Possible effects of melatonin on reperfusion injury following coronary artery bypass graft surgery.

BACKGROUND: Although coronary artery bypass graft (CABG) surgery has been reported to be one of the most effective internentions in terms of myocardial salvage, reperfusion itself can cause additional damage to the myocardium. Since there is strong evidence that free radicals are the principal offender in ischemia-reperfusion (I/R) injury, it has been suggested that treatment with antioxidant agents can be protective. Investigations have shown that melatonin secretion is partially disturbed in CABG patients. The aim of this study was to evaluate the protective effect of melatonin as an antioxidant agent on I/R injury. METHODS: 164 elective CABG candidates participated in this randomized clinical trial during the preoperative period. The candidates were randomized to receive 3 mg of melatonin tablets (physiologic dose) from 3 days before surgery until the day of discharge. Cardiac biomarkers [troponin and creatine kinase myocardial band (CKMB)] were assessed once before surgery (24 hours before surgery), and 8 and 24 hours after surgery. RESULTS: Finally, 130 patients, 65 (50%) patients in the melatonin group and 65 (50%) in the control arm finished our study. Mean age of melatonin and control groups was 59.90 ± 9.59 and 60.80 ± 8.00 years, respectively; moreover, 47 (72.30%) in melatonin and 45 (69.23%) in control group were men. No significant difference was seen in baseline cardiac biomarkers between two groups (P > 0.05). In both groups, cardiac biomarkers (CKMB and troponin) elevated after surgery in comparison to their preoperative values. There was no statistically significant difference between the control and melatonin groups regarding the 8-hour and 24-hour troponin and CKMB when adjusted for interacting factors (P > 0.05). CONCLUSION: Although physiological concentration of melatonin is protective against I/R injury, substitution of endogenous melatonin with the oral supplement which creates physiologic concentration may not prevent I/R injury. In order to have antioxidant effect, pharmacologic doses of melatonin should be employed.

Comparing the Effects of Melatonin and Zolpidem on Sleep Quality, Depression, and Anxiety in PatientsWithColorectalCancerUndergoingChemotherapy.

INTRODUCTION: Patients with cancer may have many complications involving their psychosomatic systems, such as sleep disturbance, depression, and anxiety. Thus, many research studies were conducted to reduce these complications. Zolpidem, as a short-term non-benzodiazepine treatment of insomnia, and melatonin as a chronobiological functionregulatory hormone, are commonly used for improving sleep quality. This randomized clinical trial aims to compare the effects of zolpidem and melatonin on sleep quality, depression, and anxiety in patients with colorectal cancer. METHODS: In this single-blinded trial, 90 patients with colorectal cancer undergoing chemotherapy who had obtained a score of 5 or higher on the Pittsburgh Sleep Quality Index (PSQI) were randomly divided into two groups (n=45). One group was treated with 10 mg zolpidem at bedtime, and the other group received 6 mg melatonin at bedtime for 30 days. PSQI on weeks 0, 4, 8, Groningen sleep quality scale, Hamilton rating scale for depression, and Hamilton anxiety rating scale questionnaires were performed to assess patients on weeks 0, 4, and 8. The outcome was then analyzed, and P≤0.05 was considered statistically significant. RESULTS: Both zolpidem and melatonin had significant impacts on sleep quality in week 4 (P<0.05). After stopping the treatments, the conditions were noticeably reversed on week 8 (P<0.05). Zolpidem and melatonin were relatively similar in affecting sleep duration, latency, efficiency, and disturbance. None of the two study medications had any considerable influence on anxiety and depression. CONCLUSION: Melatonin and zolpidem are promising agents for treating sleep complications and, to some extent, depression, and anxiety in cancer patients, according to the present study. However, further clinical trials are recommended to confirm the results of this study.

A Case Series of Severe Hyperammonemia Encephalopathy Related to Valproate: Can Antipsychotics Increase the Risk?

