Expression and role of deleted in malignant brain tumor protein 1 in acute respiratory distress syndrome rats induced by sepsis / 中华危重病急救医学

Objective:To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers.Methods:Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis.Results:Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/β-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). Conclusion:DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.

Progress in anti-inflammatory effects of escin / 中国药理学与毒理学杂志

The fraction of horse chestnut seeds was named escins, which mainly consists of A, B, C, and D escin. Accumulating evidence suggests that escin exerts potent anti-inflammatory and anti-edematous effects. The effects of escin on inflammation and edema have been confirmed in various models. In a study in 1961, intravenous administration of escin was found to reduce acute edema in a rat paw. In the same study, escin was found to inhibit the increase in vascular permeability induced by egg white injection. Escin dose-dependently reduced the capillary permeability in chlo?roform-induced local inflammation in the abdominal skin surface of rabbits. The anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary perme?ability in rats. Escin gel decreased the contents of PGE2, TNF-α, and IL-1β, and reduced the raw edema and capillary permeability. The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to inves?tigate the anti-inflammatory effects of escin and glucocorticoid alone or combined. Co-administration of escin with corti?sone significantly reduced the volume of exudates and the number of white blood cells of exudates. The findings sug?gest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect. The anti-inflammatory effect of escin was investigated in carrageenan-induced paw edema and acetic acid-induced capillary permeability in mice. Escin showed an anti-inflammatory effect, which is similar to that seen with dexamethasone treatment. However, escin showed a longer duration of the anti-inflammatory response than that of dexamethasone. Furthermore, escin had no signif?icant effects on spleen index, thymus index , proliferative capacity of splenocytes, lymphocyte count, and phagocytic rate. The findings suggest that escin is a potent anti-inflammatory drug with long-lasting anti-inflammatory effects without any immunosuppressive effects. Traditionally the mechanism of anti-inflammatory effect of escin is supposed to be rela?tive to release of PGF2α and corticosterone. The early studies showed that escin might promote the release of PGF2αand affect the pituitary adrenal system, stimulate the release of adrenocorticotropic hormone (ACTH) and glucocorticoid, which may explain its anti-inflammatory and anti-edema effects. Escin has glucocorticoid-like anti-inflammatory effect. However, escin did not exhibit an anti-inflammatory effect in low dose. Combination of suboptimal concentrations of escin with corticosterone inhibited the release of inflammatory factors including NO, TNF-αand IL-1βin the LPS-stimulated macrophage cells. Previous studies demonstrate that escin combined with glucocorticoid produced synergistic anti-inflammatory effects. The potential synergistic mechanisms may be associated with the property which escin regulates the glucocorticoid receptor (GR) signaling pathway. Escin can upregulate the expression of GR, promote the combina?tion of glucocorticoid and GR, then promote the activated GR transfer into the nucleus. Activated GR will inhibit the acti?vation of NF-κB directly, thus further inhibiting the expression of TNF-αand IL-1βand other inflammatory factors. Escin could inhibit 11β-HSD2 but not 11β-HSD1, thus decrease the metabolism of glucocorticoid. Escin and glucocorticoids have similar chemical structures. This indicate that one of the anti-inflammatory mechanisms of escin may be due to its stimulating GR by binding to it. Eacin might be a partial agonist of GR. A good many of researches have demonstrated the anti-inflammatory properties of escin, and shed light on the underlying mechanisms by which escin exerts these effects. Escin, as an oral or intravenous formulation, or a topical gel, inhibits inflammation, producing measurable improve?ments in edema and acute lung injury. Further clinical studies of escin are needed to demonstrate these properties in larger patient populations.

