Epithelium-derived 6-nitrodopamine modulates noradrenaline-induced contractions in human seminal vesicles.

AIMS: To evaluate the basal release of 6-nitrodopamine (6-ND) from human isolated seminal vesicles (HISV) and to characterize its action and origin. MAIN METHODS: Left HISV obtained from patients undergoing prostatectomy surgery was suspended in a 3-mL organ bath containing warmed (37 °C) and gassed (95%O2:5%CO2) Krebs-Henseleit's solution (KHS) with ascorbic acid. An aliquot of 2 mL of the supernatant was used to quantify catecholamines by LC-MS/MS. For functional studies, concentration-responses curves to catecholamines were obtained, and pEC50 and Emax values were calculated. Detection of tyrosine hydroxylase and S100 protein were also carried out by both immunohistochemistry and fluorescence in-situ hybridization assays (FISH). KEY FINDINGS: Basal release of 6-ND was higher than the other catecholamines (14.76 ± 14.54, 4.99 ± 6.92, 3.72 ± 4.35 and 5.13 ± 5.76 nM for 6-ND, noradrenaline, adrenaline, and dopamine, respectively). In contrast to the other catecholamines, the basal release of 6-ND was not affected by the sodium current (Nav) channel inhibitor tetrodotoxin (1 µM; 10.4 ± 8.9 and 10.4 ± 7.9 nM, before and after tetrodotoxin, respectively). All the catecholamines produced concentration-dependent HISV contractions (pEC50 4.1 ± 0.2, 4.9 ± 0.3, 5.0 ± 0.3, and 3.9 ± 0.8 for 6-ND, noradrenaline, adrenaline, and dopamine, respectively), but 6-ND was 10-times less potent than noradrenaline and adrenaline. However, preincubation with very low concentration of 6-ND (10-8 M, 30 min) produced significant leftward shifts of the concentration-response curves to noradrenaline. Immunohistochemical and FISH assays identified tyrosine hydroxylase in tissue epithelium of HISV strips. SIGNIFICANCE: Epithelium-derived 6-ND is the major catecholamine released from human isolated seminal vesicles and that modulates smooth muscle contractility by potentiating noradrenaline-induced contractions.

Effectiveness of experimental dentifrices based on essential oils on biofilm on complete dentures: an in vitro study

Abstract Specific products containing natural resources can contribute to the innovation of complete denture hygiene. Objective: To conduct an in vitro evaluation of experimental dentifrices containing essential oils of Bowdichia virgilioides Kunth (BvK), Copaifera officinalis (Co), Eucalyptus citriodora (Ec), Melaleuca alternifolia (Ma) and Pinus strobus (Ps) at 1%. Methodology: The variables evaluated were organoleptic and physicochemical characteristics, abrasiveness (mechanical brushing machine) simulating 2.5 years, and microbial load (Colony Forming Units - CFU/mL), metabolic activity (XTT assay) and cell viability (Live/Dead® BacLight™ kit) of the multispecies biofilm (Streptococcus mutans: Sm, Staphylococcus aureus: Sa, Candida albicans: Ca and Candida glabrata: Cg). Specimens of heat-polymerized acrylic resins (n=256) (n=96 specimens for abrasiveness, n=72 for microbial load count, n=72 for biofilm metabolic activity, n=16 for cell viability and total biofilm quantification) with formed biofilm were divided into eight groups for manual brushing (20 seconds) with a dental brush and distilled water (NC: negative control), Trihydral (PC: positive control), placebo (Pl), BvK, Co, Ec, Ma or Ps. After brushing, the specimens were washed with PBS and immersed in Letheen Broth medium, and the suspension was sown in solid specific medium. The organoleptic characteristics were presented by descriptive analysis. The values of density, pH, consistency and viscosity were presented in a table. The data were analyzed with the Wald test in a generalized linear model, followed by the Kruskal-Wallis test, Dunn's test (mass change) and the Bonferroni test (UFC and XTT). The Wald test in Generalized Estimating Equations and the Bonferroni test were used to analyze cell viability. Results: All dentifrices showed stable organoleptic characteristics and adequate physicochemical properties. CN, Ec, Ps, Pl and PC showed low abrasiveness. There was a significant difference between the groups (p<0.001) for microbial load, metabolic activity and biofilm viability. Conclusions: It was concluded that the BvK, Ec and Ps dentifrices are useful for cleaning complete dentures, as they have antimicrobial activity against biofilm. The dentifrices containing Bowdichia virgilioides Kunth showed medium abrasiveness and should be used with caution.

Release of 6-nitrodopamine from human popliteal artery and vein.