Valproate-induced hyperammonemia is a common side effect of valproate, which may occur either without any symptoms or may rarely cause symptoms of encephalopathy. Different risk factors have been defined for this side effect, including some nutritional deficiencies and polypharmacy (eg, other anticonvulsants). Three cases with psychiatric disorder who showed symptoms of severe hyperammonemia encephalopathy and had taken valproate with antipsychotics, especially risperidone, are presented here. In all cases, the symptoms were improved by discontinuation of valproate. Administration of antipsychotic may be considered as a risk factor for hyperammonemic encephalopathy related to valproate, specifically in some prone populations.

Preventive Intervention to Prevent Delirium in Patients Hospitalized in Intensive Care Unit.

Objective: Delirium is a clinical syndrome associated with multiple short- and long-term complications; therefore, prevention is an essential part of its management. This study was conducted to review the effective non-pharmacological interventions that can reduce the incidence or duration of delirium in critically ill patients. Method: A search was made in PubMed, Scopus, Psych INFO and Google Scholar databases without any time constraints. The information available was collected and sorted, and a secondary study of narrative review was done. The views of specialists on this topic were received via email and included in the texts and recommendations. Discussion: Delirium is a common, costly and potentially damaging illness in patients who are staying in hospitals, especially older patients in ICU. Thus, preventing delirium could be one of the most effective methods in preventing the complications. The present study aimed at conducting a review-validity study to generate a general view on the activities which might be effective in preventing delirium in patients.

Adaptation of the Pharmacological Management of Delirium in ICU Patients in Iran: Introduction and Definition.

Objective: Delirium is a brain dysfunction syndrome. In most cases, this syndrome is neither diagnosed accurately nor treated properly. The incidence of delirium by itself increases hospitalization period, mortality rate and the cost in health spectrum. If appropriate attempts are not made to treat this complication, the outcomes could become worse. Thus, the present study aimed at conducting a review on medications which are prescribed to treat delirium and establishing a general view on their advantages and disadvantages. Method: By searching Google Scholar, PsycINFO, Scopus, and PubMed databases as well as hand searching in key journals, data were collected without time and language limitation. After collecting the data, comparing the similar or contradictory information, and sorting them, the views of specialists were inquired and duly received via email. By acquiring consensus of opinions, the secondary manuscript was written in a narrative review form. Discussion: This narrative review paper aimed at providing a general view on defining delirium, the pathologic factors that create it, and treating this syndrome based on its development. Authentic evidence regarding delirium management was reviewed and a treatment strategy was suggested for Iranian patients.

Comparison of the Effects of Melatonin and Oxazepam on Anxiety Levels and Sleep Quality in Patients With ST-Segment-Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention: A Randomized Clinical Trial.

BACKGROUND: Anxiety and sleep disorders are prevalent problems in patients presenting with ST-segment-elevation myocardial infarction (STEMI). Usually, these problems are managed by benzodiazepines, which-albeit effective-could cause adverse effects and drug interaction. OBJECTIVE: This study was designed to compare the effects of melatonin and oxazepam in the management of anxiety and insomnia on patients following primary percutaneous coronary intervention (PCI) with a view to providing a safer alternative. METHODS: This study was designed as a randomized clinical trial. STEMI patients managed with primary PCI were enrolled and randomized into 2 groups through the permuted block randomization. The patients received either oxazepam (10 mg) or melatonin (3 mg) every night. Autoimmune disease or previous use of psychoactive medications was considered the exclusion criterion. Levels of anxiety and sleep quality were evaluated using the Hamilton Anxiety Rating Scale (HAM-A) and the Groningen Sleep Quality Score and compared between the groups. RESULTS: Each group contained 20 patients. Melatonin showed a significant advantage over oxazepam in improving sleep quality ( P = 0.040). Comparisons of the efficacy of both medications in lowering the anxiety levels when considering all the items of the HAM-A, including those related to cardiovascular disease, were significantly in favor of melatonin ( P = 0.019). CONCLUSIONS AND RELEVANCE: The results of this study suggest that melatonin, a drug with more favorable drug interaction and adverse effect profile, could be more effective than oxazepam in improving the sleep quality and anxiety levels of patients presenting with STEMI, and it could be considered a new alternative to benzodiazepines in this setting.

