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1.
Enferm. univ ; 17(1): 64-75, ene.-mar. 2020. tab, graf
Article in Spanish | LILACS-Express | LILACS, BDENF - Nursing | ID: biblio-1149258

ABSTRACT

Resumen Introducción: La participación en el colegio de enfermeras es una instancia relevante para el desarrollo de la profesión a nivel país, debido a la defensa que realiza por la enfermería desde los diferentes ámbitos de actuación; es indispensable inculcar esta visión desde la formación universitaria a través de los profesionales de enfermería que se dedican a la docencia. Materiales y métodos: Se realizó un estudio cuantitativo, transeccional y correlacional, en 49 académicos de las diferentes casas de estudio de la ciudad de Puerto Montt-Chile, en quienes se evaluó su afiliación al colegio de enfermeras, además de sus conocimientos, actitudes y motivaciones respecto a participar en dicha instancia gremial; para tal fin se aplicó un instrumento de elaboración propia (α Cronbach 0.71). Resultados: Se encontró que el 40.9% de los docentes está afiliado al colegio de enfermeras y que existe conocimiento suficiente respecto a esta organización, con una actitud desfavorable hacia el mismo, evidenciándose asociación entre la actitud y aspectos como la dinámica de trabajo (p=0.043 Correlación de Spearman: 0.158) y la afiliación al colegio (p=0.02 Coeficiente de Spearman: 0.142). Discusión: La participación colegiada permite el fortalecimiento de la profesión, además de favorecer la visibilidad, liderazgo e identidad profesional; aunque se reconocen estos aspectos no son suficientes para generar la afiliación o una actitud favorable a ésta. Conclusiones: En la promoción de la afiliación debe considerarse la tendencia a no afiliación de los docentes más jóvenes y los aspectos de motivación, ambos relevantes para destacar la participación colegial como un aspecto deontológico que forma parte del modelaje hacia los enfermeros en formación.


Abstract Introduction: The participation with the College of Nurses is a relevant action to support the development of nursing in Chile because this organization stands as an important defender to the practice. Therefore, it is advisable that nursing teachers promote this vision among the nursing community. Materials and Methods: This is a quantitative, transectional and correlational study with 49 academicians from diverse teaching centers in the city of Puerto Montt, Chile, who were assessed in terms of their affiliation to the College of Nurses, their knowledge, attitudes, and motivations regarding their participation with this organization. A locally-designed instrument (α Cronbach 0.71) was used. Results: 40.9% of the teachers were affiliated to the College of Nurses. Associations between attitudes and working dynamics (Spearman Correlation = 0.158, p =0.043), and affiliation to the College (Spearman Correlation = 0.142, p = 0.02) were found. Discussion: The participation with the College of Nurses can allow the strengthening of the profession by favoring its visibility, leadership, and professional identity, though these important gains are not always sufficient to encourage an affiliation or a positive attitude towards this organization. Conclusions: In order to better promote the affiliation to the College of Nurses, young teachers' indifference attitudes, as well as other overall motivation factors should be considered first.


Resumo Introdução: A participação no colégio de enfermeiras é uma instancia relevante para o desenvolvimento da profissão ao nível do país, devido à defesa que realiza pela enfermagem desde os diferentes âmbitos de atuação; é indispensável inculcar esta visão desde a formação universitária a través dos profissionais de enfermagem que se dedicam à docência. Materiais e métodos: Realizou-se um estudo quantitativo, transecional e correlacional, em 49 docentes das diferentes casas de estudo da cidade de Puerto Montt-Chile, em quem se avaliou sua filiação ao colégio de enfermeiras, além de seus conhecimentos, atitudes e motivações referentes a participar na instância gremial; para tal fim aplicou-se um instrumento de elaboração própria (α Cronbach 0.71). Resultados: Encontrou-se que o 40.9% dos docentes forma parte do colégio de enfermeiras e que existe conhecimento suficiente ao respeito desta organização, com uma atitude desfavorável a ele mesmo, evidenciando-se uma associação entre a atitude e aspectos como a dinâmica de trabalho (p=0.043 Correlação de Spearman: 0.158) e a filiação ao colégio (p=0.02 Coeficiente de Spearman: 0.142). Discussão: A participação colegiada permite o fortalecimento da profissão, além de favorecer a visibilidade, liderança e identidade profissional; ainda que se reconheçam estes aspectos, não são suficientes para gerar a filiação ou uma atitude favorável a esta. Conclusões: Na promoção da filiação deve considerar-se a tendência à não filiação dos docentes mais jovens e os aspectos de motivação, ambos relevantes para salientar a participação colegial como um aspecto deontológico que forma parte da modelagem aos enfermeiros em formação.

