Tipos de cirugías arteriales en pacientes diabéticos / Types of arterial surgeries in diabetic patients

Introducción: Las cirugías arteriales en los pacientes diabéticos permiten disminuir las frecuencias de amputaciones que se realizan en estos pacientes. Objetivo: Exponer los principales tipos de cirugías arteriales en los miembros inferiores que se realizan en pacientes diabéticos y sus resultados. Métodos: Estudio de búsqueda y síntesis bibliográfica en el que consultaron y tamizaron 162 documentos (artículos, registros médicos y tesis) publicados en las bases de datos de sistemas referativos MEDLINE, PubMed y SciELO e indexadas en la Web of Sciencies, Scopus, Redalyc y Latindex, con la utilización de descriptores: cirugía revascularizadora, permeabilidad arterial, pie diabético, cirugía endovascular, endarterectomía, angioplastia transluminal percutánea. Esto generó que se seleccionara 43 artículos y tres registros médicos. Resultados: La técnica en la revascularización del sector aortoiliaco incluye la cirugía derivativa anatómica [by-passaorto-femoral (bi o uni)]y la extraanatómica [by-pass (axilo-femoral, fémoro-femoral), la endarterectomía y la cirugía endovascular en el sector iliaco. Las técnicas quirúrgicas a aplicar en el sector femoropoplíteo y distal son el by-pass secuencial, endarterectomía, simpatectomía, tratamiento endovascular. Es importante tener en cuenta las características de los pacientes por separado para la decisión del tipo de cirugía. Conclusiones: Las cirugías arteriales en el paciente diabético son diversas y para su éxito es necesario valorar siempre el riesgo quirúrgico y la anatomía de las lesiones de cada paciente(AU)

Introduction: Arterial surgeries in diabetic patients allow reducing the frequency of amputations that are performed in these patients. Objective: To show the main types of arterial surgery in the lower limbs performed in diabetic patients and their results. Methods: Bibliographic search and synthesis study in which 162 materials (articles, medical records and theses) published in the MEDLINE, PubMed and SciELO reference databases were searched and indexed in the Web of Sciencies, Scopus, Redalyc and Latindex, using as descriptors: revascularization surgery, arterial permeability, diabetic foot, endovascular surgery, endarterectomy, percutaneous transluminal angioplasty. This led to the quoting of 43 articles and three medical records. Results: The technique in the revascularization of the aorto iliac sector includes the anatomical derivative surgery [aorto-femoral by-pass (bi or uni)] and extra-anatomical [by-pass (axillo-femoral, femoro-femoral), endarterectomy and endovascular surgery in the iliac sector. The surgical techniques to be applied in the femoro popliteal and distal sectors are the sequential by-pass, endarterectomy, sympathectomy, and endovascular treatment. It is important to consider the characteristics of patients separately to decide the type of surgery. Conclusions: The arterial surgeries in the diabetic patient are diverse and for the success of them it is necessary to always assess the surgical risk and the anatomy of the lesions of each patient(AU)

In Vitro Effects of Plasma Collected From Rats Administered Naftopidil on Whole Urinary Bladder Preparation Isolated From Rats / 대한배뇨장애요실금학회지

PURPOSE: Alpha-1-adrenoceptor blockers (e.g., naftopidil) are prescribed for the treatment of male lower urinary tract symptoms. Although the mechanism of action of naftopidil has been studied in various organs, that in the urinary bladder remains unknown. To clarify the direct effects of naftopidil on this organ, activities were assessed in the isolated rat whole urinary bladder.METHODS: A total of 30 female rats were used. In Experiment 1, bladder activity was measured during a cumulative administration of 2.5–75μM naftopidil (n=7). In Experiment 2, rats were divided into 2 groups: control (n=10) and naftopidil (5 mg/animal/day, oral gavage, once-daily for 2 weeks) (n=13). After the treatment period, plasma was obtained from each rat. The urinary bladders were harvested from the control rats. Isovolumetric rhythmic bladder contractions were induced at above the threshold volume, and intravesical pressure was recorded. Control plasma was added to the organ bath; after subsequent wash-out, plasma collected from rats administered naftopidil was added. In Experiment 3, the plasma levels of monoamines and amino acids were quantified using the individual plasma prepared in the Experiment 2.RESULTS: Cumulative dosing with naftopidil did not change the interval between spontaneous contractions compared to the interval at baseline. After adding control plasma, the interval was shortened compared to the baseline (P=0.008). The plasma collected from rats administered naftopidil suppressed the shortening of the interval compared to the control plasma (P=0.041). Naftopidil resulted in a decrease in the level of noradrenaline (P=0.009) and an increase in that of glycine (P=0.014).CONCLUSIONS: Although naftopidil did not directly act on the interval between spontaneous contractions of the urinary bladder, the plasma collected from rats administered naftopidil, with changing levels of monoamines and amino acids, may suppressed shortening the interval.

Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

Estudo da permeabilidade vascular pulmonar e das junções interendoteliais na malária experimental / Study of pulmonary vascular permeability and interendothelial junctions in experimental malaria

Infecções por Plasmodium spp. podem acarretar em complicações pulmonares (1 a 40% dos casos), que podem resultar no desenvolvimento da síndrome do desconforto respiratório agudo (SDRA). Esta síndrome é caracterizada por inflamação aguda, lesão do endotélio alveolar e do parênquima pulmonar, disfunção e aumento da permeabilidade da barreira alvéolo-capilar pulmonar e, consequente, formação de efusão pleural. Neste sentido, os mecanismos de regulação da permeabilidade das células endoteliais e as junções interendoteliais têm papel crítico na manutenção do endotélio pulmonar. O objetivo do estudo foi determinar precocemente o desenvolvimento da SDRA associada à malária por tomografia computadorizada por emissão de fóton único (SPECT/CT), além de identificar alterações nas junções interendoteliais das células endoteliais pulmonares primárias de camundongos DBA/2 (CEPP-DBA/2), após contato com os eritrócitos parasitados de Plasmodium berghei ANKA (EP-PbA). Os nossos resultados demonstraram que é possível identificar alterações na aeração pulmonar no 5° e 7° dia após a infecção e, consequentemente, diferenciar os animais que desenvolveriam SDRA daqueles que evoluiriam para hiperparasitemia (HP). Além disso, observamos em CEPP-DBA/2 que o contato direto com EP-PbA aumenta da abertura das junções interendoteliais e da permeabilidade vascular. Assim, avaliamos a diminuição da expressão das proteínas das junções interendoteliais que contribuem para o aumento da permeabilidade vascular, por imunofluorescência e Western Blot. Apesar da SDRA ter sido identificada há mais de 50 anos, ainda não se conhece formas de diagnóstico precoce e os mecanimos efetivos de desenvolvimento desta enfermidade, que permitam um tratamento efetivo e que evite a morte do paciente. Portanto, sugere-se que a técnica de SPECT/CT seja uma importante ferramenta de diagnóstico para identificação precoce de SDRA associado a malária

Infections by Plasmodium spp. can lead to pulmonary complications (1 to 40% of the cases), that can result in the development of acute respiratory distress syndrome (ARDS). This syndrome is characterized by the acute inflammation, injury of the alveolar endothelium and pulmonary parenchyma, dysfunction and increased permeability of the pulmonary alveolar-capillary barrier and, consequently, formation of pleural effusion. In this aspect, mechanisms of regulation of endothelial cell permeability and interendothelial junctions play a critical role in the maintenance of the pulmonary endothelium. The present study aimed to determine the early development of single-photon emission computed tomography (SPECT/CT) associated malaria ARDS in addition to identifying changes in the interendothelial junctions of the primary pulmonary endothelial cells of DBA/2 mice (CEPP-DBA/2) after contact with erythrocytes infected with Plasmodium berghei ANKA (EP-PbA). Our results demonstrated that is possible to identify changes in lung aeration on the 5th and 7th day after infection and, consequently, differentiate the animals that should develop ARDS from those that would evolve to hyperparasitemia (HP). In addition, we observed in CEPP-DBA/2 that direct contact with EP-PbA increases the opening of the interendothelial junctions and vascular permeability. Thus, we evaluated that decrease the expression of interendothelial junction proteins contribute to the increase of vascular permeability, by immunofluorescence and Western Blot. Although ARDS was identified more than 50 years ago, it is not yet known what forms of early diagnosis, and the effective mechanisms of development of this disease, that allow an effective treatment and that prevent the death of the patient. Therefore, it is suggested that the SPECT/CT technique is a valuable tool to promote the early identification of ARDS associated with malaria

Polygala anatolica Boiss. et Heldr.: is a potential remedy for inflammation and pain? / Polygala anatolica Boiss. et Heldr.: ¿es un remedio potencial para la inflamación y el dolor?

Species of Polygala genus have been used for the treatment of inflamation and pain in Turkish traditional medicine. The aim of the present study is to assess the anti-inflammatory and analgesic activities of P. anatolica. n-Hexane, ethyl acetate and methanol extracts of the aerial parts and roots of P. anatolica were investigated for their anti-inflammatory and analgesic effects. The methanol extracts prepared from the aerial parts and roots of P. anatolica were found to be active in carrageenan- and PGE2-induced paw edema models and in Whittle method. Methanolic extract of the aerial part inhibited serotonin-induced hind paw edema, while the root extract did not exert inhibitory effect in the same model. In addition, Fr. B and C obtained from the methanol extract of P. anatolica aerial parts showed significant anti- inflammatory activity. Morover, the analgesic effect of the methanol extracts prepared from the roots and aerial parts and Fr.B and Fr.C were found to be statistically significant without inducing ulceration. The methanol extract obtained from the aerial parts of the plant and its saponoside and flavonoid fractions showed anti-inflammatory and analgesic activities in the trials.

