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1.
Life Sci ; 242: 117185, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862453

RESUMO

Colorectal cancer (CRC) is a multifactorial syndrome that drives to uncontrollable cell division, genetic alterations, and functional alteration. In the present work, we evaluated the immunomodulatory properties of P-mapa, a compound extracted from Aspergillus oryzae fungus, versus Fluorouracil (5-FU) treatment in chemically induced CRC. CRC was induced by DMH in F344 rats. Animals of treated groups receive weekly 15 mg/Kg of 5-FU or 5 mg/Kg of P-mapa, over 10 weeks. Tissues were stained for aberrant crypt foci (ACF) counting and histopathology evaluation, immunostained for TLR4 pathways and quantified for TNFα Cytokine assay. DMH was efficient to induce hyperplastic lesions and ACF. Both treatments reduced significantly ACF formation and tumor aggressiveness. Immunohistochemistry for TLR4 signaling reveals that both treatments had no effect over the TLR4-NFκB signaling pathway. On the other hand, both succeed in increase interferon signaling, with activation of the TRIF-IRF3 pathway and consequently inducing IFNγ synthesis. The present results show the immunomodulatory properties of P-mapa in chemically induced CRC model. P-mapa induced a significant increase in Type-I IFNs synthesis and subsequently immune cell recruitment, resulting in an increase of IFNγ concentration in colorectal mucosa and its inhibitory effects over tumoral growth. In this scenario, P-mapa showed an interesting antitumoral effect by inhibiting tumor growth.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Ácidos Linoleicos/uso terapêutico , Ácidos Oleicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Focos de Criptas Aberrantes/patologia , Animais , Biopolímeros/uso terapêutico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ensaio de Imunoadsorção Enzimática , Fluoruracila/uso terapêutico , Masculino , Ratos , Ratos Endogâmicos F344 , Fator de Necrose Tumoral alfa/metabolismo
2.
J Craniofac Surg ; 30(8): e796-e799, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403517

RESUMO

Vascular malformations (VMs) are benign lesions of blood vessels originated from an error in vascular morphogenesis during the embryologic phase. Generally, when located in the head and neck region VMs occurs in lips, tongue, buccal mucosa, gums, or palate. The VMs are usually asymptomatic, varies in size and may cause facial asymmetries. Different therapeutic modalities are available to treat VMs, which include surgical excision, cautery, cryotherapy, laser therapy, and sclerosing agents. The authors report 2 patients with extensive VM in the tongue treated with intralesional injection of a low-dose solution of monoethanolamine oleate (MO) and lidocaine. The first patient was a 69-year-old male patient and the 2nd a 65-year-old woman. In both patients, it were performed weekly application of 1:1 MO (Ethamolin) with Lidocaine (lidocaine 3% 1:50,000) in the amount of 0.1 mL of the solution per cm3 of lesion, with a total of 12 applications for each patient at the end of the treatment, with good results and without complications. It is important to be alert in which situation sclerotherapy should be used and that small doses of the sclerotherapeutic agent is essential for the prevention of complications after the procedure. Therefore, these patients showed that the sclerotherapy with MO may be an effective and simple treatment for extensive oral benign vascular lesions. In both patients, there was a great improvement in the clinical aspect of the lesions and patient's satisfaction.


Assuntos
Lidocaína/uso terapêutico , Ácidos Oleicos/uso terapêutico , Soluções Esclerosantes/uso terapêutico , Doenças da Língua/tratamento farmacológico , Malformações Vasculares/tratamento farmacológico , Idoso , Feminino , Humanos , Injeções Intralesionais , Terapia a Laser , Lidocaína/administração & dosagem , Masculino , Ácidos Oleicos/administração & dosagem , Escleroterapia , Língua , Resultado do Tratamento
3.
Lipids Health Dis ; 18(1): 46, 2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30738430

