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Laser-assisted indocyanine green angiography allows surgeons to determine intraoperative flap perfusion and achieve the best outcomes in breast reconstruction. This study stratified outcomes based on a meta-analysis of complications including longitudinal trials comparing the clinical assessment of skin flaps during breast reconstruction. Nine studies met inclusion criteria and reported outcomes of interest (n = 2256). The risk of flap necrosis and the necessity of reoperation was statistically significantly higher in the control group.
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Corantes , Angiofluoresceinografia , Verde de Indocianina , Mamoplastia/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Feminino , Humanos , LasersRESUMO
Inflammation is the response of the body to noxious stimuli such as infections, trauma, or injury. Experimental studies have shown that vanillic acid has anti-inflammatory effects. The objective of this study was to investigate the anti-inflammatory and antipyretic properties of the derivative of vanillic acid, isopropyl vanillate (ISP-VT), in mice. The results of this study indicated that ISP-VT reduced paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin, bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, ISP-VT reduced recruitment of leukocytes and neutrophils and reduced its adhesion and rolling, and decreased myeloperoxidase enzyme activity (MPO), cytokine levels (tumor necrosis factor-α and interleukin-6), and vascular permeability. ISP-VT also significantly reduced the expression of cyclooxygenase-2 (COX-2) in subplantar tissue of mice. ISP-VT inhibited COX-2 selectively compared to the standard drug. Our results showed that although ISP-VT binds to COX-1, it is less toxic than indomethacin, as evidenced by MPO analysis of gastric tissue. Treatment with the ISP-VT significantly reduced rectal temperature in yeast-induced hyperthermia in mice. Our results showed that the main mechanism ISP-VT-induced anti-inflammatory activity is by inhibition of COX-2. In conclusion, our results indicate that ISP-VT has potential as an anti-inflammatory and antipyretic therapeutic compound.
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Anti-Inflamatórios/administração & dosagem , Carragenina/efeitos adversos , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inflamação/tratamento farmacológico , Fenóis/efeitos adversos , Ácido Vanílico/química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Modelos Moleculares , Fenóis/síntese química , Fenóis/química , Fenóis/farmacologia , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
PURPOSE: We have previously shown that domperidone-induced short-term hyperprolactinemia reduces the lung's allergic inflammatory response in an ovalbumin antigenic challenge model. Since purinergic receptor P2X7R activity leads to proinflammatory cytokine release and is possibly related to the pathogenesis of allergic respiratory conditions, the present study was designed to investigate a possible involvement of purinergic and prolactin receptors in this phenomenon. METHODS: To induce hyperprolactinemia, domperidone was injected intraperitoneally in rats at a dose of 5.1 mg × kg-1 per day for 5 days. P2X7 expression was evaluated by lung immunohistochemistry while prolactin receptor expression in bronchoalveolar lavage leukocytes was analyzed through flow cytometry. RESULTS: Previous reports demonstrated that rats subjected to short-term hyperprolactinemia exhibited a decrease in leukocyte counts in bronchoalveolar lavage, especially granulocytes. Here, it is revealed that hyperprolactinemia promotes an increased expression of prolactin receptors in granulocytes. Also, increased expression of purinergic P2X7R observed in allergic animals was significantly reduced by hyperprolactinemia. CONCLUSIONS: Both purinergic and prolactin receptor expression changes occur during the anti-asthmatic effect of hyperprolactinemia.
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Asma/metabolismo , Hiperprolactinemia/metabolismo , Pulmão/metabolismo , Receptores Purinérgicos P2X7/biossíntese , Animais , Asma/induzido quimicamente , Asma/imunologia , Expressão Gênica , Hiperprolactinemia/imunologia , Contagem de Leucócitos/tendências , Pulmão/imunologia , Masculino , Ovalbumina/toxicidade , Ratos , Ratos Wistar , Receptores Purinérgicos P2X7/genética , Fatores de TempoRESUMO
Costus spiralis, a plant used in traditional Brazilian medicine for the treatment of complications in diabetes, was investigated. Assay of hexane, ethyl acetate, methanol, and aqueous fractions obtained by partition of a crude methanol extract of dried leaves of C. spiralis revealed that AGI activity was confined to the ethyl acetate fraction. Purification of this fraction yielded schaftoside and isoschaftoside. The AGI activities of the two flavones were lower than, but comparable with, that of the anti-diabetic drug acarbose. In contrast, the IC50 value of the ethyl acetate fraction was 1.95-, 2.34-, and 2.22-fold higher than those of acarbose, schaftoside, and isoschaftoside, respectively. The results demonstrate for the first time that schaftoside and isoschaftoside are responsible, in part, for the AGI activity of C. spiralis. Our study suggests that further investigations into C. spiralis may lead to the discovery of additional compounds with antihyperglycemic activity.
