Aplicações dos óleos essenciais na odontologia: uma revisão de literatura / Applications of essential oils in dentistry: a literature review

Objetivo: Analisar as evidências disponíveis na literatura sobre o uso tópico de óleos essenciais como potencial agentes para a atividade de clínica odontológica. Métodos: Foram utilizadas as bases de dados BVS e PubMed. Selecionando artigos-chave que abordavam a aplicação de óleos essenciais em odontologia, utilizando como palavras-chave o nome científico e popular associado a "dentistry", nos idiomas português e inglês, publicados no período de 2018 a 2022. Resultados: Obteve-se uma tabela contendo os principais óleos essenciais de utilização comum ­ 54 óleos ­, sendo 34 excluídos por não possuírem ligação com a odontologia, e 20 óleos fazendo referência a utilização na prática clínica, dessa maneira analisados as suas principais propriedades, notou-se eficácia em diversas áreas como em: periodontia; endodontia; odontopediatria; cicatrização de lesões na cavidade oral; analgésicos, anti-inflamatórios e anestésicos. Conclusão: Dessa forma, pode-se observar que há aplicação de óleos essenciais na odontologia, e que possui diversos benefícios quando utilizada de maneira correta e adequada, manifestando efeitos que abordam o paciente em sua universalidade. Nesse sentido, é necessário maiores estudos nessa área, pois apresentou um número considerável de resultados positivos na utilização de óleos essenciais na atividade odontológica para poder tirar proveito dos benefícios oferecidos através dos óleos.

Objective: To analyze the available evidence in the literature regarding the topical use of essential oils as potential agents for dental clinic activities. Methods: BVS and PubMed databases were utilized. Key articles addressing the application of essential oils in dentistry were selected, using scientific and common names associated with "dentistry" as keywords in Portuguese and English, published between 2018 and 2022. Results: A table was compiled containing the main essential oils commonly used­54 oils in total. Thirty-four oils were excluded as they had no connection to dentistry, leaving 20 oils associated with clinical practice. The analysis of these oils revealed their primary properties, showing efficacy in various areas such as periodontics, endodontics, pediatric dentistry, healing of oral cavity lesions, analgesic, anti-inflammatory, and anesthetic effects. Conclusion: Thus, it can be observed that there is an application of essential oils in dentistry, and they offer various benefits when used correctly and appropriately, manifesting effects that address the patient universally. In this regard, further studies in this area are necessary as it presented a considerable number of positive results in the use of essential oils in dental practice to fully take advantage of the benefits offered by these oils.

The negative chronotropic effects of (±)-propranolol and (±)-4-NO2-propranolol in the rat isolated right atrium are due to blockade of the 6-nitrodopamine receptor.

The positive chronotropic action induced by 6-nitrodopamine (6-ND) is selectively blocked by ß1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here, the effects of ( ±)-propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranolol were investigated in the rat isolated right atrium. The atrium was mounted in glass chambers containing gassed (95%O2:5%CO2) and warmed (37 °C) Krebs-Henseleit's solution, and the isometric tension registered (PowerLab system). ( ±)-Propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranolol caused concentration-dependent falls in the spontaneous atrial frequency (pIC50: 4.80 ± 0.10, 4.64 ± 0.10, and 4.95 ± 0.10, respectively). The calculated pA2 values for ( ±)-propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranol on noradrenaline-induced positive chronotropism were 8.44 ± 0.08, 6.41 ± 0.07, and 9.21 ± 0.29, respectively. The positive chronotropism induced by 6-ND (10 pM) was blocked by ( ±)-propranolol (1 µM) and ( ±)-4-NO2-propranolol (30 nM), whereas ( ±)-7-NO2-propranolol (1 µM) had no effect on 6-ND-induced responses. The pIC50 of ( ±)-propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranolol were significantly shifted to the right in L-NAME-treated atria. The discrepancy between pA2 values of ( ±)-propranolol and its respective pIC50 indicates that the falls in atrial rate induced by ( ±)-propranolol should not be attributed to b-adrenergic antagonism. The reduced chronotropism by ( ±)-propranolol was unaffected by the sodium channel inhibitors tetrodotoxin and lidocaine but that was abolished in atria pre-treated with ( ±)-4-NO2-propranolol. The finding that ( ±)-propranolol reduces spontaneous atrial rate only in concentrations that affect 6-ND-induced positive chronotropism confirms the role of this catecholamine as an endogenous modulator of heart chronotropism. ( ±)-4-NO2-Propranolol behaves as a selective antagonist of 6-ND in the rat isolated atrium.