Methylphenidate-Induced Psychotic Symptoms in 65-Year-Old Female with ADHD.

Methylphenidate, a stimulant, is prescribed commonly in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. Methylphenidate is generally considered a safe medication, however, some rare adverse effects, such as psychotic symptoms, may occur with its therapeutic or high doses. Additionally, this medication has a potential of abuse, especially among teenagers. There are several published cases regarding methylphenidate-induced psychosis in young adults. However, psychosis due to methylphenidate has been rarely reported in the elderly. This case presents psychotic manifestations due to methylphenidate in a 65-year-old female who was taking this medication for ADHD. She consumed 3 to 4 methylphenidate hydrochloride tablets per day for several months and thought that they were sleeping pills. Antipsychotic medication was initiated and methylphenidate was discontinued which resulted in improvement of her psychosis. Alternative diagnoses, including bipolar mood disorder with psychotic feature or mood disorder due to general medical condition, were ruled out because her psychotic symptoms appeared after taking several methylphenidate tablets and disappeared after discontinuation of this medication.

Effect of memantine on post-operative cognitive dysfunction after cardiac surgeries: a randomized clinical trial.

BACKGROUND: Post-operative cognitive dysfunction (POCD) is an important complication of cardiac surgeries. Glutamate plays a critical role in physiologic and pathologic conditions in the brain. Due to the role of glutamate in ischemia, this study is designed to identify the effect of memantine in prevention of POCD early and late after cardiac surgeries. METHODS: In this randomized clinical trial, 172 patients with ages 45-75 years old who underwent elective cardiac surgery were enrolled. For patients in memantine group, 5 mg of memantine per day administered at least 48 h before surgery and increased to 10 mg per day during the first 24 h after surgery and continued for 3 months. A brief Wechsler memory test (WMT) was administered before, three to 5 days after, and 3 months after surgery for both groups. RESULTS: Both groups demonstrate standard pattern of cognitive dysfunction after surgery and in follow up. Pre- and post-operative WMT score showed significant improvement in memantine compared to control group (P < 0.001) both in unadjusted and adjusted with confounding factor analysis. Unadjusted pre-, post-operative, and follow up WMT score improved significantly after 3 months in memantine group (P = 0.006). CONCLUSION: Pre-operative administration of memantine protects patients from POCD following cardiac surgeries. In addition, it improves cognitive function 3 months after surgery. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (registration number: IRCT201303168698N12 ). Memantin effect on POCD.

The Potential Role of Naltrexone in Borderline Personality Disorder.

Objective: Management of borderline personality disorder (BPD) is a difficult challenge due to the complex features of this disorder. This article reviews the use of naltrexone in the treatment of BPD. Method: Published articles and clinical trials were searched in Google Scholar, MedLine, ELSEVIER, and Cochrane database of systematic reviews abstracts in English language between 1990 and 2017. Results: Naltrexone (NTX), a nonspecific competitive opiate antagonist, has been noted to be helpful in controlling self-injurious behavior (SIB) and dissociative symptoms in patients with BPD. Conclusion: Further studies should be conducted on the effects of naltrexone to confirm the role of this medication in the treatment of BPD.

Effect of Valerian in Preventing Neuropsychiatric Adverse Effects of Efavirenz in HIV-Positive Patients: A Pilot Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Several neuropsychiatric adverse effects of efavirenz are known. Preventing these adverse effects may improve patients' adherence to antiretroviral therapy (ART). OBJECTIVES: To evaluate the efficacy and safety of valerian in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients. METHOD: In this pilot randomized, double-blinded, placebo-controlled, clinical trial, 51 HIV-positive patients who were receiving efavirenz were recruited into the valerian (n = 25) or placebo (n = 26) group. Patients received valerian (530 mg) or placebo nightly 1 hour before sleep for 4 weeks. The neuropsychiatric status (sleep, anxiety, depression, suicidal thought, and psychosis) of patients was assessed at baseline and week 4 using validated questionnaires. RESULTS: Sleep ( P ≤ 0.001) and anxiety ( P = 0.001) significantly improved in the valerian group compared with the placebo group. Dizziness was the most common complaint of patients in first days of the intervention. In the valerian and placebo groups, 92% and 84.6% of patients experienced dizziness, respectively ( P = 0.35). Nausea was the second common adverse effect that 84% and 76.9% of patients in the valerian and placebo groups experienced ( P = 0.39). CONCLUSION: In the first 4 weeks of ART including efavirenz, valerian significantly improved sleep and anxiety in HIV-positive patients. Valerian may be considered as a potential option in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients.