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Costus/química , Inibidores Enzimáticos/farmacologia , Flavonas/farmacologia , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavonas/química , Flavonas/isolamento & purificação , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Medicina Tradicional , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: 3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is a synthetic drug used recreationally, mainly by young people. It has been suggested that MDMA has a Th cell skewing effect, in which Th1 cell activity is suppressed and Th2 cell activity is increased. Experimental allergic airway inflammation in ovalbumin (OVA)-sensitized rodents is a useful model to study Th2 response; therefore, based on the Th2 skewing effect of MDMA, we studied MDMA in a model of allergic lung inflammation in OVA-sensitized mice. METHODS: We evaluated cell trafficking in the bronchoalveolar lavage fluid, blood and bone marrow; cytokine production; L-selectin expression and lung histology. We also investigated the effects of MDMA on tracheal reactivity in vitro and mast cell degranulation. RESULTS: We found that MDMA given prior to OVA challenge in OVA-sensitized mice decreased leukocyte migration into the lung, as revealed by a lower cell count in the bronchoalveolar lavage fluid and lung histologic analysis. We also showed that MDMA decreased expression of both Th2-like cytokines (IL-4, IL-5 and IL-10) and adhesion molecules (L-selectin). Moreover, we showed that the hypothalamus-pituitary-adrenal axis is partially involved in the MDMA-induced reduction in leukocyte migration into the lung. Finally, we showed that MDMA decreased tracheal reactivity to methacholine as well as mast cell degranulation in situ. CONCLUSIONS: Thus, we report here that MDMA given prior to OVA challenge in OVA-sensitized allergic mice is able to decrease lung inflammation and airway reactivity and that hypothalamus-pituitary-adrenal axis activation is partially involved. Together, the data strongly suggest an involvement of a neuroimmune mechanism in the effects of MDMA on lung inflammatory response and cell recruitment to the lungs of allergic animals.
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Asma/imunologia , Inflamação/imunologia , Leucócitos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Células Th2/efeitos dos fármacos , Animais , Células da Medula Óssea , Líquido da Lavagem Broncoalveolar/citologia , Movimento Celular/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Contagem de Leucócitos , Pulmão/citologia , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , N-Metil-3,4-Metilenodioxianfetamina/imunologia , Células Th2/fisiologia , Traqueia/efeitos dos fármacosRESUMO
Condensation reactions of salicylaldehyde, 2-pyridinecarboxaldehyde, and pyridoxaldehyde with memantine (Me) produced novel memantine-derived Schiff bases (1-3). Speciation predictions and calculations of Log P, Log D, and of the percentage (%) of neutral species for (1-3) were carried out. In comparison with Me, the Schiff bases presented increased log P and log D in all cases and pH values, suggesting higher hydrophobicity. The determined solubilities in n-octanol were 34.7 mg/mL for memantine hydrochloride and 67.3 mg/mL for (3). According to the molecular weights and calculated logP, compounds (1-3) are suitable for transdermal administration, especially compound (3). In addition, hydrolysis of 3 with the release of pyridoxal, a daily cofactor in human metabolism, was observed. The results suggested that 3 is the most promising compound and that formation of the pyridoxal Schiff base with Me might be an effective strategy to obtain a prodrug candidate with increased lipophilicity, which would be able to passively cross biological barriers during transdermal delivery and might have applications in the treatment of Alzheimer's disease and other neurological disorders.
