Myocardial infarct-sparing effect of ischemic preconditioning abrogated in cirrhotic rat through involvement of mitochondrial permeability transition pore

Despite all studies undertaken mechanism of cirrhotic cardiomyopathy the role of cirrhosis on ischemia-reperfusion (I/R) injury and ischemic preconditioning (IPC) phenomenon hasn't been explored yet. The aim of present study is to assess the relation between cirrhosis and IPC and the mitochondrial permeability transition pore (mPTP) role in IPC cardioprotective effects in cirrhotic rats. Material and method: Rat's heart were isolated and perfused with Krebs buffer by Langendorff method. Animals were equally divided into six groups (n=6): (I) I/R; hearts were subjected to 30 min ischemia and 45 min reperfusion, (II) IPC; IPC was induced via four cycle of 5 min regional ischemia followed by 5 min of reperfusion (III) common bile duct ligated (CBDL); hearts were subjected ischemia and reperfusion in cirrhotic rats, (IV) IPC-CBDL; four cycle of 5 min regional ischemia followed by 5 min of reperfusion in cirrhotic rats (V) CSA; Cyclosporine A was added 40 min prior to main ischemia (VI) CBDL+CSA. Results: Infarct size was increased significantly in IPC-CBDL group in comparison with IPC group (p< 0.05). Addition of CSA in CBDL+CSA group significantly decreased infarct size in comparison with IPC-CBDL group (p< 0.05). Ventricular arrhythmia severity was decreased significantly in IPC group compared to IR group, whereas it was increased significantly in IPC-CBDL group compared to IPC group (p< 0.05). CSA did not decrease arrhythmia score in CBDL group. Conclusion: The results showed that the cardioprotective effects of IPC are eliminated in cirrhosis. MPTP signaling in partly involve in cirrhotic cardiomyopathy

Fresh red blood cells transfusion protects against aluminum phosphide-induced metabolic acidosis and mortality in rats

BACKGROUND: Aluminum phosphide (AlP) is used as pesticide in some countries for protection of stored grains. Human poisoning with AlP due to suicide attempt or accidental environmental exposure is associated with very high mortality partially due to development of severe metabolic acidosis. Previous studies have shown that hemoglobin has high buffering capacity and erythrocytes can potentially be used for management of metabolic acidosis. The aim of this study was to evaluate the effect of fresh packed red blood cells (RBC) transfusion on survival and cardiovascular function in AlP-poisoned rats. METHODOLOGY/PRINCIPAL FINDINGS: Rats were poisoned with AlP by gavage. Fresh packed RBC was transfused via tail vein after AlP administration. Acid-base balance, vital signs and mortality was assessed and compared in experimental groups. Infusion of fresh packed RBC (1.5 ml) one hour after AlP (4-15 mg/kg) intoxication was associated with a significant decrease in mortality rate. Packed RBC infusion improved blood pH, HCO3-, Na+ and Ca2+ levels. Plasma troponin level was also reduced and ECG changes were reversed following packed RBC infusion in AlP intoxicated rats. CONCLUSIONS: Our results showed that fresh RBC transfusion could ameliorate metabolic acidosis and enhance survival in AlP-poisoned rat. We assume that an increase in pool of RBCs may modulate acid-base balance or potentially chelate AlP-related toxic intermediates via phosphine-hemoglobin interaction

Oral Oxycodone Compared With Intravenous Morphine Sulfate for Pain Management of Isolated Limb Trauma; a Randomized Clinical Trial

Introduction: Appropriate pain relief enhances patient satisfaction and reduces patient anxiety. This study aimed to compare oral oxycodone with intravenous (IV) morphine sulfate (MS) in pain management of acute limb trauma.Method: In this randomized double-blind clinical trial, patients over 14 years old, with acute isolated limb trauma were randomized to receive either 5mg IV MS or 5 mg oral oxycodone. Pain intensity and adverse effects of medications were recorded 0, 30 and 60 minutes after drug administration and compared between the groups.Result: 58 patients were studied. Pain intensity was similar between the two studied groups at 30 minutes (P = 0.834) and 60 minutes (P = 0.880) after drug administration. Furthermore, there was no significant difference between the two groups regarding decrease in pain within the defined time interval. Drowsiness was reported more frequently in MS group after 30 minutes (p = 0.006). Patients in MS group asked for more rescue analgesia. Other adverse effects were similar in both groups.Conclusion: Oral oxycodone is as effective as IV morphine sulfate in treatment of acute musculoskeletal pain following blunt limb trauma