Comparing Efficacy and Side Effects of Memantine vs. Risperidone in the Treatment of Autistic Disorder.

Introduction: This study was aimed to compare the efficacy and side effects of memantine, an antagonist of the NMDA receptor of glutamate, with risperidone given the fact that glutamate has been noted for its possible effects in the pathogenesis of autism. Risperidone, an atypical antipsychotic, has been approved by FDA for the management of irritability associated with autism. Methods: 30 children, aged 4-17 years, entered an 8-week, randomized trial. Patients were randomly assigned to receive either risperidone or memantine. Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Clinical Global Impressions - Improvement (CGI-I) and Clinical Global Impression-Severity (CGI-S) scales were used to assess behavioral symptoms of the patients. Results: Both risperidone and memantine reduced the scores of 4 subscales of ABC as well as the 10-item and the total score of CARS significantly. However, differences between the 2 drugs in the scores of each evaluating scale were not found to be significant. Relatively, larger number of patients on risperidone showed "very much improvement" when assessed by CGI-I scale when compared with those on memantine. Discussion and conclusion: The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism. Therefore, memantine may be considered as a potential medication in the treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone.

Craving and Drug Reward: A Comparison of Celecoxib and Ibuprofen in Detoxifying Opiate Addicts.

Objective: Craving for substance abuse is a usual and complicated problem in patients, with opioid addiction who are in opioid detoxifying process. Craving has been added as one of the diagnostic criteria of substance use disorders in DSM-5. The present trial aimed at comparing the effects of celecoxib versus ibuprofen in reducing pain and decreasing the desire to use opiates in patients undergoing opiate detoxification (n = 32). Method: A total of 32 patients (both inpatients and outpatients), who were undergoing opiate detoxification procedure and met the inclusion criteria entered this 4- week study. Participants who suffered from pain due to opiate withdrawal were randomized into 2 groups: Group 1 received celecoxib 200 milligrams once per day and group 2 received ibuprofen 400 milligrams 4 times per day. Self-reported Desire for Drug Questionnaire (DDQ) and 0-10 numeric pain scale were used at baseline and at the end of the study to evaluate changes in opiate craving and pain, respectively. Data analysis was done by SPSS-21 statistical software. Results: In this study, 16 patients received celecoxib 200 milligrams once daily, and 16 received ibuprofen 400 milligrams 4 times daily. After 4 weeks of treatment with both ibuprofen and celecoxib, the results revealed that celecoxib and ibuprofen equally reduced the pain symptoms. After 4 weeks of treatment, with either ibuprofen or celecoxib, significant improvement was observed in decreasing the craving in the celecoxib group, but not in the ibuprofen group. Conclusion: The study revealed a significant difference between the celecoxib and ibuprofen group in reducing craving in patients with opiate craving after 4 weeks of treatment. However there were no significant differences between these two groups in reducing pain.

Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study.

Objective: Because of functional impairment caused by generalized anxiety disorder and due to cognitive side effects of many anti-anxiety agents, in this study we aimed to evaluate the influence of Passion flower standardized extract on reaction time in patients with generalized anxiety disorder. Method: Thirty patients aged 18 to 50 years of age, who were diagnosed with generalized anxiety disorder and fulfilled the study criteria, entered this double-blind placebo-controlled study. Reaction time was measured at baseline and after one month of treatment using computerized software. Correct responses, omission and substitution errors and the mean time of correct responses (reaction time) in both visual and auditory tests were collected. The analysis was performed between the two groups and within each group utilizing SPSS PASW- statics, Version 18. P-value less than 0.05 was considered statistically significant. Results: All the participants were initiated on Sertraline 50 mg/day, and the dosage was increased to 100 mg / day after two weeks. Fourteen patients received Pasipy (Passion Flower) 15 drops three times daily and 16 received placebo concurrently. Inter-group comparison proved no significant difference in any of the test items between assortments while a significant decline was observed in auditory omission errors in passion flower group after on month of treatment using intra-group analysis. Conclusion: This study noted that passion flower might be suitable as an add-on in the treatment of generalized anxiety disorder with low side effects. Further studies with longer duration are recommended to confirm the results of this study. .