Estudo da Reatividade Microvascular em Pacientes Hipertensos com Adiposidade Corporal Elevada / Microvascular Reactivity in Hypertensive Patients with High Body Adiposity

Resumo Fundamento: Diversos índices antropométricos têm sido propostos para determinar a associação entre excesso de peso e fatores de risco cardiovascular. Objetivo: Avaliar a relação entre adiposidade corporal e reatividade microvascular em pacientes hipertensos sob terapia anti-hipertensiva. Métodos: Pacientes hipertensos tratados de 40 a 70 anos foram submetidos à avaliação de índices antropométricos: conicidade (IC), adiposidade corporal (IAC), adiposidade visceral (IAV) e relação cintura-estatura (RCE). Os participantes foram divididos pelos tercis de percentual de gordura (%G) obtido pela bioimpedância elétrica (BIA) e submetidos a teste de reatividade microvascular (laser speckle contrast image), medida da velocidade da onda de pulso (VOP). O valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: A variação da área sob a curva (ASC) da perfusão cutânea foi inferior no tercil superior (97 ± 57% vs. 67 ± 36%; p = 0,027). O %G apresentou correlação significativa com RCE (r = 0,77; p < 0,001), IAV (r = 0,41; p = 0,018), IC (r = 0,60; p < 0,001) e IAC (r = 0,65; p < 0,001) nos homens e somente com RCE (r = 0,55; p < 0,001) e IAC (r = 0,60; p < 0,001) nas mulheres. Na regressão linear, a ASC mostrou associação independente com o %G (β =-3,15; p = 0,04) nas mulheres e com a glicemia (β = -1,15; p = 0,02) nos homens. Não houve diferença nas medidas de VOP. Conclusão: Os índices antropométricos de obesidade foram mais associados ao %G nos homens. A maior adiposidade corporal foi relacionada com menor reatividade microvascular, o que foi mais evidente nas mulheres. Não houve diferença na rigidez arterial, o que pode ter sido influenciado pelo tratamento anti-hipertensivo.

Abstract Background: Several anthropometric indexes have been proposed to determine the association between overweight and cardiovascular risk factors. Objective: To evaluate the relationship between body adiposity and microvascular reactivity in hypertensive patients under antihypertensive therapy. Methods: Treated hypertensive patients aged 40 to 70 were submitted to evaluation of anthropometric indexes: conicity (CI), body adiposity (BAI), visceral adiposity (VAI) and waist-to-height ratio (WHtR). Participants were divided by the terciles of fat percentage (%F) obtained by bioelectrical impedance. The patients underwent microvascular reactivity test (Laser Speckle Contrast Image) and pulse wave velocity (PWV) measurement. The p value <0.05 was considered statistically significant. Results: The variation of the area under the curve (AUC) of the skin perfusion was lower in the upper tercile (97±57% vs. 67±36%; p=0.027). %F showed significant correlation with WHtR (r=0.77; p<0.001), VAI (r=0.41; p=0.018), CI (r=0.60; p<0.001), BAI (r=0.65; p<0.001) in men and only with WHtR (r=0.55; p<0.001) and BAI (r=0.60; p<0.001) in women. In linear regression, AUC was independently associated with %F (β=−3.15; p=0.04) in women and with blood glucose (β=−1.15; p=0.02) in men. There was no difference in PWV measurements. Conclusion: Anthropometric indices were more associated with %F in men. Higher body adiposity was associated with lower microvascular reactivity, which was more evident in women. There was no difference in arterial stiffness, which may have been influenced by antihypertensive treatment.

Hypotension and bradycardia produced by transthoracic application of low-intensity ultrasound therapy in hearts of healthy rats - a preclinical study

