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Pirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable for increasing therapeutic efficacy of PFD. Losartan (LOS), an angiotensin II receptor antagonist, could be a suitable candidate for combination therapy because of its stabilizing effect on the pulmonary function of IPF patients. Therefore, this study aimed to investigate the effects of LOS in combination with PFD on bleomycin (BLM)-induced lung fibrosis in rats. BLM-exposed rats were treated with LOS alone or in combination with PFD. The edema, pathological changes, level of transforming growth factor-β (TGF-β1), collagen content, and oxidative stress parameters were assessed in the lung tissues. Following BLM exposure, the inflammatory response, collagen levels, and antioxidant markers in rat lung tissues were significantly improved by PFD, and these effects were improved by combination with LOS. The findings of this in vivo study suggest that the combined administration of PFD and LOS may provide more potent protection against IPF than single therapy through boosting its anti-inflammatory, anti-fibrotic, and anti-oxidant effects. These results hold promise in developing a more effective therapeutic strategy for treating of lung fibrosis., (© 2024. The Author(s).)

Introduction: Anethum graveolens (AG), commonly known as dill, is a plant from the Apiaceae family that has been traditionally used as a skin softener and purifying agent in Persian medicine. In a previous study conducted on male rats, dill was found to have anti-inflammatory effects. The current study aimed to examine the efficacy of topical application of Anethum graveolens oil on pruritus severity, skin dryness, sleep quality, and quality of life in patients undergoing hemodialysis., Methods: In the current clinical trial, the participants were randomly assigned to one of these groups: topical AG preparation, sesame oil, or a control group receiving no treatment. The study was double-blind and placebo-controlled. The topical treatment was applied twice a day for one month to areas of the skin affected by pruritus. The outcome measures included the severity of skin dryness, the Pittsburgh Sleep Quality Index, Duo's Uremic Pruritus Severity Scale, and the Itchy QoL questionnaire., Results: This study involved 106 hemodialysis patients, and after intervention for one month, the medication group had a significantly lower mean score of sleep quality (3.24 ± 2.41) than the placebo (4.54 ± 3.11) and control (5.05 ± 3.21) groups ( P =0.032). The mean change in pruritus severity was significantly greater in the medication group (-17.28 ± 8.938) than the placebo (-5.91 ± 5.398) and control (-3.43 ± 3.228) groups ( P < 0.001). Moreover, a significant difference was observed in the mean changes in quality of life between the medication, placebo, and control groups, with values of -14.88 ± 7.89, -5.34 ± 4.50, and -1.92 ± 2.86, respectively ( P < 0.001). Furthermore, both the medication and placebo groups showed improvement in skin dryness compared to the control group having the values of -1.65 ± 0.91, -1.11 ± 0.79, and -0.38 ± 0.54, respectively ( P < 0.001)., Conclusion: Topical Anethum graveolens preparation significantly improved the sleep quality and quality of life and reduced skin pruritus and dryness in hemodialysis patients. It could be considered as a simple therapeutic modality to control pruritus in hemodialysis patients. This trial is registered with IRCT2017022032671N1., Competing Interests: The authors declare that they have no conflicts of interest in this study., (Copyright © 2024 Zeinab Shaki et al.)

