RESUMO
Drug abuse and addiction can be initiated and reinstated by contextual stimuli previously paired with the drug use. The influence exerted by the context on drug-seeking behaviour can be modelled in experimental animals with place-conditioning protocols. Here, we review the effects of cannabinoids in place conditioning and the therapeutic potential of the endocannabinoid system for interfering with drug-related memories. The phytocannabinoid Δ9-tetrahydrocannabinol (THC) tends to induce conditioned place preference (CPP) at low doses and conditioned place aversion at high doses; cannabidiol is devoid of any effect, yet it inhibits CPP induced by some drugs. Synthetic CB1 receptor agonists tend to recapitulate the biphasic profile observed with THC, whereas selective antagonists/inverse agonists inhibit CPP induced by cocaine, nicotine, alcohol and opioids. However, their therapeutic use is limited by potential psychiatric side effects. The CB2 receptor has also attracted attention, because selective CB2 receptor agonists inhibit cocaine-induced CPP. Inhibitors of endocannabinoid membrane transport and hydrolysis yield mixed results. In targeting the endocannabinoid system for developing new treatments for drug addiction, future research should focus on 'neutral' CB1 receptor antagonists and CB2 receptor agonists. Such compounds may offer a well-tolerated pharmacological profile and curb addiction by preventing drug-seeking triggered by conditioned contextual cues.
Assuntos
Cocaína , Endocanabinoides , Animais , Cocaína/farmacologia , Dronabinol/farmacologia , Receptor CB1 de Canabinoide , Receptor CB2 de CanabinoideRESUMO
The use of lignocellulosic remnants of the açaí agro-business will benefit the environment with a precursor material for biomedical applications. Nanocellulose (NC) allows the biomimetic growth of biphasic ceramics on its surface, with characteristics compatible with bone tissue, including bioactive properties and biocompatibility. In this study, the composites were obtained from açaí tegument (Euterpe Oleracea Mart.) NC using acid hydrolysis. The characterization performed by scanning electron microscopy showed the characteristic crystals of hydroxyapatite (HA) and calcium triphosphate (ß-TCP) based on the results of X-ray diffraction, with the peak at 22°, showing the NC nucleation of HA and peak at 17° showing tricalcium phosphate (ß-TCP). Fourier transform infrared spectroscopy confirmed the presence of O-H at 3400 cm-1 and C-H at 2900 cm-1, which is characteristic of cellulose; peaks were also observed at 1609 cm-1, verifying the reduction in lignin content. Groups PO4-3 at approximately 1070 cm-1, P-OH at 910â»1040 cm-1, and HCO3- at 2450 cm-1 confirmed the formation of HA and ß-TCP. The zeta potential had a range of -11 ± 23.8 mV related to particle size, which had a range of 164.2 × 10-9â»4748 × 10-9 m.
RESUMO
ABSTRACT Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM), caffeic acid (1.1 µM), methyl caffeate (0.03 µM), quercetin (0.08 µM) and ferulic acid (0.02 µM) isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT) was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.
Assuntos
Animais , Masculino , Ácido Ascórbico/farmacologia , Dano ao DNA/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Cocos/química , Estresse Oxidativo/efeitos dos fármacos , Etanol/farmacologia , Fígado/efeitos dos fármacos , Fatores de Tempo , Triglicerídeos/sangue , Água/farmacologia , Peroxidação de Lipídeos , Colesterol/sangue , Reprodutibilidade dos Testes , Substâncias Reativas com Ácido Tiobarbitúrico , Ratos Wistar , Espectrometria de Massas em Tandem , Fígado/metabolismo , Antioxidantes/farmacologiaRESUMO
Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM), caffeic acid (1.1 µM), methyl caffeate (0.03 µM), quercetin (0.08 µM) and ferulic acid (0.02 µM) isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT) was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.