Curcumin Prevents Renal Damage of l-NAME Induced Hypertension in by Reducing MMP-2 and MMP-9.

In the present study, we investigated whether curcumin administration would interfere with the main renal features of l-NAME-induced hypertension model. For this purpose, we conducted both in vitro and in vivo experiments to evaluate renal indicators of inflammation, oxidative stress, and metalloproteinases (MMPs) expression/activity. Hypertension was induced by l-NAME (70 mg/kg/day), and Wistar rats from both control and hypertensive groups were treated with curcumin (50 or 100 mg/kg/day; gavage) or vehicle for 14 days. Blood and kidneys were collected to determine serum creatinine levels, histological alterations, oxidative stress, MMPs expression and activity, and ED1 expression. l-NAME increased blood pressure, but both doses of curcumin treatment reduced these values. l-NAME treatment increased creatinine levels, glomeruli area, Bowman's space, kidney MMP-2 activity, as well as MMP-9 and ED1 expression, and reduced the number of glomeruli. Curcumin treatment prevented the increase in creatinine levels, MMP-2 activity, and reduced MMP-2, MMP-9, ED1, and superoxide levels, as well as increased superoxide dismutase activity and partially prevented glomeruli alterations. Moreover, curcumin directly inhibited MMP-2 activity in vitro. Thus, our main findings demonstrate that curcumin reduced l-NAME-induced hypertension and renal glomerular alterations, inhibited MMP-2 and MMP-9 expression/activity, and reduced oxidative stress and inflammatory processes, which may indirectly impact hypertension-induced renal outcomes.

Multiple names for multi-scope analytical methods, more than a semantic issue.

The use of multiple names for multi-scope analytical methods is often confusing. More precise classification to better accommodate the scope of analytical validation and application is needed.

Construção do nome social de pessoas trans e aspectos relacionados em um município de porte médio do Sul do Brasil / The construction behind chosen names of transgender individuals and related aspects in a medium-sized city in the South of Brazil

Resumo O trabalho analisou o processo de construção do nome social e aspectos relacionados em pessoas trans de um município de porte médio do Sul do Brasil. Foram utilizados dados qualitativos de um estudo de método misto descritivo e exploratório. Incluíram-se pessoas autodeclaradas trans com 18 anos ou mais. Foram conduzidos três grupos focais com dez participantes. Estes, com idade variando entre 19 e 52 anos, apresentam nome social documentado, porém metade ainda não fez a alteração nos registros civis. A técnica da análise de conteúdo produziu duas categorias: "construção do nome social como instrumento de validação da identidade trans" e "impactos da construção do nome social na autoaceitação e nas relações familiares e sociais". Os resultados reforçam a importância do respeito ao nome como forma de contribuição para a afirmação de gênero de sujeitos trans. O nome esteve atrelado às suas vivências, individualidades e valores. Seu uso adequado, muito mais do que o cumprimento de uma legislação, significou respeito às possibilidades diversas da existência humana. Espera-se que os resultados apresentados possam ser utilizados como ferramenta de reconhecimento acerca das questões e nuances que permeiam a construção do nome social, bem como contribuam para a validação identitária.

Abstract This study analyzed the construction process of the chosen name and related aspects among transgender individuals from a medium-sized municipality in southern Brazil. Qualitative data from a descriptive and exploratory mixed-method study was used. Self-declared trans people aged 18 or over were included. Three focus groups were conducted with ten participants. These individuals, aged between 19 and 52 years, have a documented chosen name, but half have not yet changed their civil records. The content analysis technique produced two categories: "construction of the chosen name as an instrument for validating the transgender identity" and "impacts of the construction of the chosen name on self-acceptance and on family and social relationships." The results reinforce the importance of respecting the name as a way of contributing to the gender affirmation of transgender individuals. The name was linked to the experiences, individuality and values of these individuals. Its proper use, much more than respect for legislation, meant respect for the different possibilities of human existence. It is expected that the results presented can be used as a tool for recognizing the issues and nuances that permeate the construction of the chosen name and contribute to identity validation.

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart.

BACKGROUND: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. METHODS: Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff's preparation. RESULTS: 6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dtmax, whereas dopamine and noradrenaline required 10 pmol, and adrenaline required 100 pmol, to induce similar increases in LVDP and dP/dtmax. The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol). CONCLUSIONS: 6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism.

