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2.
Front Microbiol ; 10: 1642, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379789

RESUMO

The ability to conserve energy in the presence or absence of oxygen provides a metabolic versatility that confers an advantage in natural ecosystems. The switch between alternative electron transport systems is controlled by the fumarate nitrate reduction transcription factor (FNR) that senses oxygen via an oxygen-sensitive [4Fe-4S]2+ iron-sulfur cluster. Under O2 limiting conditions, FNR plays a key role in allowing bacteria to transition from aerobic to anaerobic lifestyles. This is thought to occur via transcriptional activation of genes involved in anaerobic respiratory pathways and by repression of genes involved in aerobic energy production. The Proteobacterium Acidithiobacillus ferrooxidans is a model species for extremely acidophilic microorganisms that are capable of aerobic and anaerobic growth on elemental sulfur coupled to oxygen and ferric iron reduction, respectively. In this study, an FNR-like protein (FNRAF) was discovered in At. ferrooxidans that exhibits a primary amino acid sequence and major motifs and domains characteristic of the FNR family of proteins, including an effector binding domain with at least three of the four cysteines known to coordinate an [4Fe-4S]2+ center, a dimerization domain, and a DNA binding domain. Western blotting with antibodies against Escherichia coli FNR (FNREC) recognized FNRAF. FNRAF was able to drive expression from the FNR-responsive E. coli promoter PnarG, suggesting that it is functionally active as an FNR-like protein. Upon air exposure, FNRAF demonstrated an unusual lack of sensitivity to oxygen compared to the archetypal FNREC. Comparison of the primary amino acid sequence of FNRAF with that of other natural and mutated FNRs, including FNREC, coupled with an analysis of the predicted tertiary structure of FNRAF using the crystal structure of the related FNR from Aliivibrio fisheri as a template revealed a number of amino acid changes that could potentially stabilize FNRAF in the presence of oxygen. These include a truncated N terminus and amino acid changes both around the putative Fe-S cluster coordinating cysteines and also in the dimer interface. Increased O2 stability could allow At. ferrooxidans to survive in environments with fluctuating O2 concentrations, providing an evolutionary advantage in natural, and engineered environments where oxygen gradients shape the bacterial community.

3.
Biotechnol Biofuels ; 12: 134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31168324

RESUMO

Background: One of the major problems in the production of lipids for biotechnological purposes using microalgae is maintaining a high productivity of these molecules without reducing cellular biomass. High production rates are usually obtained by cultivating microalgae under different stress conditions. However, many of these changes usually result in lower biomass productivity. Therefore, the optimization of the culture conditions and genetic modification techniques in these organisms is needed to generate robust new strains for profitable economic use. Results: In this work, we describe a new strategy for random mutation of genomic DNA in the microalgae Nannochloropsis oceanica by insertion of a Transposome complex Tn5. This complex contains an antibiotic-resistance cassette commanded by a CMV viral promoter that allows high efficiency of transformation and the generation of mutants. This strategy, complemented with a large-scale identification and selection system for mutants, such as flow cytometry with cell selection, allowed us to obtain clonal cultures of mutants with altered phenotypes in the accumulation of intracellular lipids. The characterization of some of these mutants uncovered new genes that are likely to be involved in the regulation of lipid synthesis, revealing possible cellular responses that influence the intracellular homeostasis of lipids. Conclusion: The strategies proposed here are easy to implement in different types of microalgae and provide a promising scenario for improving biotechnological applications.

