Adenosine receptor mediates nicotine-induced antinociception in formalin test

In this study, the effect of adenosine receptor agents on nicotine induced antinociception, in formalin test, has been investigated. Intraperitoneal (i.p.) administration of different doses of nicotine (0.1, 1, 10 and 100 μg kg -1) induced a dose-dependent antinociception in mice, in the both first and second phases of the test. Adenosine receptor antagonist, theophylline (5, 10, 20 and 80 mg kg-1, i.p.) also induced antinociception in the both phases, while a dose of the drug (40 mg kg-1, i.p.) did not induce any response. Theophylline reduced antinociception induced by nicotine in both phases of formalin test. The A2 receptor agonist, 5�-N-ethylcarboxamide adenosine (NECA; 1 and 5 μg kg-1, i.p.) also produced antinociception, which was reversed with different doses of theophylline (5, 10, 20 and 40 mg kg-1, i.p.). But administration of the adenosine receptor agonist, NECA did not potentiate the response of nicotine. It is concluded that adenosine system may be involved in modulation of antinociception induced by nicotine. © 2004 Elsevier Ltd. All rights reserved

The protective effect of lithium on the morphine induced apoptosis in PC12 cell line

Background: Opioids are powerful analgesics with widespread usage. Morphine induces apoptosis in many of cells such as neurons and immune cells. In this study the protective effect of lithium against apoptosis induced by morphine on PC12 cell line was investigated. Materials and Methods: We used MTT assay, annexin V-FITC test and real time RT-PCR to measure viability, apoptosis and gene expression, respectively. Different concentrations (0.2, 0.4, 0.8, 1.6 mmol/L) of morphine were used to induce apoptosis. Also, we incubated cells with 1.2 mmol/L lithium chloride for 72 hours and then added 0.8 and 1.6 mmol/L of morphine. Results: Our results indicate that morphine (0.8 and 1.6 mmol/L ) induces cell death after both 24 h and 12h exposure when using MTT test and annexin V test, respectively. The data obtained by real-time RT-PCR show that after 6 hours exposure to 0.8 (not 1.6) mmol/L of morphine, mRNA expression of Bax (a proapoptotic protein) and Bcl-2 (an antiapoptotic protein) increased and decreased, respectively. In the other part of experiment, pretreatment of PC12 cells by lithium chloride (1.2 mmol/L) for 72 hours decreased the mRNA expression of Bax which was elevated by morphine (0.8 and 1.6 mmol/L) . Interestingly, mRNA expression of Bcl-2 which was elevated by morphine (0.8 mmol/L) during 6 hours was increased by pretreatment of lithium 1.2 mmol/L . On the other hand, incubation of cells with 1.2 mmol/L lithium chloride for 72 hours did not alter the mRNA expression of Bax or Bcl-2 and had no toxic effect on the survival of PC12 cells . Conclusion: Pretreatment of lithium protects PC12 cells from morphine induced apoptosis. This effect can be related to Bax and Bcl-2 genes expression

Synthesis and properties of HA/ZnO/CNT nanocomposite

The goal of this study was to examine the tribomechanical properties of hydroxyapatite (HA)/ZnO and HA/ZnO/CNT composite ceramics (carbon nanotubes; with different ratios 0.5 wt%, 1.0 wt%, and 1.5 wt%). The composites were synthesized using the hydrothermal method in an autoclave. The structure and morphology of the composites were analyzed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX) and transmission electron microscope (TEM). The consolidation process was performed by sintering the compounds at 1150 C under an argon gas atmosphere. The effects of ZnO and CNT on the mechanical properties and wear resistance of the HA-nanoparticle-based ceramic composites were investigated using a Vickers hardness tester, nanoindentation, and reciprocating wear tester equipment. The nanohardness and elastic modulus of the sintered samples increased and the friction coefficient of the sintered samples decreased as the fraction of CNTs increased compared to the pure HA and HA/ZnO compounds. Furthermore, the wear loss of HA/ZnO/CNT composites decreased with the increase in the CNT content compared to the HA and HA/ZnO samples.We acknowledge Hanyang University's financial support through the Young Faculty Forum Fund (number 201600000001555 ). Also, some parts of the research were supported by the Fusion Research Program for Green Technologies through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. NRF-2015R1A2A2A11027580 )