Background: Acrylamide (ACR) can induce neurotoxicity through different pathways, including oxidative stress and apoptosis. Azithromycin is well-known for its antioxidant and anti-apoptotic properties., Objective: To evaluate the potential neuroprotective effect of azithromycin in an in vivo model of ACR-induced neurotoxicity, by investigating its impact on oxidative stress and apoptosis pathways., Methods: Male rats were divided into eleven groups at random (n = 6). 1:control (vehicle), 2:ACR (50 mg/kg, 11 days, I.P.), 3-7:ACR+ azithromycin (3.1, 6.25, 12.5, 25, 50 mg/kg, 11 days, I.P.), 8-9:ACR+ azithromycin (3.1, 6.25 mg/kg, from day 3-11), 10: ACR+ vitamin E (200 mg/kg, every other day, I.P.), 11. Azithromycin (50 mg/kg). Following the treatment period, a gait score examination was performed, and malondialdehyde (MDA), glutathione (GSH), Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and caspase-3 levels in the cerebral cortex were measured., Results: Gait abnormality, a drop in GSH, and an increase in lipid peroxidation, Bax/Bcl-2 ratio, and caspase-3 levels were all significantly triggered by ACR in the cerebral cortex versus the control group. Azithromycin 3.1 and 6.25 mg/kg with ACR and azithromycin 6.25 mg/kg with ACR from day 3-11 ameliorated movement disorders caused by ACR. Azithromycin in all doses and both protocols along with ACR decreased the MDA level. Azithromycin (3.1, 6.25 mg/kg) along with ACR in both protocols increased the level of GSH, reduced the Bax/Bcl-2 ratio and caspase-3 amounts in the brain tissue versus the ACR group., Conclusions: Administration of azithromycin had both preventive and therapeutic effects on ACR-induced neurotoxicity through its antioxidant and antiapoptotic properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diclofenac (DIC) is one of the most commonly prescribed non-steroidal anti-inflammatory drugs and has been shown to cause oxidative stress and liver injury. The current study investigated protective effects of metformin against DIC-induced hepatic toxicity in both in vitro and in vivo models. For the in vitro study, HepG2 cells were exposed to DIC in the presence or absence of metformin. The effect of metformin on cell viability was evaluated by MTT assay. Oxidative stress parameters (malondialdehyde (MDA), total thiol molecules (TTM), and total antioxidant capacity (TAC)) were assessed. For the in vivo study, thirty-six male Wistar rats were randomly divided into 6 groups. These groups were normal saline, metformin (200 mg/kg), DIC (50 mg/kg/day), DIC + metformin (50, 100, and 200 mg/kg/day). Histopathological studies and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), albumin, direct and total bilirubin were measured. Also, oxidative stress parameters were assessed in liver tissue. Furthermore, expression of glutathione peroxidase (GPX)-1, -3, and -4, catalase (CAT), superoxide dismutase (SOD)-1, and -3 was examined using the real-time PCR method in hepatic tissue. In the in vitro study, metformin significantly prevented DIC-induced loss in cell viability in HepG2 cells. Metformin markedly reduced DIC-induced elevation of MDA levels and increased the TAC and TTM levels. In the in vivo study, metformin significantly prevented DIC-induced changes in hematological and histological markers. Administration of metformin significantly improved oxidative stress parameters in liver tissue. In addition, metformin increased the expression of antioxidant enzymes. Our results suggest that metformin exerts a significant protective effect against DIC-induced hepatic toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Arsenic and cadmium are nonessential elements that are of importance in public health due to their high toxicity. Contact with these toxic elements, even in very small amounts, can induce various side effects, including neurotoxicity. Oxidative stress and apoptosis are part of the main mechanisms of arsenic- and cadmium-induced toxicity. Alpha-mangostin is the main xanthone derived from mangosteen, Garcinia mangostana, with anti-oxidative properties.In this study, PC12 cells were selected as a nerve cell model, and the protective effects of alpha-mangostin against neurotoxicity induced by arsenic and cadmium were investigated. PC12 cells were exposed to cadmium (5-80 µM) and arsenic (2.5-180 µM) for 24 h. Cytotoxicity, reactive oxygen species (ROS) production, and the protein expression of Bax, Bcl2, and cleaved caspase 3 were determined using MTT assay, fluorimetry, and western blot, respectively.Arsenic (10-180 µM) and cadmium (50-80 µM) significantly reduced cell viability. IC 50 values were 10.3 ± 1.09 and 45 ± 4.63 µM, respectively. Significant increases in ROS, Bax/Bcl-2 ratio, and cleaved caspase-3 were observed after arsenic and cadmium exposures. Cell viability increased and ROS production decreased when cells were pretreated with alpha-mangostin for 2 h. Alpha-mangostin reduced the increased level of cleaved caspase-3 induced by cadmium and decreased the elevated level of the Bax/Bcl-2 ratio after arsenic exposure.Alpha-mangostin significantly increased cell viability and reduced oxidative stress caused by cadmium and arsenic in PC12 cells. Moreover, alpha-mangostin reduced cadmium-induced apoptosis through the reduction in the level of cleaved caspase 3. Further studies are required to determine the different mechanisms of alpha-mangostin against neurotoxicity induced by these elements., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this research, Fe 3 O 4 @HZSM-5 magnetic nanocomposite was synthesized via a coprecipitation method for metronidazole (MNZ) degradation from aqueous solutions under ultrasonic irradiation which showed superb sonocatalytic activity. The synthesized magnetite nanocomposite was characterized by using field-emission scanning electron microscope-energy dispersive X-ray Spectroscopy, (FESEM-EDS), Line Scan, Dot Mapping, X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and Brunauer-Emmett-Teller (BET). To investigate the sonocatalytic activity of the Fe 3 O 4 @HZSM-5 magnetite nanocomposite, the sonocatalytic removal conditions were optimized by evaluating the influences of operating parameters like the dosage of catalyst, reaction time, pH, the concentration of H 2 O 2 , MNZ concentration, and pH on the MNZ removal. The MNZ maximum removal efficiency and TOC at reaction time 40 min, catalyst dose 0.4 g/L, H 2 O 2 concentration 1 mM, MNZ initial concentration 25 mg/L, and pH 7 were achieved at 98% and 81%, respectively. Additionally, the MNZ removal efficiency in the real wastewater sample under optimal conditions was obtained at 83%. The achieved results showed that using Langmuir-Hinshelwood kinetic model K L-H  = 0.40 L mg -1 , K C  = 1.38 mg/L min) can describe the kinetic removal of the process. The radical scavenger tests indicated that the major reactive oxygen species were formed by hydroxyl radicals in the Sono-Fenton-like process. Evaluation of the nanocomposite reusability showed an 85% reduction in the MNZ removal efficiency after seven cycles. Based on the results, it can be concluded that Fe 3 O 4 @HZSM-5 were synthesized as magnetic heterogeneous nano-catalysts to effectively degrade MNZ, and the observed stability and recyclability demonstrated that Fe 3 O 4 @HZSM-5 was promising for the treatment of wastewater contaminated with antibiotics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Pain in the intensive care unit is a silent fact. Considering the positive features of the nonverbal pain scale (NVPS) in assessing the pain of non-verbal patients, this study investigates the effect of training the NVPS on the ability of nurses to monitor the pain of patients in the intensive care unit., Materials and Methods: In this semi-experimental study, the effect of the NVPS training on the ability of 50 intensive care unit (ICU) nurses of Imam Khomeini Hospital affiliated to Ahvaz University of Medical Sciences was investigated. At first, the ability to diagnose the presence and intensity of pain was checked by a checklist. Then the nurses were taught how to use the scale correctly. After 2 weeks of training completion, the ability to correctly use the scale was measured again. Data analysis was performed using descriptive statistics (mean and standard deviation) and inferential statistics (McNemar, Chi-squared, paired t -test, and Fisher's exact test) in SPSS software version 16., Results: After the training on the non-verbal pain scale, there was a significant difference between the intervention and control groups in diagnosing the presence of pain related to changing the patient's position ( p = 0.023). Also, nurses ability to diagnose pain intensity during airway suction increased fourfold and for physiotherapy procedures twice as much as before training., Conclusion: Nonverbal pain scale training improves ICU nurses ability in diagnosing the presence and severity of pain in nonverbal patients., How to Cite This Article: Ghayem H, Heidari MR, Aghaei B, Norouzadeh R. The Effect of Training the Nonverbal Pain Scale (NVPS) on the Ability of Nurses to Monitor the Pain of Patients in the Intensive Care Unit. Indian J Crit Care Med 2023;27(3):195-200., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Objectives: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. Despite the promising anti-fibrotic effect, the toleration of pirfenidone (PFD) by the patients in full dose is low. Combination therapy is a method for enhancing the therapeutic efficiency of PFD and decreasing its dose. Therefore, the present study evaluated the effect of a combination of losartan (LOS) and PFD on oxidative stress parameters and the epithelial-mesenchymal transition (EMT) process induced by bleomycin (BLM) in human lung adenocarcinoma A549 cells., Materials and Methods: The non-toxic concentrations of BLM, LOS, and PFD were assessed by the MTT assay. Malondialdehyde (MDA) and anti-oxidant enzyme activity including catalase (CAT) and superoxide dismutase (SOD) were assessed after co-treatment. Migration and western blot assays were used to evaluate EMT in BLM-exposed A549 after single or combined treatments., Results: The combination treatment exhibited a remarkable decrease in cellular migration compared with both single and BLM-exposed groups. Furthermore, the combination treatment significantly improved cellular anti-oxidant markers compared with the BLM-treated group. Moreover, combined therapy markedly increased epithelial markers while decreasing mesenchymal markers., Conclusion: This in vitro study revealed that the combination of PFD with LOS might be more protective in pulmonary fibrosis (PF) than single therapy because of its greater efficacy in regulating the EMT process and oxidative stress. The current results might offer a promising therapeutic strategy for the future clinical therapy of lung fibrosis., Competing Interests: No potential conflicts of interest were reported by the authors.