Pamphlet as a tool for continuing medical education: Performance assessment in a randomized controlled interventional study

Background: Pamphlet is a tool used for distance continuous professional development programs. In this study, we assessed the impact of an educational pamphlet on improving prescription writing errors in general physicians' performance. Methods: In this randomized controlled interventional study, we prepared a training pamphlet according to the most prevalent prescription writing problems. We randomized 200 participants among general physicians affiliated with Tehran Social Security Insurance Organization, and randomly divided them into intervention and control groups. Participants' prescriptions (N= 34888) were investigated over a month, and then the prepared pamphlet was sent out to the participants in the intervention group. After three months we examined their one-month prescriptions again (N= 30296) and investigated the changes in prescription errors. Results: There was no significant difference in the mean number of prescriptions in two groups before and after intervention (p= 0.076). Mean number of medicinal items reduced significantly in intervention group. Also mean number of prescriptions including injection drugs (p= 0.024), Corticosteroids (p= 0.036), Cephalosporin (p= 0.017) and non-steroidal anti-inflammatory drugs (p=0.005) reduced significantly. No significant differences were found for other errors. Conclusion: This study showed that use of an appropriate pamphlet has a considerable impact on improving general physicians' performance and could be applied for continuous professional development

Pain Relieving Effect of Sublingual Glycerol Trinitrate in Renal Colic: a Randomized Placebo-Controlled Trial

Introduction: Renal colic is caused by colicky spasms of ureters. As has been shown in previous experiments, glycerol trinitrate (TNG) can inhibit these muscular spasms. Objective: This study was performed to assess the pain relieving effect of TNG among patients referred due to renal colic pain to the emergency department (ED). Methods: This study is a randomized, placebo-controlled study on 60 patients with renal colic who were referred to the ED, who were diagnosed clinically to have renal colic, and their pain was more than 5 based on a visual analogue scale (VAS). The patient's pain was recorded at the moment of clinical diagnosis, and each one received one capsule, either 0.4 mg TNG or placebo, plus a 100 mg indomethacin suppository. The pain score was re-assessed after 5 and 30 min. The values were recorded and compared using SPSS-16 software. Results: Sixty patients with a mean age of 35.75 ± 11.99 years were enrolled (73.3% male). Patients in the two groups were matched for age (p = 0.290), sex (p = 0.559), and the presence of microscopic hematuria (p = 0.292). Pain relief from the start point until the end of the intervention was statistical different in all studied patients (p &lt; 0.05); but the comparison between the two groups showed no significant difference in this regard (p = 0.440). Conclusion: It is likely that adding TNG to an indomethacin suppository had no significant effects on better pain management of patients referred with renal colic to the ED

Is the war on terror induced-post traumatic stress disorder; the cause of suicide attack? An approach from psycho-cognitive and neurobiological perspective