RESUMO

BACKGROUND: Intake of trans fatty acids (TFAs) from partially hydrogenated vegetable oil is associated with a variety of adverse outcomes, but little is known about the health effects of ruminant trans fats. Trans-vaccenic acid (TVA) is a naturally occurring TFA found in the fat of ruminants and in human dairy products. The present study was conducted to investigate the anticancer activity and underlying mechanisms of TVA on human nasopharyngeal carcinoma (NPC) 5-8F and CNE-2 cells. METHODS: A CCK8 assay was used to determine the effect of TVA and the Mcl-1 inhibitor S63845 on the proliferation of NPC cells. Apoptosis was measured using flow cytometry. Western blotting was used to detect the protein expression levels of factors associated with Bcl-2-family protein signaling and Akt signaling. RESULTS: TVA significantly inhibited cell proliferation in a dose-dependent manner. Mechanistic investigation demonstrated that TVA significantly decreased p-Akt levels and Bad phosphorylation on Ser-136 and Ser-112. More importantly, we discovered that the Mcl-1 inhibitor S63845 synergistically sensitized NPC cells to apoptosis induction by TVA. CONCLUSION: TVA can inhibit NPC cell growth and induced apoptosis through the inhibition of Bad/Akt phosphorylation. The combined use of TVA and Mcl-1 inhibitors offers a potential advantage for nasopharyngeal cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias Nasofaríngeas/tratamento farmacológico , Ácidos Oleicos/uso terapêutico , Antineoplásicos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Ácidos Oleicos/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína de Morte Celular Associada a bcl/antagonistas & inibidores , Proteína de Morte Celular Associada a bcl/metabolismo
4.
EBioMedicine ; 41: 62-72, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30772307

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are reaching global epidemic proportions. Lack of non-invasive diagnostic tools and effective therapies constitute two of the major hurdles for a bona fide treatment and a reversal of NASH progression and/or regression of the disease. Nitro-oleic acid (OA-NO2) has been proven effective in multiple experimental models of inflammation and fibrosis. Thus, the potential benefit of in vivo administration of OA-NO2 to treat advanced NAFLD was tested herein in a model of long-term NASH diet-induced liver damage. METHODS: Non-invasive imaging (e.g. photoacustic-ultrasound (PA-US)) was pursued to establish advanced experimental model of NASH in mice in which both steatosis and fibrosis were diagnosed prior experimental therapy with OA-NO2. Experimental controls included equimolar amounts of the non-nitrated oleic acid (OA). CLAMS and NMR-based analysis was used for energy metabolism. FINDINGS: CLAMS and NMR-based analysis demonstrates that OA-NO2 improves body composition and energy metabolism and inhibits hepatic triglyceride (TG) accumulation. Photoacoustic-ultrasound imaging revealed a robust inhibition of liver steatosis and fibrosis by OA-NO2. RNA-sequencing analysis uncovered inflammation and fibrosis as major pathways suppressed by OA-NO2 administration, as well as regulation of lipogenesis and lipolysis pathways, with a robust inhibition of SREBP1 proteolytic activation and subsequent lipogenesis gene expression by OA-NO2. These results were further supported by histological analysis and quantification of lipid accumulation, lobular inflammation (F4/80 staining) and fibrosis (collagen deposition, αSMA staining) as well as established parameters of liver damage (ALT). In vitro studies indicate that OA-NO2 inhibits TG biosynthesis and accumulation in hepatocytes and inhibits fibrogenesis in human stellate cells. INTERPRETATION: OA-NO2 improve steatohepatitis and fibrosis and may constitute an effective therapeutic approach against advanced NAFLD that warrants further clinical evaluation.


Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ácidos Oleicos/uso terapêutico , Animais , Metabolismo Energético , Lipogênese , Fígado/diagnóstico por imagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Oleicos/administração & dosagem , Ácidos Oleicos/farmacologia , Proteólise , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismo
5.
Pharmacol Res ; 141: 530-540, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30660821

RESUMO

Glial activation and scar formation impede the neurological function recovery after cerebral ischemia. Oleoylethanolamide (OEA), a bioactive lipid mediator, shows neuroprotection against acute brain ischemia, however, its long-term effect, especially on glial scar formation, has not been characterized. In this research, we investigate the effect of OEA on glial activation and scar formation after cerebral ischemia in vitro and in vivo experiments. Glial scar formation in vitro model was induced by transforming growth factor ß1 (TGF-ß1) in C6 glial cell culture, and experiment model in vivo was induced by middle cerebral artery occlusion (MCAO) in mice. The protein expressions of the markers of glial activation (S100ß, GFAP, or pSmads) and glial scar (neurocan) were detected by Western blot and/or immunofluorescence staining; To evaluate the role of PPARɑ in the effect of OEA on glial activation, the PPARɑ antagonist GW6471 was used. Behavior tests were used to assay the effect of OEA on motor function recovery 14 days after brain ischemia in mice. Our results show that OEA (10-50 µM) concentration-dependently inhibited the upregulation of S100ß, GFAP, pSmads and neurocan induced by TGF-ß1 in C6 glial cells. At the same time, OEA promoted the protein expression and nuclear transportation of PPARɑ in glial cells. PPARα antagonist GW6471 abolished the effect of OEA on glial activation. In addition, we found that delay administration of OEA inhibited the astrocyte activation and promoted the recovery of motor function after brain ischemia in mice. These results indicate that OEA may be developed into a new candidate for attenuating astrocytic scar formation and improving motor function after ischemic stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Endocanabinoides/uso terapêutico , Neuroglia/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Ácidos Oleicos/uso terapêutico , PPAR alfa/metabolismo , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Linhagem Celular , Endocanabinoides/farmacologia , Força da Mão , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Camundongos , Neuroglia/metabolismo , Neuroglia/patologia , Fármacos Neuroprotetores/farmacologia , Ácidos Oleicos/farmacologia , Ratos , Recuperação de Função Fisiológica , Caminhada
6.
J Gastroenterol Hepatol ; 34(3): 495-500, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30170340