Measurement of 6-cyanodopamine, 6-nitrodopa, 6-nitrodopamine and 6-nitroadrenaline by LC-MS/MS in Krebs-Henseleit solution. Assessment of basal release from rabbit isolated right atrium and ventricles.

This study presents the validation of a sensitive method for the determination of 6-nitrodopa, 6-nitrodopamine, 6-nitroadrenaline and 6-cyanodopamine in Krebs-Henseleit solution by LC-MS/MS with ESI+ . HRMS was used to precisely characterize the structures of the fragment ions. The method was applied to investigate the catecholamine basal release from rabbit isolated atria and ventricles. The atria and ventricles were suspended separately in a 5 ml organ bath containing Krebs-Henseleit solution with ascorbic acid (3 mM), gassed (95%O2 /5%CO2 ) at 37°C for 30 min. Strata-X 33 µm SPE cartridges were employed for the extraction of the catecholamines and the internal standard 6-nitrodopamine-d4 . The catecholamines were separated employing a 150 × 3 mm Shim-pack GIST C18-AQ (3 mm particle size), placed in an oven at 40°C and perfused by 65% of mobile phase A (MeCN/H2 O; 90/10, v/v) + 0.4% CH3 COOH and 35% mobile phase B (deionized H2 O) + 0.2% CH2 O2 at 320 µl/min in isocratic mode. The method was linear at 0.1-20 ng/ml. The method was used to identify for the first-time basal release of the three nitrocatecholamines mentioned above and a member of a novel class of catecholamines, the cyanocatecholamines.

A peptide fraction from hardened common beans (Phaseolus vulgaris) induces endothelium-dependent antihypertensive and renal effects in rats.

Beans reached the research spotlight as a source of bioactive compounds capable of modulating different functions. Recently, we reported antioxidant and oxidonitrergic effect of a low molecular weight peptide fraction (<3 kDa) from hardened bean (Phaseolus vulgaris) in vitro and ex vivo, which necessitate further in vivo assessments. This work aimed to evaluate the hypotensive effect and the involved physiological mechanisms of the hardened common bean peptide (Phaseolus vulgaris) in normotensive (Wistar) and hypertensive (SHR) animals. Bean flour was combined with a solution containing acetonitrile, water and formic acid (25: 24: 1). Protein extract (PV3) was fractioned (3 kDa membrane). We assessed PV3 effects on renal function and hemodynamics of wistar (WT-normotensive) and spontaneously hypertensive rats (SHR) and measured systemic arterial pressure and flow in aortic and renal beds. The potential endothelial and oxidonitrergic involvements were tested in isolated renal artery rings. As results, we found that PV3: I) decreased food consumption in SHR, increased water intake and urinary volume in WT, increased glomerular filtration rate in WT and SHR, caused natriuresis in SHR; II) caused NO- and endothelium-dependent vasorelaxation in renal artery rings; III) reduced arterial pressure and resistance in aortic and renal vascular beds; IV) caused antihypertensive effects in a dose-dependent manner. Current findings support PV3 as a source of bioactive peptides and raise the potential of composing nutraceutical formulations to treat renal and cardiovascular diseases.

Etnia e nominação: ancestralidades em disputa e recomposições / Ethnicity and nomination: disputed ancestries and recompositions / Ethnicité et nomination: ascendances contestées et recompositions / Etnicidad y nominación: ascendencias en disputa y recomposiciones

O nome próprio, para além de designativo de uma identidade transmitida intergeracionalmente, pode abrigar memórias sociais consubstanciais às representações de uma genealogia familiar, entrecruzada a processos históricos transgeracionais. Neste estudo de caso, as ressonâncias de sentidos atrelados ao significante "Terena" são analisadas à luz do processo social onomástico de transformação de etnônimos em sobrenomes, com base em fundamentos teóricos e metodológicos etnopsicanalíticos. Encontrou-se não haver transparência nem correspondência linear, pelo menos neste caso, entre o significante Terena na qualidade de etnônimo e na condição de sobrenome familiar, ficando em aberto em que medida a sua multivocidade se prende ao recalque da memória familiar e/ou a resistências a uma identificação genealógica que em diferentes momentos históricos terá assumido valorações distintas e eventualmente antagônicas

The proper name, in addition to designating an identity transmitted intergenerationally, can harbor social memories consubstantial with the representations of a family genealogy, intertwined with transgenerational historical processes. In this case study, the resonances of meanings linked to the signifier "Terena" are analyzed in the light of the onomastic social process of transforming ethnonyms into surnames, based on ethnopsychoanalytic theoretical and methodological foundations. It was found that there was no transparency or linear correspondence, at least in this case, between the signifier Terena as an ethnonym and the same as a family surname, leaving open the extent to which its multivocality is linked to the repression of family memory and/or to resistance to a genealogical identification that at different historical moments will have assumed different and eventually antagonistic valuations

