ABSTRACT
Background: curcumin has anti-inflammatory and antinociceptive effects and also it can be exploited for drug abuse treatment, but its low bioavailability and water solubility are the most important obstacles and limit its application. The recent achievements of nanotechnology illustrate a novel approach in treatment of drug abuse and addiction. The present study was conducted to investigate the effect of dendrosomal Nano curcumin [DNC] administration on morphine withdrawal signs in rats
Methods: male rats [250-300 gr] were anaesthetized and implanted with silastic catheters inserted into the right jugular vein. Then they were placed in the self-administration apparatus for 2 hours/day for 12 days and received saline or morphine [5mg/ml] by infusion pump. In addition, DNC [10, 5 mg/kg,IP] were injected 30 minutes before placing in apparatus and the signs of withdrawal were measured for 30 minutes after injection of naloxone [2 mag, i.p]
Results: morphine significantly induced dependence and withdrawal signs in sham group. On the other hand injection of DNC significantly decreases these signs [p<0/05]
Conclusion: DNC can decrease withdrawal signs of morphine and can be used as an effective pharmacotherapy for morphine abuse
ABSTRACT
Objective: To investigate the analgesic and anti-inflammatory property and possible involvement of opioid receptors of ethyl acetate extract from aerial parts of Daphne mucronata (D. mucronata) in mice by formalin test. Methods: Single doses of 2.5, 5.0 and 10.0 mg/kg of body weight of ethyl acetate extract of D. mucronata were intraperitoneally administered to the mice 30 min before analgesic test. The anti-nociceptive effect of preparations was evaluated based on the formalin in mice. Results: The results indicated that the extract (2.5, 5.0 and 10.0 mg/kg) increased the pain threshold of mice and induced analgesia in both phases of formalin test. Like morphine sulfate (5.0 mg/kg, i.p.), the extract also showed more effective analgesic effect on the late phase of formalin test. Pre-treatment of animals with naloxone (5.0 mg/kg i.p.) did not inhibit the effects of the extract. Conclusions: Our findings suggest that D. mucronata contains potential analgesic and anti-inflammatory compounds which support its traditional use. Moreover, it seems that the analgesic and anti-inflammatory effects of the extract is mediated by non-opioid mechanisms. Further pharmacological studies are required to determine whether the analgesic mechanisms are actually responsible for such properties.
ABSTRACT
This study investigated tissue damages induced by chronic subcutaneous administration of nano- and microparticles of manganese dioxide [MnO2] on the liver, kidneys and testes of rats. Rats [n=210] were divided into three groups: control, MnO2 nanoparticle injected and MnO2 microparticle injected. The experimental groups received subcutaneous injections with either nano- or microparticles of a solution that contained MnO2 [100 microg/kg] once per two weeks for 14 weeks. Once every two weeks, we randomly selected five rats from each group for histological evaluations of the liver, kidneys, and testes. Tissue lesions were initially evaluated by hematoxylin and eosin staining, then kidney and liver tissue sections were stained by the Jones and Masson's trichrome methods, respectively. The changes in diameter of basement membrane and cell numbers of the various parts of the nephrons in different groups were measured by Image Tools version 2 software. The liver tissues of the nano- and microparticle groups exhibited severe damage histopathologically. Cloudy swelling was observed in the cytoplasm of hepatocytes. The liver tissue and its canaliculi structures were severely damaged. Inflammation and ductular reaction signs were seen in liver tissue. Deposition of particles in the basement membrane of the nephrons were observed in the nanoparticle-treated group. There was a significant reduction in glomerular and tubular cells in the nanoparticle-treated group compared to the control and microparticle-treated groups. Some of the structural and functional parameters of the testes in the nanoparticle-treated group had significant pathobiological variations. Administration of MnO2 nanoparticles when compared with the same dose of MnO2 microparticles caused more tissue damage in all examined tissues. Reduction in particle size from micrometer to nanometer appeared to exacerbate the damaging mechanisms of these particles in the examined tissues
ABSTRACT