Understanding suicide attack is one of the highly complicated problems in the field of psychological disorders. Post-traumatic stress disorder (PTSD), may occur in individuals subjected to traumatic assaults like terrorism, warfare, sexual abuse or natural disaster. Individual's living within war affected area often develops PTSD, which may consequently leads to cognitive and memory impairment. The war induced PTSD patient, is under the influence of severe stress; terror and helplessness as it manipulate and retrieve the past trauma as a current threat. Substantial evidences support that PTSD patients are more prone to varying degree of neurological and psychological complications. In this correspondence, we wish to highlight the biological consequence of suicide attack from the perspective of war induced PTSD. Earlier research also supports that PTSD and suicide have some common basis like alterations in hypothalamic pituitary-adrenal axis, nitric oxide and catecholamine like norepinephrine and serotonin level. Thus it is important to uncover the risk of PTSD due to war on terror with precision towards suicide attack and minimize the detriment followed by it. PTSD through the development of depression, irritability and anger, is one amongst the major causes of suicide attack.In order to clarify the underlying psychological mechanism, there is a pressing need to address it from different aspects like disease causing synaptic plasticity and abnormal brain development. PTSD is a reaction to past traumatic events. For instance, the danger of perceived threat due to witness of deaths in a war, may develop a constellation of properties that may leads to PTSD. Usually, it initiates a sequence of behavioral and cognitive changes that can be anticipated to reduce the perceived threat. However, the consequences of perceived threat lead to cognitive changes and thus maintain a devastating disorder. Appraisals of such memory not only generate situational fear but also the avoidance, which leads to enhanced trepidation and over-activity. For example, a person exposed to a road side traumatic accident may avoid driving; for having an impractical faith that it may happen again, thereby affecting its social life.Patients suffering from PTSD due to war may interpret that the trauma will persist for long time and thus he is no longer safe. He or she may suffer from depression, irritability, anger outbursts, emotional numbing, flashbacks, and nightmares [1]. It has been reported that numbing is an ordinary reaction to traumatic events. Individuals should realize that it is a normal aspect of the recovery process, otherwise it can lead to permanent changes which may worsen their physical or psychological well-being [2-4]. Children experiencing the PTSD, usually underwent alterations in hypothalamic-pituitary-adrenal axis, catecholamine and norepinephrine, which results in pathological and detrimental brain development [5]. Interestingly, the inhibition of nitric oxide in hippocampus by antidepressant has promising outcome to alleviate the PTSD symptoms [6]. While, the augmented level of plasma nitrates in depressive patients are found to be associated with suicide attempts [7].Figure 1The intention of a suicide attack is to kill a large crowd or bringing mass destruction, even with the notion that he will die in this act. Suicide bombings termed as "suicide bombing" constitute an overall 4% of terrorist attacks, which dates back to the beginning of the 19th century. In most of the modern suicide terrorist is used against non-combatants for the accomplishment of impact on political situation. Although a suicide attack aims to annihilate a primary target, however it can be used as a weapon of psychological warfare to affect the large public population. The main target of this action is not those who are killed but those witnessed it [8]. Intriguingly, it is reported that the level of brain-derived neurotropic factor (BDNF) is directly associated with suicide while indirectly it can affect PTSD. Also, defining body of research proved that altered level of serotonin in dorsal raphe nucleus, amygdala, median raphe, frontal cortex, hypothalamus and hippocampus is associated with aggressive behavior and suicide [9]. PTSD-induce symptoms like impulsivity, violence, suicide attempts, depression, panic, and anxiety can also be associated with altered serotonin levels [10].ConclusionThe mechanism of suicide attack is still highly debated; and need much more to address. Since, PTSD through the development of depression, irritability and anger, accomplish various physiological and cognitive changes in the brain, so it might be one of the causes which increases the susceptibility of acceptance for being a volunteer to suicide attack? This discussion was put forward; as some war induced PTSD patients among temporary displaced people in different regions of the world showed strong willingness for suicide attack as a counter revenge of war. Therefore, we also need to address suicide attack from the perspective of psychological disorders like war induced PTSD