Le nom propre, en plus de désigner une identité transmise intergénérationnellement, peut abriter des mémoires sociales consubstantielles aux représentations d'une généalogie familiale, entremêlées de processus historiques transgénérationnels. Dans cette étude de cas, les résonances des significations liées au signifiant « Terena ¼ sont analysées à la lumière du processus social onomastique de transformation des ethnonymes en noms de famille, sur la base de fondements théoriques et méthodologiques ethnopsychanalytiques. Il a été constaté qu'il n'y avait pas de transparence ou de correspondance linéaire, du moins dans ce cas, entre le signifiant Terena en tant qu'ethnonyme et le même en tant que nom de famille, laissant ouverte la mesure dans laquelle sa multivocalité est liée au refoulement de la mémoire familiale et /ou à la résistance à une identification généalogique qui, à différents moments historiques, aura assumé des valorisations différentes et éventuellement antagonistes

El nombre propio, además de designar una identidad transmitida intergeneracionalmente, puede albergar memorias sociales consustanciales a las representaciones de una genealogía familiar, entrelazadas con procesos históricos transgeneracionales. En este estudio de caso se analizan las resonancias de significados vinculados al significante "Terena" a la luz del proceso social onomástico de transformación de etnónimos en apellidos, a partir de fundamentos teóricos y metodológicos etnopsicoanalíticos. Se constató que no existe transparencia ni correspondencia lineal, al menos en este caso, entre el significante Terena como etnónimo y el mismo como apellido familiar, dejando abierta la medida en que su multivocalidad está ligada a la represión de la memoria familiar y /oa la resistencia a una identificación genealógica que en diferentes momentos históricos habrá asumido valoraciones distintas y eventualmente antagónicas

Evaluation of the Effect of the Fibroblast Growth Factor Type 2 (FGF-2) Administration on Placental Gene Expression in a Murine Model of Preeclampsia Induced by L-NAME.

The abnormal implantation of the trophoblast during the first trimester of pregnancy precedes the appearance of the clinical manifestations of preeclampsia (PE), which is a hypertensive disorder of pregnancy. In a previous study, which was carried out in a murine model of PE that was induced by NG-nitro-L-arginine methyl ester (L-NAME), we observed that the intravenous administration of fibroblast growth factor 2 (FGF2) had a hypotensive effect, improved the placental weight gain and attenuated the fetal growth restriction, and the morphological findings that were induced by L-NAME in the evaluated tissues were less severe. In this study, we aimed to determine the effect of FGF2 administration on the placental gene expression of the vascular endothelial growth factor (VEGFA), VEGF receptor 2 (VEGFR2), placental growth factor, endoglin (ENG), superoxide dismutase 1 (SOD1), catalase (CAT), thioredoxin (TXN), tumor protein P53 (P53), BCL2 apoptosis regulator, Fas cell surface death receptor (FAS), and caspase 3, in a Sprague Dawley rat PE model, which was induced by L-NAME. The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS. These results have generated valuable information regarding the identification of molecular targets for PE and provide new insights for understanding PE pathogenesis.

ß1- and ß1/ß2-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens.

6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective ß-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective ß1- and ß1/ß2-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective ß1-adrenergic receptor antagonists atenolol (0.1 and 1 µï»¿M), betaxolol (1 µï»¿M), and metoprolol (1 µï»¿M) and the unselective ß1/ß2-adrenergic receptor antagonists propranolol (1 and 10 µï»¿M) and pindolol (10 µï»¿M) caused significant rightward shifts of the concentration-response curve to 6-ND (pA2 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective ß1- and ß1/ß2-adrenergic receptor antagonists at a higher concentration (atenolol 1 µï»¿M, betaxolol 1 µï»¿M, metoprolol 1 µï»¿M, propranolol 10 µï»¿M, and pindolol 10 µï»¿M) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective ß1-adrenoceptor agonist RO-363, the selective ß2-adrenoceptor agonist salbutamol, and the selective ß3-adrenoceptor agonist mirabegron, up to 300 µï»¿M, had no effect on the RIEVD tone. The results demonstrate that ß1- and ß1-/ß2-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.

