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1.
Talanta ; 206: 120236, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514837

RESUMO

This work presents a reliable analytical procedure combining micro-extraction by packed sorbent (MEPS) and ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry to determine 8-iso prostaglandin F2α, 8-iso prostaglandin E2 and prostaglandin E2 in dried blood spots (DBSs). To reach this goal, we optimized a fast semi-automated MEPS procedure for the clean-up and pre-concentration of the analytes extracted from a single DBS (50 µL) by a 70:30 v/v methanol:water mixture. Limits of detection of about 20 pg mL-1, satisfactory recoveries (90-110%) and very good intra- and inter-day precisions (RSD ≤10%) were obtained for all the analytes. The innovative addition of internal standards on the filter paper before DBS sampling allowed to compensate changes in the amount of analyte during storage. Since prostanoids and isoprostanoids are biomarkers involved in the pathogenesis and progression of many diseases (e.g. ductal patency, diabetic nephropathy, and acute lung injury), our analytical method offers interesting diagnostic and prognostic opportunities in the medical field. The present method is currently used for the analysis of such biomarkers in DBSs from preterm newborns collected in the clinical setting.


Assuntos
Dinoprosta/análogos & derivados , Dinoprostona/análogos & derivados , Dinoprostona/sangue , Teste em Amostras de Sangue Seco/métodos , Isoprostanos/sangue , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Dinoprosta/sangue , Humanos , Recém-Nascido , Limite de Detecção , Microextração em Fase Sólida/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
2.
BMC Vet Res ; 15(1): 349, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623621

RESUMO

BACKGROUND: NSAIDs are accepted as the most predictably efficacious medical treatment of the clinical signs of osteoarthritis (OA). The marine-based fatty-acid compound PCSO-524 has been proposed as an adjunctive treatment for canine OA, however benefits of this agent is still controversial. The purpose of this study was to evaluate and compare the effectiveness of PCSO-524 combined with the NSAID firocoxib using force plate gait analysis, orthopedic assessment score (OAS) and canine brief pain inventory score (CBPI) in dogs with OA. A prospective, randomized, double-blinded study was conducted. Seventy-nine dogs that had hip and/or stifle OA were assigned randomly into three treatment groups: firocoxib, PCSO-524 and combination of firocoxib and PCSO-524, orally for 4 weeks. Peak vertical force (PVF, expressed as a percentage of bodyweight), OAS, CBPI, serum prostaglandin E2 concentration, hematology and blood chemistry values were evaluated before treatment (Day0), as well as at the second (Day14) and fourth week (Day28) during treatment. RESULTS: Within group analysis revealed significant increases in PVF over the 4-week treatment period for firocoxib, PCSO-524 and the combination (p < 0.05). Mean increases in PVF were 3.25 ± 4.13, 2.01 ± 3.86, 4.11 ± 4.69%BW (mean ± SD) respectively. The OAS showed non-significant change in all treatment groups. There were significant decreases in CBPI pain severity score (PSS) and CBPI pain interference scores (PIS) within some groups over time, however no significant differences were found between the groups. Significantly decreased serum PGE2 concentration (p < 0.05) was found in the combination group. Significant increases in BUN and creatinine (p < 0.05) compared to pre-treatment values were found in the firocoxib and combination groups but not in the PCSO-524 group at day28, but all values in all dogs remained within the normal ranges. CONCLUSIONS: The results of this study suggested combination of both PCSO-524 and firocoxib is more effective in alleviation of inflammation and improvement of weight bearing ability when compared to the uses of either PCSO-524 or firocoxib alone. Further clinical studies are needed to confirm this, and to determine if there is any benefit of PCSO-524 over placebo.


Assuntos
4-Butirolactona/análogos & derivados , Anti-Inflamatórios não Esteroides/uso terapêutico , Doenças do Cão/tratamento farmacológico , Ácidos Graxos Insaturados/uso terapêutico , Osteoartrite/veterinária , Sulfonas/uso terapêutico , 4-Butirolactona/uso terapêutico , Animais , Dinoprostona/sangue , Cães , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Marcha/efeitos dos fármacos , Masculino , Osteoartrite/complicações , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Dor/etiologia , Dor/veterinária , Medição da Dor/veterinária , Estudos Prospectivos
3.
Int J Mol Sci ; 20(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600911

RESUMO

BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.