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Anadenanthera colubrina var. cebil (Griseb.) Altschul (Fabaceae family), commonly known as the red angico tree, is a medicinal plant found throughout Brazil's semi-arid area. In this study, a chemical analysis was performed to investigate the antidiarrheal activity and safety profile of red angico gum (RAG), a biopolymer extracted from the trunk exudate of A. colubrina. Upon FT-IR spectroscopy, RAG showed bands in the regions of 1608 cm-1, 1368 cm-1, and 1029 cm-1, which relate to the vibration of O-H water molecules, deformation vibration of C-O bands, and vibration of the polysaccharide C-O band, respectively, all of which are relevant to glycosidic bonds. The peak molar mass of RAG was 1.89 × 105 g/mol, with the zeta potential indicating electronegativity. RAG demonstrated high yield and solubility with a low degree of impurity. Pre-treatment with RAG reduced the total diarrheal stool and enteropooling. RAG also enhanced Na+/K+-ATPase activity and reduced gastrointestinal transit, and thereby inhibited intestinal smooth muscle contractions. Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that RAG can interact with GM1 receptors and can also reduce E. coli-induced diarrhea in vivo. Moreover, RAG did not induce any signs of toxicity in mice. These results suggest that RAG is a possible candidate for the treatment of diarrheal diseases.
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The aim of the present study was to evaluate the effect of the hydroxyethyl-methacrylate (HEMA) concentration and solvent content of dental adhesives on cell viability and cytokine (IL-1b, IL-6, IL-10, TNF-α) release by human dental pulp cells (HDPCs). HDPCs were obtained from fresh extracted human third molars. Experimental adhesives were prepared containing different concentrations of HEMA (0%, 10%, and 20%) with and without solvent (ethanol 10%). Cylindrical specimens were immersed on culture medium during 24 h to obtain the extracts. The cells were incubated with extracts (culture medium + components leached from the adhesives) of different adhesives, and cell viability and cytokine release were evaluated after 6 and 24 h of exposure. Adhesives containing HEMA promoted high cell viability reduction after 6 h of exposure; but after 24 h, the results were similar to the ones found among control group cells. These effects on cell viability were prominently increased with the addition of solvent. Although IL-1b release was not affected by exposure to eluates, other cytokines (IL-10, IL-6, TNF-α) were modulated by the different experiment conditions, directly influenced by the HEMA concentration and presence of solvent. Higher HEMA concentrations, combined with the presence of solvent, can promote significant reduction on HDPC viability, increasing the release of anti- and pro-inflammatory mediators.
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The influence of agronomic variables (light intensity, age of leaves, and fertilization type) on the content of macronutrients and micronutrients (potassium, calcium, sodium, magnesium, manganese, iron, zinc, and copper) of tea leaves was assessed by acid digestion, followed by flame atomic absorption spectrometry (FAAS). The thermal behavior of mate tea leaves (Ilex paraguariensis) was also studied in this work. Samples of mate (Ilex paraguariensis) were collected in an experiment conducted under agronomic control at Erva-Mate Barão Commerce and Industry LTD (Brazil). The results showed that the mineral content in mate is affected by the agronomic variables investigated. In general, the content of mineral compounds analyzed is higher for younger leaves and for plants cultivated in shadow. Thermal analysis of samples indicated a similar behavior, with three typical steps of decomposition: loss of water, degradation of low-molecular weight compounds, and degradation of residual materials.
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Temperatura Alta , Ilex paraguariensis/química , Ilex paraguariensis/crescimento & desenvolvimento , Micronutrientes/análise , Folhas de Planta/química , Meio AmbienteRESUMO
AIMS: To evaluate the influence of lactation on lung immune function during allergic inflammation. MAIN METHODS: Female rats, 60-90days old, were divided into three groups: no lung allergy virgins (N group), ovalbumin (OVA)-immunized and sensitized virgins (V group), and OVA-immunized and sensitized lactating females (L group). On gestation day (GD) 10, all animals in L group received a subcutaneous injection of 0.1mg·kg(-1) OVA plus aluminum hydroxide. On GD17, the L group received a subcutaneous booster injection of 10µg OVA plus 10mg aluminum hydroxide. After 7days, an inhalatory challenge with 1% OVA was given in 15min sessions for 3 consecutive days. Animals from the V group received the same treatment, meaning both tests and time intervals between OVA treatment and inhalatory challenge were the same as in the L group. Twenty-four hours after the last inhalation session, the animals were euthanized, and the following tests were performed: total and differential bronchoalveolar lavage (BAL) and femoral marrow lavage (FML) leukocyte counts, quantification of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) levels in BAL fluid, and quantification of plasma corticosterone and catecholamine levels. KEY FINDINGS: The L group presented lower BAL total leukocyte counts and decreases in the number of eosinophils and macrophages compared with the V group. They also expressed higher BAL IFN-γ and lower plasma corticosterone levels. Plasma norepinephrine levels were higher in the L group than in the N and V groups. SIGNIFICANCE: Lactating female rats presented less intense allergic lung inflammation. Our findings suggest that lactation may protect females from asthmatic crises.