6-Nitrodopamine (6-ND) is a novel catecholamine that is released from human umbilical cord vessels, and it causes vascular relaxation by acting as a dopamine D2-receptor antagonist. Here it was investigated whether human peripheral vessels obtained from patients who have undergone surgery for leg amputation release 6-ND, and its action in these tissues. Popliteal artery and vein strips present basal release of 6-ND, as measured by liquid chromatography coupled to tandem mass spectrometry. The release was significantly reduced when the tissues were pre-treated with the nitric oxide synthase inhibitor L-NAME (100 µM), or when the endothelium was mechanically removed. In U-46619 (3 nM) pre-contracted rings, 6-ND induced concentration-dependent relaxations (pEC50 8.18 ± 0.05 and 8.40 ± 0.08, in artery and vein rings, respectively). The concentration-dependent relaxations induced by 6-ND were unaffected in tissues pre-treated with L-NAME, but significantly reduced in tissues where the endothelium has been mechanically removed. In U-46619 (3 nM) pre-contracted rings, the selective dopamine D2 receptor antagonist L-741,626 also caused concentration-dependent relaxations (pEC50 8.92 ± 0.22 and 8.79 ± 0.19, in artery and vein rings, respectively). The concentration-dependent relaxations induced by L-741,626 were unaffected in tissues pre-treated with L-NAME, but significantly reduced in tissues where the endothelium has been mechanically removed. This is the first demonstration that 6-nitrodopamine is released from human peripheral artery and vein rings. The results also indicate that endothelium-derived dopamine is a major contractile agent in the popliteal artery and vein, and that selective dopamine D2-receptor antagonists such as 6-ND, may have therapeutic potential in the treatment of human peripheral vascular diseases.

Simvastatin protects against intestinal ischemia/reperfusion-induced pulmonary artery dysfunction.

AIMS: The lung is an important target organ damage in intestinal ischemia/reperfusion (II/R), but mechanisms involved in II/R-induced pulmonary artery (PA) dysfunction, as well as its treatment, are not clear. The present study aimed to investigate the mechanisms involved in the II/R-induced PA dysfunction and a possible protective role of acute simvastatin pretreatment. MAIN METHODS: Male Wistar rats were subjected to occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion (II/R) or sham-operated surgery (sham). In some rats, simvastatin (20 mg/kg, oral gavage) was administrated 1 h before II/R. KEY FINDINGS: II/R reduced acetylcholine-induced relaxation and phenylephrine-induced contraction of PA segments, which were prevented by acute simvastatin pretreatment in vivo or restored by inducible nitric oxide synthase (iNOS) inhibition in situ with 1400 W. Elevated reactive oxygen species (ROS) levels and higher nuclear translocation of nuclear factor kappa B (NFκB) subunit p65 were observed in PA of II/R rats and prevented by simvastatin. Moreover, simvastatin increased superoxide dismutase (SOD) activity and endothelial nitric oxide synthase (eNOS) expression in PA of the II/R group as well as prevented the increased levels of interleukin (IL)-1ß and IL-6 in lung explants following II/R. SIGNIFICANCE: The study suggests that pretreatment with a single dose of simvastatin prevents the II/R-induced increase of inflammatory factors and oxidative stress, as well as PA endothelial dysfunction and adrenergic hyporreactivity. Therefore, acute simvastatin administration could be therapeutic for pulmonary vascular disease in patients suffering from intestinal ischemic events.

Persistent SARS-CoV-2 antigen presence in multiple organs of a naturally infected cat from Brazil

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the disease coronavirus 2019 (COVID-19) in humans. SARS-CoV-2 has been identified in cats with or without clinical signs. Case presentation: We describe the pathological and molecular findings in a six-month-old asymptomatic cat with SARS-CoV-2 infection from Brazil, belonging to a human family with COVID-19 cases. The pool of nasopharynx and oropharynx swabs at day zero tested positive by RT-qPCR for SARS-CoV-2. No amplification resulted from molecular testing performed on days 7 and 14. The cat was hit by a car and died 43 days after the molecular diagnosis. Immunohistochemistry at post-mortem examination demonstrated nucleocapsid protein in samples from the lungs, kidneys, nasal conchae, trachea, intestine, brain and spleen. Conclusion: The present study has highlighted the possibility that viral antigens can be detected by immunohistochemistry in multiple organs six weeks after infection, although the same tissues tested negative by RT-PCR.(AU)

Persistent SARS-CoV-2 antigen presence in multiple organs of a naturally infected cat from Brazil

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the disease coronavirus 2019 (COVID-19) in humans. SARS-CoV-2 has been identified in cats with or without clinical signs. Case presentation: We describe the pathological and molecular findings in a six-month-old asymptomatic cat with SARS-CoV-2 infection from Brazil, belonging to a human family with COVID-19 cases. The pool of nasopharynx and oropharynx swabs at day zero tested positive by RT-qPCR for SARS-CoV-2. No amplification resulted from molecular testing performed on days 7 and 14. The cat was hit by a car and died 43 days after the molecular diagnosis. Immunohistochemistry at post-mortem examination demonstrated nucleocapsid protein in samples from the lungs, kidneys, nasal conchae, trachea, intestine, brain and spleen. Conclusion: The present study has highlighted the possibility that viral antigens can be detected by immunohistochemistry in multiple organs six weeks after infection, although the same tissues tested negative by RT-PCR.