5.
Ultrastruct Pathol ; 42(2): 81-90, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29419351

RESUMO

In this study, we describe, compare, and discuss several subcellular alterations found in Colorectal Adenocarcinoma and peritumoral tissue using transmission electron microscopy, morphometry, and statistical analysis. Tissue samples from anterior resections were collected from patients diagnosed with Colorectal Adenocarcinoma in the University Hospital of Caracas. Samples were processed according to the typical protocol for their observation through transmission electron microscopy. The resulting images were analyzed using specialized software for the collection of morphometric data. Several anomalies were common for both tissues, including but not limited to, rough endoplasmic reticulum and mitochondrial swelling, nuclear invagination, nuclear enlargement, and cellular swelling. In general, alterations within the tumor were more frequent and intense. Extensive organellar degradation and other evidences of cellular damage seemed to extend past the edge of the tumor into the peritumoral tissue. There seems to be a clear process of lateral cancerization present in the peritumoral area. The tissue layers composed of smooth muscle cells, probably due to their structural features, may allow greater diffusion of harmful substances produced by the tumor. A more in-depth analysis of peritumoral tissue considering organellar damage and morphometric data may provide relevant insight about the changing microenvironment promoted by the close proximity of a tumor.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/ultraestrutura , Neoplasias Colorretais/patologia , Neoplasias Colorretais/ultraestrutura , Idoso , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Microscopia Eletrônica de Transmissão/métodos , Pessoa de Meia-Idade
6.
J. coloproctol. (Rio J., Impr.) ; 37(2): 100-108, Apr.-June 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-893963

RESUMO

ABSTRACT Objective: Transanal repair of rectocele and full rectal mucosectomy with one circular stapler is a procedure designed for the treatment of Obstructive Defecation Syndrome by doctor Fco. Sergio Regadas in 2005. We compare the use of multiple instruments and their mechanical technology effect in the treatment of anorectocele. Patients and methods: Female patients complaining about sensation of incomplete evacuation, ages between 40 and 55. The evaluation was made with the function of evacuation protocol: colonic transit time, colon radiology, ecodefecography, anorectal manometry and psychological test. The technique used was transanal repair of rectocele and full rectal mucosectomy with one circular stapler, using staplers CPH-34, CPH-34HV and EEA-3135-HEM, with measurement of the rectal wall resected: vertical length in centimetres, horizontal length in centimetres, weight in grams and volume in cubic centimetres; afterwards histological study of the tissue thickness, and applied the ANOVA and SPSS 12 tests for the statistical analysis. Results: The results obtained by comparing the resections made with the CPH-34, the CPH-34HV and the EEA-3135-HEM in respect of vertical length, horizontal length, weight and volume, were found to have no significant differences; neither in the histological study of the tissue thickness in respect of characteristics and structure. Conclusion: The effect of mechanical technology in the treatment of anorectocele with transanal repair of rectocele and full rectal mucosectomy with one circular stapler procedure using the CPH-34, the CPH-34HV and the EEA-3135-HEM, does not show any difference. Leaving the application of each to the operator competencies.


RESUMO Objetivo: TRREMS (Transanal Repair of Rectocele and full rectal Mucosectomy with one circular Stapler, Reparo transanal de retocele e mucosectomia retal total com um grampo circular) é um procedimento que visa o tratamento da Síndrome da Defecação Obstrutiva pelo Dr. Francisco Sergio Regadas em 2005. Comparamos o uso de diversos instrumentos e o efeito mecânico da tecnologia no tratamento da anorretocele. Pacientes e métodos: Pacientes do gênero feminino com queixa de sensação de evacuação incompleta (SEI), com idades entre 40 e 55 anos. A avaliação foi efetuada com o protocolo de função de evacuação: tempo de trânsito colônico, radiologia do cólon, ecodefecografia, manometria anorretal e teste psicológico. A técnica empregada foi TRREMS, com o uso de grampeadores CPH-34, CPH-34HV e EEA-3135-HEM, com medição da parede retal ressecada: comprimento vertical em centímetros, comprimento horizontal em centímetros, peso em gramas e volume em centímetros cúbicos; subsequentemente, foi realizado estudo histológico da espessura do tecido, com aplicação de ANOVA e do programa SPSS 12 para a análise estatística. Resultados: Observamos que os resultados obtidos com a comparação das ressecções realizadas com CPH-34, CPH-34HV e EEA-3135-HEM com relação ao comprimento vertical, comprimento horizontal, peso e volume, bem como os resultados do estudo histológico da espessura do tecido com relação às características e estrutura, não apresentavam diferenças significativas.