2.
Neuroscience ; 288: 1-9, 2015 Mar 12.
Article in English | MEDLINE | ID: mdl-25542419

ABSTRACT

Drug addiction is associated with dysfunction in the medial prefrontal cortex (mPFC). However, the modifications of neuronal activity in mPFC underlying the reinforcing properties of addictive drugs are still unclear. Here we carried out single-unit recording experiments to study the neuronal activity in the prelimbic (PL) cortex of anesthetized rats, after expression of locomotor sensitization to amphetamine. In control rats, an acute injection of amphetamine induced mainly an inhibitory effect on firing rate (FR) and this response was negatively correlated with the basal FR. Sensitized rats showed a higher proportion of excited neurons and the response to amphetamine was independent of basal FR. Moreover, in control rats, acute amphetamine decreased burst rate, whereas in sensitized rats acute amphetamine increased burst rate. These findings indicate that amphetamine sensitization renders mPFC neurons hyperexcitable. Taken together, these data support the hypothesis that early withdrawal is associated with an increase in the activity of the mPFC, which could strengthen the PL-Nucleus Accumbens connection, thus facilitating amphetamine-induced locomotor sensitization.


Subject(s)
Amphetamine/pharmacology , Central Nervous System Stimulants/pharmacology , Cerebral Cortex/drug effects , Neurons/drug effects , Action Potentials/drug effects , Animals , Cerebral Cortex/physiology , Cerebral Cortex/physiopathology , Male , Motor Activity/drug effects , Neurons/physiology , Rats, Sprague-Dawley
4.
Psychol Rep ; 88(1): 189-200, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11293028

ABSTRACT

The present study assessed the relationship between numbing and three associated conditions of alexithymia, apathy, and depression, utilizing data collected on 353 Vietnam combat veterans diagnosed with Posttraumatic Stress Disorder from in- and out-patient settings and an outreach center at various Department of Veterans Affairs Medical centers. All subjects completed four self-report measures: the Glover Numbing Scale, the Beck Depression Inventory, the Apathy Evaluation Scale, and the Toronto Alexithymia Scale-20. The correlation matrix indicated that scores on the four measures were moderately to highly correlated. Principal components analysis with a varimax rotation indicated a five-factor solution that provided evidence for the factorial validity of each of the constructs assessed. Results of the factor analysis of items from the four measures were consistent with numbing being a separate and distinct construct from alexithymia, apathy, and depression. In general, results indicated that all constructs measured were separate and distinct from one another.


Subject(s)
Affective Symptoms/etiology , Depressive Disorder, Major/etiology , Mood Disorders/etiology , Stress Disorders, Post-Traumatic/psychology , Affective Symptoms/diagnosis , Depressive Disorder, Major/diagnosis , Humans , Male , Middle Aged , Mood Disorders/diagnosis , Psychological Tests , Severity of Illness Index , Stress Disorders, Post-Traumatic/diagnosis , Surveys and Questionnaires
5.
Mol Pharmacol ; 56(3): 478-84, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10462535

