfunction and altered intra-renal microcirculation. Recently, sodium butyrate (SB) has been focused on since it possesses anti-inflammatory activities. Thus, based on the lack of information on the effects of SB in acute kidney injury (AKI), we investigated the possible effects of SB after CIN in rats. METHODS: Wistar rats were divided into three groups: (1 sham) control, (2 MI) AKI treated with contrast medium and (3 MI + SB) AKI plus SB. Six days after contrast administration, blood and kidney were removed for the determination of creatinine, interleukin (IL)-6 levels, oxidative damage parameters and histologic analyses. Nuclear factor kappa B (NF-κB), pIκBα and vasodilator-stimulated phosphoprotein (VASP) protein content were determined by immunoblotting. RESULTS: After 6 days, the levels of creatinine increased significantly in the MI group, and this was attenuated using SB. SB treatment was associated with a decrease on the levels of lipid peroxidation, but not the protein oxidation, and IL-6 levels, as well as tubular damage. These effects are probably mediated, in part, by a decrease on the activation of NF-κB in the kidney, but not alteration in pVASP content. CONCLUSIONS: The current experiment suggests that NF-κB induced an inflammatory response after CIN and SB could inhibit NF-κB expression protecting against CIN in rats.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Butiratos/farmacologia , Meios de Contraste/toxicidade , NF-kappa B/metabolismo , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Moléculas de Adesão Celular/metabolismo , Creatinina/sangue , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Proteínas dos Microfilamentos/metabolismo , Oxirredução/efeitos dos fármacos , Fosfoproteínas/metabolismo , Ratos , Ratos Wistar
18.
Rev. bras. ter. intensiva ; 23(2): 222-227, abr.-jun. 2011.
Artigo em Português | LILACS | ID: lil-596447

RESUMO

Será descrito a base fisiológica dos componentes da barreira hematoencefálica e suas propriedades. Além disto, pretende-se abordar o efeito particular das metaloproteinases e seu controle sobre as propriedades da matriz extracelular e a relação disto com disfunção da barreira hemotoencefálica. Finalmente se demonstrará o papel da metaloproteinases nas alterações do sistema nervoso central em doenças associadas ao paciente criticamente enfermo.


This paper aims to describe the physiological basis of the blood-brain barrier components and its properties. Additionally, the particular effects of metalloproteinases and their control over the extracellular matrix and its relationship with blood-brain barrier dysfunction are discussed. Finally, the role of metalloproteinases on changes in the central nervous system in critically ill patients is discussed.

19.
Cir. parag ; 32(1): 25-26, jun. 2009.
Artigo em Espanhol | LILACS, BDNPAR | ID: lil-521548

RESUMO

La etiología del tumor desmoide permanece desconocida considerada por algunos patólogos como fibrosarcomas de bajo grado (4), tiene relación bien definida con la poliposis adenomatosa familiar (3), otras causas predisponentes, señaladas en la literatura, gravidez talvez por la alteración hormonal del embarazo, presencia de traumatismo previo. La sospecha del tumor desmoide debe ser hecha por el cuadro clínico, examen físico local examen de anatomía patológica, exámenes de imágenes, ya que el cuadro clínico puede ser no característico (1) en lesiones iniciales pacientes obesos, por loque estudios ecograficos, tomogrficos, tienen papel importante en la identificación el limite de la lesión.


Assuntos
Fibromatose Agressiva , Neoplasias
20.
Rev. colomb. quím. (Bogotá) ; 38(1): 97-105, abr. 2009. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-636647

RESUMO

Se estudió la hidrogenación enantio selectiva de 4-metoxiacetofenona sobre catalizadores de Pt/TiO2 reducidos a 773K y modificados con cinconidina (CD). Los catalizadores se caracterizaron por fisiadsorción de N2, quimiadsorción de H2, DRX y XPS. Las transformaciones se llevaron a cabo en un reactor tipo STR a distintas concentraciones de cinconidina (CD) con el propósito de evaluar la incidencia de algunos parámetros de reacción como el orden de adición del modificador y la presión de hidrógeno. Se demostró que a bajas concentraciones de CD es posible obtener excesos enantioméricos cercanos al 30%. Se encontró que la estructura de la molécula puede afectar el comportamiento observado.


The enantioselective hydrogenation of 4-methoxyacetophenone over Pt/TiO2 catalyst reduced to 773 K in the presence of cinchonidine (CD) was studied. The catalysts were characterized by N2 physisorption, H2 chemisorption, XRD and XPS. The reactions were carried out in a STR reactor at various concentrations of CD. The effect of several reaction parameters was investigated, such as the addition order of the modifier and hydrogen pressure. Lower concentrations of CD can produce an enantiomeric excess near to 30%. The structure of the molecule can influence the behavior observed.


Neste trabalho, foi estudada a hidrogenação enantioselective do 4-metoxiaceto-fenona em catalisadores Pt/TiO2 reduzidos a 773 K e modificados com cinconidina (CD). Os sólidos foram caracterizados por adsorção de nitrogênio a 77K, quimisorção de hidrogênio a temperatura ambiente, DRX, TEM e XPS. As reações foram realizadas em um reator STR a diferentes concentrações de CD. Alem de isso o efeito de vários parâmetros de reação foi estudado, como ordem de adição do modificador e pressão do hidrogênio. Baixas concentrações do CD podem produzir excesso enantiomêricos próximos aos 30%. A estrutura da molécula pode influenciar o comportamento obtido.

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