RESUMO

Gastric varices (GVs) are a major complication of portal hypertension in patients with liver cirrhosis. The mortality rate associated with the bleeding from GVs is not low. Balloon-occluded retrograde transvenous obliteration (BRTO) was first introduced by Kanagawa et al. as a treatment for isolated GVs in 1994. It has been performed most frequently in Asia, especially in Japan. Ethanolamine oleate was the original sclerosant used in the therapy. Since the late 2000s, BRTO using sodium tetradecyl sulfate foam or polidocanol foam as a sclerosant has been performed in many countries other than Japan. Then, early in the 2010s, modified BRTO techniques including vascular plug-assisted retrograde transvenous obliteration and coil-assisted retrograde transvenous obliteration were developed as an alternative treatment for GVs. This article provides a historical overview of BRTO using various sclerosants and modified BRTO techniques, such as plug-assisted retrograde transvenous obliteration and coil-assisted retrograde transvenous obliteration.


Assuntos
Oclusão com Balão/métodos , Varizes Esofágicas e Gástricas/terapia , Oclusão com Balão/tendências , Varizes Esofágicas e Gástricas/etiologia , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Ácidos Oleicos/uso terapêutico , Polidocanol/uso terapêutico , Soluções Esclerosantes/uso terapêutico , Tetradecilsulfato de Sódio/uso terapêutico
7.
J Craniomaxillofac Surg ; 47(1): 106-111, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30527382

RESUMO

PURPOSE: To describe the effectiveness and safety of a sclerotherapy protocol with 5% ethanolamine oleate (EO) at 0.1 mL/3 mm for oral vascular anomalies (OVAs). Our hypothesis is that EO applied at a concentration of 5% may decrease the number of sessions necessary for clinical healing. MATERIALS AND METHODS: We describe a cohort of 15 consecutive patients. OVAs <20 mm were included. Clinical data of the OVAs were collected. Descriptive and bivariate statistical analyses were performed. RESULTS: Fifteen of the 19 OVAs were varicosities and the lower lip was the most affected site (n = 7). The median size was 6 mm, and one session was required in 89.5% of cases for clinical healing within 28 days. The pain/burning score was low (<2) for most lesions (63.1%) and the degree of satisfaction was high (>8) for all OVAs. The number of applications, final volume of drug and time to resolution differed significantly according to the size of the anomaly. CONCLUSION: The protocol with 5% EO was shown to be effective and safe to treat OVAs <20 mm, and with a decrease in the number of sessions, volume and time to resolution, without complications and with high patient satisfaction.


Assuntos
Malformações Arteriovenosas/terapia , Ácidos Oleicos/administração & dosagem , Ácidos Oleicos/uso terapêutico , Escleroterapia/métodos , Varizes/terapia , Doenças Vasculares/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Lábio , Masculino , Pessoa de Meia-Idade , Soluções Esclerosantes/uso terapêutico , Resultado do Tratamento
8.
Crit Rev Food Sci Nutr ; 59(11): 1802-1815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29341787

RESUMO

Early life nutritional exposures could modify the gene expression and susceptibility of allergic diseases (AD). This systematic review aimed to evaluate whether early life (the first 1,000 days) natural exposure to polyunsaturated fatty acids (PUFA) and ruminant trans fatty acids (R-TFA) could affect the AD risk. We searched PubMed, EMBASE, PsycINFO, Scopus, the Cochrane Library, and ClinicalTrials.gov from inception through September 10, 2017 for relevant full-text articles in English. Observational studies were selected if they examined the effects of early life PUFA or R-TFA on AD (eczema, asthma, wheeze, and allergic rhinitis) or sensitization. The quality of studies was examined by the Newcastle-Ottawa Scale, and the best evidence synthesis (BES) was applied. We included 26 observational studies, and 8 of them showed high quality. BES showed a moderate evidence for the protective effect of vaccenic acid (VA, an R-TFA) on eczema, while insufficient or no evidence was found in other associations. Meta-analysis showed that higher n-6/n-3 ratio and linoleic acid were associated with higher risk of eczema (pooled odds ratio [OR] = 1.06, 95% confidence intervals [CI]: 1.00 -1.13; 1.08, 95% CI: 1.01 -1.15). However, VA was inversely associated with eczema pooled OR = 0.42, 95% CI: 0.25 -0.72). Early life natural exposure to VA showed evident benefit on decreasing the risk of eczema, while PUFA and other R-TFA showed limited effects on AD. More robust studies especially for R-TFA are required.