Assuntos
Caquexia/etiologia , Dieta , Óleos de Peixe/farmacologia , Hipercalcemia/metabolismo , Leucina/farmacologia , Neoplasias/complicações , Animais , Caquexia/metabolismo , Caquexia/patologia , Cálcio/metabolismo , Dinoprostona/sangue , Dinoprostona/metabolismo , Modelos Animais de Doenças , Hipercalcemia/tratamento farmacológico , Hipercalcemia/etiologia , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Neoplasias/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/sangue , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo
4.
Biomed Pharmacother ; 118: 109347, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545273

RESUMO

λ-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, antitumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE2 signal pathway. BA pretreatment significantly reduced the inflammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1α, IL-1ß, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE2 in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE2 signaling pathway activation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Extremidades/patologia , Triterpenos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Carragenina , Ciclo-Oxigenase 2/metabolismo , Citocinas/sangue , Dinoprostona/sangue , Edema/sangue , Edema/induzido quimicamente , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Triterpenos/farmacologia
5.
J Therm Biol ; 84: 36-44, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31466775

RESUMO

It is still an open question as to whether or not aseptic injuries affect the generation of fever due to exogenous pyrogens including bacterial products. Therefore, in the present paper we have investigated the course of endotoxin fever in rats induced with lipopolysaccharide (LPS; given intraperitoneally in a dose of 50 µg/kg) 48 h after subcutaneous administration of turpentine oil (TRP; 0.1 mL per rat) that causes aseptic necrosis of tissues. We found that febrile response was significantly augmented in the animals pre-treated with turpentine compared to control rats (pre-treated with saline), and that observed excessive elevation of body temperature (Tb) was accompanied by enhanced release of fever mediators: interleukin-6 (IL-6) and prostaglandin E2 (PGE2) into plasma. Moreover, we found that sensitization to pyrogenic effects of lipopolysaccharide was associated with the increase in plasma level of high mobility group box 1 protein (HMGB1), one of the best-known damage-associated molecular patterns (DAMP), which was recently discovered as inflammatory mediator. Since the injection of anti-HMGB1 antibodies weakened observed hyperpyrexia in the animals pre-treated with turpentine, we conclude that HMGB1 is a plasma-derived factor released in the course of aseptic injury that enhances pyrogenic effects of LPS.


Assuntos
Febre/sangue , Proteína HMGB1/sangue , Animais , Dinoprostona/sangue , Febre/induzido quimicamente , Membro Posterior/patologia , Interleucina-6/sangue , Lipopolissacarídeos , Masculino , Necrose , Pirogênios , Ratos Wistar , Terebintina/farmacologia
6.
Int J Mol Sci ; 20(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323789

RESUMO

The ginseng berry contains a variety of biologically active compounds and has a higher ginsenoside content than its roots. This study focused on the hepatoprotective activity of ginseng berry extract prepared by enzyme treatment (EGB) compared to the non-enzyme-treated ginseng berry extract (GB) and quality control of EGB. The feeding effect of EGB on alcohol-induced liver damage (AILD) was investigated by measuring the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with those of EtOH-fed mice. Furthermore, cytokine levels in the culture supernatants of EGB- or GB-treated RAW 264.7 cells were determined by enzyme-linked immunosorbent assay. The developed method was applied to the simultaneous quantification of four major ginsenosides in EGB using UPLC-QTOF/MS. Treatment with EGB at a dose of 0.5 or 1 mg/mouse significantly suppressed the AST and ALT levels in mice with AILD. Enzyme-treated ginseng berry was also found to suppress the production of inflammatory mediators like nitric oxide (NO), tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, showing higher activity than that of GB. The amount of ginsenoside Re, F5, F3, and Rd in the EGB obtained using UPLC-QTOF/MS was 45.9, 3.3, 4.0, and 6.2 mg/g, respectively. These results suggest that EGB has a potential effect on AILD, and its hepatoprotective effect provides beneficial insights into developing new candidates for the prevention and cure of AILD. Also, this study demonstrated the utility of UPLC-QTOF/MS-based major compounds for quality control (QC) of EGB.