7.
Acta Crystallogr E Crystallogr Commun ; 72(Pt 11): 1648-1650, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27840728

RESUMO

In the title compound, C7H14N4·2C6H5ClO, which crystallized with two crystallographically independent 4-chloro-phenol mol-ecules and one 1,3,6,8-tetra-aza-tri-cyclo-[4.3.1.13,8]undecane (TATU) mol-ecule in the asymmetric unit, the independent components are linked by two O-H⋯N hydrogen bonds. The hydrogen-bond acceptor sites are two non-equivalent N atoms from the aminal cage structure, and the tricyclic system distorts by changing the C-N bond lengths. In the crystal, these hydrogen-bonded aggregates are linked into chains along the c axis by C-H⋯N hydrogen bonds. The crystal structure also features C-H⋯π contacts.

8.
J. coloproctol. (Rio J., Impr.) ; 36(3): 124-129, July-Sept. 2016. graf
Artigo em Inglês | LILACS-Express | ID: lil-796284

RESUMO

Abstract Objective This study aims to determine changes in the proportions of types I and III collagen in hemorrhoids and to verify the sliding anal canal lining theory. Patients and method The study is focused on a sample of 17 patients, 9 females and 8 males (age range: 30–70 years), with grade III and grade IV hemorrhoids. Tissue from 4 fetuses (age: 16 weeks of gestation) was used as control sample. All the participants gave their informed consent. Samples were gathered in 2014. All patients underwent open hemorrhoidectomy by using the technique described by Milligan and Morgan, published in Lancet journal in 1937. The hemorrhoid samples were stained with hematoxylin–eosin for the histologic study to confirm the hemorrhoidal tissue diagnosis. The picrosirius red staining protocol was used after the histologic analysis. The method used for image processing is described in the text. Images were imported to the Image Tool for Windows software. The same process was used on the embryonic tissue. Data resulting from the analysis of images were processed using STATISTICA, a software for statistical analysis. Results When compared, it was found that the two tissues presented very different values, with hemorrhoids containing the highest type III collagen values. Conclusion Our results seem to imply that hemorrhoids have a larger proportion of type III collagen than fetal tissue. They also suggest a possible age-related deterioration of the tissue.


Resumo Objetivo Esse estudo tem por objetivo determinar mudanças nos percentuais do colágeno dos tipos I e III em hemorroidas e verificar a teoria do revestimento de canal anal deslizante. Pacientes e método O estudo está focado em uma amostra de 17 pacientes (9 mulheres e 8 homes; faixa etária: 30-70 anos), com hemorroidas de graus III e IV. Utilizamos tecido de quatro fetos (idade: 16 semanas de gestação) como amostra de controle. Todos os participantes deram consentimento informado. As amostras foram reunidas em 2014. Todos os pacientes passaram por uma hemorroidectomia aberta; para tanto, foi empregada a técnica descrita por Milligan e Morgan, publicada no periódico Lancet em 1937. As amostras de hemorroida foram coradas com hematoxilina-eosina com vistas ao estudo histológico para confirmação do diagnóstico de tecido hemorroidal. Após a análise histológica, o material foi corado com o protocolo de picrosirius red. O método empregado para o processamento das imagens está descrito no texto. As imagens foram importadas pelo software Image Tool for Windows. O mesmo processo foi empregado no tecido embrionário. Os dados resultantes da análise das imagens fora processados com o programa STATISTICA, um software para análise estatística. Resultados Por comparação, constatamos que os dois tecidos apresentavam valores muito diferentes, e as hemorroidas continham os mais altos valores de colágeno do tipo III. Conclusão Nossos resultados parecem implicar que hemorroidas possuem um percentual mais elevado de colágeno do tipo III versus tecido fetal. Os resultados também sugerem uma possível deterioração do tecido, relacionada à idade.