Abstract Objective: To investigate the cardiovascular effects produced by transthoracic application of low-intensity pulsed ultrasound therapy (LIPUST). Methods: Three-month-old male Wistar rats (± 300 g, N=16) were randomly allocated in two groups, namely SHAM (control group, faked procedures) and UST (animals treated with LIPUST). These animals, under anesthesia, were instrumented (femoral artery and vein catheterization) for hemodynamic recordings (mean blood pressure [MBP], heart rate [HR]) and blood biochemical profile (lipids, creatine kinase-myocardial band [CK-MB]). Then, LIPUST (spatial average-temporal average [ISATA] 1-MHz, power 0.1 to 1.2 W/cm2, pulsed 2:8 ms, cycle at 30%, for three minutes) was applied to animals from the UST group, externally to their thorax. SHAM animals were equally manipulated, but without application of ultrasound energy. After the hemodynamic and biochemical measurements, animals were sacrificed, and their hearts were mounted in a Langendorff apparatus for coronary reactivity evaluation. Standard histology techniques were employed to analyze the hearts. Results: LIPUST application caused statistically significant reductions in MBP (92±4 vs. 106±1 mmHg) and HR (345±14 vs. 380±17 rpm) when compared with SHAM procedures. UST rats exhibited higher CK-MB levels (318±55 vs. 198±26 U/dL) and lower plasma triglycerides levels (38±7 vs. 70±10 mg/dL) than SHAM animals. Coronary reactivity was not significantly changed by LIPUST. Cardiac histopathology showed an increase in capillary permeability in treated animals when compared with SHAM animals. Conclusion: Noninvasive LIPUST induces significant metabolic and hemodynamic changes, including intensity-dependent bradycardia and hypotension, indicating a possible therapeutic effect for cardiac events.

Clinical profile of dengue fever in children presented at a tertiary care hospital

Background: Dengue fever is a benign syndrome caused by an arthropod-borne virus and is characterized by Biphasic fever, myalgia, and arthralgia, rash, leucopenia, and lymphadenopathy. Dengue hemorrhagic fever and dengue shock syndrome are a severe, often fatal febrile disease caused by 1 of 4 dengue virus. It is characterized by increased capillary permeability, abnormalities of hemostasis and protein-losing shock syndrome. The aim of this study was to assess the clinical profile, complications and outcome of dengue infection in children.Methods: All children attending the hospital with symptoms and signs suggestive of dengue fever were tested for NS1 antigen and IgM/ IgG dengue antibody serology (depending on the day of fever) by enzyme-linked immunosorbent assay (ELISA) technique.Results: Of the 174-dengue serology positive children, fever was the most common major symptom (97.7%) followed by vomiting (85.6%), loss of appetite (81.6%), abdominal pain (77%), body pain/leg pain (62.6%). Severe dengue as per WHO criteria was seen in 29 (16.7%) children. Thrombocytopenia (platelet count less 1,00,000) was observed in 82 children (47%), Platelet count less than 20,000 in 8 children (4.5%). Dengue shock syndrome was seen it 26 children (15%). Mortality was nil.Conclusions: In children, if symptoms like fever, vomiting, loss of appetite, abdominal pain and body pain are present, a strong possibility of dengue fever is present especially in an epidemic setting. Early suspicion and effective management can reduce the severity.

Relationship between Rho GTPase family regulation and vascular endothelial barrier function / 药学学报

Injury of vascular endothelial barrier function is implicated in several pathophysiological processes. The integrity of vascular endothelium is regulated by cytoskeleton and cell-cell junctions. Small guanosine triphosphatases of the Rho family (Rho GTPases) are known to play a central role in vascular endothelial barrier function. It has been reported that RhoA, Rac1, Cdc42 and RhoB are involved and they exert both positive and negative effect on endothelial barrier integrity, depending on their subcellular location. When inflammatory factors such as thrombin attack the vascular endothelial cells, GEF of RhoA will be widely distributed throughout the cells. Thus, activated RhoA causes aggregation of F-actin fibers in a short time and disrupts the vascular endothelial barrier, a process named acute cell contraction. However, RhoA may also induce the production and maturation of intercellular junctions in new cells. Rac1 and Cdc42 help to maintain the integrity of vascular endothelial barrier at the resting state. They cause the phosphorylation of LIM kinase and inhabitation of cofilin, resulting in less remodeling of cytoskeletal in the vascular endothelial cells. On the other hand, Cdc42 can translocate to the cortex rapidly after a stimulation, where Cdc42 will activate the myosin Ⅱ and promote the reorganization of adjective junction to facilitate the recovery of vascular endothelial barrier. In this review, we overviewed how Rho GTPases regulate the vascular endothelial barrier integrity.