Las especies del género Polygala se han utilizado para el tratamiento de la inflamación y el dolor en la medicina tradicional turca. El objetivo del presente estudio es evaluar las actividades antiinflamatorias y analgésicas de P. anatolica. Se investigaron los extractos de n-hexano, acetato de etilo y metanol de las partes aéreas y raíces de P. anatolica por sus efectos antiinflamatorios y analgésicos. Los extractos de metanol preparados a partir de las partes aéreas y raíces de P. anatolica se encontraron activos en modelos de edema de pata inducidos por carragenina y PGE2 por el método de Whittle. El extracto metanólico de la parte aérea inhibió el edema de la pata trasera inducido por serotonina, mientras que el extracto de raíz no ejerció un efecto inhibidor en el mismo modelo. En suma, la fracción B y C obtenidos a partir del extracto metanólico de partes aéreas de P. anatolica mostraron actividad antiinflamatoria significativa. Además, el efecto analgésico de los extractos de metanol preparados a partir de las raíces y las partes aéreas y la fracción B y C resultaron ser estadísticamente significativas sin inducir la ulceración. El extracto de metanol obtenido de las partes aéreas de la planta y sus fracciones de saponósidos y flavonoides mostraron actividades antiinflamatorias y analgésicas en los ensayos.

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p <0.03).. Study limitations: A single-center study evaluating only aspects related to histamine. Conclusions: Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.

β₂-Adrenoceptor Blockade Deteriorates Systemic Anaphylaxis by Enhancing Hyperpermeability in Anesthetized Mice

PURPOSE: Patients treated with propranolol, a nonselective β-adrenoceptor antagonist, develop severe anaphylaxis, but the mechanism remains unknown. We determined effects of β₁- and β₂-adrenoceptor antagonists on the anaphylaxis-induced increase in vascular permeability in mice. METHODS: In anesthetized ovalbumin-sensitized C57BL mice, mean arterial blood pressure (MBP) was measured, and Evans blue dye extravasation and hematocrit (Hct) were assessed at 20 minutes after antigen injection. The following pretreatment groups (n=7/group) were studied: (1) sensitized control (non-pretreatment), (2) propranolol, (3) the selective β₂-adrenoceptor antagonist ICI 118,551, (4) the selective β₁-adrenoceptor antagonist atenolol, (5) adrenalectomy, (6) the selective β₂-adrenoceptor agonist terbutaline, and (7) non-sensitized groups. RESULTS: The antigen injection decreased MBP, and increased Hct and vascular permeability in the kidney, lung, mesentery, and intestine, but not in the liver or spleen. Pretreatment with ICI 118,551, propranolol and adrenalectomy, but not atenolol, reduced the survival rate and augmented the increases in Hct and vascular permeability in the kidney, intestine, and lung as compared with the sensitized control group. Pretreatment with terbutaline abolished the antigen-induced alterations. Plasma epinephrine levels were increased significantly in the sensitize control mice. CONCLUSIONS: Blockade of β₂-adrenoceptor can deteriorate systemic anaphylaxis by augmenting hyperpermeability-induced increase in plasma extravasation by inhibiting beneficial effects of epinephrine released from the adrenal glands in anesthetized mice.

Perioperative implication of the endothelial glycocalyx / 대한마취과학회지

The endothelial glycocalyx (EG) is a gel-like layer lining the luminal surface of healthy vascular endothelium. Recently, the EG has gained extensive interest as a crucial regulator of endothelial funtction, including vascular permeability, mechanotransduction, and the interaction between endothelial and circulating blood cells. The EG is degraded by various enzymes and reactive oxygen species upon pro-inflammatory stimulus. Ischemia-reperfusion injury, oxidative stress, hypervolemia, and systemic inflammatory response are responsible for perioperative EG degradation. Perioperative damage of the EG has also been demonstrated, especially in cardiac surgery. However, the protection of the EG and its association with perioperative morbidity needs to be elucidated in future studies. In this review, the present knowledge about EG and its perioperative implication is discussed from an anesthesiologist's perspective.

Basiliximab-Induced Non-Cardiogenic Pulmonary Edema in a Kidney Transplant Patient / 대한이식학회지

Induction therapy with basiliximab is widely administered after kidney transplantation to prevent acute rejection. Herein, we report a case of non-cardiogenic pulmonary edema induced by basiliximab. To the best of our knowledge, such case has not been reported to date in Korea. A 54-year-old man with polycystic kidney disease received kidney transplantation. As induction therapy, he was prescribed basiliximab. On day 4, the second dose of basiliximab was administered. The patient complained of acute hypoxia 23 hours later, which led to circulatory collapse. He was discharged 3 weeks later with stable renal function. Pulmonary edema was presumed to have been caused by increased pulmonary capillary permeability. A possible hypothesis for this event occurring after the second basiliximab injection is steroid-related effects. Non-cardiogenic pulmonary edema is a complication that might occur after basiliximab induction therapy. Physicians should be aware of this potentially life-threatening complication.