Investigating the role of p-creb and c-fos protein expression in nicotine-induced anxiogenesis in rats

BACKGROUND AND OBJECTIVE: Nicotine is one of the most common addictive substances that has many effects on the central nervous system, including dose-dependent anxiety that is mediated by various proteins. Since the mechanisms and proteins involved in nicotine anxiety are unclear, the purpose of the present study was to investigate the role of p-CREB (cAMP Response Element-Binding Protein) and c-Fos proteins in the basolateral amygdala (BLA) on nicotine-induced anxiety behaviours. METHODS: In this experimental study, 24 male Wistar rats were divided into three groups of 7 (saline, nicotine 0.3 and 0.7 mg/kg, intraperitoneally) in behavioral experiment and four groups of 3 (control: No injection and test, Saline, nicotine 0.3 and 0.7 mg/kg) in immunohistochemical experiments. Anxiety-like behaviours were evaluated with OAT (Open Arm Time), OAE (Open Arm Entry), and locomotor activity in the elevated plus maze. The expression of p-CREB and c-Fos proteins in BLA region was also assessed by immunohistochemistry. FINDINGS: Intraperitoneal administration of nicotine at a dose of 0.7mg/kg decreased OAT (5.4±0.42) and OAE (29.4±0.61) compared to saline group (15.2±0.82) and (42.1±0.45), indicating an anxiety-like effect (respectively, p<0.001, p<0.01). In addition, there was a significant difference in the expression of p-CREB (H(3)= 6.99, p<0.05) and c-Fos (H(3)=13.11, p<0.01) protein in the BLA between treatment groups. P-CREB protein expression was higher in the BLA area of control group than in the other groups. C-Fos protein expression was significantly lower in the BLA region of the animals of control, nicotine 0.3 mg/kg and 0.7 mg/kg groups compared to saline group (p<0.01). CONCLUSION: The results of this study indicated that systemic administration of nicotine induced anxiety-like behaviors at high doses. Also, the expression of P-CREB and c-Fos protein was unchanged and decreased in the treatment groups, respectively. © 2020, Babol University of Medical Sciences. All rights reserved

The effect of beforehand and simultaneous oral contraceptive administration on urine total and free morphine concentration in tolerance and dependency models of rat

Background: Addiction to opioid drugs is considered as a problem throughout the world. Addiction can be studied concerning: social, medical and psychological aspects. The social aspect of addiction is quite important. For example, the negative result of addiction test is a requirement for marriage and job by law. On the other hand, frauds in addiction tests have been reported (such as displacement of urine from bladder, alkalization or acidification of urine and taking of diuretics or oral contraceptives). Materials and Methods: In the present study, two different chronic morphine administration protocols (tolerance and dependency models) were applied. Estrogen and progesterone were given prior and simultaneously with morphine. After the last injection of morphine, urine samples were taken every 6 h for 24 h. Then morphine was quantitatively detected by High Performance Liquid Chromatography (HPLC). Data analysis was performed using two-way ANOVA and repeated measures ANOVA test followed by Student-Newman-Keuls test. Conjugated morphine was measured by the subtraction of free part of morphine from the total one in the urine samples. Results: Our results indicated that prior administration of estrogen and progesterone increased the metabolism of morphine 6 and 12 h after the last injection, while no significant change was detected after 18 and 24 h. Conclusion: In summary, it can be concluded that estrogen and progesterone transiently affect the metabolism of morphine. Thus, the effect of the sex hormones on morphine metabolism is not clinically important