Assuntos
Anti-Inflamatórios/uso terapêutico , Frutas/química , Fígado/efeitos dos fármacos , Panax/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Dinoprostona/sangue , Ginsenosídeos/química , Ginsenosídeos/uso terapêutico , Interleucina-6/sangue , Lipopolissacarídeos/toxicidade , Fígado/lesões , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa
7.
J Vet Pharmacol Ther ; 42(5): 572-579, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31353535

RESUMO

The aim of this study was to determine the pharmacokinetics and prostaglandin E2 (PGE2 ) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight, adult, female, Huacaya alpacas. A dose of 2.2 mg/kg administered IV and 3.3 mg/kg administered TD using a cross-over design. Plasma flunixin concentrations were measured by LC-MS/MS. Prostaglandin E2 concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE2 concentrations decreased after IV flunixin meglumine administration but there was minimal change after TD application. Mean t1/2 λz after IV administration was 4.531 hr (range 3.355 to 5.571 hr) resulting from a mean Vz of 570.6 ml/kg (range, 387.3 to 1,142 ml/kg) and plasma clearance of 87.26 ml kg-1  hr-1 (range, 55.45-179.3 ml kg-1  hr-1 ). The mean Cmax, Tmax and t1/2 λz for flunixin following TD administration were 106.4 ng/ml (range, 56.98 to 168.6 ng/ml), 13.57 hr (range, 6.000-34.00 hr) and 24.06 hr (18.63 to 39.5 hr), respectively. The mean bioavailability for TD flunixin was calculated as 25.05%. The mean 80% inhibitory concentration (IC80 ) of PGE2 by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE2 identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.


Assuntos
Camelídeos Americanos/sangue , Clonixina/análogos & derivados , Administração Cutânea , Administração Intravenosa , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Área Sob a Curva , Clonixina/administração & dosagem , Clonixina/sangue , Clonixina/metabolismo , Clonixina/farmacocinética , Dinoprostona/sangue , Dinoprostona/metabolismo , Feminino , Meia-Vida
8.
Prostaglandins Other Lipid Mediat ; 143: 106343, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31195125

RESUMO

Prostaglandins (PGs) play a pivotal role in uterine reproductive process including maternal recognition of pregnancy, cell proliferation, and myometrium contractions in mammals. In this study, we investigated the immunolocalizations and expression levels of Prostaglandin E2 synthases cyclo-oxygenase (COX)-1 and COX-2, as well as one of PGE2 receptor subtypes 4 (EP4) in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus) during the breeding and non-breeding seasons. Histologically, the thickness of endometrium: myometrium ratio in the uteri of the breeding season was higher than that of the non-breeding season. The immunostainings of COX-1, COX-2 and EP4 were observed in stromal cells, glandular cells and myometrium cells in the breeding and non-breeding seasons. The protein and mRNA expression levels of COX-1, COX-2 and EP4 were higher in the uteri of the breeding season than those of in the non-breeding season. The mean mRNA levels of COX-1, COX-2 and EP4 were positively correlated with uterine weights. In addition, the PGE2 concentration of uterine tissues as well as plasma PGE2, 17ß-estradiol, progesterone, LH and FSH levels were also significantly higher in the breeding season compared to those of the non-breeding season. These results suggested that PGE2 might play an important autocrine or paracrine role in the regulation of seasonal changes in the uterine functions of the wild Daurian ground squirrels during the breeding and non-breeding seasons.


Assuntos
Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Regulação Enzimológica da Expressão Gênica , Receptores de Prostaglandina E Subtipo EP4/genética , Sciuridae/genética , Estações do Ano , Animais , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/sangue , Dinoprostona/metabolismo , Feminino , Tamanho do Órgão , Transporte Proteico , RNA Mensageiro/genética , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Sciuridae/anatomia & histologia , Útero/anatomia & histologia , Útero/citologia , Útero/metabolismo
9.
Int. j. morphol ; 37(2): 428-437, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002239

RESUMO

Oxidative stress and inflammation are the key players in the development of motor dysfunction post-spinal cord ischemic reperfusion injury (SC-IRI). This study investigated the protective effect of concomitant pre-administration of melatonin and alpha-tocopherol on the early complications (after 48 hours) of spinal cord IRI injury in rats. Melatonin or α-tocopherol were preadministered either individually or in combination for 2 weeks, then rats were exposed SC-IRI. Neurological examinations of the hind limbs and various biochemical markers of oxidative stress and inflammation in the SC tissue were assessed. Solely pre-administration of either melanin or α-tocopherol significantly but partially improved motor and sensory function of the hind limbs mediated by partial decreases in SC levels of MDA, AOPP and PGE2 levels and activities of SOD, partial significant decreases in plasma levels of total nitrate/nitrite and significant increases in AC activity of GSH-Px. However, combination therapy of both drugs resulted in the maximum improvements in all neurological assessments tested and biochemical endpoints. In conclusion, by their synergistic antioxidant and antiinflammatory actions, the combination therapy of melatonin and α-tocopherol alleviates SC-IRI induced paraplegia.