Retrospective cohort study on the correlation between high value of lactic acid and risk of death in 127 patients with extensive burn during shock stage / 中华烧伤杂志

Objective@#To analyze the relationship between serum lactic acid value and risk of death in patients with extensive burn during shock stage and the related influencing factors.@*Methods@#Clinical data of 127 patients (111 males and 16 females) with extensive burn admitted to Institute of Burn Research of the First Affiliated Hospital of Army Medical University from January 2009 to December 2013 and Department of Plastic Surgery and Burns of the Affiliated Hospital of Southwest Medical University from January 2016 to December 2018, who met the admission criteria, were retrospectively analyzed. The patients aged 21 to 62 years, with total burn area more than 50% total body surface area. All patients were treated with antishock therapy after admission. (1) According to the treatment outcome, the patients were divided into survival group (n=98) and death group (n=29). The gender, age, total burn area, partial-thickness burn area, full-thickness burn area, abbreviated burn severity index (ABSI), admission time after injury, number of patients with inhalation injury, number of patients with acute renal failure, and serum lactic acid values on admission and at post admission hour (PAH) 12, 24, 36, and 48 were recorded. (2) According to the optimal positive cut-off value of serum lactic acid 48 hours after admission, the patients were divided into high lactic acid group and normal lactic acid group. Age, gender, total burn area, indexes at PAH 48 including urea nitrogen, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total serum bilirubin, alkaline phosphatase (ALP), albumin, white blood cell count, platelet count, lymphocyte count, prothrombin time (PT), hematocrit value, oxygenation index, respiratory index (RI), the alveolar-arterial oxygen partial pressure difference, mean arterial pressure (MAP) at PAH 48, the average urine volume within 48 hours after admission, the total volume of intravenous fluid infusion within 48 hours after admission, the volume of fluid infusion per kilogram of body mass within the first 24 hours after admission, the volume of fluid infusion per one percent of body surface area per kilogram of body mass within the first 24 hours after admission, the volume of urine per kilogram of body mass per hour within the first 24 hours after admission, and the percentage of hospital death were recorded. Data were processed with t test, chi-square test, and Fisher′s exact probability test. Cox regression analysis was used to screen independent risk factors affecting the prognosis of patients. Receiver operating characteristic curve (ROC) of serum lactic acid value at PAH 48 of 127 patients was drawn to predict patients′ death and determine the optimal positive cut-off value. Multivariate logistic regression analysis was used to screen independent risk factors causing increase of serum lactic acid.@*Results@#(1) There were significantly statistical differences in total burn area, full-thickness burn area, and ABSI of patients between survival group and death group (t=6.257, 4.476, 5.727, P<0.01), while other indexes between the two groups were close. (2) The serum values of lactic acid of patients in death group on admission and at PAH 12, 24, 36, and 48 were (4.00±0.28), (4.50±0.26), (4.02±0.31), (3.48±0.22), (3.40±0.19) mmol/L, respectively, which were significantly higher than those in survival group [(3.30±0.21), (3.20±0.19), (2.33±0.17), (1.85±0.18), (1.50±0.09) mmol/L, t=14.552, 29.603, 38.133, 40.648, 74.973, P<0.05 or P<0.01]. (3) Cox regression analysis showed that the serum value of lactic acid at PAH 48 was the independent risk factor affecting the prognosis of patients, with risk ratio of 1.853 and 95% confidence interval of 1.342-2.559, P<0.01. (4) The total area under ROC of serum value of lactic acid at PAH 48 to predict death of 127 patients was 0.811, with 95% confidence interval of 0.699-0.924, P<0.01. The optimal positive cut-off value of serum value of lactic acid was 1.75 mmol/L, with sensitivity of 75.0% and specificity of 79.5% for predicting death. (5) There were significantly statistical differences in total burn area, ALT, AST, ALP, PT, total serum bilirubin, total volume of intravenous fluid infusion within 48 hours after admission, volume of fluid infusion per kilogram of body mass within the first 24 hours after admission, and percentage of hospital deaths of patients between high lactic acid group (n=34) and normal lactic acid group (n=93), t=3.592, 6.797, 10.367, 2.089, 2.880, 4.517, 2.984, 4.044, χ2=58.498, P<0.05 or P<0.01, while other indexes were close between the two groups. (6) Multivariate logistic regression analysis showed that AST and total serum bilirubin were independent risk factors for increase of serum lactic acid, with odds ratios of 1.021 and 1.064 and 95% confidence intervals of 1.001-1.040 and 1.001-1.132, P<0.05.@*Conclusions@#Serum value of lactic acid at PAH 48 can independently predict the death of patients with extensive burns. Liver injury is an important risk factor causing hyperlacticemia during burn shock stage. Widespread increase of vascular permeability and large amount of fluid resuscitation are the core factors leading to aggravation of abdominal organ injury.