Assessing the impacts of sunday trading restrictions on urban public transport: An example of a big city in central Poland

The paper evaluates the temporal and spatial variability of the use of city public transport resulting from statutory Sunday trading restrictions and the COVID-19 pandemic as exemplified by Łódź, a big city in central Poland. Data on the number of tickets validated in urban public transport vehicles is provided in three forms. The first one presents the number of validations in all vehicles in an hourly distribution, the second one shows the number of validations according to individual tram and bus lines, while the third one gives information on the number of validated tickets assigned to a tram/bus stop within the range of which the validation was made. The outcomes from the conducted research show an increased fluctuation in public transport load on Sundays depending on whether it was possible to conduct all types of commercial activity. This variability is observed to a much lesser extent in the presence of other mobility constraints (the pandemic situation). A spatial shift in mobility towards the periphery and inter-district connections is also observed, which may indicate changes in travel destinations

Effect of pretreatment with intracerebroventricular injection of minocycline on morphine-induced memory impairment in passive avoidance test: Role of P-CREB and c-Fos expression in the dorsal hippocampus and basolateral amygdala regions

Minocycline as a member of the tetracycline family is a lipophilic broad-spectrum antibiotic, which can display some non-antibiotic properties such as antioxidant, antiapoptosis, neuroprotection and modulation of pharmacological traits of drugs of abuse (ie, reward, sensitization and/or analgesia). Thus, the aim of the present study was to investigate the effect of intracerebroventricular (ICV) injection of minocycline on morphine-induced memory impairment and motor function in male Wistar rats. The behavioural responses were measured by a passive avoidance test for evaluating memory, and in the open field for studying motor function. Furthermore, the expression of Phospho-cAMP response element-binding protein (P-CREB) and c-Fos were assessed using immunohistochemistry in the dorsal hippocampus and basolateral amygdala (BLA). Our results showed that morphine dose-dependently impairs memory consolidation, but not motor function. Maximum effect was achieved with morphine at dose of 5 mg/kg. Pretreatment with ICV injection of minocycline (50 μg/rat) prevented morphine-induced memory impairment, but there was no effect on motor function. The results of immunohistochemistry analysis demonstrated that morphine decreased expression of P-CREB positive cells compared to saline control group in the BLA, but not in the dorsal hippocampus. On the other hand, pretreatment of animals with ICV injection of minocycline increased the expression of P-CREB in both brain areas. Moreover, there was no significant change in the expression of c-Fos positive cells in above-mentioned regions. In summary, our results indicated that pretreatment with ICV injection of minocycline prevented morphine-induced memory impairment and increased P-CREB expression in the dorsal hippocampus and BLA, which may explain its memory improvement property. © 2019 John Wiley & Sons Australia, Lt

Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system

Eugenol is the main constituent of clove oil with anti-inflammatory properties. In this work, for the first time, O/W nanoemulsion of eugenol was designed for the evaluation of anti-inflammatory effects as a topical delivery system. Topical formulations containing 1, 2 and 4 of eugenol as well as a nanoemulsion system containing 4 eugenol and 0.5 piroxicam were prepared. Further to physicochemical examinations, such as determination of particle size, polydispersity index, zeta potential and physical stability, anti-inflammatory activity was examined in carrageenan-induced paw edema in rats. The optimum formulation was found to contain 2 eugenol (oil phase), 14 Tween 20 (surfactant) and 14 isopropyl alcohol (co-surfactant) in water. Nanoemulsion with polydispersity index of 0.3 and median droplet diameter of 24.4 nm (d50) was obtained. Animal studies revealed that the nanoemulsions exhibited significantly improved anti-inflammatory activity after 1.5 h, compared with marketed piroxicam gel. Additionally, it was shown that increasing the concentration of eugenol did not show higher inhibition of inflammation. Also, the nanoemulsion having piroxicam showed less anti-inflammatory properties compared with the nanoemulsion without piroxicam. © 2015 Taylor & Francis