ABSTRACT

2, 5-bis(5-Hydroxymethyl-2-thienyl)furan (NSC 652287), is a representative of a series of thiophene derivatives that exhibit potent and selective antitumor activity against several tumor cell lines in the National Cancer Institute Anticancer Drug Screen. NSC 652287 has noticeable activity for the renal cell lines and produces cures in certain corresponding xenografts. The cellular mechanisms of action of NSC 652287 were therefore investigated in this study in greater detail. The most sensitive renal carcinoma cell line, A498, exhibited cell cycle arrest in G(0)-G(1) and G(2)-M at 10 nM NSC 652287, with increased p53 and p21(WAF1) protein. At higher concentrations, NSC 652287 still induced p53 elevation but with p21(WAF1) reduction and massive apoptosis. These results collectively suggested that NSC 652287 induced DNA damage. Using alkaline elution techniques, we found that NSC 652287 induced both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks. These DNA-protein cross-links (DPC) persisted for at least 12 h after drug removal and their frequency was correlated with cytotoxicity in the renal cell lines studied. The most sensitive cells (A498) produced the highest DPC followed by the cell line with intermediate sensitivity (TK-10). DPC were minimal in the two resistant cell lines, ACHN and UO-31. Nonetheless, a similar degree of DPC occurred at doses imparting equitoxic effects. These results indicate that DNA is a primary target for the novel and potent anticancer thiophene derivative, NSC 652287. NSC 652287 did not cross-link purified DNA or mammalian topoisomerase I suggesting the importance of active metabolite(s) for the cross-linking activity.


Subject(s)
Antineoplastic Agents/pharmacology , Cross-Linking Reagents/pharmacology , DNA, Neoplasm/drug effects , Furans/pharmacology , Kidney Neoplasms/drug therapy , Apoptosis , Cell Division/drug effects , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/metabolism , DNA Topoisomerases, Type I/metabolism , DNA, Neoplasm/metabolism , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , G2 Phase/drug effects , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Mitosis/drug effects , Thiophenes/pharmacology , Tumor Cells, Cultured , Tumor Suppressor Protein p53/metabolism
6.
Biochem Pharmacol ; 57(11): 1283-95, 1999 Jun 01.
Article in English | MEDLINE | ID: mdl-10230772

ABSTRACT

The tricyclic compound 2,5-bis(5-hydroxymethyl-2-thienyl)furan (NSC 652287) has shown a highly selective pattern of differential cytotoxic activity in the tumor cell lines comprising the National Cancer Institute (NCI) Anticancer Drug Screen. The mechanism underlying the selective cytotoxicity is unknown. We hypothesized that differential sensitivity to the compound observed in several renal tumor cell lines could be the result of selective accumulation or differential metabolism of this agent. We demonstrated here that the capacity of certain renal cell lines to accumulate and retain the compound, determined by accumulation of [14C]NSC 652287-derived radioactivity and by flow cytometric determination of unlabeled compound, paralleled the sensitivity of the renal cell lines to growth inhibition by NSC 652287: A-498 > TK-10 >> ACHN approximately/= to UO-31. The ability of the cell lines to metabolize [14C]NSC 652287 to a reactive species capable of binding covalently to cellular macromolecules also directly correlated with sensitivity to the compound. Different patterns of metabolites were generated by relatively more drug-sensitive cell lines in comparison with drug-resistant cell lines. The metabolizing capacity for NSC 652287 was localized primarily to the cytosolic (S100) fraction. The rate of metabolism in the cytosolic fraction from the most sensitive renal cell line, A-498, was faster than that observed in the cytosolic fractions from the other, less sensitive cell lines. The data support the hypothesis that both selective cellular accumulation and the capacity to metabolize NSC 652287 to a reactive species by certain renal carcinoma cell types are the basis for the differential cytotoxicity of this compound class.