Influência da pré-cloração na clarificação de águas para abastecimento utilizando coagulante à base de tanino / Pre-chlorination effects on drinking water treatment using tannin-based coagulant

RESUMO Diferentes técnicas de tratamento de água destinada ao abastecimento público, como a pré-cloração e o uso de coagulantes orgânicos, têm sido relatadas como alternativas econômica, técnica e ambientalmente viáveis. Entretanto, o resultado da interação entre esses processos deve ser estudado para sua aplicação com segurança. Dessa forma, este estudo objetivou avaliar a influência da pré-cloração na clarificação de água para abastecimento público, utilizando coagulante à base de tanino. Os ensaios foram conduzidos em jar test com o uso de Tanfloc SG como coagulante, variando as dosagens de 2,5 a 45,0 mg L−1, e de oxidante hipoclorito de sódio (NaClO) nas concentrações de cloro residual livre (HClO(NaClO)) de 0,8 e 5,0 mg L−1, no tratamento da água do ribeirão João Leite. As dosagens ótimas de coagulante foram determinadas para as seguintes condições de tratamento: adição somente de tanino; tanino e NaClO aplicados simultaneamente; e tanino adicionado após 30 min da pré-cloração. Nessas condições, o pH de coagulação foi analisado de 6,0 a 8,5. Foram avaliados parâmetros como turbidez, cor aparente, pH e HClO(NaClO). A melhor condição de tratamento com pré-cloração foi a adição simultânea de NaClO e coagulante tanino nas dosagens de 0,8 mg L−1 (HClO(NaClO)) e 10,0 mg L−1, respectivamente, com remoção de turbidez de 71,6% e cor aparente de 62,7%. Os resultados demonstraram que a pré-cloração afetou negativamente o processo de tratamento, e para maior concentração de HClO(NaClO) maior foi a dosagem de tanino requerida, sem apresentar aumento significativo nas eficiências de remoção de turbidez e cor aparente.

ABSTRACT Different techniques in the treatment of water intended for public supply such as pre-chlorination and use of organic coagulants have been reported as economic, technical and environmental viable alternatives. However, the result of the interaction between these processes should be studied for their safe application. Thus, this study aimed to evaluate the influence of pre-chlorination on coagulation and flocculation of water for public supply using a tannin-based coagulant. The assays were conducted in Jar Test using Tanfloc SG as a coagulant, varying the dosages from 2.5 to 45.0 mg L−1, and sodium hypochlorite oxidant (NaClO) in the concentrations of free residual chlorine (HClO(NaClO)) of 0.8 and 5.0 mg L−1, in the water treatment of João Leite River. Optimal coagulant dosages were determined for the following treatment conditions: addition of tannin only; tannin and NaClO applied simultaneously; and, tannin added after 30 min of pre-chlorination. Under these conditions, the coagulation pH was analyzed from 6.0 to 8.5. Parameters such as turbidity, apparent color, pH and HClO (NaClO) were evaluated. The best treatment condition with pre-chlorination was the simultaneous addition of NaClO and coagulant at dosages of 0.8 mg L−1(HClO(NaClO)) and 10.0 mg L−1 respectively, with turbidity removal of 71.6% and apparent color of 62.7%. In general, the results showed that pre-chlorination negatively affected the process being that the higher concentration of HClO(NaClO) the higher tannin dosage, without presenting a significant increase in the efficiencies of turbidity and apparent color removal.

In vitro anticancer activity of methanolic extract of Granulocystopsis sp., a microalgae from an oligotrophic oasis in the Chihuahuan desert.

With the purpose of discovering new anticancer molecules that might have fewer side effects or reduce resistance to current antitumor drugs, a bioprospecting study of the microalgae of the Cuatro Cienegas Basin (CCB), an oasis in the Chihuahuan desert in Mexico was conducted. A microalgae was identified as Granulocystopsis sp. through sequencing the rbcL gene and reconstruction of a phylogenetic tree, and its anticancer activities were assessed using various in vitro assays and different cell lines of human cancers, including lung, skin melanoma, colorectal, breast and prostatic cancers, as well as a normal cell line. The values of IC50 of the microalgae methanolic extract using the MTT assay were lower than 20 µg/ml, except that in the lung cancer line and the normal cell line. In vitro, the microalgae extract caused the loss of membrane integrity, monitored by the trypan blue exclusion test and exhibited marked inhibition of adhesion and cell proliferation in cancer cell lines, through the evaluation of the clonogenic assay. Also, typical nuclear changes of apoptotic processes were observed under the microscope, using the dual acridine orange/ethidium bromide fluorescent staining. Finally, the microalgae extract increased the activity of caspases 3 and 7 in skin melanoma, colon, breast and prostate cancer cells, in the same way as the apoptotic inductor and powerful antitumoral drug, doxorubicin. This study shows the anticancer activity from Granulocystopsis sp., a microalgae isolated from the CCB.

Structural basis for the design of allosteric inhibitors of the Aurora kinase A enzyme in the cancer chemotherapy.