Effect of Omega-3 Fatty Acids on Depressive Symptoms in HIV-Positive Individuals: A Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: The antidepressant effect of omega-3 fatty acids has been described in the non-HIV population. The effect of omega-3 fatty acid supplementation on the mood status of HIV-positive patients has not been evaluated yet. OBJECTIVE: In this study, the effect of omega-3 fatty acids on depressive symptoms was evaluated in HIV-positive individuals. METHOD: A total of 100 HIV-positive patients with Beck Depression Score ≥16, were assigned to receive either omega-3 fatty acids or placebo twice daily for 8 weeks. Depressive symptoms of each participant were evaluated at baseline (month 0) and at the end of months 1 and 2 of the study. Beck Depression Inventory Second Edition, depression subscale of the Hospital Anxiety and Depression Scale, and Patient Health Questionnaire were used for assessment of depressive symptoms. RESULTS: Reduction in mean ± SD of all depression scores during the study period was statistically significant within the omega-3 group and when compared with the placebo group (for both comparisons, P < 0.001). Also, the mean differences of all depression scores were decreased significantly during the intervals: months 0, 1, and 2 (P < 0.001 for all comparisons). Among the participants, 7 (7%) and 4 (4%) patients in the omega-3 and the placebo group, respectively, experienced mild gastrointestinal problems, but the incidence of adverse drug reactions related to the interventions was not statistically different between the groups (P = 0.09). CONCLUSION: Omega-3 fatty acids improved depressive symptoms in HIV-positive individuals without any significant adverse reaction.

Evaluating the Potential Effect of Melatonin on the post-Cardiac Surgery Sleep Disorder.

BACKGROUND: Postoperative neurological injuries, including cognitive dysfunction, sleep disorder, delirium, and anxiety, are the important consequences of coronary artery bypass graft surgery (CABG). Evidence has shown that postoperative sleep disturbance is partly due to disturbed melatonin secretion in the perioperative period. The aim of this study was to evaluate the effect of melatonin on postoperative sleep disorder in patients undergoing CABG. METHOD: One hundred forty-five elective CABG patients participated in a randomized double-blind study during the preoperative period. The patients were randomized to receive either 3 mg of melatonin or 10 mg of Oxazepam one hour before sleep time. Each group received the medication from 3 days before surgery until the time of discharge. Sleep quality was evaluated using the Groningen Sleep Quality Score (GSQS), and the incidence of delirium was evaluated by nursing records. Sleep quality and anxiety scores were compared before and after surgery through the Wilcoxon signed-rank test. The analysis of covariance (ANCOVA) and independent t-test were used to compare the sleep and anxiety scores between the groups. P values ≤ 0.05 were considered statistically significant. RESULTS: Totally, 137 patients at a mean age of 60 years completed the study (76% male). The analysis of the data showed that sleep was significantly disturbed after surgery in both groups. The patients in the Oxazepam group demonstrated significantly higher disturbance in their mean postoperative GSQS score than did their counterparts in the melatonin group (p value < 0.001). A smaller proportion of the participants experienced delirium in the melatonin group (0.06%) than in the Oxazepam group (0.12%); however, this difference was not statistically significant. CONCLUSION: The result of the present study revealed that melatonin improved sleep in post-cardiac surgery patients more than what was observed with Oxazepam. Therefore, melatonin may be considered an effective alternative for Benzodiazepines in the management of postoperative sleep disorder.