Background and Purpose: Nurses' self-perception of their performance toward family members of patients is one of the most important issues in predicting family adaptive behaviors. This study analyzed the psychometric properties of the Persian version of intensive care unit (ICU) nurses' perceptions questionnaire of self-performance with families of critically ill patients., Methods: Among 135 intensive care nurses, to determine face validity, 10 nurses were asked to comment on, comprehensibility, grammar, and writing of items. Exploratory factor analysis was used to assess construct validity., Results: The intra-cluster correlation coefficient (ICC) was 0.82 and Cronbach's alpha was 0.74. Exploratory factor analysis showed the first nine related factors have 65.22% variance., Conclusion: Persian version of ICU nurses' perceptions of self-performance with families of critically ill patients had good reliability and validity., (© Copyright 2022 Springer Publishing Company, LLC.)

Introduction: Autism spectrum disorder (ASD) is a complex, behaviorally defined disorder of the immature brain as a result of genetic and environmental risk factors, such as prenatal exposure to valproic acid (VPA). This syndrome is known for its high prevalence. On the other hand, postnatal manipulations have been shown to affect brain development, cortical neuroscience, and pituitary-adrenal activity. In early handling (EH) procedure, pups are removed from their mother on a daily basis from birth to lactation, are physically touched, and exposed to the (a) new environment. In the present study, the effect of EH on anxiety-like behaviors in rats exposed pre- and post-natally to valproic acid was investigated., Methods: Pregnant Wistar rats were randomly separated into six groups which are prenatal saline, Prenatal VPA, Prenatal VPA + EH and postnatal saline, Postnatal VPA, Postnatal VPA + EH. VPA administration was performed either on ED12.5 (600 mg/kg, i.p.) or PD 2-4 (400 mg/kg, s.c.). In the groups receiving EH, pups underwent physical handling from PD 1 to 21. On postnatal day 21 all offspring were weaned and the behavioral tests were performed on 30 and 31 days of age. Elevated plus maze and open field tests were used to investigate anxiety-like behaviors., Results: The results revealed that intraperitoneal injection of valrpoic acid (600 mg.kg) during pregnancy significantly reduced OAT% in males (p < 0.01) and females in a non-significant manner (p > 0.05). In comparison, rearing counts of prenatal VPA groups significantly increased in female sex (p < 0.05) in the EPM test. Following postnatal VPA administration (400 mg/kg), decrease in the time spent in central zone occurred in female rats in the open filed (p < 0.05), as well as a significant increase in the number of grooming of the male sex (p < 0.05). Applying Early Handling to male and female Wistar rats receiving prenatal VPA significantly reversed the OAT% fall (p < 0.05). EH in postnatally VPA exposed animals significantly decreased the OAT% and OAE% criteria, while increasing the locomotor activity of the female sex (p < 0.05). Compared with the postnatal VPA group, no significant change was reported in the EPM performance of postnatal VPA + EH group in neither of sexes (p > 0.05)., Conclusion: The findings of this study suggest that injections of valproic acid during pregnancy lead to anxiety-like behaviors in male offspring, which EH can improve (attenuate) to some extent. VPA injections on the second to the fourth day of infancy did not have a profound effect on anxiety level. Further behavioral studies need to be performed using other devices to investigate anxiety-like behaviors and to determine the mechanisms involved in these behaviors., (Copyright © 2021. Published by Elsevier Inc.)

Arsenic (As) toxicity has deleterious effects on human health causing disorder in the brain. The aim of this study was to investigate the possible neuroprotective effect of resveratrol (RSV) on arsenic-induced neurotoxicity in rats. Neurotoxicity in rats was developed by treating As 10 mg/kg/day for 21 days orally. Animals were put into seven groups: control, vehicle, As, As+RSV10, As+RSV20 mg/kg, RSV10, and RSV20 mg/kg. Behavioral assessments such as the social interaction test, novel object recognition test, elevated plus maze, open field, the Morris water maze, in addition to assessment of biomarkers such as ferric reducing ability of plasma assay, glutathione assay, and malondialdehyde assay, were used to evaluate the effects of RSV on cognitive impairment and molecular changes induced by As. The results showed that cognitive performance impaired in As rats. RSV20 mg/kg significantly could ameliorate behavioral changes like spatial learning in days 3 and 4 ( p < 0.05), recognition learning and memory ( p < 0.01), disabilities in motor coordination and stress ( p < 0.05), increased anxiety ( p < 0.05), and social interaction deficit (sociability ( p < 0.001) and social memory ( p < 0.05)). RSV20 mg/kg also attenuated molecular modifications like decreased antioxidant power ( p < 0.001), reduced glutathione content ( p < 0.05), and increased malondialdehyde level ( p < 0.05) induced by As. In addition to oxidative stress assessments, RSV10 mg/kg could significantly increase FRAP ( p < 0.01) and GSH ( p < 0.05); however, MDA was not significantly increased. Our current behavioral findings suggest that RSV has neuroprotective effects against AS toxicity., Competing Interests: No conflict of interest was reported by the authors., (Copyright © 2021 Zahra Taheri Zadeh et al.)

Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease., Objective: We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease., Methods: MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured., Results: ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P<0.001 and P<0.001, respectively). Up-regulation of miR-122 in the sample of patients with normal ALT and AST activities was also observed, indicating that miR-122 is a good marker with high sensitivity and specificity for diagnosing liver damage., Conclusion: miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Olanzapine, an atypical antipsychotic, causes weight gain and metabolic disorders in humans. Safranal, one of the active components of Crocus sativus (saffron), has been shown to have anti-obesity, lipid and blood pressure lowering and anti-diabetes effects. In this investigation, the effect of safranal on metabolic disorders induced by olanzapine was studied., Materials and Methods: Fourty-two female Wistar rats were divided into 7 groups of 6 animals. The two groups were selected as controls, which received olanzapine and safranal solvents, respectively. The third group treated by olanzapine 5 mg/kg. Groups 4, 5 and 6 treated by olanzapine 5 mg/kg plus safranal (2.5, 5 and 10 mg/kg) and the last group received safranal 10 mg/kg. The injections were performed intraperitoneally for 14 days and on the 15 th day the rats were killed and their serum were collected to measure metabolic factors including glucose, insulin, triglyceride, total cholesterol and HDL cholesterol. Leptin level in plasma was also measured. Mean systolic blood pressure was measured using tail cuff method at the end of study. The rats were weighed every other day and amount of food consumed was measured daily., Results: Olanzapine significantly elevated body weight, food intake, fasting blood glucose, TG, leptin, and mean systolic blood pressure (MSBP). It also significantly decreased HDL cholesterol blood level. Safranal significantly improved all these complications at three doses., Conclusion: Based on the results of this study, safranal is thought to be used as an effective combination in controlling metabolic complications caused by olanzapine.

Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.

Objective: This study evaluated the antianxiety effect of Citrus aurantium aroma (neroli oil) inhalation on patients with acute coronary syndrome (ACS). Design: A double-blind, placebo-controlled randomized trial. Setting/Location: This study was conducted in the Coronary Care Unit of Torfeh Hospital in Tehran, Iran, from September 2017 to February 2018. Subjects: A total of 140 hospitalized ACS patients (mean age = 56.72 ± 11.38 years) Interventions: Eligible patients were randomly assigned to citrus aroma and placebo groups to receive inhalation aromatherapy 2 days after hospitalization. Citrus aroma was 30% essential oil of Citrus aurantium L. flowers in paraffin, which was administrated three times a day. The placebo group received paraffin similarly. Outcome measures: The rate of anxiety was measured at baseline and after intervention using the State-Trait Anxiety Inventory. Results: At baseline, citrus aroma and placebo groups were similar in demographic characteristics as well as anxiety scores. After intervention, mean anxiety scores in the two groups become significantly different; the scores were 34.66 ± 9.6 and 42.36 ± 6.4 for citrus aroma and placebo groups, respectively ( p  < 0.0001). No side effect was observed. Conclusions: According to the current findings, aromatherapy with Citrus aurantium L. aroma (neroli oil) may be a safe and efficient intervention and can be considered an easy and applicable method to reduce anxiety in patients with ACS.

Background: Moral distress is a growing problem for healthcare professionals that may lead to dissatisfaction, resignation, or occupational burnout if left unattended, and nurses experience different levels of this phenomenon., Objectives: This study aims to investigate the factor structure of the Persian version of the Moral Distress Scale-Revised in intensive care and general nurses., Research Design: This methodological research was conducted with 771 nurses from eight hospitals in the Mazandaran Province of Iran in 2017. Participants completed the Moral Distress Scale-Revised, data collected, and factor structure assessed using the construct, convergent, and divergent validity methods. The reliability of the scale was assessed using internal consistency (Cronbach's alpha, Theta, and McDonald's omega coefficients) and construct reliability., Ethical Considerations: This study was approved by the Ethics Committee of Mazandaran University of Medical Sciences., Findings: The exploratory factor analysis ( N = 380) showed that the Moral Distress Scale-Revised has five factors: lack of professional competence at work, ignoring ethical issues and patient conditions, futile care, carrying out the physician's orders without question and unsafe care, and providing care under personal and organizational pressures, which explained 56.62% of the overall variance. The confirmatory factor analysis ( N = 391) supported the five-factor solution and the second-order latent factor model. The first-order model did not show a favorable convergent and divergent validity. Ultimately, the Moral Distress Scale-Revised was found to have a favorable internal consistency and construct reliability., Discussion and Conclusion: The Moral Distress Scale-Revised was found to be a multidimensional construct. The data obtained confirmed the hypothesis of the factor structure model with a latent second-order variable. Since the convergent and divergent validity of the scale were not confirmed in this study, further assessment is necessary in future studies.

Phenol is classified as priority pollutant. Phenol and its derivatives are stable in water, environmental contamination, and health concerns that are used as raw material in many chemical industries. This study investigated the removal of phenol by electro-H 2 O 2 /UV system. The response surface methodology (RSM) using central composite design (CCD) was used to modeling and optimization of experimental parameters such as pH, contact time, initial concentration of phenol, concentration of hydrogen peroxide, and current density. The obtained results demonstrated that the efficiency of the electro-H 2 O 2 /UV system was maximum (>99%) under the optimal conditions for the phenol removal from aqueous solutions, 2 mM of hydrogen peroxide concentration, 50 mg/L of initial phenol concentration, pH of 5, 10 mA/cm 2 of current density, reaction time of 25 min and 2.1 kW h/m 3 of energy consumption. Therefore, the electro-H 2 O 2 /UV system is an efficient method for the removal of organic compounds from industrial wastewater.

Phenol and its derivatives are available in various industries such as refineries, coking plants, steel mills, drugs, pesticides, paints, plastics, explosives and herbicides industries. This substance is carcinogenic and highly toxic to humans. The purpose of the study was to investigate the removal of phenol from wastewater of the steel industry using the electrocoagulation-photo-Fenton (EC-PF) process. Phenol and chemical oxygen demand (COD) removal efficiency were investigated using the parameters pH, Fe 2+ /H 2 O 2 , reaction time and current density. The highest removal efficiency rates of phenol and COD were 100 and 98%, respectively, for real wastewater under optimal conditions of pH = 4, current density = 1.5 mA/cm 2 , Fe 2+ /H 2 O 2 = 1.5 and reaction time of 25 min. Combination of the two effective methods for the removal of phenol and COD, photocatalytic electrocoagulation photo-Fenton process is a suitable alternative for the removal of organic pollutants in industry wastewater because of the low consumption of chemicals, absence of sludge and other side products, and its high efficiency.