Edemogenic test and hydrogen peroxide degradation rate of bleaching gels with different desensitizing agents / Teste edemogênico e taxa de degradação do peróxido de hidrogênio de géis clareadores com diferentes agentes dessensibilizantes

Objective: The at-home bleaching technique leads to the intimate contact of the bleaching gel with gingival tissues, so this study evaluated the immediate inflammatory response, through the edemogenic test, induced by at-home bleaching gels of 10% carbamide peroxide with different desensitizing agents, the quantification of hydrogen peroxide released and bleaching gels pH. Material and Methods: Forty-eight rats were divided into groups (n=12): CTRL-control group, WP-Whiteness Perfect 10% (FGM Produtos Odontológicos, Joinville, SC, Brazil), OPA-Opalescence 10% (Ultradent Products Inc., South Jordan, IT, USA), and PB-Power Bleaching (BM4, Palhoça, SC, Brazil). For the edemogenic test, all rats received an intravenous injection of Evan's Blue; after 30 min, 0.2 mL of each bleaching gels was injected into the subcutaneous tissue of the rats, and the results of the vascular permeability were assessed after 3 and 6h. The amount of HP released and pH of each product was also determined. Data were submitted to statistical test (p <0.05 ). Results: At 3h, the PB showed higher vascular permeability than the other groups. At 6h, the PB produced similar vascular permeability than WHI, and higher than OPA and CTRL groups. The OPA group had a higher vascular permeability at 6h compared to 3h; there is no difference in other groups. The PB group had higher HP concentrations than the other groups. Conclusion: In general, the PB caused a more considerable amount of inflammatory edema and higher amount of HP released. This results suggesting that these bleaching gels cause greater aggression in soft gingival tissues that eventually ends up in contact with bleaching products. (AU)

Objetivo: A técnica de clareamento domiciliar leva ao contato íntimo do gel clareador com tecidos gengivais, assim, este estudo avaliou a resposta inflamatória imediata, através do teste edemogênico, induzido por gel de clareamento caseiro à base de peróxido de carbamida a 10% com diferentes agentes dessensibilizantes, a quantificação de peróxido de hidrogênio liberado e o pH dos géis branqueadores. Material e Métodos: Quarenta e oito ratos foram divididos em 4 grupos (n = 12): grupocontrole CTRL, WP-Whiteness Perfect 10% (FGM Produtos Odontológicos, Joinville, SC, Brasil), OPA-Opalescence 10% (Ultradent Products Inc., South Jordan, IT, EUA) e PB-Power Bleaching (BM4, Palhoça, SC, Brasil). Para o teste edemogênico, todos os ratos receberam uma injeção intravenosa de Evan's Blue; após 30 min, 0,2 mL de cada gel clareador foi injetado no tecido subcutâneo dos ratos, e os resultados da permeabilidade vascular foram avaliados após 3 e 6 horas. A quantidade de HP liberada e o pH de cada produto também foram determinados. Os dados foram submetidos ao teste estatístico (P <0,05). Resultados: Às 3h, o PB apresentou maior permeabilidade vascular que os demais grupos. Às 6h, o PB produziu permeabilidade vascular semelhante ao WHI e maior que os grupos OPA e CTRL. O grupo OPA apresentou maior permeabilidade vascular às 6h em relação às 3h; Não existe essa diferença em outros grupos. O grupo PB apresentou maiores concentrações de HP que os demais grupos. Conclusão: Em geral, o PB causou maior quantidade de edema inflamatório e maior quantidade de HP liberado. Estes resultados sugerem que estes géis branqueadores causam maior agressividade nos tecidos gengivais moles que eventualmente acabam em contato com produtos de branqueamento. (AU)

The effect of gingival aging in diabetic and non-diabetic status: an experimental study / El efecto del envejecimiento gingival en el estado diabetico y no diabetico. Estudio experimental

Major gingivalperiodontal changes according to age have been observed in both diabetic and nondiabetic rats. Male Wistar rats weighing 200220 g were divided into two groups: 1) Nondiabetic (ND) and 2) Diabetic (D) by receiving an intraperitoneal (ip) dose of streptozotocin (STZ) (50 mg /kg). Animals from both groups (ND and D) were euthanized at 4, 8, 12, 17 y 25 weeks after treatment with saline solution or STZ. Glycemia values in ND rats were 5 to 6 mmol/L, while in D, glycemia increased progressively between weeks 4 and 25, with values ranging from 18.3±2.1 to 39.3±2.7 mmol/L. Oxidative stress differed significantly in gums of ND and D rats. ND: lipid peroxidation: Malondialdehyde (MDA): 8.52±1.2 to 15.5±2(nmol/mgP); superoxide dismutase (SOD): 37.1±4.2 to 21.2±1.3 (U/100mgP); D: MDA 13.1±1.6 to 22.9±2.7 (nmol/L); superoxide dismutase (SOD): 17.7±0.8 to 9.±0.2 (U/100mgP). Vascular permeability (VP) and gingival edema (E) showed significant changes between ND and D rats from 4 to 25 weeks. ND: PV: 10±0.2 to 16.1±1.3 (EB ug/g dry t); E: 0.9±0.1 to 4.1±1.3 ml; D: PV: 12±1.2 to 24.4±1.6 (EB ug/g dry t); E: 2.2±0.2 to 8.4±1.3 ml. Aging produced progressive natural changes in oxidative stress, VP and gingival E. In diabetic animals, changes in oxidative stress, VP and gingival E were observed early and were progressively more significant than for ND. According to these results, nondiabetic gingival modifications develop naturally with age, while in aging associated to diabetic disease, hyperglycemia increases progressively and early (AU)