Effect of Melatonin on Cardiac Injury after Primary Percutaneous Coronary Intervention: a Randomized Controlled Trial.

Several studies have reported that the antioxidant properties of melatonin can provide cardiac protection through scavenging of free radicals. This study sought to investigate the efficacy of melatonin on cardiac biomarkers, myocardial-specific protein high sensitive troponin-T (hs-TnT) and creatine kinase-MB (CK-MB), in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). In this randomized clinical trial, a total of 40 patients with STEMI planned to undergo pPCI were randomly assigned to two groups of receiving melatonin plus standard treatment [n=20] and control group, receiving only standard therapy [n=20]. The following parameters including hsTnT and CK-MB were assessed preoperatively (baseline) and at 6 hours after procedure. Melatonin could significantly reduce the level of CK-MB (118.2 ± 21.09 IU/L in the treated group versus 198.24 ± 20.94 IU/L in the control group; p-value = 0.01). However, there was no difference in the mean hs-TnT level between two groups (2491 ± 664 µg/L vs. 2801 ± 620 µg/L; p value = 0.73). Our results revealed that melatonin can be considered as a safe adjunctive medication to the standard regimen after pPCI for the aim of decreasing cardiovascular events. Meanwhile, this was a pilot study with a small number of patients and further studies are needed to confirm the beneficial effect of melatonin in patients with STEMI.

Comparing the Efficacy of 8 Weeks Treatment of Cipram® and its Generic Citalopram in Patients With Mixed Anxiety-Depressive Disorder.

BACKGROUND: Patients with mixed anxiety-depressive disorder (MADD) suffer both anxiety and depression. Antidepressants, especially, selective serotonin reuptake inhibitors are among agents of choice for treating this condition. OBJECTIVES: This study compared the efficacy of Cipram® with its generic, citalopram. PATIENTS AND METHODS: Forty adult outpatients (between 18 to 55 years of age) with a diagnosis of MADD who met the trial criteria, entered this double-blind, randomized study. Subjects were assigned to receive either generic citalopram or Cipram® for 8 weeks. Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) were utilized to assess depression and anxiety at baseline, weeks 4 and 8 of the study. Statistical analysis was performed using SPSS 14.0. RESULTS: Twenty patients received citalopram (mean dosages of 22 mg/day during the first 4 weeks and 33 mg/day during weeks 4 to 8) and 20 received Cipram® (mean dosages of 22 mg/day during the first 4 weeks and 29 mg/day during weeks 4 to 8). Both treatments were noted to be effective in improving the symptoms of MADD at weeks 4 and 8. The mean differences of HAM-D and HAM-A between Citalopram and Cipram® groups were significantly different at the end of week 4 (HAM-D: P = 0.038, HAM-A: P = 0.025), but not at the end of week 8 (HAM-D: P = 0.239, HAM-A: P = 0.204). Both medications were tolerated well by the patients. CONCLUSIONS: This study suggests that the efficacy of citalopram is similar to that of Cipram® in the treatment of MADD after 8 weeks. Meanwhile, Cipram® may reduce depression and anxiety quicker than its generic, citalopram.

Association between Perioperative Parameters and Cognitive Impairment in Post-Cardiac Surgery Patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) has been an important complication of cardiac surgery over the years. Neurocognitive dysfunction can affect quality of life and lead to social, functional, emotional, and financial problems in the patient's life. To reduce POCD, we sought to identify the association between cognitive dysfunction and perioperative factors in patients undergoing cardiac surgery. METHODS: One hundred one patients aged between 45 and 75 years undergoing elective cardiac surgery were enrolled in this study. All the surgeries were performed on-pump by the same medical team. A brief Wechsler Memory Test (WMT) was administered before surgery, 3 to 5 days after the surgery, and 3 months after discharge. All related perioperative parameters were collected in order to study the effect of these parameters on the postoperative WMT scores and WMT score change. RESULTS: The study population consisted of 101 patients, comprising 14 (13.8%) females and 87 (86.2%) males aged between 45 and 75 years. In univariate analysis, the baseline WMT score, serum levels of lactate dehydrogenase and T3, cross-clamp time, and preexistence of chronic obstructive pulmonary disease showed significant effects on the postoperative WMT score (p value < 0.05), whereas only the baseline WMT score and chronic obstructive pulmonary disease showed strong effects on the postoperative WMT score in the multiple regression model. In addition, the multiple regression model demonstrated a significant association between the baseline WMT score, serum creatinine level, and nitrate administration and the WMT score change. CONCLUSION: Our study showed that preexisting chronic obstructive pulmonary disease and preoperative high serum creatinine levels negatively affected cognitive function after surgery. In addition, there was a strong relationship between the patients' basic cognition and POCD. Preoperative nitrate administration led to a significant improvement in POCD. It is also concluded that the preoperative administration of specific medicines like nitrates can reduce neurological complications after cardiac surgery.