El estrés oxidativo y la inflamación son claves en el desarrollo de la disfunción motora posterior a lesión isquémica de la médula espinal (SC-IRI). Este estudio investigó acerca del efecto protector de la administración previa concomitante de la melatonina y alfa-tocoferol en las complicaciones tempranas (después de 48 horas) de la lesión de IRI de la médula espinal en ratas. La melatonina o el α-tocoferol se administraron individualmente o en combinación durante 2 semanas, luego las ratas fueron expuestas a SC-IRI. Se evaluaron los exámenes neurológicos de las miembros pélvicos y diversos marcadores bioquímicos de estrés oxidativo e inflamación en el tejido subcutáneo. Solo la administración previa de melatonina o α-tocoferol mejoró parcial y significativamente la función motora y sensorial de los miembros pélvicos mediadas por disminuciones parciales en los niveles de SC de los niveles de MDA, AOPP y PGE2 y las actividades de la SOD, disminuciones significativas parciales en los niveles plasmáticos del total nitrato / nitrito y aumentos significativos en la actividad de AC de GSH-Px. Sin embargo, se observaron los mejores resultados durante la combinación de ambos fármacos en todas las evaluaciones neurológicas y en los puntos finales bioquímicos. En conclusión, debido a sus acciones antioxidantes y antiinflamatorias sinérgicas, la terapia de melatonina y α-tocoferol alivia la paraplejía inducida por SC-IRI.


Assuntos
Animais , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia do Cordão Espinal/tratamento farmacológico , Melatonina/administração & dosagem , Antioxidantes/administração & dosagem , Paraplegia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Dinoprostona/sangue , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Tocoferóis/farmacologia , Melatonina/farmacologia , Nitritos/sangue , Antioxidantes/farmacologia
10.
J Trace Elem Med Biol ; 54: 134-141, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109603

RESUMO

BACKGROUND: Sodium para-aminosalicylic acid (PAS-Na), an anti-tuberculosis drug, has been demonstrated its function in facilitating the Mn elimination in manganism patients and Mn-exposed models in vivo and improving the symptoms of Mn poisoning. But whether it can improve the growth retardation and inflammatory responses induced by Mn have not been reported. OBJECTIVES: This study was designed to investigate the preventive effects of PAS-Na on the development of retardation and inflammatory responses in Mn-exposed rats. METHODS: Male Sprague Dawley (SD) rats (8 weeks old, weighing 180 ± 20 g) were randomly divided into normal control group and Mn-exposed group in the 4 weeks experiment observation and normal control group, Mn-exposed group, PAS-Na preventive group and PAS-Na control group in the 8 weeks experiment observation. The Mn-exposed group received an intraperitoneal injection (i.p.) of 15 mg/kg MnCl2 and the normal control group i.p. physiological Saline in the same volume once a day for 4 or 8 weeks, 5 days per week. The PAS-Na preventive group i.p. 15 mg/kg MnCl2 along with back subcutaneous (s.c.) injection of 240 mg/kg PAS-Na once a day for 8 weeks, 5 days per week. PAS-Na control group received s.c. injection of 240 mg/kg PAS-Na along with i.p. injection of saline once daily. The body weight was determined once a week until the end of the experiment. The manganese contents in the blood were detected by graphite furnace atomic absorption spectrometry. The inflammatory factor levels (TNF-α, IL-1ß, IL-6, and PGE2) in the blood were detected by using enzyme-linked immunosorbent assay (Elisa) and each organ taking from rats were weighed and recorded. RESULTS: Mn exposure significantly suppressed the growth in rats and increased heart, liver, spleen and kidney coefficients as compared with the control group. The whole blood Mn level and serum levels of IL-1ß, IL-6, PGE2, and TNF-α in sub-chronic Mn-exposure group were markedly higher than those in the control group. However, preventive treatment with PAS-Na obviously reduced the whole blood Mn level, the spleen and liver coefficients of the Mn-exposed rats. And serum levels of IL-1ß and TNF-α were significantly reduced by 33.9% and 14.7% respectively in PAS-Na prevention group. CONCLUSIONS: PAS-Na could improve the growth retardation and alleviate inflammatory responses in Mn-exposed rats.