9.
Acta Crystallogr E Crystallogr Commun ; 71(Pt 11): 1356-60, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-26594510

RESUMO

In the title ternary co-crystalline adduct, C7H14N4·2C6H5NO3, mol-ecules are linked by two inter-molecular O-H⋯N hydrogen bonds, forming a tricomponent aggregates in the asymmetric unit. The hydrogen-bond formation to one of the N atoms is enough to induce structural stereoelectronic effects in the normal donor→acceptor direction. In the title adduct, the two independent nitro-phenol mol-ecules are essentially planar, with maximum deviations of 0.0157 (13) and 0.0039 (13) Å. The dihedral angles between the planes of the nitro group and the attached benzene rings are 4.04 (17) and 5.79 (17)°. In the crystal, aggregates are connected by C-H⋯O hydrogen bonds, forming a supra-molecular dimer enclosing an R 6 (6)(32) ring motif. Additional C-H⋯O inter-molecular hydrogen-bonding inter-actions form a second supra-molecular inversion dimer with an R 2 (2)(10) motif. These units are linked via C-H⋯O and C-H⋯N hydrogen bonds, forming a three-dimensional network.

10.
Dent Mater ; 31(11): 1290-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26364144

RESUMO

OBJECTIVE: To evaluate the biocompatibility and osteoinductive properties of Bioroot™ RCS (BR, Septodont, France) compared to Kerr's Pulp Canal Sealer™ (PCS, Kerr, Italy) using the mouse pulp-derived stem cell line A4, which have an osteo/odontogenic potential in vitro and contribute to efficient bone repair in vivo. METHODS: A4 cells were cultured at the stem cell stage in the presence of solid disks of BR or PCS, whereas untreated A4 cells were used as control. After 3, 7, 10 days of direct contact with the sealers, cell viability was quantified using Trypan Blue exclusion assay. Immunolabelings were performed to assess the expression of odontoblast markers i.e. type 1 collagen, DMP1 or BSP. Finally, sealer-treated cells were induced toward osteo/odontogenic differentiation to assess the impact of the sealers on mineralization by Von Kossa staining. Statistical significance was evaluated by one-way analysis of variance and t-test (p<0.05). RESULTS: BR did not alter the viability and morphology of A4 pulpal cells compared to control group (p>0.05); however, living cell percentage of PCS was significantly lower compared to control and BR groups (p<0.05). BR preserved the intrinsic ability of A4 cells to express type 1 collagen, DMP1 or BSP at the stem cell stage. It did not alter the integrity of collagen fibers surrounding the cells and promoted overexpression of BSP and DMP1 at the cell surface. In contrast to PCS, BR did not compromise the mineralization potential of pulpal A4 stem cells. SIGNIFICANCE: Bioroot™ RCS was not as cytotoxic as PCS. It did not recruit the pulpal stem cells toward differentiation but preserve their osteo-odontogenic intrinsic properties. Bioroot™ RCS might provide more suitable environment to induce stem cells for hard tissue deposition.


Assuntos
Polpa Dentária , Odontogênese , Células-Tronco , Animais , Diferenciação Celular , Linhagem Celular , Teste de Materiais , Camundongos
11.
PLoS Pathog ; 11(8): e1005073, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26241960

RESUMO

In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion diseases. We found that overactivation of ROCK signaling occurred in neuronal stem cells infected by pathogenic prions (PrPSc) and impaired the sprouting of neurites. In reconstructed networks of mature neurons, PrPSc-induced ROCK overactivation provoked synapse disconnection and dendrite/axon degeneration. This overactivation of ROCK also disturbed overall neurotransmitter-associated functions. Importantly, we demonstrated that beyond its impact on neuronal polarity ROCK overactivity favored the production of PrPSc through a ROCK-dependent control of 3-phosphoinositide-dependent kinase 1 (PDK1) activity. In non-infectious conditions, ROCK and PDK1 associated within a complex and ROCK phosphorylated PDK1, conferring basal activity to PDK1. In prion-infected neurons, exacerbated ROCK activity increased the pool of PDK1 molecules physically interacting with and phosphorylated by ROCK. ROCK-induced PDK1 overstimulation then canceled the neuroprotective α-cleavage of normal cellular prion protein PrPC by TACE α-secretase, which physiologically precludes PrPSc production. In prion-infected cells, inhibition of ROCK rescued neurite sprouting, preserved neuronal architecture, restored neuronal functions and reduced the amount of PrPSc. In mice challenged with prions, inhibition of ROCK also lowered brain PrPSc accumulation, reduced motor impairment and extended survival. We conclude that ROCK overactivation exerts a double detrimental effect in prion diseases by altering neuronal polarity and triggering PrPSc accumulation. Eventually ROCK emerges as therapeutic target to combat prion diseases.