Nitric oxide storage levels modulate vasodilation and the hypotensive effect induced by photobiomodulation using an aluminum gallium arsenide (AlGaAs) diode laser (660 nm).

The aim of this study was to evaluate the participation of nitric oxide (NO) in the hypotensive and vasorelaxation effect induced by PBM using an aluminum gallium arsenide (AlGaAs) diode laser (660 nm). Male Wistar rats were treated with the inhibitor of nitric oxide synthase (L-NAME). A red laser (660 nm; 63 J/cm2; 56 s/point) was applied to the abdominal region at six different points. Thoracic aorta was dissected for vascular reactivity study, and a laser (660 nm; 96 J/cm2; 56 s) was applied after incubation with the NO donor DETA-NO, PBS, or hydroxicobalamin. Endothelial cells (HUVEC) were treated with DETA-NO or CuSO4, and then, PBM (63 J/cm2) was applied, and the nitric oxide was detected. Hypertensive L-NAME rats did not exhibit a decrease in blood pressure after PBM. PBM promoted vasodilation in the aorta isolated from normotensive rats, and less effect in the aorta of L-NAME rats and the addition of the NO donor, DETA-NO, promoted greater vasodilation by PBM in the aorta of L-NAME rats. In endothelial cells, an increase in NO, after PBM, was detected; however, with the addition of CuSO4, which catalyzes the decomposition of NO storage, there was no detection of NO after PBM. The results of this study demonstrate that the hypotensive and vasodilatory effect of PBM with a red laser at 660 nm is modulated by the release of nitric oxide from the storage.

Role of Nitric Oxide in the Cardiovascular System of South American Rattlesnakes (Crotalus durissus).

AbstractUnderstanding the basis of vascular tonus regulation is fundamental to comprehending cardiovascular physiology. In the present study, we used the recently developed decerebrate rattlesnake preparation to investigate the role of nitric oxide (NO) in the control of vascular tonus in a squamate reptile. This preparation allowed multiple concomitant cardiovascular parameters to be monitored, while avoiding the deleterious effect of anesthetic drugs on autonomic modulation. We observed that both systemic and pulmonary circuits were clearly responsive to NO signaling. NO increased vascular conductance in the systemic and pulmonary systems. Vasodilation by NO of the systemic circulation was compensated by cardiovascular alterations involving venous return, cardiac output, and cardiac shunt adjustments. The cardiac shunt seemed to be actively used for hemodynamic adjustments via modulation of the pulmonary artery constriction. N(ω)-nitro-L-arginine methyl ester injection demonstrated that NO contributes to modulating resting vasodilation in the systemic circuit. In contrast, NO-mediated vasodilation did not have an important role in the pulmonary circulation in inactive decerebrated snakes at 25°C. These responses vary importantly from those described for anesthetized snakes.

As três versões do pai: o parricídio, o nome e o dizer / The three versions of the father: the parricide, the name and the existential saying

RESUMO: O presente artigo desenvolve as respostas freudianas à questão "O que é um pai?", partindo da observação de Lacan no Seminário, livro 11 de que Freud encontrou a regulação do seu desejo nos mitos da morte do pai. Divide-se em três partes: Édipo, primeiro parricídio; Totem, o retorno do pai como nome; Moisés, o pai como Um dizer. Por fim, levanta-se a questão de que o desejo em Lacan estaria subjacente a suas elaborações sobre a relação entre o pai e o nome.

Abstract: This article develops freudians' answers to the question "What is a father?" starting from Lacan's observation in Seminar book 11 that Freud finds the regulation of his desire in the myths of the father's death. It is divided into three parts: Oedipus, the first parricide; Totem, the return of the father as a name: Moses, the father as One saying. Finally, it raises the question of what desire would underlie Lacan's elaborations on the relationship between the father and the name

Canagliflozin reduces the contractile response of isolated heart of normal adult rats / Canagliflozin reduce la respuesta contráctil del corazón aislado de ratas adultas normales