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)

How relevant are vascular endothelial growth factor and intercellular adhesion molecule in the systemic capillary leak syndrome of psoriasis?

Abstract: Psoriasis is a chronic disease, characterized by erythematous scaly lesions, presented in eight different forms: plaques, guttate, pustular, erythrodermic, inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development depends on genetic factors, external stimulus and immune response alteration.1 Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved. In the worst cases, systemic complications linked to endothelial alterations may occur. A literature review was conducted for a better understanding of what roles VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion molecule) have, among other cytokines, in systemic capillary leak syndrome, involved in erythrodermic and pustular psoriasis, the most unstable forms of the disease.

Role of β-arrestin-1 in penehyclidine hydrochloride-induced inhibition of LPS-caused increase in pulmonary microvascular permeability in human pulmonary microvascular endothelial cells / 中华麻醉学杂志

Objective To evaluate the role of β-arrestin-1 in penehyclidine hydrochloride (PHC)-induced inhibition of lipopolysaccharide (LPS)-caused increase in pulmonary microvascular permeability in human pulmonary microvascular endothelial cells (PMVECs).Methods Human PMVECs were seeded in 6-well plates (2 ml/well) or in culture flasks (4 ml/flask) at the density of 1 × 105 cells/ml and divided into 5 groups (n=15 each) using a random number table:empty plasmid transfection group (group C),LPS plus empty plasmid transfection group (LPS group),PHC plus LPS plus empty plasmid transfection group (P+LPS group),LPS plus β-arrestin-1 short hairpin RNA (shRNA) transfection group (LPS+shRNA group) and PHC plus LPS plus β-arrestin-1 shRNA transfection group (P+LPS+shRNA group).In LPS and LPS+shRNA groups,the cells were transfected with empty plasmid 1.5 μg or with plasmid containing 15 nmol/L β-arrestin-1 shRNA,LPS with the final concentration of 0.1 μg/ml was added at 24 h of incubation,and the cells were then incubated for 1 h.In P+LPS and P+LPS+shRNA groups,the cells were transfected with empty plasmid 1.5 μg or with plasmid containing 15 nmol/L β-arrestin-1 shRNA,PHC with the final concentration of 2 μg/ml was added at 24 h of incubation,LPS with the final concentration of 0.1 μg/ml was added at 1 h of incubation,and the cells were then incubated for 1 h.The cell permeability was measured using Transwell chambers.The expression of heat shock protein (HSP27) was detected by immunofluorescence.The expression of β-arrestin-1,p38 mitogen-activated protein kinase (p38MAPK) and phosphorylated p38MAPK (p-p38MAPK) was detected by Western blot.The ratio of pp38MAPK/p38MAPK was calculated.Results Compared with group C,the cell permeability was significantly increased,the expression of HSP27 was up-regulated,p-p38MAPK/p38MAPK ratio was increased,and the expression of β-arrestin-1 was down-regulated in LPS,LPS + shRNA and P + LPS + shRNA groups (P＜0.05),and no significant change was found in the parameters mentioned above in group P+LPS (P＞ 0.05).Compared with group LPS,the cell permeability was significantly decreased,the expression of HSP27 was down-regulated,p-p38MAPK/p38MAPK ratio was decreased,and the expression of β-arrestin1 was up-regulated in group P +LPS,and p-p38MAPK/p38MAPK ratio was significantly increased (P＜0.05),and no significant change was found in the other parameters in group P+LPS+shRNA (P＞0.05).Compared with group P+LPS,the cell permeability was significantly increased,the expression of HSP27 was up-regulated,p-p38MAPK/p38MAPK ratio was increased,and the expression of β-arrestin-1 was down-regulated in group P+LPS+shRNA (P＜0.05).Conclusion The mechanism by which PHC inhibits LPS-induced increase in pulmonary microvascular permeability is totally related to β-arrestin-1 in human PMVECs.