Se han observados importantes cambios gingivoperiodontales en función de la edad tanto en ratas no diabéticas como en ratas diabéticas. Ratas machos Wistar de 200220 g de peso corporal fueron separadas en dos grupos: 1) No diabéticas(ND) ; 2) Diabéticas (D), por haber recibido una dosis intraperitoneal (ip) de estreptozotocina (STZ) (50 mg /kg). Ambos grupos de ratas (ND y D) fueron sacrificados a las 4, 8, 12, 17 y 25 semanas de edad después del tratamiento con solución salina o con STZ. En ratas ND las los valores de glucemia fueron de 5 a 6 mmol/L, en tanto que en las D las glucemias se observaron progresivamente aumentadas entre las 4 y las 25 semanas con valores entre 18.3±2.1 a 39.3±2.7 mmol/L. El estrés oxidativo mostró diferencias significativas entre las encías de animales ND respecto a los D; ND: peroxidacion lipidica: Malondihaldeido (MDA): 8.52±1.2 a 15.5±2(nmol/mgP);superoxido dismutasa (SOD):37.1±4.2 a 21.2±1.3 (U/100mgP); D : MDA 13.1±1.6 a 22.9±2.7 (nmol/L); Superoxidodismutasa :SOD 17.7±0.8 a 9.±0.2 (U/100mgP). La permeabilidad vascular(PV) y el edema(E) gingival mostraron cambios significativos entre las 4 y las 25 semanas de edad entre los animales ND respecto a los D : ND : PV : 10±0.2 a 16.1±1.3 (EB ug/g t seco); E :0.9±0.1 a 4.1±1.3 ml; D: PV :12±1.2 a 24.4±1.6 (EB ug/g t seco); E 2.2_/0.2 a 8.4± 1.3 ml. El envejecimiento produjo cambios progresivos naturales en el estrés oxidativo, PV y E gingival. En tanto que en el estado diabético los cambios del estrés oxidativo, PV y E gingival se observan temprano y fueron progresivamente más significa tivos comparados con los ND. De acuerdo a estos resultados las modificaciones gingivales no diabéticas se desarrollan naturalmente en función de la edad, en cambio en la senectud asociada con enfermedad diabética la hiperglucemia aumenta progresiva y tempranamente (AU)

Effect of rhubarb on extravascular lung water in patients with acute respiratory distress syndrome

Summary Objective: The aim of this study was to evaluate the effect of rhubarb on extravascular lung water (EVLW) in patients with acute respiratory distress syndrome (ARDS). Method: A total of 80 patients with ARDS were randomly divided into a treatment group (40 cases) and control group (40 cases). Patients in the treatment group received rhubarb (30.0 g/d) and patients in the control group received conventional therapy for seven consecutive days. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were determined using pulse contour cardiac output (PiCCO) technology, and the oxygenation index was measured by blood gas analysis at baseline and on days 3, 5 and 7 after treatment. Results: The oxygenation index was higher and the levels of EVLWI and PVPI were lower after treatment in the two groups; however, these indexes showed significant differences on the 5th and 7th days after rhubarb treatment compared with the results in the control group (p<0.05). Conclusion: Rhubarb can decrease EVLWI and PVPI, and improve oxygenation in patients with ARDS.

Impacts of albumin synergized with hydroxyethyl starch on early microvascular albumin leakage after major abdominal surgery in rabbits

Abstract Purpose: To investigate the impacts of albumin synergized with hydroxyethyl starch (HES) on early microvascular albumin leakage after major abdominal surgery in rabbits. Methods: Forty male Japanese rabbits were randomly divided into four groups: the control group, the saline group, the albumin group, and the Syn group (hydroxyethyl starch+albumin). The latter three groups were performed gastrectomy plus resection of pancreatic body and tail and splenectomy. The serum albumin concentration was detected before and 48h after surgery, and the conditions of mesenteric microvascular leakage in these 4 groups were observed under microscope 48 h after surgery to calculate the leakage rate. Results: Compared with the saline group, the albumin group and the Syn group exhibited significantly increased serum albumin concentrations 48h after surgery (P<0.05). The albumin leakage rate was the most obvious in the albumin group, followed by the saline group, while that in the Syn group was the minimal, and there existed significant differences among these groups (P<0.05) . Conclusion: Simple administration of albumin in the early stage after major abdominal surgery could increase the albumin leakage, while the synergization of albumin and hydroxyethyl starch could reduce the albumin leakage.