Testicular cancer is the most common cancer among young adult men and easily detected at an early stage by periodic testicular self-examination (TSE); however, health care providers seldom teach TSE, thus opportunities for early detection are missed. We aimed to evaluate the efficacy of TSE education on the knowledge, performance, and health beliefs of Turkish young men. This quasi-experimental follow-up research was conducted on 174 male Health Science university students in Turkey. The data was collected by a modified socio-demographic form and questionnaire, and the Turkish version of Champion Health Belief Model Scale which was performed at two stages: before and 3 months after education. Before education, 66.2% of the students did not know anything about TSE, and the main reason for not to perform TSE was the lack of knowledge prior to education. The results showed a significant increase in the perceived benefits in terms of TSE after education (p < 0.05). Furthermore, a positive improvement in the behavior of the students toward TSE was observed after education. These results indicate that TSE training is effective in young men, but TSE training should be repeated periodically for better efficacy. These results support that health professionals should have a more active role in the training of adult young men in colleges in terms of TSE.

Purpose: To translate, adapt, and assess the psychometric properties of the Sex After MI Knowledge Test in Iranian context (where MI is myocardial infarction)., Design and Methods: A cross-sectional descriptive survey was performed. The sample comprised 250 patients with MI. Confirmatory factor analysis was applied to extract three indicators., Findings: The Sex After MI Knowledge Test indicated good reproducibility (Cronbach's α = .76, Intraclass correlation (ICC) = 0.729, CI = 0.7280-0.781, p < .001 ICC: Intraclass correlation). Nonnormed and normed fit indices (FI) were 0.89, and incremental and comparative FIs were 0.90. Goodness-of-fit index (GFI) and adjusted GFI were below the criteria. After a varimax rotation, the first six items of the instrument explained 58.71% of total variance., Practice Implications: The instrument showed acceptable psychometric properties in terms of construct validity and internal consistency. The instrument might be used to stimulate conversations patients with MI regarding sexual knowledge and concerns., (© 2017 Wiley Periodicals, Inc.)

In this study we investigated the protective effects and possible mechanisms of pirfenidone (PF) in paraquat (PQ)-induced lung injury and fibrosis in mice. Lung injury was induced by injection of PQ (20 mg/kg). Thereafter, mice orally received water and PF (100 and 200 mg/kg) for four weeks. After 28 days, the inflammation and fibrosis were determined in the lungs by analysis of histopathology, bronchoalveolar lavage fluid (BALF) cell count, lung wet/dry weight ratio, hydroxyproline content, and oxidative stress biomarkers. Expression of several genes involved in fibrogenesis and modulation of reactive oxygen species (ROS) production, such as TGF-β1, α-SMA, collagen Iα and IV, NOX1, NOX4, iNOS, and GPX1 were determined using RT-qPCR. PF significantly decreased the lung fibrosis and edema, inflammatory cells infiltration, TGF-β1 concentration, and amount of hydroxyproline in the lung tissue. PF dose-dependently improved the expression level of the studied genes to the near normal. Decreasing of lung lipid peroxidation and catalase activity, and increasing of SOD activity in the treated mice were significant compared to the control group. Pirfenidone ameliorate paraquat induced lung injury and fibrosis partly through inhibition of inflammation and oxidative stress, and downregulation of genes encoding for profibrotic cytokines and enzymatic systems for ROS production., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Mycotoxins are natural toxins, produced by several fungal species and are associated with morbidity or even mortality in animals, plants, and humans. In this study, 120 samples of herbs and spices in both bulk and packaged forms were prepared in order to measure aflatoxin level in different regions of Iran., Methods: The aflatoxin was extracted during Mar to May 2015, using 80% methanol and then purified via immunoaffinity column. Measurements were performed, using high-performance liquid chromatography, equipped with a fluorescence detection system at excitation and emission wavelengths of 365 and 435 nm, respectively., Results: The highest prevalence of aflatoxin contamination in food products was attributed to aflatoxin B1 (30.8%). In addition, the highest prevalence of aflatoxin contamination was reported in red pepper (100%). Examination of effective factors indicated the substantial impact of moisture on aflatoxin level ( P =0.046)., Conclusion: Even at low levels of aflatoxin, contamination could be a serious threat, given the prevalent use of spices (either raw or not) as ingredients in food preparation. Therefore, regular monitoring of spices, especially chili pepper, is highly recommended., Competing Interests: Conflict of Interests The authors declare that there is no conflict of interests.