Lallemantia royleana [Balangu] is a well known Iranian medicinal plant that its seed mucilage has many applications in modern pharmacology. Plant mucilage traditionally was used as a gel supplement, and natural matrix for sustained release of drugs. But it seems that these compounds are not a simple additive and also have many undiscovered pharmacological properties. In this research, the anesthetic action of gel prepared from Balangu mucilage alone and its mixture with lidocaine hydrochloride are compared with the effect of commercial 2% lidocaine gel by rat tail flick test. Mucilage of Balangu seed alone showed analgesic effect. Duration and potency of anesthesia induced by gel containing mucilage alone [0.01 g/mL] were identical to commercial 2% lidocaine gel. But, local anesthetic potency and duration of gel made from 2% lidocaine-mucilage gel mixture was significantly higher than commercial 2% lidocaine gel. The gel prepared from mucilage causes a good analgesia with unknown mechanism. Besides, mixture of Balangu mucilage prepared gel with lidocaine improves lidocaine anesthesia. The increase in potency of lidocaine action results from mucilage dermal penetration enhancing effects; and longer anesthetic duration of this mixture are related to the capability of mucilage based gel for sustained drug release
ABSTRACT
It has been shown that administration of WIN55,212-2, a cannabinoid receptor agonist, into the basolateral amygdala [BLA], dose-dependently increases the thermal latency to withdrawal in the tail-flick test and decreases pain related behaviors in both phases of the formalin test. Recent human and animal imaging data suggest that the nucleus accumbens [NAc] is an important neural substrate of pain modulation. Because the NAc also receives abundant glutamatergic fibers from the BLA which converge with hippocampal fibers on the same NAc neurons, it is reasonable to ask whether AMPA/kainate and NMDA receptor antagonists may also include in the amygdala-accumbens pathway in pain modulation. In the present study, we examined the role of NMDA and AMPA/kainate receptors within the NAc in antinociception induced by intra-BLA injection of the cannabinoid receptor agonist WIN55,212-2 in rats. Seventy two adult male albino Wistar rats weighing 230-280 g were implanted with two separate cannulae into the BLA and the NAc. Also, animals received intra-accumbal infusions of either NMDA receptor antagonist, AP5 [0.5, 2.5 and 5 microg/0.5 ul saline] or AMPA/kainate receptor antagonist, CNQX [0.1,0.5 and 2.5 pg/0.5 microl DMSO] 2 min before microinjection of WIN55,212-2 into the BLA[15 microg/rat]. Antinociceptive effects of WIN55,212-2 were measured in the formalin test [50 microl injection of formalin 2.5% subcutaneously into the hindpaw] and pain-related behaviors were monitored for 60 min. Results showed that intra-accumbal AP5 and CNQX dose-dependently prevented antinociception induced by intra-BLA administration of WINS5,212-2 in time set intervals. Additionally, intra-accumbal APS administration of both APS [5 microg/0.5 microl saline] and CNQX [2.5 microg/0.5 microl DMSO], alone, could not significantly change the pain scores in the rats. It seems that glutamate receptors located in the NAc, partially mediate the antinociceptive responses of cannabinoid within the BLA in persistent inflammatory model of pain
ABSTRACT
Today, Fuzzy expert systems have helped physicians in cases of uncertainty in medical decision making for prescribing drugs. Narrowing of coronary heart and reduction in heart blood flow are important causes of coronary heart disease [CHD]. Control of blood lipid level is a routine treatment in CHD patients. But damage to liver is a common side effect of lipid lowering drug medication. Measurement of plasma Alanine aminotransferase level is considered as a marker of liver damage. The aim of this study was to determination of optimal dose of atorvastatin using Fuzzy expert system. In this study, Fuzzy expert system based on drug dose determination was chosen for prescribing atorvastatin dose as a lipid lowering drug that sets with demographic information of patients. Here, optimum dose is defined as a dose that decreases plasma LDL with the least side effects. In our model, decrease in LDL, Cholesterol and LDL/ HDL blood ratio consider as positive consequence and increase in plasma ALT as the side effect of this drug. Output of our model is compared double blindly with prescription of many different randomly chosen expert physicians in the same practical case and the physician decision shows%65 similarity with our model. Practically, this percent of similarity between model and practical results was considered to be sufficient to approve this model. This result showed that the quality of this fuzzy models output is close to clinically approved decision. Thus this model can be considered as an applicable decision making model for physician and pharmaceutical industries about dosing of this drug in a similar situation