Avaliação do citoesqueleto e da barreira endotelial pulmonar na malária experimental / Evaluation of the cytoskeleton and pulmonary endothelial barrier in experimental malaria

Infecções por Plasmodium sp. podem levar a um quadro respiratório grave, com complicações pulmonares denominadas lesão pulmonar aguda e síndrome do desconforto respiratório agudo (LPA/SDRA). Inflamação aguda, lesão do endotélio alveolar e do parênquima pulmonar, disfunção e aumento da permeabilidade da barreira alvéolo-capilar e, consequente, formação de edema, caracterizam esta síndrome. O modelo experimental, que utiliza o parasita murino Plasmodium berghei ANKA e camundongos da linhagem DBA/2, é empregado no estudo de mediadores imunológicos e fatores que propiciam o estabelecimento das lesões pulmonares associados à LPA/SDRA. Diversos estímulos podem atuar diretamente no aumento da permeabilidade endotelial por meio da desestabilização dos microtúbulos, rearranjo dos microfilamentos de actina e contração das células endoteliais, via sinalização de Rho-GTPases, causando disfunção da barreira endotelial. Desta forma, este trabalho tem como objetivo avaliar as alterações do citoesqueleto em células endoteliais primárias pulmonares de camundongos DBA/2 (CEPP-DBA/2), as vias de sinalização das principais Rho-GTPases e o estresse oxidativo, causados pela presença de eritrócitos parasitados com esquizontes de P. berghei ANKA (EP-PbA). As CEPP-DBA/2 foram estimuladas com TNF, VEGF ou IFNγ, em diferentes tempos de exposição, seguido da incubação com EP-PbA. Assim, foram realizados ensaios de imunofluorescência para análise do rearranjo de microfilamentos de actina e da desestabilização de microtúbulos. As vias de sinalização das Rho-GTPases foram avaliadas por Western blot, para as expressões proteicas de RhoA, Cdc42 e MLC. Além disso, ensaio fluorométrico foi realizado para detectar a produção de espécies reativas de oxigênio, resultantes do estímulo com eritrócitos parasitados. CEPP-DBA/2 estimuladas por EP-PbA, VEGF, TNF ou IFNγ, em associação ou não, apresentaram alterações morfológicas nos microfilamentos de actina e aumento dos espaços interendoteliais. Imagens de imunofluorescência também mostram desestabilização de microtúbulos e desfosforilação de FAK, causadas por EP-PbA. Os ensaios de permeabilidade validam que os eritrócitos parasitados com formas maduras de P. berghei induziram aumento da permeabilidade microvascular nas CEPP-DBA/2. Além disso, estas células, estimuladas com EP-PbA, demonstraram elevada produção de espécies reativas de oxigênio (EROs), o que pode estar contribuindo com o desenvolvimento de estresse oxidativo e com a injúria endotelial, assim como, com o aumento da permeabilidade vascular. O mais interessante é que estas alterações endoteliais podem estar relacionadas ao aumento da razão RhoA/Cdc42, da expressão proteica de MLC fosforilada e do sinal de ativação de RhoA. Em conjunto, estes resultados mostram envolvimento dos eritrócitos parasitados com esquizontes de Plasmodium berghei ANKA na desorganização do citoesqueleto e na disfunção da barreira alvéolo-capilar, via RhoA/Rho-kinase, o que pode estar contribuindo com a patogênese da LPA/SDRA associada à malária

Infections by Plasmodium sp. can lead to a serious respiratory condition with pulmonary complications, named acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Acute inflammation, alveolar endothelium and lung parenchyma injuries, dysfunction and increased permeability of the pulmonary alveolar-capillary barrier and consequent formation of edema characterize this syndrome. Several stimuli can directly increase endothelial permeability through actin microfilaments rearrangement, via Rho- GTPases signaling, leading to endothelial barrier dysfunction. DBA/2 mice infected with Plasmodium berghei ANKA develop ALI/ARDS similar to that observed in humans. The purpose of this research was to assess cytoskeletal changes in DBA/2 mice primary microvascular lung endothelial cells (PMLEC), verify the signaling pathways of the Rho- GTPases and analyze the oxidative stress on these cells in the presence of P. berghei ANKA-infected red blood cells (PbA-iRBC). PMLEC were stimulated by TNF, VEGF or IFNγ followed by incubation with PbA-iRBC. Immunofluorescence assays were performed to analyze actin microfilaments rearrangement and microtubules destabilization. Western blot for RhoA, Cdc42 and MLC proteins were conducted to assess alterations in signaling pathways of Rho-GTPases. In addition, a fluorimetric assay was performed to detect the production of reactive oxygen species resulting from PbA-iRBC stimulus. P. berghei ANKA, VEGF, TNF and IFNγ stimuli, in association or not, caused morphological disturbances in actin microfilaments of PMLEC and an increase of intercellular spaces. Moreover, immunofluorescence images showed microtubules destabilization and FAK dephosphorylation in these cells, caused by PbA-iRBC. The permeability assay showed that PbA-iRBC induced an increase of microvascular permeability in PMLEC. In addition, PMLEC stimulated by PbA-iRBC, showed elevated production of ROS, which may be contributing to oxidative stress and increasing the damage of endothelial cells, as well as an increase of vascular permeability. Interestingly, these endothelial changes may be related to the increased RhoA/Cdc42 protein expressions ratio, augmented protein expression of phosphorylated MLC and RhoA activation signal. Taken together, these data demonstrate the involvement of P. berghei ANKA-infected red blood cells in cytoskeleton disorganization and alveolar-capillary barrier dysfunction, through of RhoA / Rho-kinase signaling pathway, which may contribute to ALI/ARDS pathogenesis