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

BACKGROUND AND PURPOSE: Status epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE. We also evaluated whether the nitrergic system could participate in this effect of licofelone. METHODS: We have utilized lithium-pilocarpine model of SE in adult Wistar rats to assess the potential effect of licofelone on seizure susceptibility. Licofelone was administered 1 h before pilocarpine. To evaluate probable role of nitric oxide (NO) system, L-arginine (60 mg/kg, i.p.), as a NO precursor; L-NAME (15 mg/kg, i.p.), as a non-selective nitric oxide synthase (NOS) inhibitor; aminoguanidine (100 mg/kg, i.p.), as an inducible NOS (iNOS) inhibitor and 7-nitroindazole (60 mg/kg, i.p.), as a neuronal NOS inhibitor were injected 15 min before licofelone. Also, licofelone and diazepam 10 mg/kg were administered 30 minutes after onset of SE. RESULTS: Pre-treatment with licofelone at the dosage of 10 mg/kg, significantly prevented the onset of SE in all subjects (p \u3c 0.001). L-arginine significantly inverted this anticonvulsant effect (p \u3c 0.05). However, L-NAME and aminoguanidine, potentiated the anticonvulsant effect of licofelone (p \u3c 0.05, p \u3c 0.01). Licofelone could not terminate seizures after onset which was terminated by diazepam. CONCLUSIONS: Our findings showed that anticonvulsive effects of licofelone on SE could be mediated by iNOS. Also, we suggest that COX/5-LOX activation is possibly required in the initial stage of onset but SE recruits extra excitatory pathways with prolongation

Biological and pharmacological effects of Delphinium elbursense

Antidepressant, antihypoxic and antioxidant activities of aerial parts of Delphinium elbursense were investigated employing nine various assay systems. Antidepessant activity was examined by using forced swimming test and tail suspension test in mice. The extracts at all tested doses show significant activity as compared to control group. Antihypoxic activity was investigated in two models, haemic and circulatory. The effects were pronounced and dose-dependent in both model of hypoxia. Extracts showed weak antioxidant activity in some models. IC50 for 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical-scavenging activity was 116.2 ± 5.6 mg ml-1. Extracts showed nitric oxide-scavenging activity between 0.1 and 1.6 mg ml-1 (IC50 = 502.3 ± 18 mg ml-1) and a very weak Fe2+ chelating ability (IC50 = 1.01 ± 0.03 mg ml-1). It also exhibited low antioxidant activity in hemoglobin-induced peroxidation of linoleic acid but was capable of scavenging hydrogen peroxide in a concentration dependent manner. Extract show antihemolytic activity againts hydrogen peroxide (H2O2) induced hemolysis (558.7 ± 31 mg ml-1). The total phenolic compounds in extract were determined as gallic acid equivalents (52.24 ± 1.7) and total flavonoid contents were calculated as quercetin equivalents (17.26 ± 0.6) from a calibration curve.Keywords: Antidepressant, antihypoxic, Delphinium elbursense, flavonoid contents, forced swimming test, medicinal plants, phenolic contents, tail suspension testAfrican Journal of Biotechnology Vol. 9(34), pp. 5542-5549, 23 August, 201

Protective effects of Lithium on Sumatriptan-induced memory impairment in mice

Lithium is a drug used for the treatment of bipolar disorder. It has several mechanisms of action, and recently it is shown that lithium can antagonize the 5-HT1B/1D serotonin receptors. Sumatriptan is a 5- HT1B/1D receptor agonist used for the treatment of cluster headaches and migraine which might cause memory impairment as a potential side effect. In this study, effects of lithium on sumatriptan-induced memory impairment have been determined in a two trial recognition Y-maze and passive avoidance tests. Male mice weighing 25-30 g were divided into several groups randomly. In Y-maze test, effects of lithium (1,5,10,20,40,80 mg/kg) and sumatriptan (1,5,10 mg/kg) were assessed on memory acquisition, then lithium (0.1,1,10 mg/kg) and sumatriptan (1,10 mg/kg) were studied in passive avoidance test. Effects of lithium (1mg/kg) on sumatriptan (10 mg/kg)-induced memory impairment were studied in both of tests. The present study demonstrated that sumatriptan impaired memory in Y-maze and passive avoidance tests (P0.05), but significantly reversed sumatriptan-induced memory impairment in Y-maze and passive avoidance tests (P<0.001, P<0.05, respectively). It is concluded that lithium reverses the sumatriptan-induced memory impairment probably through 5-HT1B/1D receptors antagonism. © 2016 Tehran University of Medical Sciences. All rights reserved