Aurora kinases are essential enzymes for the control of cell cycle. The specific role of aurora kinase A (AURKA) is the regulation of spindle assembly and stability by promoting centrosome maturation and separation. Because AURKA is an essential protein for the normal occurrence of the cycle, mutations and deregulations in the activities of this protein are associated with several cancers. The kinase activity of AURKA is controlled by autocatalytic phosphorylation, which is facilitated after binding to a regulator protein, the Target Protein for Xenopuskinesin-like protein 2 (TPX2). SCOPE OF REVIEW: This review highlights the physiological and pathophysiological properties of AURKA, the structure of the AURKA/TPX2 complex and the main structural features that can be explored for the design of selective AURKA inhibitors. MAJOR CONCLUSIONS: The design of selective AURKA inhibitors remains as a challenge as most of the currently available inhibitors target only the ATP binding cleft and are nonselective among kinases. However, by exploring the inactive form of the kinase, researchers get access to an adjacent hydrophobic pocket, allowing the design of more selective inhibitors. Additionally, the possibility of designing potent allosteric AURKA inhibitors look very promising from the clinical perspective, since it tends to yield the most selective class of compounds. GENERAL SIGNIFICANCE: Herein we detailed the binding modes of the most selective AURKA inhibitors currently reported. We believe this will aid researchers in defining the structural patterns necessary for selective AURKA inhibition, guiding the design of more potent compounds to be therapeutically explored in cancer patients.

The Occurrence of Multidrug Resistant Bacteria in the Urine of Healthy Dogs and Dogs with Cystitis.

The objectives of this study were to evaluate the occurrence of microorganisms, the antimicrobial susceptibility profile, and the presence of multidrug resistant (MDR) bacteria in the urine of clinically healthy dogs and dogs with cystitis. The urine was collected through cystocentesis. Subsequently, culture and antimicrobial susceptibility tests were performed. The isolates were classified based on their resistance profile, to evaluate the presence of MDR bacteria. Statistical analyses were performed using the chi-squared or Fisher's exact tests. Bacterial isolates were present in 24.39% of the dogs in the control group, and 60.27% of the dogs in the cystitis group. The cystitis group was associated with a higher risk of bacterial isolates than the control group (odds ratio = 7.5; 95% confidence interval = 2.81-22.40). The main isolates were Staphylococcus spp., Escherichia coli, Proteus spp., and Enterobacter spp. in both groups. A high percentage of isolates were resistant to ampicillin in both groups. The lowest resistance presented by the isolates in both groups was to meropenem. Only the resistance to quinolones was different between the groups. The proportions of MDR isolates were 70% (7/10) and 65.91% (29/44) in the control and cystitis groups, respectively. The results showed the presence of MDR bacteria in the urine of both the healthy dogs, and the dogs with cystitis. The drug resistance was high, reinforcing the importance of establishing an effective treatment approach against urinary tract infections in pets, to minimize the spread of bacterial resistance and its impact on public health.

Efeito na atividade de água em farinha mista extrudada de cascas e albedo de maracujá (Passiflora edulis Flavicarpa Degener) e arroz (Oryza sativa L. ) e farinha de maracujá industrializada / Effect of water activity in extruded passion fruit peel (Passiflora edulis Flavicarpa Degener) and rice (Oryza sativa L. ) flour and industrialized passion fruit flour

O objetivo deste trabalho foi verificar o efeito da atividade de água (Aw) nas farinhas de cascas e albedo de maracujá (FCAM) e farinha de arroz (FA) processadas por extrusão, gerando uma farinha mista pré-cozida de casca e albedo e arroz (FMCAMA). A determinação da (Aw) foi realizada utilizando aparelho digital Aqualab®, modelo CX-2, à temperatura de 25ºC. Os resultados da (Aw) foram mais baixos para as amostras de farinha de cascas e albedo de maracujá e arroz nas amostras FMCAMA1 (0,276±0,015), FMCAMA2 (0,227±0,005) e FMCAMA3 (0,259±0,034) do que para as amostras de FMI industrializada: FMI1 (0,618±0,005), FMI2 (0,553±0,003) e FMI3 (0,540±0,004).

Oxidative Stress in Rheumatoid Arthritis: What the Future Might Hold regarding Novel Biomarkers and Add-On Therapies.

Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction-self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?-represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis.

Medication errors in emergency departments: is electronic medical record an effective barrier? / Erros de medicação em unidades de pronto atendimento: prontuário eletrônico, barreira eficaz?

ABSTRACT Objective: To compare medication errors in two emergency departments with electronic medical record, to two departments that had conventional handwritten records at the same organization. Methods: A cross-sectional, retrospective, descriptive, comparative study of medication errors and their classification, according to the National Coordinating Council for Medication Error Reporting and Prevention, associated with the use of electronic and conventional medical records, in emergency departments of the same organization, during one year. Results: There were 88 events per million opportunities in the departments with electronic medical record and 164 events per million opportunities in the units with conventional medical records. There were more medication errors when using conventional medical record - in 9 of 14 categories of the National Coordinating Council for Medication Error Reporting and Prevention. Conclusion: The emergency departments using electronic medical records presented lower levels of medication errors, and contributed to a continuous improvement in patients´ safety.