Assuntos
Ácidos Graxos Insaturados/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Ácidos Graxos Trans/uso terapêutico , Animais , Asma , Bases de Dados Factuais , Eczema , Humanos , Ácidos Oleicos/uso terapêutico , Rinite Alérgica , Ruminantes
9.
Biochem Pharmacol ; 157: 235-243, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195735

RESUMO

Recent studies have demonstrated the utility of drugs modulating the endogenous cannabinoid system to control excessive alcohol intake. Among them, drugs interacting with acylethanolamide receptors including cannabinoid CB1 receptor antagonists/inverse agonists, peroxisome proliferator-activated receptor alpha (PPARα) agonists or peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated utility in the reduction of alcohol intake in animal models. However, few studies have addressed the potential utility of combining these classes of drugs, especially because of expected safety problems. In the present work we took the advantage of the availability of two novel dual ligands for these receptors, to test the hypothesis that these types of drugs might reproduce and even improve the pharmacological profile of those drugs interacting with single targets. To this end we tested (R)-3-[(4-Benzyl-2-oxooxazolidin-3-yl)methyl]-N-[4-(dodecylcarbamoyl)phenyl]benzamide (NF 10-360), a dual PPARα/γ agonist, and N-[1-(3,4-dihydroxyphenyl)propan-2-yl]oleamide (OLHHA), a dual CB1 receptor antagonist/PPARα agonist, in animal models of alcohol consumption. Both drugs were effective in reducing alcohol intake and alcohol self-administration, being OLHHA a very potent alcohol intake inhibitor (EC50 0.2 mg/kg). OLHHA also reduced self-administration of the opioid oxycodone. OLHHA actions on alcohol self-administration were replicated in alcohol-preferring Marchigian-Sardinian msP rats. Repeated administration of OLHHA did result neither in tolerance nor in toxicological or deleterious metabolic changes in the liver of msP rats. These data support the feasibility of developing novel dual ligands interacting with cannabinoid targets to treat alcohol use disorder in humans.


Assuntos
Alcoolismo/tratamento farmacológico , Ácidos Oleicos/uso terapêutico , PPAR alfa/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Alcoolismo/sangue , Alcoolismo/metabolismo , Animais , Modelos Animais de Doenças , Etanol/administração & dosagem , Ligantes , Fígado/metabolismo , Masculino , Ácidos Oleicos/administração & dosagem , Oxicodona/administração & dosagem , PPAR gama/agonistas , Ratos Long-Evans , Ratos Wistar , Autoadministração
10.
Sci Rep ; 8(1): 12921, 2018 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-30150699

RESUMO

There are nearly 250,000 Gulf War (GW) veterans who suffer from Gulf War Illness (GWI), a multi-symptom condition that remains untreatable. The main objective was to determine if targeting peroxisomal function could be of therapeutic value in GWI. We performed a pilot study that showed accumulation of very long chain fatty acids (VLCFA), which are metabolized in peroxisomes, in plasma from veterans with GWI. We then examined if targeting peroxisomal ß-oxidation with oleoylethanolamide (OEA) restores these lipids to the normal levels and mitigates neuroinflammation and neurobehavioral deficits in a well-established mouse model of GWI. In GWI mice, treatment with OEA corresponded with cognitive benefits and reduced fatigue and disinhibition-like behavior in GWI mice. Biochemical and molecular analysis of the brain tissue showed reduced astroglia and microglia staining, decreased levels of chemokines and cytokines, and decreased NFκB phosphorylation. Treatment with OEA reduced accumulation of peroxisome specific VLCFA in the brains of GWI mice. These studies further support the translational value of targeting peroxisomes. We expect that OEA may be a potential therapy for treating neurobehavioral symptoms and the underlying lipid dysfunction and neuroinflammation associated with GWI. Oleoylethanolamide is available as a dietary supplement, making it appealing for human translational studies.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Endocanabinoides/uso terapêutico , Ácidos Oleicos/uso terapêutico , Síndrome do Golfo Pérsico/tratamento farmacológico , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/metabolismo , Humanos , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Síndrome do Golfo Pérsico/metabolismo , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA
11.
Biochim Biophys Acta Mol Basis Dis ; 1864(9 Pt B): 3069-3084, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29960042