Assuntos
Proteínas PrPSc/metabolismo , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Quinases Associadas a rho/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Imunofluorescência , Imunoprecipitação , Dispositivos Lab-On-A-Chip , Camundongos , Camundongos Endogâmicos C57BL , Neuritos/metabolismo , Neurogênese , Proteínas PrPC/metabolismo
12.
Acta Crystallogr C Struct Chem ; 71(Pt 4): 284-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25836286

RESUMO

The title molecular salt, C11H21N4(+)·C6H4NO3(-)·C6H5NO3, (II), crystallizes with two independent three-component aggregates in the asymmetric unit. In the cations, the cyclohexane rings fused to the cage azaadamantane systems both adopt a chair conformation. In the crystal structure, the aggregates are connected by C-H···O hydrogen bonds, forming a supramolecular unit enclosing an R4(4)(24) ring motif. These units are linked via C-H···O and C-H···N hydrogen bonds, forming a three-dimensional network. Even hydrogen-bond formation to one of the N atoms is enough to induce structural stereoelectronic effects in the normal donor→acceptor direction. The C-N bond distances provide structural evidence for a strong anomeric effect. The structure also displays O-H···O and N-H···O hydrogen bonding. Geometric optimization and natural bond orbital (NBO) analysis of (II) were undertaken by utilizing DFT/B3LYP with the 6-31+G(d,p) basis set. NBO second-order perturbation theory calculations indicate donor-acceptor interactions between nitrogen lone pairs and the antibonding orbital of the C-C and C-N bonds for the protonated polyamine, in agreement with the occurrence of bond-length and bond-angle changes within the aminal cage structure.

13.
Bol Asoc Med P R ; 107(3): 75-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26742201

RESUMO

Peripheral arterial disease is a frequent under-diagnosed and poorly recognized clinical entity that can affect a great number of patients. Recognition of risk factors is crucial and a through evaluation of symptoms and use of diagnostic tools to better decide when an intervention is warranted. Lower extremity bypass surgery is one alternative method for treatment of PAD. It is indicated for type D and C lesions with low cardiac risk according to the TASC classification system. Preoperative assessment is imperative for every vascular procedure since it has been associated with major postoperative cardiovascular events; myocardial infarction being the most common. After excluding active disease, functional capacity and clinical risk predictors must be determined via METs and the Revised Cardiac Risk Index (RCRI), respectively. If a patient is considered to have a high cardiac risk, then noninvasive studies should be performed. Aspirin and a statin should be administrated preoperatively and postoperatively. Clopidogrel can be utilized as an alternative if a contraindication to aspirin exists. Periodic follow up consisting of clinical evaluations assessing and return or progression of symptoms of claudication, presence of pulses, ankle-brachial index (ABI) measurement, and smoking cessation counseling should be performed in every patient after vascular surgery.


Assuntos
Doença Arterial Periférica/cirurgia , Procedimentos Cirúrgicos Vasculares , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Perna (Membro)/irrigação sanguínea , Doença Arterial Periférica/classificação , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Cuidados Pós-Operatórios , Pré-Medicação , Cuidados Pré-Operatórios
14.
Acta Crystallogr Sect E Struct Rep Online ; 70(Pt 6): o687-8, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24940265

RESUMO

The asymmetric unit of the title compound, C28H42N2O5·H2O, consists of one half of the organic mol-ecule and one half-mol-ecule of water, both of which are located on a mirror plane which passes through the central C atoms and the hydroxyl group of the heterocyclic system. The hydroxyl group at the central ring is disordered over two equally occupied positions. The six-membered ring adopts a chair conformation, and the 2-hy-droxy-benzyl substituents occupy the sterically preferred equatorial positions. The aromatic rings make dihedral angles of 75.57 (9)° with the mean plane of the heterocyclic ring. The dihedral angle between the two aromatic rings is 19.18 (10)°. The mol-ecular structure features two intra-molecular phenolic O-H⋯N hydrogen bonds with graph-set motif S(6). In the crystal, mol-ecules are connected via O-H⋯O hydrogen bonds into zigzag chains running along the a-axis direction.