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Hipersensibilidade/imunologia , Inflamação/imunologia , Lactação/imunologia , Pulmão/imunologia , Administração por Inalação , Hidróxido de Alumínio/farmacologia , Animais , Medula Óssea/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Catecolaminas/sangue , Corticosterona/sangue , Feminino , Interferon gama/metabolismo , Lactação/sangue , Contagem de Leucócitos , Pulmão/metabolismo , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Ratos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIMS: Prolactin is a major immunomodulator. The present study evaluated the effects of short-term hyperprolactinemia induced by domperidone before ovalbumin antigenic challenge on the lung's allergic inflammatory response. MAIN METHODS: To induce hyperprolactinemia, domperidone was injected in rats at a dose of 5.1mg·kg(-1) per day, i.p., for 5days from 10th to 14th day after OVA immunization. Total and differential leukocyte counts from bronchoalveolar lavage (BAL), femoral marrow lavage (FML), and blood were analyzed. The percentages of mucus and collagen production were evaluated. Levels of corticosterone and prolactin in serum, interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor α (TNF-α) in lung explants supernatants were measured and interferon gamma (IFN-γ) in bronchiolar lavage cells suspensions (BAL) was measured. KEY FINDINGS: The rats that were subjected to short-term hyperprolactinemia exhibited a decrease in leukocyte counts in bronchoalveolar lavage, cellularity decrease in femoral marrow lavage fluid, a lower percentage of mucus, and an increase in lung IL-4, IL-6, IL-10, TNF-α and IFN-γ expression. SIGNIFICANCE: Hyperprolactinemia induced before antigenic challenge decreased allergic lung inflammation. These data suggest that prolactin may play a role in the pathophysiology of asthma. The present study demonstrates a prospective beneficial side effect of domperidone for asthmatic patients.
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Asma/imunologia , Hiperprolactinemia/imunologia , Pulmão/imunologia , Animais , Asma/sangue , Asma/induzido quimicamente , Asma/patologia , Citocinas/sangue , Citocinas/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperprolactinemia/sangue , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/patologia , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Prolactina/toxicidade , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: During migraine attacks, patients generally have photophobia and phonophobia and seek for environments with less sensorial stimulation. Present work aimed to quantify cortical partial directed coherence (PDC) of electroencephalographic (EEG) recordings from migraine patients and controls in occipital, parietal, and frontal areas with or without photic stimulation. Our hypothesis is that migraine patients with visual aura might have neuronal networks with higher coherence than controls even in interictal periods due to a predisposition in sensory cortical processing. METHODS: Eleven adult women with migraine with visual aura (at least 48 h without previous attacks) and seven healthy adult woman were submitted to EEG recording in basal state and during photic stimulation. RESULTS: When compared to healthy volunteers, migraine patients show different coherence profiles. Migraine patients had greater coherence than controls during the basal period (without photic stimulation), showing predisposition for sensory processing in many frequency ranges. After photic stimulation, patients showed a decrease in cortical coherence while controls had an increase. CONCLUSIONS: When compared to healty subjects, migraineurs show increased cortical coherence before photic stimulation, but a decrease when stimulation starts. This may be the expression of a resilience mechanism that allows migraineurs the interictal period. The PDC analysis permits to address a patient coherence profile, or "coherence map," that can be utilized for management of the headache disorder or following up treatments.
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The aim of the present study was to evaluate whether neonatal exposure to lipopolysaccharide (LPS; 50 µg/kg, i.p., on postnatal day 2) induces depressive- and/or anxiety-like effects and sexually dimorphic responses in rats challenged with LPS (100 µg/kg, i.p.) in adulthood. The results revealed that males presented a less depressive state in the forced swim test and exhibited no changes in general motor activity in the open field test. Females exhibited an increase in sickness behavior, revealing different behavioral strategies in response to a bacterial disease. The male rats also exhibited higher cell proliferation, reflected by bone marrow and peripheral blood counts, and female rats exhibited a decrease in corticosterone levels. No changes were observed in the elevated plus maze or peripheral cytokine levels (interleukin-1β and tumor necrosis factor-α). Neonatal exposure to LPS induced sexually dimorphic behavioral, neuroendocrine, and immune effects after an LPS challenge in adulthood, differentially affecting male and female susceptibility to disease later in life...