Assuntos
Ácido Ascórbico/farmacologia , Ácidos Cafeicos/farmacologia , Cocos/química , Dano ao DNA/efeitos dos fármacos , Etanol/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Colesterol/sangue , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Ratos Wistar , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Substâncias Reativas com Ácido Tiobarbitúrico , Fatores de Tempo , Triglicerídeos/sangue , Água/farmacologiaRESUMO
Coconut water (CW) is a natural nutritious beverage, which contains several biologically active compounds that are traditionally used in the treatment of diarrhea and rehydration. Several works with CW have been related with antioxidant activity, which is very important in the diabetic state. To evaluate the hypoglycemic and nephroprotective activities of CW, alloxan-induced diabetic rats were pre- and post-treated by gavage with CW (3 mL/kg), caffeic acid (CA) (10 and 15 mg/kg), and acarbose (Acb) (714 µg/kg) during a period of 16 days. Body weight, blood glucose, glycated hemoglobin (HbA1c), and Amadori products in plasma and kidney homogenates were evaluated in all groups and used as parameters for the monitoring of the diabetic state. The results showed that rats of the CW+diabetic group had maintenance in blood glucose compared with the control group (P<.05) in addition to a decrease of HbA1c levels and increase of body weight when compared with the diabetic group rats (P<.05). The animals of the CA and CA+diabetic groups did not have significant variation of body weight (P<.05) during the experiment; however, they showed decrease in their HbA1c and urea levels in plasma as well as Amadori products in kidney homogenates when compared with the diabetic group (P<.05). Our results indicate that CW has multiple beneficial effects in diabetic rats for preventing hyperglycemia and oxidative stress caused by alloxan.
Assuntos
Bebidas , Cocos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Hipoglicemiantes/administração & dosagem , Acarbose/administração & dosagem , Aloxano , Animais , Antioxidantes/administração & dosagem , Ácidos Cafeicos/administração & dosagem , Hemoglobinas Glicadas/análise , Hiperglicemia/prevenção & controle , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Ratos , Ratos Wistar , Ureia/sangueRESUMO
The incidence of biliary complications (BCs) after living donor liver transplantation (LDLT) can reach 40%. Published data on the pediatric population are limited, and treatment protocols vary. Our aim was to describe the clinical scenario for BCs and treatment approaches after LDLT. Between October 1995 and December 2012, 489 pediatric LDLT procedures were performed. BCs developed in 71 patients (14.5%). Biliary strictures (BSs) developed in 45 (9.2%) patients, and bile leaks (BLs) developed in 33 patients (6.7%). The BL diagnosis was clinical in all cases, and 69.7% of the patients underwent surgery. Nearly half of the BS cases had clinical features or suggestive ultrasound findings. Liver biopsy findings suggested BSs in 51.7%. Percutaneous transhepatic cholangiography was performed in 95.6% of the BS patients. The success rate was 77% [mean number of percutaneous biliary interventions (PBIs) = 3.9 ± 1.98, median drainage time = 8 months]. In conclusion, BL patients can be managed with conservative therapy, even though most of these patients will ultimately be treated with surgery. Diagnosing a BS requires a high degree of clinical suspicion because the available resources for its identification can fail in up to 50% of cases. A higher number of PBIs and the use of a drainage catheter for a longer time may be required to achieve better results with this technique.
Assuntos
Constrição Patológica/diagnóstico , Transplante de Fígado , Fígado/cirurgia , Adolescente , Síndrome de Alagille/terapia , Atresia Biliar/terapia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Criança , Pré-Escolar , Colangiografia , Constrição Patológica/etiologia , Drenagem/métodos , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Fibrose/terapia , Hepatite Autoimune/terapia , Humanos , Lactente , Estimativa de Kaplan-Meier , Falência Hepática Aguda/terapia , Doadores Vivos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Transplantados , Tirosinemias/terapiaRESUMO
Portal vein thrombosis is a complication that occurs anytime after liver transplantation and can compromise the patient and graft survival. We describe a combined technique for PV recanalization in cases of PV obstruction after liver transplantation. Four children (1%), of 367 subjected to liver transplantation from June 1991 to December 2008, underwent PV recanalization through a combined approach (transhepatic and minilaparotomy). All children received left lateral hepatic segments, developed Portal vein thrombosis (n=3) and stenosis (n=1), and presented with symptoms of portal hypertension after transplantation. PV recanalization was tried by transhepatic retrograde access, and a minilaparotomy was performed when percutaneous recanalization was unsuccessful. Three patients underwent a successful portal recanalization and stent placement with the combined technique. In one patient, the recanalization was unsuccessful because of an extensive portomesenteric thrombosis. The other three children had the portal flow reestablished and followed with Doppler US studies. They received oral anticoagulation for three consecutive months after the procedure and the clinical symptoms subsided. In case of PV obstruction, the combined approach is technically feasible with good clinical and hemodynamic results. It' is a minimally invasive procedure and can be tried to avoid or delay surgical treatment or retransplantation.