15.
Artigo em Inglês | MEDLINE | ID: mdl-24046632

RESUMO

The asymmetric unit of the title compound, C23H30N2O2, contains one half-mol-ecule, with a twofold axis splitting the mol-ecule in two identical halves. The structure of the racemic mixture has been reported previously [Rivera et al. (2009 ▶) J. Chem. Crystallogr. 39, 827-830] but the enanti-omer reported here crystallized in the ortho-rhom-bic space group P21212 (Z = 2), whereas the racemate occurs in the triclinic space group P-1 (Z = 2). The observed mol-ecular conformation is stabilized by two intra-molecular O-H⋯N hydrogen bonds, which generate rings with graph-set motif S(6). In the crystal, mol-ecules are linked via non-classical C-H⋯O inter-actions, which stack the mol-ecules along the b axis.

16.
Appl Environ Microbiol ; 79(7): 2172-81, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23354702

RESUMO

Gene transcription (microarrays) and protein levels (proteomics) were compared in cultures of the acidophilic chemolithotroph Acidithiobacillus ferrooxidans grown on elemental sulfur as the electron donor under aerobic and anaerobic conditions, using either molecular oxygen or ferric iron as the electron acceptor, respectively. No evidence supporting the role of either tetrathionate hydrolase or arsenic reductase in mediating the transfer of electrons to ferric iron (as suggested by previous studies) was obtained. In addition, no novel ferric iron reductase was identified. However, data suggested that sulfur was disproportionated under anaerobic conditions, forming hydrogen sulfide via sulfur reductase and sulfate via heterodisulfide reductase and ATP sulfurylase. Supporting physiological evidence for H2S production came from the observation that soluble Cu(2+) included in anaerobically incubated cultures was precipitated (seemingly as CuS). Since H(2)S reduces ferric iron to ferrous in acidic medium, its production under anaerobic conditions indicates that anaerobic iron reduction is mediated, at least in part, by an indirect mechanism. Evidence was obtained for an alternative model implicating the transfer of electrons from S(0) to Fe(3+) via a respiratory chain that includes a bc(1) complex and a cytochrome c. Central carbon pathways were upregulated under aerobic conditions, correlating with higher growth rates, while many Calvin-Benson-Bassham cycle components were upregulated during anaerobic growth, probably as a result of more limited access to carbon dioxide. These results are important for understanding the role of A. ferrooxidans in environmental biogeochemical metal cycling and in industrial bioleaching operations.


Assuntos
Acidithiobacillus/metabolismo , Ferro/metabolismo , Enxofre/metabolismo , Anaerobiose , Perfilação da Expressão Gênica , Sulfeto de Hidrogênio/metabolismo , Redes e Vias Metabólicas/genética , Oxirredução , Proteoma , Transcriptoma
17.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 10): o3041-2, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23125806

RESUMO

The title chiral quaternary ammonium salt, C(13)H(25)N(4) (+)·I(-), was synthesized through the Menschutkin reaction between the cage aminal (2S,7S)-1,8,10,12-tetra-aza-tetra-cyclo-[8.3.1.1(8,12).0(2,7)]penta-decane and ethyl iodide. The quaternization occurred regioselectively on the nitrogen with major sp3 character. The crystal structure consists of anions and cations separated by normal distances. Ions are not linked through C-H⋯I hydrogen bonds.

18.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 2): o301, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22346939

RESUMO

The imidazole ring in the title compound, C(27)H(22)N(8), adopts a slight envelope conformation with the C atom carrying the phenyl ring being the flap atom. The phenyl ring is almost perpendicular to the mean plane of the imidazole ring [dihedral angle = 88.90 (7)°]. The (1H-benzotriazol-1-yl)methyl groups bound to the imidazole ring are positioned on the same side of the imidazole ring. The dihedral angle between these benzotriazolyl rings is 17.71 (5)°. The crystal packing is stabilized by a C-H⋯π inter-action, which connects the mol-ecules into zigzag chains running along the b axis.