RESUMO Objetivo: Comparar os erros de medicações de duas unidades de pronto atendimento que possuíam prontuário eletrônico aos de duas unidades que possuíam prontuário convencional manual em uma mesma instituição. Métodos: Estudo transversal, retrospectivo, descritivo, que comparou a incidência de erros de medicações e sua classificação, segundo o National Coordinating Council for Medication Error Reporting and Prevention, associado ao uso do prontuário eletrônico e do convencional, em unidades de pronto atendimento de uma mesma instituição por um ano. Resultados: Foram observados 88 eventos por milhão de oportunidades nas unidades com prontuário eletrônico e 164 por milhão de oportunidades nas unidades com prontuário convencional. Houve mais erros de medicações nas unidades com prontuário convencional − em 9 das 14 categorias da National Coordinating Council for Medication Error Reporting and Prevention analisadas. Conclusão: Com a utilização do prontuário eletrônico, as unidades de pronto atendimento apresentaram menores índices de erros de medicações, contribuindo para melhoria continuada na segurança do paciente.

Electrical field-induced contractions on Crotalus durissus terrificus and Bothrops jararaca aortae are caused by endothelium-derived catecholamine.

Endothelium is the main source of catecholamine release in the electrical-field stimulation (EFS)-induced aortic contractions of the non- venomous snake Panterophis guttatus. However, adrenergic vasomotor control in venomous snakes such as Crotalus durissus terrificus and Bothrops jararaca has not yet been investigated. Crotalus and Bothrops aortic rings were mounted in an organ bath system. EFS-induced aortae contractions were performed in the presence and absence of guanethidine (30 µM), phentolamine (10 µM) or tetrodotoxin (1 µM). Frequency-induced contractions were also performed in aortae with endothelium removed. Immunohistochemical localization of both tyrosine hydroxylase (TH) and S-100 protein in snake aortic rings and brains, as well as in human tissue (paraganglioma tumour) were carried out. EFS (4 to 16 Hz) induced frequency-dependent aortic contractions in both Crotalus and Bothrops. The EFS-induced contractions were significantly reduced in the presence of either guanethidine or phentolamine in both snakes (p<0.05), whereas tetrodotoxin had no effect in either. Removal of the endothelium abolished the EFS-induced contractions in both snakes aortae (p<0.05). Immunohistochemistry revealed TH localization in endothelium of both snake aortae and human vessels. Nerve fibers were not observed in either snake aortae. In contrast, both TH and S100 protein were observed in snake brains and human tissue. Vascular endothelium is the main source of catecholamine release in EFS-induced contractions in Crotalus and Bothrops aortae. Human endothelial cells also expressed TH, indicating that endothelium- derived catecholamines possibly occur in mammalian vessels.

Antioxidant and Protective Effects of Schinus terebinthifolius Raddi Against Doxorubicin-Induced Toxicity.

Doxorubicin is an anticancer drug whose toxic effects on non-cancer cells are associated with increased oxidative stress. This study investigated the chemical composition, antioxidant activity of the methanolic extract of Schinus terebinthifolius Raddi leaves (MESL) as well as effects against doxorubicin-induced toxicity in human erythrocytes, K562 human erythroleukemia cells, and mouse hearts. The chemical composition indicated the presence of phenolic compounds, flavonoids, tannins, and ascorbic acid. MESL showed antioxidant activity by scavenging free radicals and inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent, and was able to increase the enzymatic activity of superoxide dismutase and glutathione peroxidase in human erythrocytes, without influencing the activity of enzyme catalase. The increase of oxidative hemolysis and malondialdehyde levels in erythrocytes incubated with doxorubicin was reduced by treatment with MESL. The cytotoxic activity of doxorubicin in erythroleukemia cells treated with MESL was unmodified. Additionally, the extract protected mice against the doxorubicin-induced cardiotoxicity. In conclusion, the MESL exhibits antioxidant activity, reducing doxorubicin-induced oxidative stress without changing the anticancer action of the drug, and protects against doxorubicin-induced cardiotoxicity. Hence, these findings suggest that these effects are via anti-oxidative by inhibiting free radicals, decreased oxidative stress, and increased antioxidant enzyme activity.

Detection of Putative Stem-cell Markers in Invasive Ductal Carcinoma of the Breast by Immunohistochemistry: Does It Improve Prognostic/Predictive Assessments?

INTRODUCTION: Experimental evidences from the last 2 decades supports the existence of a special type of neoplastic cell with stem-like features [cancer stem cell (CSC)] and their role in the pathophysiology and therapeutic resistance of breast cancer. However, their clinical value in human breast cancer has not been fully determined. MATERIALS AND METHODS: An immunohistochemistry panel of 10 putative CSC markers (CD34, C-KIT, CD10, SOX-2, OCT 3/4, p63, CD24, CD44, CD133, and ESA/EPCAM) was applied to 74 cases of breast cancer, followed in a Regional Cancer Center of Minas Gerais State, Brazil, from 2004 to 2006. Possible associations between CSC markers and classic variables of clinicopathologic relevance were investigated. RESULTS: The most frequently positive CSC markers were CD44, CD24, CD133, and ESA (the others were present in <15% of the cases). Two CSC profiles were defined: CD24/CD44 (CSC-1) and CD133/ESA (CSC-2). CSC-1 was significantly associated to patients older than 40 years, tumors of <2.0 cm in diameter, early clinical stages (P<0.05), and increased death risk of 4 times (P=0.03; 95% confidence interval, 1.09-14.41). CSC-2 was related to increased relapse risk of 3.75 times (P=0.04; 95% confidence interval, 1.02-13.69). CONCLUSION: The detection of the most frequently positive CSC markers by immunohistochemistry is of clinicopathologic and prognostic relevance.