Signs and symptoms (typical and atypical symptoms) of acute coronary syndromes (ACS) differ between men and women. Identification of gender differences has implications for both health care providers and the general public. The aim of this study was to determine the symptom predictors of the acute coronary syndromes in men and women. In this prospective study, nurse data collectors directly observed 256 men and 182 women (N = 438) with symptoms suggestive of ACS in the Emergency Departments of eight hospitals in Tehran. ACS was eventually diagnosed in 183 (57.2%) men and 137 (42.8%) women on the basis of standard electrocardiogram and cardiac enzyme (CPK-MB) level. In men, chest symptoms (OR = 3.22, CI = 0.137-0.756, P = 0.009), dyspnea (OR = 2.65, CI = 1.78-4.123 P = 0.001) and diaphoresis (OR = 2.175, CI = 1.020-4.639, P = 0.044) were significantly associated with the diagnosis of ACS 3.78, 2.72 and 1.87 times more than in women having these symptoms, respectively. These results indicated that chest symptoms, diaphoresis and dyspnea were the more pronounced typical symptoms of ACS in men compared to women. Additionally, the numbers of typical symptoms can be considered as more predictive of ACS in men (OR = 1.673, CI = 1.211-2.224, P < 0.001) than women (OR = 1.271, CI = 1.157-2.331, P = 0.212). Therefore, clinicians need to take men showing typical symptoms into consideration carefully., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Due to unsatisfactory response or intolerable side effects of current drugs, treatment of essential tremor remains inadequate. Thus, we aimed to investigate the protective and therapeutic effects of aqueous and ethanolic extracts of Crocus sativus (saffron), and its active consistent, safranal, on the harmaline-induced tremor in mice., Materials and Methods: To induce tremor, harmaline (30 mg/kg) was injected intraperitoneally. Test groups were also given the aqueous and ethanolic extracts of saffron (40, 80, and 160 mg/kg) as well as safranal (0.1, 0.3, and 0.5 ml/kg), intraperitoneally, 10 min before harmaline administration (prophylactic study) or 10 min after the onset of tremors (curative study). The latency of onset, duration, and intensity of tremor were recorded., Results: The extracts (80 and160 mg/kg) dose dependently attenuated duration of harmaline-induced tremors as did reference drug, propranolol (2 and 5 mg/kg). Only the highest dose of extracts (160 mg/kg) attenuated intensity of harmaline-induced tremors throughout the study. Safranal at the doses of (0.1 and 0.3 ml/kg) but not 0.5 ml/kg attenuated duration and intensity of tremor. Onset of tremor increased with the extracts (80 and 160 mg/kg) in prophylactic study, as the effect observed with propranolol at the dose of 5 mg/kg. Safranal did not affect the latency of tremor., Conclusion: Both aqueous and ethanolic extracts of saffron and with a less effect, low doses of safranal, have relatively protective and suppressive effects on the harmaline-induced tremor and different constituents of extracts seem to participate in the protective effects against harmaline induced tremor.

Introduction: The importance of optimal clinical nursing education in professional skills development is undeniable. In clinical education, nursing students are often faced with problems. Recognizing nursing students' perception on clinical education is the first step to remove the barriers of this challenge. Methods This descriptive cross-sectional study was conducted to determine the nursing students' perspectives on clinical education. 150 nursing students were selected randomly from nursing and midwifery schools (Tehran). Data collection instrument was a researcher made questionnaire consisting of five domains: objective and curricula, instructor, feedback to student in clinical field, clinical environment, supervision and evaluation. Mean and standard deviation were calculated for each item, using SPSS, ver.14. Chi- square test was used to compare the nursing students' perspectives on clinical education based on age, sex and the work experience. The significance level was considered 0.05., Results: Mean age of the students was 21.58±26.97 students (66%) were male. 44 students (30.1%) had work experience (3.58±6.48 month). Male and female students had different perceptions in domains of clinical education (p<0.05). Nursing student had different perceptions as to objectives and curricula (p=0.039), how to deal with students in the clinical environment (p=0.032), supervision, and evaluation (p<0.001) with respect to their work experience duration. The most positive responses were in clinical instructor (81.5%) and the most negative ones were the clinical environment (33.66%), respectively., Conclusion: Providing an optimal clinical environment and improving the supervision and evaluation of student practice should prioritized in schools of nursing and midwifery.

Family support in the intensive care units is a challenge for nurses who take care of dying patients. This article aimed to determine the Iranian nurses' experience of supporting families in end-of-life care. Using grounded theory methodology, 23 critical care nurses were interviewed. The theme of family support was extracted and divided into 5 categories: death with dignity; facilitate visitation; value orientation; preparing; and distress. With implementation of family support approaches, family-centered care plans will be realized in the standard framework.

The aim of this study was to evaluate the seroprevalence and distribution of antibodies to the bluetongue virus (BTV) among dairy Holstein cattle of central Iran. From September 2010 to August 2011, 892 blood samples from Holstein dairy cattle were collected from healthy animals. Blood samples were divided according to type of farm (industrial and non-industrial), season (warm and cold), location (North, South, East, and West), cattle production groups (calf, heifer, dairy and dry) and age groups (under 6 months, 6 months-2 years and over 2 years). The sera were screened using a commercially competitive enzyme-linked immunosorbent assay (c-ELISA) kit. Twenty-four sera (2.69 %) were found to be positive for BTV. Bluetongue virus seroprevalence was significantly higher (χ(2)=8.29, df=3, p < 0.05) in cattle in southern locations as compared to those in other locations. Older animals (>2 years) showed a relatively higher seroprevalence, but the difference was not statistically significant (p=0.06). No statistically significant difference in BTV seroprevalence was noted between farming systems, seasons and cattle production groups (p > 0.05). The results demonstrate that the seroprevalence of BTV is low in cattle from the Isfahan province, central Iran. Further studies are needed to determine the serotypes and vectors of BTV in the central region of Iran.

In traditional Iranian medicine, the core of the fruit of Anacardium occidentale (cashew nut) has been used in the management of the pain. In this study gastric ulcerogenicity effect of the percolated extract of A. occidentale was investigated in rats. The extract or indomethacin (200, 300, 400 and 800 mg/kg) was administrated orally. In the control group normal saline (5 ml/kg) was used. After getting extract, indomethacin or normal saline, animals were slaughtered. The stomachs were detached and 10ml of 2% formalin injected in to the stomach for fixing the internal coat of the gastric wall. The stomachs were then slitted open near the bigger curvature and lacerations in the glandular part were evaluated. The ulcer index was determined using j-score. Data demonstrated that the oral dose of 200mg/kg of the extract did not provoke any ulcerogenic consequence in the rat's stomach. Gastric ulcerginicity of the extract at the doses of 300, 400 and 800 mg/kg was less than the similar doses of indomethacin (p<0.01). Therefore, A. occidentale is an appropriate plant for ongoing search for establishing an analgesic agent with low gastro-intestinal side effects for clinical use.

Therapeutic effect of Hypericum perforatum L. has been well known. The aim of this study is to investigate the anticonvulsant effects of Hypericum methanolic extract against seizure induced by picrotoxin in mice. The study were performed on four groups of animals. They received percolated extract of Hypericum perforatum at the doses of 25, 50, 100 & 200 mg/kg intra peritoneally. After 20 minutes animals received picrotoxin 10 mg/kg for induction of seizure. Latency of seizure, duration of seizure, death latency and percent of mortality were determined. The results indicated that latency of seizure increased in pretreated group with the dose of 50 mg/kg (p<0.01). The higher dose of extract 200 mg/kg significantly decrease duration of seizure and death latency. It maybe due to unknown ingredients in this plant or producing concentrations higher than the therapeutic level. The results showed that Hypericum perforatum L. at the dose of 50 mg/kg maybe have some beneficial effect in seizure induced by picrotoxin and this plant is suitable for continuing search in this field.