SUMMARY: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a unique class of glucose-declining renal-targeted drugs. The SGLT2i Canagliflozin (CANA) is an anti-hyperglycemic drug that reduces various cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. This study aimed to explore the potential effects of CANA on the isolated healthy adult rat hearts to show if CANA has positive inotropic or cardiac depressant effects via analyzing the amplitude and frequency of cardiac contractions. In isolated normal adult rat hearts, the effects of CANA on cardiac contractility were examined. In a dose-response curve, CANA led to a significant cardiac depressant effect in a dose-dependent manner. This cardiac depressant effect of CANA (10-6 M) was not prevented by atropine. However, this cardiac depressant effect was partially antagonized by both Isoproterenol (10-5 M) and Calcium chloride (10-6 M), suggesting beta-adrenoceptor and calcium channel blocking actions. In addition, the cardiac depressant effect of CANA (10-6 M) was mitigated in part by Nitric oxide synthase inhibitor, L-NAME, suggesting that its action probably depends to some extent on the accumulation of nitric oxide, which decreases the rise of intracellular Calcium. Data from this study demonstrate that CANA has a significant cardiac relaxant effect in isolated hearts of healthy adult rats by different possible mechanisms. This inhibitory effect on cardiac contractility may help improve the diastolic ventricular filling providing a therapeutic potential to help the other cardioprotective mechanisms of CANA in the prevention and treatment of heart failure.

RESUMEN: Los inhibidores del cotransportador de sodio- glucosa 2 (SGLT2i) representan una clase única de fármacos dirigidos a los riñones que disminuyen la glucosa. El SGLT2i Canagliflozin (CANA) es un fármaco antihiperglucémico que reduce varios resultados cardiovasculares y renales en pacientes con diabetes mellitus tipo 2. Este estudio tuvo como objetivo explorar los efectos potenciales de CANA en corazones aislados de ratas adultas sanas para indicar si CANA tiene efectos inotrópicos o depresores cardíacos positivos mediante el análisis de la amplitud y la frecuencia de las contracciones cardíacas. En corazones aislados de ratas adultas normales, se examinaron los efectos de CANA sobre la contractilidad cardíaca. En una curva de dosis-respuesta, CANA condujo a un efecto depresor cardíaco significativo de manera dependiente de la dosis. Este efecto depresor cardíaco de CANA (10-6 M) no fue impedido por la atropina. Sin embargo, este efecto depresor cardíaco fue parcialmente antagonizado tanto por el isoproterenol (10-5 M) como por el cloruro de calcio (10-6 M), lo que sugiere acciones bloqueadoras de los receptores beta adrenérgicos y de los canales de calcio. Además, el efecto depresor cardíaco de CANA (10-6 M) fue mitigado en parte por el inhibidor de la sintasa de óxido nítrico, L-NAME, lo que sugiere que su acción probablemente depende en cierta medida de la acumulación de óxido nítrico, lo que disminuye el aumento de calcio intracelular. Los datos de este estudio demuestran que CANA tiene un efecto relajante cardíaco significativo en corazones aislados de ratas adultas sanas por diferentes mecanismos posibles. Este efecto inhibitorio sobre la contractilidad cardíaca puede ayudar a mejorar el llenado ventricular diastólico proporcionando un potencial terapéutico para ayudar a los otros mecanismos cardioprotectores de CANA en la prevención y tratamiento de la insuficiencia cardíaca.

Lepidium meyenii (maca) and soy isoflavones reduce cardiac stunning of ischemia-reperfusion in rats by mitochondrial mechanisms.

BACKGROUND AND AIM: Phytoestrogens are traditionally used for cardiovascular risks but direct effects on the ischemic heart remain unclear. Plants with phytoestrogens are used for reducing menopausic symptoms and they could also be cardioprotectives. Here we investigated whether maca (Lepidium meyenii) contains isoflavones and prevents cardiac stunning, in comparison to soy isoflavones. EXPERIMENTAL PROCEDURE: Both products were orally and daily administered to rats during 1 week before exposing isolated hearts to ischemia/reperfusion (I/R). Young male (YM), female (YF) and aged female (AgF) rats treated with maca (MACA, 1 g/kg/day) or soy isoflavones (ISOF, 100 mg/kg/day) were compared to acute daidzein (DAZ, 5 mg/kg i.p.) and non-treated rat groups. Isolated ventricles were perfused inside a calorimeter to simultaneously measure contractile and calorimetrical signals before and during I/R. RESULTS AND CONCLUSIONS: Maca has genistein and daidzein. MACA and ISOF improved the post-ischemic contractile recovery (PICR) and muscle economy (P/Ht) in YM and YF hearts, but not in AgF hearts. DAZ improved PICR and P/Ht more in YM than in YF. The mKATP channels blockade reduced both PICR and P/Ht in DAZ-treated YM hearts, without affecting them in ISOF or MACA-treated YM hearts. In MACA treated YF hearts, the simultaneous blockade of NOS and mKATP channels, or the mNCX blockade reduced cardioprotection. Results show that subacute oral treatment with maca or with soy isoflavones was strongly preventive of cardiac ischemic dysfunction, more than the acute administration of a pure isoflavone (daidzein, genistein). Maca induced synergistic and complex mechanisms which prevented mitochondrial calcium overload.