Assuntos
Ácido Aminossalicílico/uso terapêutico , Manganês/efeitos adversos , Animais , Antituberculosos/uso terapêutico , Dinoprostona/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Intoxicação por Manganês/sangue , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
11.
Biomed Res Int ; 2019: 4605748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111054

RESUMO

Background and Aims: Hydrotalcite plays an important role in the therapy of gastric ulcer induced by nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about the mechanism. We designed two experiments to study the preventive and curative effects of hydrotalcite on NSAIDs-related gastric injury in rats and to investigate the relationship between the protective and curative mechanism of hydrotalcite and the secretion of epidermal growth factor (EGF)/prostaglandin E2 (PGE2). Methods: Two experiments were separately designed to evaluate the preventive and curative effects of hydrotalcite. A total of 25 male rats and 25 female rats were randomly divided into five groups (vehicle group, model group, omeprazole group, hydrotalcite group, and ranitidine group) in each experiment. Rats were treated with indomethacin by gavage to build the model of acute gastric mucosal injury. The concentrations of EGF and PGE2 in blood specimens and mucosal injury indexes by gross inspection were measured and an immunohistochemical technique was also employed to test the levels of EGF, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) in gastric mucosa. Results: Comparing with model group in both preventive and curative experiments, hydrotalcite decreased the gastric injury in the mucosa of stomach significantly (7±4.5 vs. 16±11.25, 1.5±2 vs. 2.5±6; P<0.01, P<0.05). The levels of EGF and PGE2 in blood serum were markedly higher in hydrotalcite group than that in model group and ranitidine group in preventive experiment (574.39±34.28 vs. 486.22±41.73, 488.07±24.44; P<0.01, P<0.01). The expression levels of COX-2 in gastric mucosa were also higher in hydrotalcite group than that in model group in both preventive and therapeutic experiments (12±4 vs. 9±6, 14±7 vs. 9±4; P<0.01, P<0.05). Conclusions: Hydrotalcite promotes gastric protection and healing via several mechanisms, including increased levels of PGE2 in blood serum, activation of EGF, and antagonising the inhibition of cyclooxygenase (COX) caused by NSAIDs.


Assuntos
Hidróxido de Alumínio/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Indometacina/efeitos adversos , Hidróxido de Magnésio/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/sangue , Dinoprostona/metabolismo , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/sangue , Fator de Crescimento Epidérmico/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Proteínas de Membrana/metabolismo , Omeprazol/farmacologia , Ranitidina/farmacologia , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Úlcera Gástrica/patologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-30731263

RESUMO

This paper reports an online SPE-LC-MS/MS method for the simultaneous quantification of prostaglandins (PGE2 and PGF2α) in menstrual fluid samples. To meet this goal human peripheral serum was used as surrogate matrix. The analytes were trapped on an OASIS HLB cartridge for 3 min, for sample cleanup and enrichment, and then transferred during only 42 s to an HSS T3 C18 analytical column, for separation and analysis. Prostaglandins (PGs) were detected by selected reaction monitoring in negative ion mode, PGE2 (m/z 351 → 315) and PGF2α (m/z 353 → 193) using isotope-labeled internal standard (PGE2-d4, m/z 355 → 319). The concentration linear range was of 10.34-1.034 ng mL-1 and the lower limit of quantification (LLOQ) was 10.34 ng mL-1 for both PGs. Validation parameters were successfully assessed according to the European Medicines Agency guideline (EMA), also comprising the FDA normative. The method showed no matrix effect and process efficiency around 100%, in addition to only 15 min of analysis time with lower solvent consumption. The method application was carried out using two menstrual fluid sample groups: control (n = 15) and treatment group (n = 7; samples from women that used Tahiti lemon juice). The PGF2α levels were found to be higher in treated group than in control group (p ≤ 0.05), denoting an effect of the intake of Tahiti lemon juice on the menstrual inflammatory process. The on-line method herein reported could be useful for the analysis of PGs from large research studies.