RESUMO

Maintaining the equilibrium between saturated and unsaturated fatty acids within membrane phospholipids (PLs) is crucial to sustain the optimal membrane biophysical properties, compatible with selective organelle-based processes. Lipointoxication is a pathological condition under which saturated PLs tend to accumulate within the cell at the expense of unsaturated species, with major impacts on organelle function. Here, we show that human bronchial epithelial cells extracted from lungs of patients with Obstructive Pulmonary Diseases (OPDs), i. e. Cystic Fibrosis (CF) individuals and Smokers, display a characteristic lipointoxication signature, with excessive amounts of saturated PLs. Reconstitution of this signature in cellulo and in silico revealed that such an imbalance results in altered membrane properties and in a dramatic disorganization of the intracellular network of bronchial epithelial cells, in a process which can account for several OPD traits. Such features include Endoplasmic Reticulum-stress, constitutive IL8 secretion, bronchoconstriction and, ultimately, epithelial cell death by apoptosis. We also demonstrate that a recently-identified lipid-like molecule, which has been shown to behave as a "membrane-reshaper", counters all the lipointoxication hallmarks tested. Altogether, these insights highlight the modulation of membrane properties as a potential new strategy to heal and prevent highly detrimental symptoms associated with OPDs.


Assuntos
Membrana Celular/efeitos dos fármacos , Fibrose Cística/tratamento farmacológico , Ácidos Graxos/metabolismo , Manitol/análogos & derivados , Ácidos Oleicos/farmacologia , Fosfolipídeos/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Brônquios/citologia , Linhagem Celular , Membrana Celular/metabolismo , Membrana Celular/patologia , Simulação por Computador , Fibrose Cística/patologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Ácidos Graxos/química , Feminino , Humanos , Masculino , Manitol/farmacologia , Manitol/uso terapêutico , Pessoa de Meia-Idade , Simulação de Dinâmica Molecular , Ácidos Oleicos/uso terapêutico , Fosfolipídeos/química , Cultura Primária de Células , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/citologia
12.
Fish Shellfish Immunol ; 78: 195-201, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29684607

RESUMO

Infection with Aphanomyces invadans is one of the most destructive diseases of freshwater fishes. Indian major carps, the dominant cultured species in the Indian sub-continent are highly susceptible to this disease. Till date, there is no effective treatment for control of this disease and immunization can be one of the strategies to reduce disease-related losses. In the present study, inactivated germinated zoospores of A. invadans were evaluated as antigen in conjunction with and without adjuvant Montanide™ ISA 763 A VG, for assessing their efficacy in rendering protection against A. invadans infection. For the experiment, rohu Labeo rohita, (n = 160, 74 ±â€¯12 g) were divided into 4 groups (C, A, G and GA) with 40 fish in each group. The fish in groups i.e., C, A, G and GA were injected intraperitoneally with PBS, adjuvant emulsified with PBS, inactivated germinated zoospores, and inactivated germinated zoospores emulsified with adjuvant, respectively. After 21 days of immunization, the fish were given a booster dose as above. After 7 days of the booster dose, the fish were challenged with zoospores of A. invadans to determine the relative percent survival (RPS). The results revealed that all the fish in C, A and G group succumbed to infection (0% RPS), although there was delayed mortality in fish from A and G groups in comparison to the C group. However, the fish in GA group showed significantly higher (P < 0.05) protection (66.7% RPS). In addition, following booster immunization (before challenge), the antibody level in the GA group was significantly higher (P < 0.05) than the control group. In western blotting, sera from G and GA groups showed reactivity with peptides of about 54 KDa. Following challenge (on 14th day), the antibody level as well as total antiprotease activity in fish of all the groups was significantly decreased in comparison to pre-challenge, except fish in GA group not exhibiting any gross lesions. In addition, sera of surviving fish of GA group showed significant inhibition of germination of zoospores and germlings growth in comparison to other groups (P < 0.05). Further, histopathological examination of the muscle tissue revealed that, in fish of GA group without any gross lesions, there were well developed granulomas and extensive mononuclear cell infiltration restricted to the site of injection, whereas in other groups, there was extensive myonecrosis with proliferating hyphae. These preliminary findings indicate that inactivated germinated zoospores of A. invadans in combination with adjuvant could stimulate good immune response and confer remarkable protection in rohu.