Encefalitis por anticuerpos contra receptor NMDA. A propósito de un caso / Encephalitis by antibodies against NMDA receptor. About a case

Introducción: En la encefalitis por anticuerpos contra receptores N-Metil-D-Aspartato (NMDA) se genera una disfunción neuronal del ácido gamma-aminobutírico (GABA), con desregulación del glutamato y la dopamina. Los teratomas y las infecciones virales se presumen causales de la respuesta autoinmunitaria. La clínica evoluciona por etapas con un pródromo similar a una infección viral con posteriores manifestaciones psiquiátricas y convulsiones, seguidas de disfunción motora, cognitiva y autonómica. El diagnóstico se basa en la clínica y la presencia de anticuerpos del receptor NMDA. El tratamiento incluye inmunoterapia y eventual eliminación del tumor. La enfermedad puede ser letal o provocar daño irreversible en regiones corticales. Objetivo: Destacar la importancia del diagnóstico precoz en los casos de encefalitis autoinmune para una mayor efectividad de los tratamientos postulados. Reporte de caso: Paciente femenina de 13 años de edad, con diagnóstico de diabetes tipo I; presenta dolor y pérdida de fuerza con movimientos involuntarios en miembro superior izquierdo con dificultad en la deambulación, más episodio convulsivo tónico clónico generalizado seguido de manifestaciones neuropsiquiátricas. Se sospecha encefalitis autoinmune, se dosan anticuerpos anti ácido glutámico descarboxilasa (GAD) y anti NMDA, con resultados positivos. Recibe corticoterapia, inmunoglobulina endovenosa, rituximab y plasmaferesis. Presenta escasa mejoría clínica, con persistencia de síntomas secuelares psiquiátricos y neurológicos. Discusión: Es importante sospechar esta entidad aunque las manifestaciones clínicas iniciales sugieran otras etiologías. El tratamiento inmunosupresor agresivo no debería demorarse aun cuando no se haya confirmado la positividad de los anticuerpos NMDA. El buen pronóstico depende del inicio precoz del tratamiento.

Introduction: The encephalitis by antibodies against NMDA receptors, a neuronal dysfunction of gamma-aminobutyric acid (GABA) is generated, with deregulation of glutamate and dopamine. Teratomas and viral infections are presumed to be the cause to the autoimmune response. The clinic evolves in stages with a prodrome similar to a viral infection with subsequent psychiatric manifestations and seizure, followed by motor, cognitive and autonomic dysfunction. Diagnosis is based on clinical symptoms and the presence of NMDA receptor antibodies. The treatment includes immunotherapy and, eventually, elimination of the tumor. The disease can be lethal or cause irreversible damage in cortical regions. Objective: Highlight the importance of early diagnosis in cases of autoimmune encephalitis for greater effectiveness of postulated treatments. Case report.:13 year old female patient diagnosed with type I diabetes; presents pain, loss of strength and involuntary movements of the upper left limb and ambulation difficulties, associeted with a generalized tonic-clonic seizure episode followed by neuropsychiatric manifestations. Autoinmune encefalitis was suspected so antiglutamic acid decarboxylase (GAD) and anti-NMDA antibodies were dosed, which throw a positive result. The patient receives corticotherapy, intravenous immunoglobulin, rituximab and plasmapheresis. Presenting little clinical improvement, with persistence of psychiatric and neurological sequelae symptoms. Discussion: It is important to suspect this entity although the initial clinical manifestations suggests other etiologies. Aggressive immunosuppressive therapy should not be delayed even when the positivity of NMDA antibodies has not been confirmed. The good prognosis depends on the early start of the treatment.

Action of ear acupuncture in people with chronic pain in the spinal column: a randomized clinical trial / Ação da auriculoacupuntura em pessoas com dor crônica na coluna vertebral: ensaio clínico randomizado / Acción de la auriculoacupuntura en personas con dolor crónico en la columna vertebral: ensayo clínico aleatorio

ABSTRACT Objectives: to assess the action of ear acupuncture on disability and tissue temperature in people with chronic pain in the spinal column. Method: a clinical trial with a sample of 110 people, randomized into three groups: Treatment, Placebo and Control. The assessment instruments were the Rolland Morris Disability Questionnaire (RMDQ) and a thermographic camera, administered before the first treatment session, one week after and 15 days after (follow-up) the fifth session of ear acupuncture. In the analysis of the data, the Kruskal Wallis, Student-Newman Keuls and Wilcoxon tests were applied. Results: there was a significant reduction in disability in the Treatment and Placebo groups between the initial and final assessments (p<0.05) and between the initial assessments and follow-up (p<0.05). In the final assessment, the Treatment group presented improvement of disability when compared with the Placebo and Control groups (p<0.05). There was an increase in mean tissue temperature of the dorsal region between the initial and follow-up assessments in Treatment and Control groups (p<0.05), and between the final assessments and follow-up in the Treatment and Placebo groups (p<0.05). Conclusion: ear acupuncture was efficacious in reducing disability and increasing tissue temperature in people with chronic pain in the spinal column. Brazilian Register of Clinical Trials (RBR-5X69X2).