Assuntos
Cromatografia Líquida/métodos , Dinoprosta/sangue , Dinoprostona/sangue , Menstruação/sangue , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Dinoprosta/isolamento & purificação , Dinoprostona/isolamento & purificação , Feminino , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Adulto Jovem
13.
J Vet Pharmacol Ther ; 42(3): 309-317, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30802981

RESUMO

The aim of this study was to determine the pharmacokinetics and prostaglandin E2 (PGE2 ) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight adult female Boer goats. A dose of 2.2 mg/kg was administered intravenously (IV) and 3.3 mg/kg administered TD using a cross-over design. Plasma flunixin concentrations were measured by LC-MS/MS. Prostaglandin E2 concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE2 concentrations decreased after flunixin meglumine for both routes of administration. Mean λz -HL after IV administration was 6.032 hr (range 4.735-9.244 hr) resulting from a mean Vz of 584.1 ml/kg (range, 357.1-1,092 ml/kg) and plasma clearance of 67.11 ml kg-1  hr-1 (range, 45.57-82.35 ml kg-1  hr-1 ). The mean Cmax , Tmax, and λz -HL for flunixin following TD administration was 0.134 µg/ml (range, 0.050-0.188 µg/ml), 11.41 hr (range, 6.00-36.00 hr), and 43.12 hr (15.98-62.49 hr), respectively. The mean bioavailability for TD flunixin was calculated as 24.76%. The mean 80% inhibitory concentration (IC80 ) of PGE2 by flunixin meglumine was 0.28 µg/ml (range, 0.08-0.69 µg/ml) and was only achieved with IV formulation of flunixin in this study. The PK results support clinical studies to examine the efficacy of TD flunixin in goats. Determining the systemic effects of flunixin-mediated PGE2 suppression in goats is also warranted.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Clonixina/análogos & derivados , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacologia , Clonixina/sangue , Clonixina/farmacocinética , Clonixina/farmacologia , Estudos Cross-Over , Dinoprostona/sangue , Feminino , Cabras/sangue , Injeções Intravenosas/veterinária , Distribuição Aleatória
14.
Lasers Med Sci ; 34(2): 255-262, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29992491

RESUMO

Physical exercise generates several benefits in a short time in patients with diabetes mellitus. However, it can increase the chances of muscle damage, a serious problem for diabetic patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat these injuries, despite the serious adverse effects. In this way, photobiomodulation therapy (PBMT) with low-level laser therapy (LLLT) and/or light emitting diode therapy (LEDT) can be used as an alternative in this case. However, its efficacy in tissue repair of trauma injuries in diabetes mellitus until now is unknown, as well as the combination between PBMT and NSAIDs. The objective of the present study was to evaluate the effects of NSAIDs and PBMT applied alone or combined on functional and biochemical aspects, in an experimental model of muscle injury through controlled trauma in diabetic rats. Muscle injury was induced by means of a single trauma to the animals' anterior tibialis muscle. After 1 h, the rats were treated with PBMT (830 nm; continuous mode, with a power output of 100 mW; 3.57 W/cm2; 3 J; 107.1 J/cm2, 30 s), diclofenac sodium for topical use (1 g), or combination of them. Our results demonstrated that PBMT + diclofenac, and PBMT alone reduced the gene expression of cyclooxygenase-2 (COX-2) at all assessed times as compared to the injury and diclofenac groups (p < 0.05 and p < 0.01 respectively). The diclofenac alone showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). Prostaglandin E2 levels in blood plasma demonstrated similar results to COX2. In addition, we observed that PBMT + diclofenac and PBMT alone showed significant improvement compared with injury and diclofenac groups in functional analysis at all time points. The results indicate that PBMT alone or in combination with diclofenac reduces levels of inflammatory markers and improves gait of diabetic rats in the acute phase of muscle injury.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/radioterapia , Diclofenaco/administração & dosagem , Diclofenaco/uso terapêutico , Terapia com Luz de Baixa Intensidade , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Administração Tópica , Animais , Terapia Combinada , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Dinoprostona/sangue , Regulação da Expressão Gênica , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/efeitos da radiação , Ratos Wistar
15.
Acta Cir Bras ; 33(11): 945-953, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30517321