Assuntos
Aphanomyces/imunologia , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Imunização/veterinária , Manitol/análogos & derivados , Manitol/uso terapêutico , Ácidos Oleicos/uso terapêutico , Animais , Emulsificantes/farmacologia , Formaldeído/farmacologia , /veterinária , Polímeros/farmacologia , Vacinas de Produtos Inativados/uso terapêutico
13.
J Periodontal Res ; 53(5): 777-784, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29687443

RESUMO

BACKGROUND: There is rapidly developing interest into the role of several anti-inflammatory agents to resolve inflammation in periodontal disease. A bioactive polyunsaturated fatty acid, 10-oxo-trans-11-octadecenoic acid (KetoC), is known to have various beneficial physiological effects; however, the effect of KetoC on inflammation remains unclear. Here, we investigated the effect of KetoC on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide, and explored the intracellular mechanism responsible for its anti-inflammatory effects. METHODS: RAW 264.7 cells were pre-treated with or without KetoC, and then stimulated with or without P. gingivalis lipopolysaccharide. Levels of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1ß were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Specific antagonists for G protein-coupled receptor (GPR)40 and GPR120 were used to clarify the receptor for KetoC. The intracellular mechanism was investigated using western blotting analysis to separate nuclear and cytosolic NF-κB p65 protein. RESULT: KetoC (5 µmol/L) was not toxic to RAW 264.7 cells, and significantly reduced the expression of TNFα and IL-6 mRNA and protein, and IL-1ß mRNA. No protein production of IL-1ß was observed. Additionally, when bound to GPR120, KetoC trended to downregulate nuclear NF-κB p65 protein levels. However, the antagonist for GPR40 failed to diminish the action of KetoC. CONCLUSION: KetoC suppressed the proinflammatory cytokines TNFα, IL-6 and IL-1ß via NF-κB p65, by binding to its receptor GPR120. KetoC is a promising candidate in future studies as a bioactive anti-inflammatory agent in treating periodontal disease.


Assuntos
Anti-Inflamatórios , Lipopolissacarídeos/efeitos adversos , Ácidos Oleicos/farmacologia , Porphyromonas gingivalis , Animais , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Ácidos Oleicos/metabolismo , Ácidos Oleicos/uso terapêutico , Doenças Periodontais/tratamento farmacológico , Células RAW 264.7 , Receptores Acoplados a Proteínas-G/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
J Craniofac Surg ; 29(6): 1514-1517, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29621088

RESUMO

BACKGROUND: Infantile hemangiomas (IH) are the most common benign vascular tumors in childhood. Approximately 10% to 15% of these tumors require drug or surgical intervention. There are many options for IH treatment, of which propranolol is currently considered the gold standard. This study aims to compare the therapeutic results of 2 distinct drugs (ethanolamine oleate and propranolol), in order to increase the available therapeutic arsenal for the treatment of IH, thereby benefiting a larger group of patients. METHODS: A retrospective observational study was conducted to assess 16 patients with facial IH, allocated into 2 groups (n = 8). All patients met the same inclusion and exclusion criteria. The resulting evolution assessment was based on photographic documentation produced in a professional setting, and was performed before, during, and after treatment. Two measurement scales, photographic-based assessment of infantile hemangioma characteristics, and outcomes were used for comparison between the 2 therapeutic methods. RESULTS: Both assessment methods did not present any significant statistical difference (P > 0.05) at 1 year of follow-up. CONCLUSION: Both therapeutic modalities are able to offer the patient similar and satisfactory final esthetic results.


Assuntos
Neoplasias Faciais , Hemangioma Capilar , Ácidos Oleicos/uso terapêutico , Propranolol/uso terapêutico , Face/patologia , Neoplasias Faciais/tratamento farmacológico , Neoplasias Faciais/patologia , Hemangioma Capilar/tratamento farmacológico , Hemangioma Capilar/patologia , Humanos , Lactente , Estudos Retrospectivos
15.
Med Oral Patol Oral Cir Bucal ; 23(2): e180-e187, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29476682

RESUMO

BACKGROUND: Although sclerotherapy is a common treatment for benign oral vascular lesions, there is no well-standardized protocol for this purpose. The aim of the present study was to describe the clinical characteristics of patients treated by sclerotherapy with ethanolamine oleate (EO), in order to contribute to a better understanding of this technique. MATERIAL AND METHODS: Medical records and images of 90 patients treated by the same sclerotherapy protocol were retrieved and analysed. Thus, 43 cases with complete information were selected and described. RESULTS: The most affected age group was 41-70 years, with a female predominance and 86% of patients being Caucasian. Lips were the most affect site (70%) followed by the tongue (16%). Regarding clinical appearance, approximately 90% of lesions were classified as nodules, and 90% of patients reported no pain. Approximately 40% of lesions were 0.5-1.0 cm in size. In 58% of the patients, only one application of ethanolamine oleate was necessary. The application doses varied according to the lesion size and number of applications. Complete clinical regression occurred in 91% of cases, whereas 9% showed partial regression. CONCLUSIONS: Sclerotherapy with EO is an acceptable, effective and affordable treatment for benign oral vascular lesions.