RESUMO Objetivos: avaliar a ação da auriculoacupuntura na incapacidade e na temperatura tissular de pessoas com dor crônica na coluna vertebral. Método: ensaio clínico com amostra de 110 pessoas, randomizadas em três grupos: Tratado, Placebo e Controle. Os instrumentos de avaliação foram o Questionário de Incapacidade de Rolland Morris e uma câmera termográfica, aplicados antes da primeira sessão de tratamento, uma semana após e 15 dias após (follow up) à quinta sessão de auriculoacupuntura. Na análise dos dados, aplicaram-se os testes Kruskal-Wallis, Student-Newman-Keuls e Wilcoxon. Resultados: houve redução significativa da incapacidade nos grupos Tratado e Placebo entre as avaliações inicial e final (p<0,05) e entre as avaliações inicial e follow up (p<0,05). Na avaliação final, o grupo Tratado apresentou melhora da incapacidade se comparado ao Placebo e ao Controle (p<0,05). Houve aumento na temperatura média tissular da região dorsal entre as avaliações inicial e follow up no Tratado e Controle (p<0,05). Entre as avaliações final e follow up no Tratado e Placebo (p<0,05). Conclusão: a auriculoacupuntura foi eficaz para reduzir a incapacidade e aumentar a temperatura tissular em pessoas com dor crônica na coluna vertebral. Registro Brasileiro de Ensaios Clínicos (RBR-5X69X2).

RESUMEN Objetivos: evaluar la acción de la auriculoacupuntura en la incapacidad y en la temperatura del tejido de personas con dolor crónico en la columna vertebral. Método: ensayo clínico con muestra de 110 personas, asignadas aleatoriamente en tres grupos: Tratado, Placebo y Control. Los instrumentos de evaluación fueron el Cuestionario de Incapacidad de Rollad Morris y una cámara termográfica, aplicados antes de la primera sesión de tratamiento, una semana después y quince días después (follow up) de la quinta sesión de auriculoacupuntura. En el análisis de los datos se aplicaron las pruebas Kruskal-Wallis, Student-Newman Keuls y Wilcoxon. Resultados: hubo reducción significativa de la incapacidad en los grupos Tratado y Placebo, entre las evaluaciones inicial y final (p<0,05) y entre las evaluaciones inicial y follow up (p<0,05). En la evaluación final, el grupo Tratado presentó mejoría de la incapacidad si comparado al Placebo y al Control (p<0,05). Hubo aumento en la temperatura media del tejido de la región dorsal entre las evaluaciones inicial y follow up en el Tratado y Control (p<0,05), y entre las evaluaciones final y follow up en el Tratado y Placebo (p<0,05). Conclusión: la auriculoacupuntura fue eficaz en reducir la incapacidad y en aumentar la temperatura del tejido en personas con dolor crónico en la columna vertebral. Registro Brasileño de Ensayos Clínicos (RBR-5X69X2).

Bem-estar espiritual e coping religioso/espiritual em pessoas com insuficiência renal crônica / Spiritual well-being and spiritual/religious coping in people with chronic kidney disease

Resumo Objetivo: Avaliar a variação temporal e a correlação entre o bem-estar espiritual e coping religioso/espiritual de pessoas com insuficiência renal crônica em tratamento hemodialítico. Metodologia: Estudo descritivo, analítico e longitudinal. A amostra inicial contou com 118 participantes com perda de 31 ao final das coletas, o que reduziu a amostra final para 87 participantes. Foram aplicados, por meio de entrevista, o questionário sociodemográfico e clínico, a Escala de Coping Religioso/Espiritual Breve (CRE-Breve) e a Escala de Bem-estar Espiritual (EBE) em três coletas distintas, realizadas a cada dois meses. Resultados: Verificou-se que as pessoas com insuficiência renal crônica em hemodiálise fazem uso do enfrentamento religioso e espiritual. A média do CRE positivo foi 3,34, que reflete um escore alto. O EBE total e o EBE religioso associaram-se significativamente à importância dada à religião/espiritualidade (p < 0,001). Conclusão: Os pacientes com insuficiência renal crônica em tratamento hemodialítico entrevistados neste estudo utilizam o coping religioso/espiritual de forma positiva e significativa, da mesma forma que consideram importante a religião/espiritualidade em suas vidas.

Resumen Objetivo: Evaluar la variación temporal y la correlación entre el bienestar espiritual y el afrontamiento religioso/espiritual en personas con insuficiencia renal crónica sometidas a hemodiálisis. Metodología: Estudio descriptivo, analítico y longitudinal. La muestra inicial contó con 118 participantes, pero al final de la recopilación de datos hubo una pérdida de 31, lo que redujo la muestra a 87. Se aplicaron mediante entrevistas el cuestionario sociodemográfico y clínico, la Escala de Coping Religioso/Espiritual Breve (CRE-Breve) y la Escala de Bem-estar Espiritual (EBE). La recopilación de datos se realizó en tres etapas, con intervalos frecuentes de dos meses. Resultados: Se encontró que las personas con insuficiencia renal crónica sometidas a hemodiálisis suelen recurrir al afrontamiento religioso y espiritual. La media positiva de CRE fue de 3,34, lo que reflejó una alta puntuación. Por su parte, el EBE total y el EBE religioso se asociaron significativamente con la importancia que se le da a la religión/espiritualidad (p < 0,001). Conclusiones: Los pacientes con insuficiencia renal crónica sometidos a hemodiálisis utilizan el afrontamiento religioso/espiritual de manera positiva y significativa; así mismo, consideran importante la religión/ espiritualidad en sus vidas.