Non-addictive opium alkaloids selectively induce apoptosis in cancer cells compared to normal cells.

BACKGROUND: Cytotoxic effects of some of the members of papaveraceae family have been reported in Iranian folk medicine. Recent reports has indicated that alkaloids fraction of opium may be responsible for its cytotoxic effect; however, the mechanism of this effect is not fully understood. This study has been designed to investigate the selective cytotoxic, genotoxic and also apoptosis induction effects of noscapine, papaverine and narceine, three non-addictable opium alkaloids, on HT29, T47D and HT1080 cancer cell lines. Mouse NIH3T3 cell line was chosen to present non-cancerous cells and Doxorubicin was selected as the positive control. METHODS: Cells were treated by different concentrations of Noscapine, Papaverine, Narceine and doxorubicin; viability was assessed by MTT assay. The genotoxicity and apoptosis induction were tested with comet assay and Annexin-V affinity when the concentration of each these drugs is less than its IC50. In addition, the DNA damage and caspase activity of the T47D cells were examined and the results were compared. RESULTS: This study noted the cytotoxicity and genotoxicity of noscapine and papaverine, specifically on cancerous cell lines. Furthermore, papaverine induces apoptosis in all studied cancer cell lines and noscapine showed this effect in T47D and HT29 cells but not in NIH-3 T3 cells as noncancerous cell line. narceine also showed genototoxicity in the studied cell lines at its IC50 concentration. CONCLUSIONS: This experiment suggests that noscapine and papaverine may be of use in cancer treatment due to their specific cytotoxicity and genotoxicity. However, further in vivo studies are needed to confirm its usefulness in cancer treatment.

A Randomized Placebo-controlled Trial of Clonidine Impact on Sedation of Mechanically Ventilated ICU Patients.

Clonidine has sedative and analgesic properties. Randomized studies examining these properties in mechanically ventilated ICU patients are scarce. This study was designed to assess the impact of clonidine on sedative agent use in mechanically ventilated patients. In a prospective, randomized, double blind, placebo-controlled study in a general ICU of a university medical center in Tehran, Iran, 40 patients, over 18 years on mechanical ventilation for 3 days or more randomized into 2 equal groups of clonidine and placebo. Clonidine arm received usual sedation and enteral clonidine 0.1 mg TID and escalated to 0.2 mg TID on the second day if hemodynamics remained stable. Ramsay Sedation Score was used to assess sedation. Opioids and midazolam were used in all patients. 10 patients in clonidine and 3 in placebo arms had history of drug abuse (P = 0.018). The mean of sedatives used in the clonidine/placebo arms (mg/day) were; MED (Morphine Equivalent Dose) 91.4 ± 97.9/112.1 ± 98.8 P=0.39, midazolam 7.1 ± 7.9/8.3 ± 9.2 P=0.66 and propofol 535.8 ± 866.7/139.1 ± 359.9 P=0.125. After adjusting for addiction and propofol, clonidine reduced MED use by 79.6 mg/day (P=0.005) and midazolam by 5.41 mg/day (P = 0.05). Opioids and midazolam need reduced by clonidine co-administration regardless of history of drug abuse. Acceptable side effect profile and the lower cost of clonidine could make it an attractive adjunct to sedative agents in ICU.