Anti-inflammatory and analgesic effects in vivo and bacteriostasis effect in vitro of diuretic mixture / 药物评价研究

Objective To investigate the analgesic and anti-inflammatory effects of diuretic mixture and its bacteriostasis effect in vitro,and to provide scientific basis for clinical application.Methods Ear swelling test induced by xylene,twisting reaction test induced by acetic acid,capillary permeability increase in abdominal cavity of mice induced by acetic acid,and pain test induced by formalin were used to observe the analgesic and anti-inflammatory effects of diuretic mixture at high,middle and low doses (crude drug 18.0,9.0,and 4.5 g/kg).Bacteriostatic activities of diuretic mixture were tested by K-B paper disc diffusion method.Results Diuretic mixture alleviated ear edema in mouse model at high dose (P ＜ 0.01).Diuretic mixture at high,middle,and low dose could effectively decrease the twisting reaction (P ＜ 0.01),inhibit capillary permeability (P ＜ 0.05 or 0.01),and ease the ache degree of mice induced by formalin in the first phase (P ＜ 0.01),but there was no significant difference in the degree of pain intensity of phase Ⅱ.The inhibitory rates of diuretic mixture on Staphylococcus aureus and Escherichia coli were 95.04％ and 37.44％,respectively.Conclusion Diuretic mixture has significant effects on analgesia and anti-inflammation and against S.aureus and E.coli in vitro.

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.

Reliability of extravascular lung water index and pulmonary vascular permeability index in assessing severity of acute respiratory distress syndrome in critically ill patients / 中华麻醉学杂志

Objective To investigate the reliability of extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) in assessing the severity of acute respiratory distress syndrome (ARDS) in critically ill patients.Methods Forty-six patients with ARDS,who were admitted in our emergency intensive care unit,aged 18-72 yr,weighing 46-72 kg,of Acute Physiology and Chronic Health Evaluation Ⅱ score 11-25,were divided into 3 groups:PaO2/FiO2 ≤ 100 mmHg severe group (n =16);100 mmHg ＜PaO2/FiO2 ≤ 200 mmHg moderate group (n =14);200 mmHg ＜PaO2/FiO2 ≤ 300 mmHg mild group (n=16).Before treatment,and at 24 and 72 h after diagnosis of ARDS,PVPI,EVLWI,cardiac index (CI),and intrathoracic blood volume index (ITBVI) were measured,and blood gas analysis was performed.PaO2/FiO2 was calculated.The 28 day fatality after admission to hospital was recorded.Person correlation of PVPI and EVLWI with PaO2/FiO2,ITBVI and CI was analyzed.Results The PVPI,EVLWI and fatality rate were significantly higher at each time point in moderate group and severe group than in mild group,and in severe group than in moderate group (P＜0.05).The correlation coefficient between PVPI and PaO2/FiO2 was 0.778,and between EVLWI and PaO2/FiO2 was-0.437 (P＜0.05).There was no correlation between CI and ITBVI (P＞0.05).The correlation coefficient between EVLWI and PaO2/FiO2 was-0.448,and between EVLWI and ITBVI was 0.347 (P＜0.05).There was no significant difference between the correlation coefficient between PVPI and PaO2/FiO2 and the correlation coefficient between EVLWI and PaO2/FiO2 (P＜0.05).Conclusion PVPI and EVLWI both can assess the severity of ARDS in critically ill patients,showing a consistent reliability.