19.
FASEB J ; 26(2): 678-90, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22038049

RESUMO

Cytoskeleton modifications are required for neuronal stem cells to acquire neuronal polarization. Little is known, however, about mechanisms that orchestrate cytoskeleton remodeling along neuritogenesis. Here, we show that the silencing of the cellular prion protein (PrP(C)) impairs the initial sprouting of neurites upon induction of differentiation of the 1C11 neuroectodermal cell line, indicating that PrP(C) is necessary to neuritogenesis. Such PrP(C) function relies on its capacity to negatively regulate the clustering, activation, and signaling activity of ß1 integrins at the plasma membrane. ß1 Integrin aggregation caused by PrP(C) depletion triggers overactivation of the RhoA-Rho kinase-LIMK-cofilin pathway, which, in turn, alters the turnover of focal adhesions, increases the stability of actin microfilaments, and in fine impairs neurite formation. Inhibition of Rho kinases is sufficient to compensate for the lack of PrP(C) and to restore neurite sprouting. We also observe an increased secretion of fibronectin in the surrounding milieu of PrP(C)-depleted 1C11 cells, which likely self-sustains ß1 integrin signaling overactivation and contributes to neuritogenesis defect. Our overall data reveal that PrP(C) contributes to the acquisition of neuronal polarization by modulating ß1 integrin activity, cell interaction with fibronectin, and cytoskeleton dynamics.


Assuntos
Integrina beta1/metabolismo , Neuritos/metabolismo , Neurogênese/fisiologia , Proteínas PrPC/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Animais , Sequência de Bases , Diferenciação Celular , Linhagem Celular , Polaridade Celular , Citoesqueleto/metabolismo , Fibronectinas/metabolismo , Quinases Lim/metabolismo , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Proteínas PrPC/antagonistas & inibidores , Proteínas PrPC/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo
20.
Bol Asoc Med P R ; 103(4): 17-21, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22737825

RESUMO

UNLABELLED: Peripheral artery disease (PAD) of the lower extremities is frequently underdiagnosed and undertreated. The results of screening for PAD in adults attending outpatient clinics at different sites in Puerto Rico from 2007 to 2010 are presented. METHODS: A total of 33 outpatients screening clinics were conducted at different sites throughout the Island. Following the ACC/AHA Guideline recommendations, asymptomatic patients who qualified were screened for PAD using the ankle-brachial index (ABI). An ABI < 0.9 was considered positive for PAD. We estimated the prevalence of PAD in the study population and used logistic regression models to assess factors associated with a positive screening test for PAD. RESULTS: A total of 933 patients were screened for PAD. Out of the 933 patients, the ABI was < 0.9 in 390 (41.8%) of them. Bivariate analysis showed a significant difference in PAD screening results by gender (P = 0.004) and history of arterial hypertension (P = 0.004). Regarding clinical characteristics, leg edema 44.7% (P = 0.001), intermittent claudication 40.3% (P = 0.002), distal extremity coldness 29.0% (P = 0.012), and weak lower extremity pulses 67.5% (P < 0.001) were more prevalent on patients with an ABI < 0.9. In the multivariate analysis, male gender (OR = 1.92, 95% CI: 1.18, 3.11) and arterial hypertension (OR = 2.16, 95% CI: 1.28, 3.65) were significantly associated with PAD after adjusting for specific confounders. CONCLUSIONS: Arterial hypertension, cigarette smoking, diabetes mellitus, and dyslipidemia are known key factors in development of PAD. Practicing physicians must be aware of the importance of an early diagnosis of PAD, particularly in the asymptomatic patient, so as to institute preventive and management measures.


Assuntos
Hipertensão , Doença Arterial Periférica , Humanos , Prevalência , Porto Rico , Fatores de Risco
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