Abstract Objective: To assess temporal variation and correlation between spiritual well-being and spiritual/religious coping in people with chronic kidney disease on hemodialysis. Methodology: Longitudinal, descriptive and analytical study. Initial sample was composed of 118 participants, but at the end of data collection, there was a loss of 31 participants, which is why the sample was reduced to 87. A socio-demographic and clinical questionnaire, the Brief Spiritual/ Religious Coping Scale (Brief-SRCOPE Scale), and The Spiritual Well-Being Scale (SWB) were applied using interviews. Data collection were carried out in three stages, at two-month frequent intervals. Results: It was found that people with chronic kidney disease on hemodialysis tend to resort spiritual and religious coping. The spiritual/religious coping mean positive was 3.34, reflecting a high score. On the other hand, total SWB and the religious SWB were significantly associated with the importance given to spirituality/religion (p < 0.001). Conclusions: Patients with chronic kidney disease on hemodialysis make use of spiritual/religious coping positively and significantly; likewise, they regard religion/spirituality as important in their lives.

Impactos da dor crônica na vida das pessoas e a assistência de enfermagem no processo / Impacts of chronic pain on people's life and nursing care in the process

Objetivo: Refletir sobre os impactos da dor crônica na vida das pessoas e a assistência de enfermagem no processo. Metodología: Trata-se de um ensaio reflexivo, fundamentado em uma revisão teórica. O estudo foi desenvolvido entre os meses de maio de 2015 a julho de 2016. Os dados foram analisados e logo organizados nos seguintes eixos temáticos: O impacto da dor crônica sobre a qualidade de vida das pessoas, Dor como quinto sinal vital: a importância de sua avaliação e Assistência de enfermagem ao paciente com dor crônica. Resultados: Vários são os impactos que a dor acarreta na vida das pessoas e, quando este sintoma se torna crônico, a repercussão sobre a qualidade de suas vidas é mais intensa. Portanto, uma avaliação abrangente, holística e multiprofissional da pessoa com dor faz-se necessária, de forma que o enfermeiro, por meio do estabelecimento do processo de enfermagem, desempenhe um papel fundamental pelo processo de reconhecimento e controle desta condição com a implementação de diagnósticos acurados e intervenções efetivas. Conclusão: A dor crônica merece atenção especial do enfermeiro, de forma que a avaliação e o tratamento sejam os mais abrangentes possível, a fim de minimizar o impacto negativo da dor sobre a vida das pessoas.

Objetivo: Reflexionar sobre el impacto del dolor crónico en la vida de las personas y en los cuidados de enfermería en el proceso. Metodología: Ensayo reflexivo, el cual se fundamentó en una revisión teórica. El estudio se realizó entre los meses de mayo de 2015 a julio de 2016. Los datos se analizaron y luego se organizaron en los siguientes ejes temáticos: El impacto del dolor crónico sobre la calidad de vida de las personas, El dolor como quinta señal vital: la importancia de su evaluación y Cuidados de enfermería a los pacientes con dolor crónico. Resultados: El dolor impacta de varias formas en la vida de las personas y, cuando este síntoma se vuelve crónico, repercute más intensamente en la calidad de vida. Por lo tanto, se hace indispensable realizar una evaluación completa, holística y multi-profesional de la persona que padece algún dolor, de manera que el enfermero, al establecer el proceso de enfermería, desempeñe un papel fundamental en el reconocimiento y control de esta condición con la implementación de diagnósticos precisos y de intervenciones efectivas. Conclusiones: El dolor crónico requiere de una atención especial por parte del enfermero para que la evaluación y el tratamiento sean lo más completos posible, con el fin de minimizar el impacto negativo del dolor sobre la vida de las personas.

Objective: To reflect about impact of chronic pain on people's life and on the nursing care in the process. Methodology: This is a reflexive essay, based on a theoretical review. The study was developed between May 2015 and July 2016. The data were analyzed and after organized in thematic axes as follows: The impact of chronic pain on people's quality of life, Pain as a fifth vital sign: the importance of its evaluation, and Nursing care to the patient with chronic pain. Results: Pain impacts in several ways on people's life, and, when this symptom becomes chronic, it resonates more intensively on quality of life. A comprehensive, holistic, and multi-professional evaluation to person with pain is necessary, so that nurse, setting up the nursing process, plays a central role in recognition and control of this status with the implementation of accurate diagnoses and effective interventions. Conclusions: Chronic pain needs a special attention by nurse so that assessment and treatment to be as complete as possible, in order to minimize the negative impact of pain on people's life.