Study on Anti-inflammatory Function of Gold Buckwheat Fermented Tea / 世界科学技术-中医药现代化

This study was aimed to observe the effect of gold buckwheat fermented tea on both acute and chronic inflammation in mice. Ear swelling was induced by xylene. Toe swelling was induced by carrageenan. The acute inflammation model was induced by the increasing of capillary permeability in the abdomen of mice by acetic acid. The chronic inflammation model of granuloma was used in the evaluation of anti-inflammatory function of gold buckwheat fermented tea. The results showed that the gold buckwheat fermented tea can obviously decrease the rate of xylene-induced ear swelling and the degree of carrageenan-induced toe swelling in mice. And the gold buckwheat fermented tea had antagonism effect on acute inflammation caused by acetic acid through the increasing of capillary permeability in abdomen of mice. Furthermore, the gold buckwheat fermented tea had obvious inhibition effects on proliferation of granuloma in chronic inflammation. It was concluded that the gold buckwheat fermented tea had the prevention and treatment effect on both acute and chronic inflammation.

Será choque séptico? Um caso raro de choque distributivo / Is this septic shock? A rare case of distributive shock

Os autores apresentam um caso raro de choque em doente sem antecedentes pessoais significativos, admitido na unidade de terapia intensiva por suspeita de choque séptico. Inicialmente, foi tratado com fluidoterapia sem melhoria, tendo sido aventada a hipótese de síndrome de hiperpermeabilidade capilar, após confirmação de hipoalbulinemia paradoxal grave, hipotensão e hemoconcentração exuberante - tríade característica da doença. Os autores discutiram o diagnóstico diferencial e ainda realizaram uma revisão do diagnóstico e do tratamento da doença.

The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration - a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease.

Role of Toll-like receptor 4 in mechanical ventilation-induced increase in pulmonary capillary permeability in diabetic mice / 中华麻醉学杂志

Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mechanical ventilationinduced increase in pulmonary capillary permeability in diabetic mice.Methods Two types of mice,aged 8-10 weeks,weighing 20-25 g,were used in this study:free wild type mice (C3H/HeN) and TLR4 gene mutation type (C3H/HeJ).Diabetes was induced by intraperitoneal streptozotocin 150 mg/kg (in citric acid buffer solution 0.1 mol/L) and confirmed by blood glucose level ＞ 16 mmol/L.Each type of diabetic mice was randomly divided into 2 groups (n =14 each):group diabetes + sham operation (group DS) and group diabetes + mechanical ventilation (group DM).The animals were anesthetized with intraperitoneal ketamine,midazolam and atropine.Tracheal intubation was performed and the animals kept spontaneous breathing in group DS.The animals were mechanically ventilated (FiO2 50％,RR 70 bpm,VT 15 ml/kg,PEEP 2 cmH2O) for 4 h in group DM.Arterial blood samples were obtained at 4 h of ventilation for blood gas analysis,PaO2 and PaCO2 were recorded,and NO concentration in the serum was measured.Then the animals were sacrificed and the lungs were removed for determination of W/D lung weight ratio (W/D ratio),content of evans blue (EB),and expression of caveolin-1,endothelial nitric oxide synthase (eNOS) and phosphor-eNOS (p-eNOS) (by Western blot).The ratio of p-eNOS/eNOS was calculated.Results Compared with group DS,PaO2,PaCO2 and p-eNOS/eNOS ratio were significantly decreased,and W/D ratio,EB content and caveolin-1 expression were increased in group DM (P ＜ 0.05).Compared with C3H/HeN mice,W/D ratio,caveolin-1 expression and EB content were significantly decreased,peNOS/eNOS ratio and serum NO concentrations were increased (P ＜ 0.05),and no significant changes in PaO2 and PaCO2 were found in C3H/HeJ mice in group DM (P ＞ 0.05).Conclusion TLR4 increases the pulmonary capillary permeability after mechanical ventilation in diabetic mice through effectively combining with caveolin-1 and reducing NO bioavailability.