Assuntos
Vasos Sanguíneos/anormalidades , Hemangioma/terapia , Neoplasias Bucais/terapia , Boca/irrigação sanguínea , Ácidos Oleicos/uso terapêutico , Soluções Esclerosantes/uso terapêutico , Escleroterapia , Adolescente , Adulto , Idoso , Criança , Anormalidades Congênitas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
16.
Int J Oral Maxillofac Surg ; 47(7): 900-907, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29329829

RESUMO

The aim of this study was to evaluate the effectiveness and safety of 5% ethanolamine oleate (EO) foam in the treatment of low-flow venous malformations in the head and neck region. Seventeen consecutive patients (six male, 11 female) and 34 low-flow venous malformations were enrolled. The vascular anomalies ranged between 20mm and 80mm in size. The typical clinical indication was a swelling (88.2%) with a purple colour (85.3%); the most frequent location was the tongue (23.5%). Ethanolamine oleate foam was produced via the Tessari method and applied at 10mg per 1cm to the vascular anomalies. This process resulted in the highest clinical healing score in 64.7% of cases, and half of the patients reported a high level of satisfaction (score >9). In the majority of cases (88.2%), the patients reported that the pain immediately postoperative was mild or moderate. There were direct relationships between vascular anomaly size and the volume of EO applied, the number of sessions, and healing (P<0.05). No recurrence was observed during 6 months of follow-up. This case series showed the effectiveness and safety of 5% EO foam for the treatment of venous malformations in the head and neck region.


Assuntos
Malformações Arteriovenosas/terapia , Cabeça/irrigação sanguínea , Pescoço/irrigação sanguínea , Ácidos Oleicos/uso terapêutico , Soluções Esclerosantes/uso terapêutico , Escleroterapia/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Phlebology ; 33(5): 344-352, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28516809

RESUMO

Purpose This manuscript describes the technique of real-time MRI-guided sclerotherapy for low-flow venous malformations in the head and neck based on our institutional experience. Materials and methods Ethanolamine oleate is used as the sclerosant and is mixed with gadolinium for visualization during the procedure. The five procedural steps include: (I) an initial tri-plane T2-weighted sequence to visualize the lesion; (II) a T1 FSE or trueFISP sequence to assess needle placement and advancement within the lesion; (III) a tri-plane T1 FLASH sequence to monitor sclerosant injection; (IV) a T1 FSE or VIBE sequence to assess sclerosant coverage of the malformation before needle removal; (V) a post-procedural tri-plane T1 fat-saturated sequence to confirm sclerosant coverage of the lesion. Periprocedural medications typically include steroids, antibiotic prophylaxis, and non-steroidal anti-inflammatory medication. Patients are typically admitted for overnight observation. Conclusion Real-time MRI-guided sclerotherapy for low-flow venous malformations in the head and neck is effective and safe.


Assuntos
Imagem por Ressonância Magnética , Ácidos Oleicos/uso terapêutico , Soluções Esclerosantes/uso terapêutico , Escleroterapia , Doenças Vasculares/terapia , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/terapia , Adolescente , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Encéfalo/diagnóstico por imagem , Feminino , Gadolínio/química , Cabeça/diagnóstico por imagem , Cabeça/fisiopatologia , Humanos , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Pescoço/fisiopatologia , Esteroides/uso terapêutico , Processos Estocásticos , Doenças Vasculares/diagnóstico por imagem
18.
Eur J Nutr ; 57(3): 1123-1135, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28229279