Diferença e diversidade sexual na psicanálise, nos costumes e no direito / Difference and sexual diversity in psychoanalysis, in customs and in law / Différence et diversité sexuelle en psychanalyse, dans les coutumes et dans le droit / Diferencia y diversidad sexual en psicoanálisis, los costumbres y el derecho

O tema evoca um conflito de paradigmas entre os fundamentos da civiliação judaico-cristã, a evolução dos costumes na pós-modernidade, a psicanálise como uma prática relativa à regulação do gozo no campo da psicopatologia e o discurso do Direito que regula a distribuição do gozo no laço social. A psicanálise nasce sob o paradigma da modernidade. Freud desvela a origem perversa e polimorfa da sexualidade, que é posteriormente submetida à lei por meio da função do Nome-do-Pai. Muitos filósofos pós-modernos rejeitam o primado da diferença anatômica entre os sexos, da fantasia infantil da castração e da ficção que atribui ao pai o protagonismo na interdição do incesto. Vamos contrastar os conceitos de diferença, diversidade e autodefinição sexual.

The title evokes a conflict of paradigms between the foundations of Judeo-Christian civilization, the evolution of customs in postmodernity, psychoanalysis as a practice related to the regulation of enjoyment in the field of psychopathology and the discourse of Law that regulates the distribution of enjoyment in social bonding. Psychoanalysis was born under the paradigm of modernity. Freud unveiled the perverse and polymorphic origin of sexuality, which is subsequently subjected to law through the function of the Name of the Father. Many postmodern philosophers reject the primacy of the anatomical difference between the sexes, the infantile fantasy of castration and the fiction that bestows the leading role upon the father in the prohibition of incest. As a result, this article contrasts the concepts of difference and diversity and sexual self-definition.

Le thème évoque un conflit de paradigmes entre les fondements de la civilisation judéo-chrétienne, l'évolution des coutumes dans la postmodernité, la psychanalyse en tant que pratique liée à la régulation de la jouissance dans le domaine de la psychopathologie et le discours du Droit qui règle la répartition de la jouissance dans le lien social. La psychanalyse est née sous le paradigme de la modernité. Freud dévoile l'origine perverse et polymorphe de la sexualité, qui est ensuite soumise à la loi par la fonction du Nom du Père. De nombreux philosophes postmodernes rejettent la primauté de la différence anatomique entre les sexes, du fantasme infantile de castration et de la fiction qui attribue au père le protagonisme dans l'interdiction de l'inceste. Nous comparons les concepts de différence et de diversité et d'autodéfinition sexuelle.

El tema evoca un conflicto de paradigmas entre los fundamentos de la civilización judeocristiana, la evolución de las costumbres en la postmodernidad, el psicoanálisis como práctica relacionada a la regulación del goce en el campo de la psicopatología y el discurso del Derecho que regula la distribución del goce en el vínculo social. El psicoanálisis nace bajo el paradigma de la modernidad. Freud revela el origen perverso y polimórfico de la sexualidad que, posteriormente, se somete a la ley a través de la función del Nombre del Padre. Muchos filósofos postmodernos rechazan la primacía de la diferencia anatómica entre los sexos, de la fantasía infantil de la castración y de la ficción que atribuye al padre el protagonismo en la interdicción del incesto. Comparemos los conceptos de diferencia, diversidad y autodefinición sexual.

Fibroblast Growth Factor Type 2 (FGF2) Administration Attenuated the Clinical Manifestations of Preeclampsia in a Murine Model Induced by L-NAME.