Predicting hemorrhagic transformation by microvascular permeability using perfusion CT in acute cerebral infarction in elderly patients / 中华老年医学杂志

Objective To study the possibility of microvascular permeability (PS) value derived from perfusion CT (PCT) in predicting hemorrhagic transformation (HT) in acute cerebral infarction in elderly patients.Methods 52 consecutive patients with middle cerebral artery acute ischemic stroke who received thrombolytic therapy were divided into HT group and control group,and patients in HT group were further divided into hemorrhagic infarction (HI) group and parenchymal hematoma (PH) group.PCT data and Alberta stroke program early CT scores (ASPECTS) from CT angiography source images (CTA-SI) achieved within 6 hours after symptom onset of each group was retrospectively analyzed and statistically processed.Results In 52 patients,there were 22 cases developed HT,14 cases with HI,8 cases with PH.Cerebral blood flow (CBF) and cerebral blood volume (CBV) values were decreased and permeability surface area product (PS) was increased in ipsilateral in HT group and control group as compared with the contralateral (all P＜0.05).PS value in ipsilateral was significantly higher in HT group than in control group (P＜0.01),but CBF and CBV values in affected side showed no significant difference between the HT group and control group.The area under the receiver operator characteristic (ROC) curve of PS Az value was 0.968.When PS ≥5.77 ml · min-1 · 100 g-1,the sensitivity and specificity of predicting HT were 95.5％ and 86.7％ respectively.The ASPECTS was lower in HT group than in the control group (P＜0.01),and ASPECTS was higher in HI group than in PH group (P＜0.01).The differences in PCT results in affected side between the HI group and PH group was not significant.Conclusions The significantly increased PS value can be a reference in predicting HT risk and guiding thrombolytic therapy.

Biomarcadores pronósticos de gravedad del dengue / Biomarkers for the prognosis of severe dengue

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Introduction: There are very few strategies for the early detection of the patients who might develop the severe form of the illness. Objective: To evaluate the utility of serum levels of some immune response mediators as early biomarkers for the severe dengue prognosis during the early phase of the illness. Materials and methods: Using a case-control design nested in a multicenter cohort from the AEDES network (a Colombian multicenter study), we compared TNF a, ST2, TRAIL and IDO levels in samples which were obtained during the early phase of the illness. Results: ST2, TRAIL and TNF a levels were higher in severe dengue patients compared with uncomplicated patients (p<0.0001), as follows: OR=24.8, CI95%= 6.1- 98.0; OR=18.0, CI95%= 4.6-69.1; OR=NC, CI95%= NC, respectively. We did not find statistically significant differences between IDO levels in severe dengue and uncomplicated dengue (p=1.000, OR=1.0, CI95%= 0.2-6.1). Conclusions: In the early phase of the dengue infection (96 hours), ST2, TRAIL and TNF a quantifications could contribute to the prediction of complications of the illness.