Subject(s)
Carcinoma, Renal Cell/pathology , Furans/pharmacology , Kidney Neoplasms/pathology , Thiophenes/pharmacology , Carbon Radioisotopes , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Flow Cytometry , Furans/metabolism , Humans , Radiopharmaceuticals , Tumor Cells, Cultured
7.
Chem Res Toxicol ; 11(11): 1283-90, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9815188

ABSTRACT

Glutathione (GSH) conjugates of hydroquinone (HQ) and 2-bromohydroquinone (2-BrHQ) produce severe renal proximal tubular necrosis in rats. Since the reactivity of quinones lies, in part, in their ability to alkylate proteins, our goal was to develop an immunochemical method with which to investigate the role of protein adduct formation in quinone-thioether-mediated toxicity. An immunogen was synthesized by coupling 2-bromo-6-(N-acetylcystein-S-yl)hydroquinone (2-BrHQ-NAC) to keyhole-limpet hemocyanin (KLH). Anti-2-BrHQ-NAC-KLH antibodies were raised in rabbits and purified by affinity chromatography. Antibody binding to the 2-BrHQ-NAC epitope was confirmed by competitive enzyme-linked immunosorbent assay (ELISA) with a bovine serum albumin conjugate of 2-BrHQ-NAC. Affinity-purified anti-2-BrHQ-NAC-KLH antibodies recognized adducted proteins in the kidneys of rats treated with HQ, 2-BrHQ, 2-bromo-bis(glutathion-S-yl)hydroquinone, 2-(glutathion-S-yl)hydroquinone, 2, 5-bis(glutathion-S-yl)hydroquinone, and 2,3, 5-tris(glutathion-S-yl)hydroquinone. Immunoreactive proteins were found in all renal subcellular fractions of 2-BrHQ-treated rats, and the distribution of adducts was similiar to that obtained by quantifying 2-Br[14C]HQ covalent adducts. Western blot analysis revealed that three proteins, at 42, 46, and 79 kDa, were adducted by all the compounds examined. The identification of these adducted proteins will be required to assess their significance in quinol-thioether-mediated nephrotoxicity.


Subject(s)
Hydroquinones/chemistry , Proteins/chemistry , Sulfides/chemistry , Animals , Antibody Specificity , Blotting, Western , Cattle , Cytosol/metabolism , Enzyme-Linked Immunosorbent Assay , Immunochemistry , Kidney/enzymology , Kidney/metabolism , Male , Rabbits , Rats , Rats, Inbred F344 , Subcellular Fractions/enzymology , Subcellular Fractions/metabolism
8.
Antimicrob Agents Chemother ; 41(7): 1521-30, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9210678

ABSTRACT

We have isolated and sequenced a novel 11-kDa virucidal protein, named cyanovirin-N (CV-N), from cultures of the cyanobacterium (blue-green alga) Nostoc ellipsosporum. We also have produced CV-N recombinantly by expression of a corresponding DNA sequence in Escherichia coli. Low nanomolar concentrations of either natural or recombinant CV-N irreversibly inactivate diverse laboratory strains and primary isolates of human immunodeficiency virus (HIV) type 1 as well as strains of HIV type 2 and simian immunodeficiency virus. In addition, CV-N aborts cell-to-cell fusion and transmission of HIV-1 infection. Continuous, 2-day exposures of uninfected CEM-SS cells or peripheral blood lymphocytes to high concentrations (e.g., 9,000 nM) of CV-N were not lethal to these representative host cell types. The antiviral activity of CV-N is due, at least in part, to unique, high-affinity interactions of CV-N with the viral surface envelope glycoprotein gp120. The biological activity of CV-N is highly resistant to physicochemical denaturation, further enhancing its potential as an anti-HIV microbicide.


Subject(s)
Anti-HIV Agents/isolation & purification , Bacterial Proteins , Carrier Proteins/isolation & purification , HIV Envelope Protein gp120/metabolism , Acquired Immunodeficiency Syndrome/transmission , Amino Acid Sequence , Anti-HIV Agents/chemistry , Anti-HIV Agents/metabolism , Base Sequence , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Cell Fusion , Cell Survival/drug effects , Enzyme-Linked Immunosorbent Assay , Humans , Molecular Sequence Data , Molecular Weight , Protein Binding , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Titrimetry , Ultrafiltration
9.
Cancer Res ; 56(5): 1006-11, 1996 Mar 01.
Article in English | MEDLINE | ID: mdl-8640754