RESUMO

PURPOSE: To investigate the effect of oxymatrine on periodontitis in rats and related mechanism. Methods: Ninety SD rats were divided into control, model, 10, 20 and 40 mg/kg oxymatrine and tinidazole groups. The periodontitis model was established in later 5 groups. The 10, 20 and 40 mg/kg oxymatrine groups were intragastrically administrated with 10, 20 and 40 mg/kg oxymatrine, respectively. The tinidazole group was intragastrically administrated with 100 mg/kg tinidazole. The treatment duration was 4 weeks. The tooth mobility, gingival and plaque indexes, serum inflammatory factor levels and gingival tissue matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) protein levels were detected. Results: After treatment, compared with model group, in 40 mg/kg oxymatrine group the rat general conditions were obviously improved, the tooth mobility, gingival index and plaque index were significantly decreased (P<0.05), the serum tumor necrosis factor-α, interleukin-1ß and prostaglandin E2 levels were significantly decreased (P<0.05), the MMP-2 and MMP-9 protein levels were significantly decreased (P<0.05), and the TIMP-2 protein level was significantly increased (P<0.05). Conclusions: Oxymatrine can alleviate the experimental periodontitis in rats. The mechanism may be related to its inhibiting inflammatory factor secretion and regulating MMPs/TIMP protein expression.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Metaloproteinases da Matriz/efeitos dos fármacos , Periodontite/tratamento farmacológico , Quinolizinas/farmacologia , Inibidores Teciduais de Metaloproteinases/efeitos dos fármacos , Animais , Índice de Placa Dentária , Dinoprostona/sangue , Feminino , Gengiva/patologia , Interleucina-1beta/sangue , Masculino , Metaloproteinases da Matriz/análise , Periodontite/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Tinidazol , Inibidores Teciduais de Metaloproteinases/análise , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
16.
Handb Clin Neurol ; 157: 565-597, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30459026

RESUMO

Systemic inflammation-associated syndromes (e.g., sepsis and septic shock) often have high mortality and remain a challenge in emergency medicine. Systemic inflammation is usually accompanied by changes in body temperature: fever or hypothermia. In animal studies, systemic inflammation is often modeled by administering bacterial lipopolysaccharide, which triggers autonomic and behavioral thermoeffector responses and causes either fever or hypothermia, depending on the dose and ambient temperature. Fever and hypothermia are regulated changes of body temperature, which correspond to mild and severe forms of systemic inflammation, respectively. Mediators of fever and hypothermia are called endogenous pyrogens and cryogens; they are produced when the innate immune system recognizes an infectious pathogen. Upon an inflammatory challenge, hepatic and pulmonary macrophages (and later brain endothelial cells) start to release lipid mediators, of which prostaglandin (PG) E2 plays the key role, and cytokines. Blood PGE2 enters the brain and triggers fever. At later stages of fever, PGE2 synthesized within the blood-brain barrier maintains fever. In both cases, PGE2 is synthesized by cyclooxygenase-2 and microsomal PGE2synthase-1. Mediators of hypothermia are not well established. Both fever and hypothermia are beneficial host defense responses. Based on evidence from studies in laboratory animals and clinical trials in humans, fever is beneficial for fighting mild infection. Based mainly on animal studies, hypothermia is beneficial in severe systemic inflammation and infection.


Assuntos
Febre/complicações , Hipotermia/complicações , Síndrome de Resposta Inflamatória Sistêmica/complicações , Animais , Regulação da Temperatura Corporal , Dinoprostona/sangue , Humanos , Fígado/patologia , Macrófagos/patologia
17.
J Am Chem Soc ; 140(51): 18132-18139, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30495929

RESUMO

Small-molecule detection is important for many applications including clinical diagnostics, drug discovery, and measurements of environmental samples and agricultural products. Current techniques for small-molecule detection suffer from various limitations including low analytical sensitivity and complex sample processing. Furthermore, as a result of their small size, small molecules are difficult to detect using an antibody pair in a traditional sandwich assay format. To overcome these limitations, we developed an ultrasensitive competitive immunoassay for small-molecule detection using Single Molecule Arrays (Simoa). We show that the competitive Simoa assay is approximately 50-fold more sensitive than the conventional ELISA. We performed theoretical calculations to determine the factors that influence the sensitivity of competitive Simoa assays and used them to achieve maximal sensitivity. We also demonstrate detection of small molecules in complex biological samples. We show that the competitive Simoa assay is a simple, fast, and highly sensitive approach for ultrasensitive detection of small molecules.


Assuntos
Dinoprostona/sangue , Hidrocortisona/sangue , Animais , Anticorpos/imunologia , Bovinos , Dinoprostona/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Hidrocortisona/imunologia , Imunoensaio/métodos , Fenômenos Magnéticos , Modelos Químicos , Saliva/química , Soroalbumina Bovina/química , beta-Galactosidase/química
18.
Medicine (Baltimore) ; 97(37): e12206, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30212951

RESUMO

The aim of this study was to investigate the effects of prophylactic oral ibuprofen on the closure rate of patent ductus arteriosus (PDA).This was a retrospective study and data on infants born before 36 weeks were collected. The prophylactic group was treated with ibuprofen (10, 5, and 5 mg/kg) from days 1 to 3 after birth, respectively. The conventional group was treated with the same dose of ibuprofen from days 4 to 6 once they were echocardiographically confirmed with PDA on day 3 after birth. The placebo group was treated with 5% glucose.The closure rate of PDA in the prophylactic group significantly increased on day 7 compared with the placebo group (P = .02), but showed no difference compared with the conventional group (P = .12). Serum NT-proBNP in the prophylactic and conventional groups decreased compared with the placebo group (P = .03 vs P = .07).Prophylactic oral ibuprofen can increase the closure rate of PDA in premature infants; however, it showed no significant advantages compared with conventional treatment. Serum NT-proBNP can be used to observe PDA treatment responses in premature infants.