RESUMO

PURPOSE: Obesity is associated with impaired immune defences and chronic low levels of inflammation and oxidation. In addition, this condition may lead to premature aging. The aim of the study was to evaluate the effects of a nutritional supplementation with monounsaturated and n-3 polyunsaturated fatty acids on several functions and oxidative stress parameters in peritoneal immune cells of obese mice, as well as on the life span of these animals. METHODS: Obesity was induced in adult female ICR/CD1 by the administration of a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of obese mice received the same HFD, supplemented with 1500 mg of 2-hydroxyoleic acid (2-OHOA) and another with 3000 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Several functions and oxidative stress parameters of peritoneal leukocytes were evaluated. RESULTS: The groups of obese mice treated with 2-OHOA or with EPA and DHA showed a significant improvement in several functions such as chemotaxis, phagocytosis, digestion capacity, Natural killer activity and lymphoproliferation in response to mitogens. All of these functions, which were decreased in obese mice, increased reaching similar levels to those found in non-obese controls. Both treatments also improved oxidative stress parameters such as xanthine oxidase activity, which decreased, catalase activity and glutathione levels, which increased. CONCLUSION: These data suggest that dietary supplementation with monounsaturated and n-3 polyunsaturated fatty acids could be an effective nutritional intervention to restore the immune response and oxidative stress state, which are impaired in obese mice.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Doenças do Sistema Imunitário/prevenção & controle , Sistema Imunitário/fisiopatologia , Obesidade/dietoterapia , Ácidos Oleicos/uso terapêutico , Estresse Oxidativo , Animais , Proliferação de Células , Células Cultivadas , Quimiotaxia de Leucócito , Dieta Hiperlipídica/efeitos adversos , Feminino , Doenças do Sistema Imunitário/etiologia , Fatores Imunológicos/uso terapêutico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Leucócitos/imunologia , Leucócitos/patologia , Peroxidação de Lipídeos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/patologia , Camundongos Endogâmicos ICR , Mitógenos/farmacologia , Obesidade/etiologia , Obesidade/patologia , Obesidade/fisiopatologia , Fagocitose/efeitos dos fármacos , Análise de Sobrevida
19.
Cardiovasc Intervent Radiol ; 41(2): 317-322, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29038875

RESUMO

PURPOSE: To report a sclerotherapy technique for rectal varices consisting of direct puncture of the superior rectal vein with a small-bore sheathed needle via the greater sciatic foramen without insertion of a sheath or catheter. MATERIALS AND METHODS: The subjects of this retrospective study were three consecutive patients who underwent embolization of rectal varices, two for rupture of rectal varices and one for hepatic encephalopathy and hyperammonemia. A 5% solution of ethanolamine oleate with iodinated contrast agent (5% EOI) was injected through puncture of the superior rectal vein and carried in the blood flow, after which n-butyl cyanoacrylate mixed with lipiodol (NBCA-Lip) was immediately injected to stop the blood flow. RESULTS: The 5% EOI and NBCA-Lip were successfully injected in all three patients. There was no movement of NBCA-Lip on plain radiographs or computed tomography (CT) immediately after injection, and the 5% EOI remained within the rectal varices. The mean procedure time was 53 min (42-60 min). On contrast-enhanced CT 1 month after the procedure, there was no contrast enhancement of the rectal varices that had been seen on preoperative CT in any of the three patients, confirming that the rectal varices had disappeared. CONCLUSION: Sclerotherapy for rectal varices using an approach for puncture of the superior rectal vein with a small-bore sheathed needle via the greater sciatic foramen was technically feasible and clinically effective.


Assuntos
Varizes Esofágicas e Gástricas/terapia , Ácidos Oleicos/uso terapêutico , Doenças Retais/terapia , Soluções Esclerosantes/uso terapêutico , Escleroterapia/métodos , Idoso , Meios de Contraste , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Feminino , Humanos , Agulhas , Punções , Radiografia , Doenças Retais/diagnóstico por imagem , Reto/irrigação sanguínea , Reto/diagnóstico por imagem , Estudos Retrospectivos , Escleroterapia/instrumentação , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Biochim Biophys Acta Biomembr ; 1859(9 Pt B): 1629-1635, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28495596

RESUMO

Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA) and eicosapentaenoic acid (EPA), mediate neuroactive effects in experimental models of traumatic peripheral nerve and spinal cord injury. Cellular mechanisms of PUFAs include reduced neuroinflammation and oxidative stress, enhanced neurotrophic support, and activation of cell survival pathways. Bioactive Omega-9 monounsaturated fatty acids, such as oleic acid (OA) and 2-hydroxy oleic acid (2-OHOA), also show therapeutic effects in neurotrauma models. These FAs reduces noxious hyperreflexia and pain-related anxiety behavior following peripheral nerve injury and improves sensorimotor function following spinal cord injury (SCI), including facilitation of descending inhibitory antinociception. The relative safe profile of neuroactive fatty acids (FAs) holds promise for the future clinical development of these molecules as analgesic agents. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.


Assuntos
Ácidos Graxos Monoinsaturados/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Neuralgia/tratamento farmacológico , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Traumatismos da Medula Espinal/tratamento farmacológico , Humanos , Ácido Oleico/uso terapêutico , Ácidos Oleicos/uso terapêutico , Traumatismos dos Nervos Periféricos/complicações , Traumatismos da Medula Espinal/complicações
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