ABSTRACT

3-tert-Butyl-4-hydroxyanisole and tert-butyl-hydroquinone (TBHQ) are antioxidants known to promote renal and bladder carcinogenesis in the rat, although the mechanisms of these effects are unclear. Because glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic, and because 2-tert-butyl-5-(glutathion-S-yl)hydroquinone [5-(GSyl)TBHQ], 2-tert-butyl-6-(glutathion-S-yl)hydroquinone [6-(GSyl)TBHQ], and 2-tert-butyl-3,6-bis-(glutathion-S-yl)hydroquinone [3,6-bis-(GSyl)-TBHQ] have been identified recently as metabolites of TBHQ in the male rat, we investigated the effects of these metabolites in the male rat. At the highest dose tested (400 micromol/kg,i.v.) 5-(Gsyl)TBHQ and 6-(GSyl)TBHQ caused 2-fold increases in the urinary excretion of gamma-glutamyl transpeptidase and alkaline phosphatase, and pigments arising from the polymerization of metabolites were deposited in the kidney. 3,6-bis-(GSyl)TBHQ (200 micromol/kg) was the most potent of the GSH conjugates tested and produced significant increases in the urinary excretion of gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, and glucose (2-, 2-, 22-, and 11-fold increases, respectively). Alterations in the biochemical parameters correlated with the degree of single cell and tubular necrosis in the S(3)-M segment of the proximal tubule, as observed by light microscopy. In addition to nephrotoxicity, 3,6-bis-(GSyl)TBHQ increased the bladder wet weight 2-fold and caused severe hemorrhaging of the bladder. The half-wave oxidation potentials of 5-(Gsyl)TBHQ and 6-(GSyl)TBHQ were similar to that of TBHQ, whereas the half-wave oxidation potential of 3,6-bis-(Gsyl)TBHQ was approximately 100 mV higher than that of TBHQ. The TBHQ-GSH conjugates also catalyzed the formation of 8- hydroxydeoxyguanosine, indicating that GSH conjugation does not impair the redox activity of TBHQ. Because some chemicals may induce carcinogenesis by a mechanism involving cytotoxicity followed by sustained regenerative hyperplasia, our results suggest that the toxicity of GSH conjugates of TBHQ to kidney and bladder may contribute to the promoting effect of 3-tert-butyl-4-hydroxyanisole and TBHQ in these tissues.


Subject(s)
Antioxidants/toxicity , Butylated Hydroxyanisole/metabolism , Glutathione/metabolism , Hydroquinones/toxicity , Kidney/pathology , Urinary Bladder/pathology , Urogenital Neoplasms/metabolism , Animals , Kidney/drug effects , Male , Rats , Rats, Inbred F344 , Urinary Bladder/drug effects
11.
Toxicol Appl Pharmacol ; 128(2): 239-50, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7940539

ABSTRACT

Early subcellular targets of 2-Br-(diglutathion-S-yl)hydroquinone (2-Br-(diGSyl)HQ)-mediated nephrotoxicity were investigated by morphological and biochemical criteria. After treatment of male Fischer 344 rats with 2-Br-(diGSyl)HQ (30 mumol/kg), proximal tubular morphology was examined by electron microscopy. Changes in the plasma membrane, nuclei, and endoplasmic reticulum were observed within 30 min of 2-Br-(diGSyl)HQ administration. These changes consisted of loss of the brush border membrane, margination of heterochromatin, and reorganization of the endoplasmic reticulum into discrete aggregates. The desquamation of the brush border membrane into the tubular lumen corresponded with the rapid excretion of gamma-glutamyl transpeptidase and alkaline phosphatase in urine. As the injury developed, cell swelling with loss of cytosolic density and loss of chromatin staining was observed, and between 2 and 4 hr the nuclei underwent extensive karyorrhexis and karyolysis. Agarose gel electrophoresis of DNA isolated from the corticomedullary junction at 4 hr exhibited extensive fragmentation, which was random in nature. Mitochondria assumed a condensed configuration 2 hr after 2-Br-(diGSyl)HQ administration, but this was not followed by high-amplitude swelling prior to cell death and necrosis. Biochemical assessment of mitochondria, isolated from 2-Br-(diGSyl)HQ-treated rats at 2 hr, exhibited a significant (20%) decrease in respiratory control ratios (RCR), a consequence of an increase in State 4 respiration. At later time points (8 hr) State 4 respiration returned to control values, but the respiratory control ratio (RCR) remained significantly depressed due to decreases in State 3 respiration. At this time blood urea nitrogen concentrations were significantly elevated (41 +/- 3, mean +/- SD, n = 10). The data suggest that the plasma membrane and the nucleus are early targets of 2-Br-(diGSyl)HQ-induced cytotoxicity, and that alterations in mitochondrial structure and respiratory function occur following the initial injury.