Assuntos
Permeabilidade do Canal Arterial/tratamento farmacológico , Ibuprofeno/uso terapêutico , Recém-Nascido Prematuro , Dinoprostona/sangue , Ecocardiografia , Eletrocardiografia , Feminino , Idade Gestacional , Humanos , Ibuprofeno/administração & dosagem , Ibuprofeno/efeitos adversos , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Retrospectivos
19.
Clin Lab ; 64(7): 1213-1216, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30146838

RESUMO

BACKGROUND: This study explores the role of prostaglandin E2 (PGE2) in the etiology of urolithiasis in acute renal colic by analyzing the PGE2 levels in blood and urine throughout the clinical course of renal colic. METHODS: From June 2015 to November 2017, a total of 60 patients with acute renal colic were enrolled in the study. Blood and urine samples were taken before and after administration of drug to inhibit prostaglandin synthesis; further blood and urine samples were obtained from the patients 2 weeks after their recovery. The concentration of PGE2 in blood and urine samples was determined by using a Human Prostaglandin E2 ELISA Kit. RESULTS: The mean concentration of PGE2 was 420 ± 50.3 ng/L in blood and 600 ± 70.1 ng/L in urine when the patients had renal colic. After drug therapy, these concentrations fell to 300 ± 40.4 ng/L in blood and 500 ± 54.5 ng/L in urine. After 2 weeks the PGE2 concentration was 220 ± 47.5 ng/L and 300 ± 50.2 ng/L in blood and urine, respectively. Compared with PGE2 levels after medication, these concentrations were significantly higher during acute renal colic (p < 0.05). CONCLUSIONS: The synthesis and release of PGE2 increase at the onset of renal colic, suggesting that PGE2 plays an important role in acute renal colic. Administration of a prostaglandin synthesis inhibitor is a reliable way to treat renal colic.


Assuntos
Dinoprostona/sangue , Dinoprostona/urina , Cetorolaco de Trometamina/uso terapêutico , Cólica Renal/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Dinoprostona/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cólica Renal/patologia , Resultado do Tratamento , Adulto Jovem
20.
Infect Dis Obstet Gynecol ; 2018: 7027683, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30154640

RESUMO

Periodontal disease is an infection that, in pregnant women, can act as a risk factor for preterm delivery by increasing local and systemic inflammatory responses. Objective. To analyze the presence of periodontal disease, proinflammatory cytokines, and prostaglandin E 2 (PGE2) in pregnant patients at high risk for preterm delivery. Materials and Methods. Pilot study for a case-control study. We included 46 pregnant patients (23 patients at risk of preterm delivery as cases and 23 patients without risk of preterm delivery as controls). We excluded patients who received periodontal treatment, antibiotics, or antimicrobials over the last 3 months as well as those with infections or diseases such as diabetes or hypercholesterolemia. The patients underwent a periodontal assessment, and their levels of cytokines (interleukin- [IL-] 2, IL-6, IL-10, and tumor necrosis factor- [TNF-] α) and prostaglandin E2 (PGE2) were quantified. Results. Patients with periodontal disease showed higher levels of cytokines (IL-2, IL-6, IL-10, and TNF-α) and PGE 2 . Patients at high risk for preterm birth showed higher IL levels compared with patients at low risk for preterm delivery. PGE 2 increased with the severity of periodontal disease. PGE 2 was higher in patients at low risk for preterm delivery, although this difference was not significant. Conclusion. Periodontal disease can increase the systemic inflammatory response as well as the levels of PGE 2 and inflammatory cytokines in pregnant patients.


Assuntos
Citocinas/sangue , Dinoprostona/sangue , Doenças Periodontais/sangue , Nascimento Prematuro/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Doenças Periodontais/complicações , Projetos Piloto , Gravidez , Nascimento Prematuro/etiologia , Índice de Gravidade de Doença , Adulto Jovem
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