Background: In preeclampsia, a hypertensive disorder of pregnancy, the poor remodeling of spiral arteries leads to placental hypoperfusion and ischemia, provoking generalized maternal endothelial dysfunction and, in severe cases, death. Endothelial and placental remodeling is important for correct pregnancy evolution and is mediated by cytokines and growth factors such as fibroblast growth factor type 2 (FGF2). In this study, we evaluated the effect of human recombinant FGF2 (rhFGF2) administration in a murine model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME) to test if rhFGF2 administration can lessen the clinical manifestations of PE. Methods: Pregnant rats were administrated with 0.9% of NaCl (vehicle), L-NAME (60 mg/kg), FGF2 (666.6 ng/kg), L-NAME+FGF2 or L-NAME + hydralazine (10 mg/kg) from the 10th to 19th days of gestation. Blood pressure (BP), urine protein concentrations and anthropometric values both rat and fetuses were assessed. Histological evaluation of organs from rats delivered by cesarean section was carried out using hematoxylin and eosin staining. Results: A PE-like model was established, and it included phenotypes such as maternal hypertension, proteinuria, and fetal growth delay. Compared to the groups treated with L-NAME, the L-NAME + FGF2 group was similar to vehicle: the BP remained stable and the rats did not develop enhanced proteinuria. Both the fetuses and placentas from rats treated with L-NAME + FGF2 had similar values of weight and size compared with the vehicle. Conclusion: The intravenous administration of rhFGF2 showed beneficial and hypotensive effects, reducing the clinical manifestations of PE in the evaluated model.

Lipopolysaccharide reduces urethral smooth muscle contractility via cyclooxygenase activation.

Lipopolysaccharide (LPS) is a component of gram-negative bacteria wall that elicits inflammatory response in the host through the toll-like receptor 4 (TLR4) activation. In the lower urinary tract (LUT), bacteria-derived LPS has been associated with lower urinary tract symptoms (LUTS); however, little is known about the effects of LPS in the urethral smooth muscle (USM). In the present study, we evaluated the functional and molecular effects of LPS in mouse USM in vitro, focusing on the LPS-induced TLR4-signaling pathway. Male C57BL6/JUnib and TLR4 knockout mice (TLR4 KO) were used. The USM contraction was performed in the presence of LPS (62.5-500 µg/mL), indomethacin (10 µM), L-NAME (100 µM), and TAK 242 (1 µM). The RT-PCR assay for the IL-1ß, NF-kB, and COX-2 genes was also evaluated in the presence of LPS (125 µg/mL) and caspase 1 inhibitor (20 µM). Our results showed that LPS reduces mouse USM contraction elicited by phenylephrine and vasopressin. This LPS-induced urethral inhibitory effect was not reversed by the TLR4 inhibition or its absence in the TLR4 KO mice. Conversely, indomethacin (but not L-NAME) reversed the LPS-induced USM hypocontractility. Molecular protocols indicated upregulation of IL-1ß, NF-kß, and COX-2 mRNA upon LPS incubation, which were blunted by caspase 1 inhibition. Our data showed that LPS reduced mouse USM contraction independently of TLR4 activation, involving caspase 1 and IL1ß, NF-kB, and COX-2 gene overexpression. Therefore, this alternative pathway might be a valuable target to reduce the LPS-induced urethral dysfunction under infection and inflammatory conditions.

The basal release of endothelium-derived catecholamines regulates the contractions of Chelonoidis carbonaria aorta caused by electrical-field stimulation.

The contractions of Chelonoidis carbonaria aortic rings induced by electrical field stimulation (EFS) are not inhibited by blockade of the voltage-gated sodium channels by tetrodotoxin but almost abolished by the α1/α2-adrenoceptor antagonist phentolamine. The objective of this study was to identify the mediator(s) responsible for the EFS-induced contractions of Chelonoidis carbonaria aortic rings. Each ring was suspended between two wire hooks and mounted in isolated 10 ml organ chambers filled with oxygenated and heated Krebs-Henseleit's solution. Dopamine, noradrenaline and adrenaline concentrations were analysed by liquid chromatography coupled to tandem mass spectrometry. The contractions caused by dopamine and EFS were done in absence and presence of the nitric oxide (NO) synthesis inhibitor L-NAME, the NO-sensitive guanylyl cyclase inhibitor ODQ, the D1-like receptor antagonist SCH-23390, the D2-like receptor antagonists risperidone, quetiapine, haloperidol, and the tyrosine hydroxylase inhibitors salsolinol and 3-iodo-L-tyrosine. Basal concentrations of dopamine, noradrenaline and adrenaline were detected in Krebs-Henseleit solution containing the aortic rings. The catecholamine concentrations were significantly reduced in endothelium-denuded aortic rings. L-NAME and ODQ significantly potentiated the dopamine-induced contractions. The D2-like receptor antagonists inhibited the EFS-induced contractions of the aortic rings treated with L-NAME, whereas SCH 23390 had no effect. Similar results were observed in the contractions induced by dopamine in L-NAME treated aortic rings. These results indicate that catecholamines released by endothelium regulate the EFS-induced contractions. This may constitute a suitable mechanism by which reptilia modulate specific organ blood flow distribution.This paper has an associated First Person interview with the first author of the article.