Subject(s)
Glutathione/analogs & derivatives , Hydroquinones/toxicity , Kidney Tubules, Proximal/drug effects , Alkaline Phosphatase/urine , Analysis of Variance , Animals , Blood Urea Nitrogen , Cell Membrane/drug effects , Cell Membrane/pathology , Cell Nucleus/drug effects , Cell Nucleus/pathology , DNA/drug effects , DNA/metabolism , Dose-Response Relationship, Drug , Electrophoresis, Agar Gel , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/pathology , Glutathione/toxicity , Kidney Tubules, Proximal/ultrastructure , Male , Microscopy, Electron , Microvilli/drug effects , Microvilli/enzymology , Microvilli/pathology , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Oxygen Consumption/drug effects , Rats , Rats, Inbred F344 , gamma-Glutamyltransferase/urine
12.
Drug Metab Dispos ; 22(4): 503-10, 1994.
Article in English | MEDLINE | ID: mdl-7956722

ABSTRACT

2-Br-(diglutathion-S-yl)hydroquinone (2-Br-(diGSyl)HQ) is a potent nephrotoxicant, causing glucosuria, enzymuria, proteinuria, elevations in blood urea nitrogen, and severe histological alterations to renal proximal tubules at doses of 10-15 mumol/kg. In contrast, 2-Br-3-(glutathion-S-yl)hydroquinone (2-Br-3-(GSyl)HQ) is substantially less nephrotoxic than 2-Br-(diGSyl)HQ and requires a dose of at least 50 mumol/kg to cause modest elevations in blood urea nitrogen concentrations. The reason or reasons for this difference in potency is unclear, but since inhibition of renal gamma-glutamyl transpeptidase (gamma-GT) prevents 2-Br-(diGSyl)HQ-mediated nephrotoxicity, metabolism of these conjugates by the kidney must play an important role. To address this question we have compared the metabolism and toxicity of 2-Br-(diGSyl)HQ and 2-Br-3-(GSyl)HQ in the in situ perfused rat kidney (ISPRK). Following infusion of 20 mumol 2-Br-3-(GSyl)HQ into the right renal artery of male Sprague Dawley rats, a total of 23.5 +/- 1.9% (mean +/- SE) of the dose was accounted for in urine and bile over a period of 180 min. 2-Bromo-3-(cystein-S-yl)hydroquinone and 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone were identified in urine, and unchanged 2-Br-3-(GSyl)HQ was identified in urine and bile. The product arising from the oxidative cyclization of 2-bromo-3-(cystein-S-glycine)hydroquinone, 2H-(3-glycine)-7-hydroxy-8-bromo-1,4-benzothiazine, was also identified in urine.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Glutathione/analogs & derivatives , Hydroquinones/metabolism , Hydroquinones/toxicity , Kidney Diseases/chemically induced , Kidney/metabolism , Animals , Glutathione/metabolism , Glutathione/toxicity , Kidney/drug effects , Male , Mitochondria/drug effects , Mitochondria/metabolism , Oxygen Consumption/drug effects , Perfusion , Rats , Rats, Sprague-Dawley
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