It is reported that dihydroxy chalcones have analgesic and anti-inflammatory effects. Study of the structure activity relationship (SAR) shows that benzofuran-3-one derivatives may be more effective in this respect. In this study, a new (Z)-2-(3,4-dihydroxybenzylidene)-5-methoxybenzofuran-3(2H)-one (compound 5) was synthesized and its analgesic and anti-inflammatory effects were evaluated by formalin, carrageenan and hot-Plate methods in mice. The results showed that, compound 5 induced significant antinociceptive and anti-inflammatory effect (P<0.01). Maximum analgesia (42.6%) was obtained at dose of 25 mg/kg in the first phase of formalin test. The effect of compound 5 was higher (87.7%) in chronic phase of inflammation induced by formalin (P<0.01). Administration of 25 mg/kg of compound 5 inhibited the inflammation induced by carrageenan, 32.8% and 41.7%, 1 and 3 hour after carrageenan injection, respectively. In addition, this dose of compound 5, induces significant analgesia (20.2%) in hot plate test 45 minutes after injection (P<0.01). Therefore it seems that compound 5 has potential for discovery of a compound with potent anti-inflammatory and analgesic effects and its scaffold could be use for further structural modifications.

Matricaria recutita L. is a well-known medicinal plant that is suggested as being carminative, analgesic, and anticonvulsant in traditional medicine. In the present investigation the effect of hydro-methanolic percolated extract of this plant on seizure induced by picrotoxin was studied in male mice. This study was performed on animals pretreated with doses of 100, 200, and 300 mg/kg of extract or 40 mg/kg phenobarbital as the reference drug via intraperitoneal injection. After 20 min each animal received 12 mg/kg picrotoxin for induction of seizure. Latency of onset time of seizure, duration of seizure, death latency, and death rate were determined in experimental and control groups. The results showed that latency of the beginning time of seizure was increased in groups that were pretreated with different doses of extract. The most effective dose was 200 mg/kg (P < 0.05). In addition, this dose delayed the time of death in mice (P < 0.01). The extract had no effect on the death rate. The results indicate that the extract of M. recutita possesses suitable effects on seizure induced by picrotoxin, and more experiments are needed in this field.

There have been many reports indicating the analgesic and anti-inflammatory effects of 3,4-dihydroxychalcones. We have designed and synthesized a rigid 3,4-dihydroxychalcone (RDHC) as a possible drug effecting inflammation and nociception. The analgesic and anti-inflammatory effects were evaluated by formalin and hot-plate tests, respectively. The results showed that RDHC induced significant antinociceptive and anti-inflammatory effects (P < 0.01). Maximum analgesia (63.7%) was observed at 37.5 mg/kg in the first phase of the formalin test. The effect of RDHC was higher in the chronic phase (inflammation phase) of the formalin test (86.4%, P < 0.01). In addition, a significant analgesia (maximum possible effect; MPE = 30.1%) was observed in the hot plate test 45 min after injection of 37.5 mg/kg RDHC (P < 0.01). As a result of our findings, this new RDHC could be suggested for further pharmacological studies.

A series of 3-benzylidene-7-alkoxychroman-4-one derivatives were synthesized and evaluated for their antioxidant activities. The antioxidant activity was assessed using three methods, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and thiobarbituric acid reactive substances (TBARS) assays. 3-Benzylidene-7-alkoxychroman-4-one derivatives bearing catecholic group on benzylidene moiety exhibited excellent antioxidant activity. Compounds having catechol moiety exhibited potent antioxidant activities in all tested methods and they were more active than the reference drug, Trolox.

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA) irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6 having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4 position of piperazine ring of enoxacin showed the highest cytotoxicity potential on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml, respectively). While some of the other tested compounds exhibited clear phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential of phototoxicity. These findings suggest the high potential of 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic compound with low potency of phototoxic reactions. The mentioned chemical was identified to be of special interest for further characterization.

Tribulus terrestris has been used in traditional medicine for relieving rheumatic pain and as an analgesic plant for a long time. In this investigation the analgesic effect of methanolic extract of this plant on male albino mice was evaluated by formalin and tail flick test. Extraction of the fruits of the plant was done by two different methods (suxheletion and percolation) with methanol 80%. The percolated extract was injected intraperitoneally in mice at 50, 100, 200, 400, and 800 mg/kg. The results showed that a dose of 100 mg/kg of percolated extract had the highest significant analgesic effect compared to the control group (P < 0.01) in formalin and tail flick test. There is no significant difference in the analgesic effect of suxheleted and percolated extract. The analgesic effect of the extract was lower than morphine, 2.5 mg/kg in both tests, and higher than ASA 300 mg/kg in chronic phase of pain in formalin test (P < 0.05). Pretreatment of animal with naloxone did not change the analgesia induced by the plant extract in both tests, therefore the involvement of opioid receptor in the analgesic effect of this plant was excluded. The results of ulcerogenic studies indicate that the gastric ulcerogenecity of plant extract is lower than the indomethacin in the rat's stomach. It can therefore be concluded that T. terrestris extract has a suitable analgesic effect and further studies are required to produce a more effective product of this plant to substitute for conventional analgesic drugs.

Echium amoenum Fisch & C.A. Mey. has been used in Iranian traditional medicine as demulcent and analgesic in common cold from long ago. In this investigation, the analgesic effect of the methanolic extract of the petals of this plant on male albino mice was evaluated by formalin and hot-plate test. The methanolic percolated extract with different doses 5, 10, 20 and 30 mg/kg were injected intraperitoneally to mice. The results showed that the dose of 10 mg/kg of extract had the highest analgesia in formalin (P<0.05) and hot-plate test (P<0.01) compared to the control group. The analgesic effect of extract was lower than morphine 2.5 mg/kg and ASA 300 mg/kg in the chronic phase of pain in formalin test (P<0.05) and in hot-plate test too (P<0.05). Pretreatment of animal with naloxone 4 mg/kg, s.c. 5 min before extract, decreased the analgesia induced by extract in hot-plate and acute phase of formalin tests; therefore, the opioid receptor may be involved at least partly in the analgesic effect of Echium amoenum extract. The results suggested that Echium amoenum extract has a suitable analgesic effect and further studies are required to evaluate these effects and the potential of the plant.