Reguladores de integridad endotelial como posibles predictores de la gravedad en casos de dengue / Regulators of endothelial integrity as severity predictors in dengue

Introducción. El dengue es una de las enfermedades trasmitidas por mosquitos de mayor impacto en el mundo. La evolución clínica de la enfermedad suele ser impredecible, por lo cual su adecuado manejo en las fases tempranas podría incidir en la mejoría del paciente. Objetivo. Evaluar los niveles séricos de algunos reguladores endoteliales (VEGF, sICAM-1, endoglina soluble, Ang-1 y Ang-2) como marcadores de predicción de la gravedad del dengue. Materiales y métodos. Se hizo un estudio de casos y controles anidado en una cohorte. En la fase temprana, los niveles de los reguladores endoteliales se midieron con ELISA. La relación entre las variables clínicas y los reguladores se analizó mediante regresión logística utilizando como variable de salida la gravedad del dengue. Con base en la relación entre las variables de interés y el resultado, se estableció un posible modelo predictor de la gravedad empleando la mejor área bajo la curva (ROC). Resultados. La mediana de la edad fue de 24 años. Los casos graves se asociaron con niveles séricos de Ang-2 a partir de un punto de corte mayor o igual a 1.490 pg/ml, ( Odds ratio, OR=3,1 p=0,015). Los niveles séricos de Ang-2, así como un área de 0,73 bajo la curva ROC, contribuyeron al modelo de predicción de la gravedad, conjuntamente con las variables de exantema, trastorno de conciencia y dolor abdominal, con OR de 3,2 (IC 95% 1,16-8,9; p=0,024). Conclusión. El regulador endotelial Ang-2 podría ser un predictor de la gravedad en el dengue.

Introduction: Dengue is currently among the mosquito-borne diseases of greatest global impact. The clinical course of the disease can be unpredictable, so proper handling in its early stages is critical to ensure optimal outcomes. Objective: To evaluate serum regulators of endothelial integrity (VEGF, sICAM-1, sEndoglina, Ang-1, and Ang-2) as predictive markers of dengue severity. Materials and methods: We conducted a case-control study nested in an appropriate cohort. Endothelial regulator levels were first measured by ELISA, after which analysis was performed using logistic regression of clinical and regulatory variables, with severity as an output variable. A possible severity prediction model, based on the variables of interest and output, was defined using the best area under the ROC curve. Results: The median subject age was 24 years. Severe cases were associated with Ang-2 serum levels of =1,490 ng/ml (OR=3.1; p=0.015). Serum levels of Ang-2 (=1,490 ng/ml) contributed to the severity prediction model, as did a 0.73 area under the ROC curve, together with the variables rash, impaired consciousness and abdominal pain, with an OR of 3.2 (CI 95%: 1.16 to 8.9; p=0.024). Conclusion: The endothelial regulator Ang-2 could be a predictor of severity in dengue.

Neutrophil Extravasation Cascade: What Can We Learn from Two-photon Intravital Imaging?

Immune cells (leukocytes or white blood cells) move actively and sensitively based on body conditions. Despite their important role as protectors inside the body, it is difficult to directly observe the spatiotemporal momentum of leukocytes. With advances in imaging technology, the introduction of two-photon microscopy has enabled researchers to look deeper inside tissues in a three-dimensional manner. In observations of immune cell movement along the blood vessel, vascular permeability and innate immune cell movements remain unclear. Here, we describe the neutrophil extravasation cascade, which were observed using a two-photon intravital imaging technique. We also provide evidence for novel mechanisms such as neutrophil body extension and microparticle formation as well as their biological roles during migration.

Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability.</p><p><b>METHODS</b>Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers.</p><p><b>RESULTS</b>A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 μmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture.</p><p><b>CONCLUSIONS</b>The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.</p>

Theragnostic ultrasound using microbubbles in the treatment of prostate cancer

The use of gas-filled microbubbles in perfusion monitoring as intravascular ultrasound contrast agents has recently become more common. Additionally, microbubbles are employed as carriers of pharmaceutical substances or genes. Microbubbles have great potential to improve the delivery of therapeutic materials into cells and to modify vascular permeability, causing increased extravasation of drugs and drug carriers. Prostate cancer is the most common neoplasm in Europe and America, with an incidence twice to three times that of lung and colorectal cancer. Its incidence is still rising in Asian countries, including Japan and Korea. In this review, we present current strategies regarding the synthesis of microbubbles with targeted ligands on their surfaces, with a focus on prostate cancer.

Efficacy Observation of Modified Yiqi Chutan Recipe Treating Mid-late Stage NSCLC Patients by CT Perfusion / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Modified Yiqi Chutan Recipe (MYCR) on blood flow perfusion in treating mid-late stage non-small cell lung cancer (NSCLC) patients by using multislice CT perfusion (CTP) , and to assess the relationship between each CTP parameter and the prognosis as well.</p><p><b>METHODS</b>Totally 87 mid-late stage NSCLC patients were randomly assigned to the treatment group (44 cases, Shenyi Capsule + MYCR +chemotherapy) and the control group (43 cases, chemotherapy alone) in the ratio of 1:1. And 21 days consisted of 1 therapeutic course, 4 courses in total. All of them underwent CTP of primary tumor and routine thoracic CT examination (plain CT and enhancement CT) 3 times (before therapy, after 2 and 4 cycles). CT findings were analyzed for tumor size and perfusion parameters [blood flow (BF), blood volume (BV), permeability surface (PS), mean transit time (MTT), and time to peak (TP) before and after treatment, and relationship between perfusion parameters and prognosis was also assessed.</p><p><b>RESULTS</b>In 87 cases, 7 dropped out and 80 cases were available, 40 in the treatment group and 40 in the control group. (1) The relief rate was 47.5% (19/40) and the total stable rate was 77.5% (31/40) in the treatment group, and they were 40.0% (16/40) and 65.0% (26/40) in the control group, with no statistical difference between the two groups (χ² = 0.672, 1.227; P > 0.05). (2) Compared with before treatment group in the same group, BF and PS decreased, and MTT increased in the two groups after 2 and 4 courses (P < 0.05); BE and PS decreased, and MTT increased in the control group after 2 courses (P < 0.05). Compared with the control group after 4 courses, BE decreased more significantly in the treatment group (P < 0.05). (3) After 4 courses, all patients were assigned to the remission group (35 cases) and the non-remission group (45 cases) according to the RECIST standard. Compared with before treatment in the same group, BF, BF, and PS all decreased, and MTT increased in the remission group after treatment (all P < 0.05); BF increased in the non-remission group after treatment (P < 0.05). (4) All patients were assigned to the BE increase group (34 cases) and the BE decrease group (46 cases) according to changed BE values after treatment. Results showed the mean survival rate was 246 days in the BF increase group (the 1-year accumulative survival rate being 13.0%) and 387 days in the BE decrease group (the 1-year accumulative survival rate being 53.1%). The life span was prolonged and the 1-year accumulative survival rate was elevated in the BE increase group, with statistical difference as compared with the BE decrease group (χ² = 19.057, P < 0.01).</p><p><b>CONCLUSIONS</b>Shenyi Capsule plus MYCR could reduce BE in mid-late stage NSCLC patients , improve vascular permeability, showing better synergistic effect with chemotherapy. CTP could not only reflect the change of tumor size, but also reflect vascular function of the tumor. Meanwhile, changes of CTP parameters were closely associated with prognosis. Patients with post-treatment decreased BE value had better prognosis and longer life span.</p>

Effects of different frequency microvibrations in the vascular endothelial growth factor expression and permeability of vascular endothelial cell / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to evaluate the vascular endothelial growth factor (VEGF) expression and permeability of vascular endothelial cell under microvibration.</p><p><b>METHODS</b>Human umbilical vein endothelial cell (HUVEC) were cultured, randomly vibrated under low frequency of 0.2, 0.5, 2, 5 Hz, 30 min per day. The VEGF mRNA level was detected by Tagman probe real-time fluorescence quantitative polymerase chain reaction (PCR), and the VEGF protein expression level was detected by Western blot. The permeability of vascular endothelial cell was evaluated.</p><p><b>RESULTS</b>Compared with the blank control group, the mRNA and protein expression level of VEGF were significantly increased under 0.2, 0.5 Hz thelial, and increase the permeability microvibration (P<0.05), and decreased under 2, 5 Hz microvibration (P<0.01). The vascular endothelial permeability in creased under 0.2, 0.5 Hz microvibration (P<0.01), whereas the permeability decreased under 2, 5 Hz microvibration (P<0.01).</p><p><b>CONCLUSION</b>0.2-0.5 Hz microvibration can up-regulate the expression of VEGF mRNA and protein in vascular endothelial, and increase the permeability.</p>