Effects of adenosine receptor agonists and antagonists on morphine-induced catalepsy in mice were investigated. The adenosine agonists, NECA (5'-N-ethylcarboxamidoadenosine) and S-PIA (S(+)-N6-(2-phenylisopropyl)adenosine) in doses which did not induce any response, increased the cataleptogenic effect produced by morphine. However, the morphine response was decreased and increased by the lower and higher doses of the adenosine receptor agonist, CHA (N6-cyclohexyladenosine), respectively. The adenosine receptor antagonist, theophylline, decreased, but 8-phenyltheophylline increased, the response induced by morphine. Naloxone inhibited the catalepsy induced by morphine or morphine + NECA but not that induced by NECA alone. It is concluded that adenosine A2 receptor activation increases, while adenosine A1 receptor stimulation decreases, the morphine cataleptogenic response. The response to morphine may be mediated through opioid and adenosine receptor mechanisms.

Subcutaneous injection of diluted formalin (0.25 microliter of 0.5%) caused a biphasic pain response in mice. The first phase of pain was observed during the first 5 min., while the second phase occurred 10-30 min. after formalin administration. With the formalin test, it was found that the antinociception produced by the GABA-A antagonist, picrotoxin, and the GABA-B antagonist, phaclofen, was abolished when employed in combination. The opioid antagonist naloxone and antimuscarinic atropine also decreased the picrotoxin response. However, sulpiride, SCH 23390, phenoxybenzamine and propranolol did not alter the picrotoxin response. Administration of naloxone, sulpiride and propranolol showed a pain response. The data indicate that dopaminergic and adrenergic mechanisms may not be involved in the picrotoxin antinociceptive effect. However, postsynaptic GABA-A and GABA-B may be involved in the drug effect, and involvement of opioid or cholinergic systems can not be excluded.

In the present work, the effects of neurotransmitter antagonists on theophylline-induced changes in body temperature were investigated. Intraperitoneal (i.p.) administration of a low dose of theophylline (25 mg/kg) induced slight hyperthermia, while high doses (75 and 100 mg/kg) induced hypothermia. The hypothermic effect of theophylline was decreased by pretreatment of animals with the dopamine D2 receptor antagonists sulpiride (15 and 30 mg/kg i.p.) and pimozide (0.125 and 0.25 mg/kg i.p.), the muscarinic receptor antagonist atropine (2.5 and 5 mg/kg i.p.) and the 5-HT receptor antagonist metergoline (0.25 mg/kg i.p.). However, the dopamine D1 receptor antagonist SCH 23390 (0.05 and 0.5 mg/kg i.p.), the alpha-adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg i.p.) did not after the theophylline response. In reserpinized mice, theophylline caused a dose-dependent rise in body temperature. The response was blocked in animals pretreated with phenoxybenzamine, propranolol and atropine. Single treatment of animals with either SCH 23390 or sulpiride, and also with a combination of the two drugs, decreased the hyperthermia induced by theophylline in reserpinized mice. Pimozide or metergoline did not have any effect in this respect. These data suggest that the hypothermic response to theophylline may be mediated through dopaminergic, cholinergic and serotonergic mechanisms. The hyperthermic action of theophylline in reserpinized animals may be mediated through dopaminergic, cholinergic and adrenergic systems. Overall it seems likely that theophylline interacts with modulatory mechanisms involved in thermoregulation.

The effects of morphine on core body temperature of mice in the presence or absence of catecholamine receptor antagonists were examined. Administration of different doses of morphine (20, 30 and 40 mg/kg) to mice caused a hypothermic effect. Pre-treatment of animals with the opioid receptor antagonist naloxone (1, 1.5 and 3 mg/kg), the D-2 receptor antagonists sulpiride (25 and 50 mg/kg), pimozide (0.0625, 0.125 and 0.25 mg/kg) and the adenosine receptor antagonist theophylline (25 and 50 mg/kg) decreased the morphine-induced hypothermia. The D-1 receptor antagonist SCH 23390 (0.1 and 0.2 mg/kg), the peripheral D-2 antagonist domperidone (10 and 30 mg/kg), the serotonin (5-HT) antagonist methysergide (5 and 10 mg/kg), the adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg) and the β-adrenoceptor antagonist propranolol (5 and 10 mg/kg) did not inhibit the morphine response. The antimuscarinic drug atropine (5 and 10 mg/kg) caused a slight decrease in the morphine response. In animals pre-treated with reserpine (5 mg/kg), a hyperthermic response was observed after morphine injection. It is concluded that indirect dopaminergic or adenosine receptor mechanism(s) may be involved in the morphine-induced hypothermia in mice.

The effects of the activation of adenosine receptors on core body temperature of mice have been studied in the present investigation. Intraperitoneal (i.p.) injection of non-selective adenosine agonists 5'-N ethyl- carboxamide adenosine (NECA; 0.001, 0.01 and 0.05 mg/kg), R-(N(6)-phenylisopropyl)-adenosine (R-PIA; 0.01, 0.1 and 0.25 mg/kg) and selective A(1) adenosine agonist N(6)-cyclohexyladenosine (CHA; 0.1, 0.25 and 0.4 mg/kg) reduced core body temperature. However, R-PIA and CHA were less potent than NECA in reducing the core body temperature. Theophylline (12.5, 25 and 50 mg/kg) blocked the hypothermia of the adenosine agonists. Pre-treatment of animals with selective A(1) adenosine antagonist 8-phenyltheophylline (8-PT; 0.5, 1 and 2 mg/kg) decreased the hypothermic response of CHA but not of NECA and R-PIA. 8-PT potentiated the hypothermia induced by R-PIA. These results suggest that activation of both A(1) and A(2) adenosine receptors decreases core body temperature in mice.