Attenuation of doxorubicin-induced cardiotoxicity by mdivi-1: a mitochondrial division/mitophagy inhibitor

Doxorubicin is one of the most effective anti-cancer agents. However, its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Given the multiple beneficial effects of the mitochondrial division inhibitor (mdivi-1) in a variety of pathological conditions including heart failure and ischaemia and reperfusion injury, we investigated the effects of mdivi-1 on doxorubicin-induced cardiac dysfunction in naïve and stressed conditions using Langendorff perfused heart models and a model of oxidative stress was used to assess the effects of drug treatments on the mitochondrial depolarisation and hypercontracture of cardiac myocytes. Western blot analysis was used to measure the levels of p-Akt and p-Erk 1/2 and flow cytometry analysis was used to measure the levels p-Drp1 and p-p53 upon drug treatment. The HL60 leukaemia cell line was used to evaluate the effects of pharmacological inhibition of mitochondrial division on the cytotoxicity of doxorubicin in a cancer cell line. Doxorubicin caused a significant impairment of cardiac function and increased the infarct size to risk ratio in both naïve conditions and during ischaemia/reperfusion injury. Interestingly, co-treatment of doxorubicin with mdivi-1 attenuated these detrimental effects of doxorubicin. Doxorubicin also caused a reduction in the time taken to depolarisation and hypercontracture of cardiac myocytes, which were reversed with mdivi-1. Finally, doxorubicin caused a significant elevation in the levels of signalling proteins p-Akt, p-Erk 1/2, p-Drp1 and p-p53. Co-incubation of mdivi-1 with doxorubicin did not reduce the cytotoxicity of doxorubicin against HL-60 cells. These data suggest that the inhibition of mitochondrial fission protects the heart against doxorubicin-induced cardiac injury and identify mitochondrial fission as a new therapeutic target in ameliorating doxorubicin-induced cardiotoxicity without affecting its anti-cancer properties

The Use of Ice Pack for Pain Associated with Arterial Punctures

BACKGROUND: Arterial punctures for monitoring respiratory problems are one of the most painful procedures in hospitalized patients. The knowledge regarding non-pharmacologic methods of pain management, including cold application is limited. OBJECTIVE: This aim of this study was to determine if the application of ice pack before the procedure would decrease the pain perception of patients during the arterial puncture. MATERIALS AND METHODS: This experimental study was undertaken among patients admitted to emergency ward in a public educational center affiliated to Ilam University of Medical Sciences, Ilam/Iran. Sixty-one eligible subjects were randomly assigned to two groups. The treatment group (n=31) received ice pack before arterial puncture, whereas the control group (n=30) received no intervention for pain management. Pain immediately and 5 minute after the arterial puncture were scored on a visual analog scale (VAS) from 0 to 10. RESULTS: The mean of pain score immediately after the arterial puncture were 3.12 (1.68) and 4.6 (1.56) for treatment and control group, respectively (p0.05). Patients with previous arterial puncture reported higher pain intensity. CONCLUSION: Cold pack is a simple, non-invasive and inexpensive technique for pain management before the arterial puncture. However, there is a need for further research regarding this topic

Intranasal midazolam sedation as an effective sedation route in pediatric patients for radiologic imaging in the emergency ward: A single-blind randomized trial

OBJECTIVES: Prevention and reduction of pain, anxiety, and fear during medical procedures is one of the most important factors that should be considered in pediatric emergencies. The aim of this study was to compare the efficacy of oral versus intranasal midazolam in sedation during radiologic imaging in the largest province of Iran, Kerman. MATERIALS AND METHODS: Eighty children were enrolled in this single-blind clinical trial based on convenience sampling and were divided into two groups receiving 0.5 mg/kg midazolam in oral route administration and 0.2 mg/kg midazolam in intranasal route administration. Finally, 75 patients remained for evaluating medication acceptability, sedation level, onset time of sedation, additional sedative dose, adverse effects of sedation, and provider satisfaction. RESULTS: Children in the intranasal group accepted medication more easily (89.8 vs. 36.9; P� 0.001), while these children received a lower sedation dose, but the sedation level in both methods was similar (P = 0.72). Our findings showed that children in the intranasal sedation group had a faster onset of sedation compared to the oral group (17.94 ± 8.99 vs. 34.50 ± 11.45; P� 0.001). The frequency of midazolam side effects had no difference between the groups (29.7 vs. 15.8; P = 0.15). CONCLUSION: Intranasal midazolam with a lower sedation dose induces a faster onset and better acceptance. Intranasal midazolam can be used as an effective sedative method for pediatric patients, especially in emergency wards. © 2020 Turkish Journal of Emergency Medicine | Published by Wolters Kluwer-Medknow

Intravenous calcium Gluconate alleviates Lead-induced abdominal pain, a randomized clinical trial

Background: In 2016, in a lead poisoning outbreak in Iran, physicians reported thousands of opium users who presented to emergency departments (EDs) with intractable severe abdominal pain which did not respond to any narcotic medication. During the same period of time, we investigated the efficacy of intravenous calcium gluconate in alleviating lead-induced abdominal pain. Methods: In a single-center, single blinded, randomized controlled trial, a convenient sample of adult opium-addicted patients who presented to an academic ED with abdominal pain and had an initial diagnosis of lead poisoning were included and randomly subjected to two treatment groups receiving conventional treatment (morphine 0.1 mg/kg + normal saline; group 1) and conventional treatment plus 1 g of intravenous calcium gluconate (group 2) to alleviate their abdominal pain. The visual analogue scale (VAS) was determined by each patient (0 to 100 mm) before treatment, and 15, 30, and 60 min after intervention. Results: A total of 50 patients (25 in each group) were enrolled. Blood lead levels, VAS scores before treatment, and mean administered dose of morphine were similar between the two groups. After treatment, mean VAS score dropped to 64.7± 10.4 vs. 67.1± 10.9 at 15 min (P = 0.437), 64.6± 10.9 vs. 58.0 ± 11.2 at 30 min (P = 0.041), and 63.8± 10.7 vs. 53.6± 10.9 at 60 min (P = 0.002) in groups 1 and 2, respectively. Conclusion: Intravenous calcium gluconate administration along with morphine can improve abdominal pain in lead poisoning due to the ingestion of lead-contaminated opium. Further interventional studies are recommended to see if response to calcium salts in suspected lead-induced abdominal pain can rule in lead toxicity. Trial registration: IRCT20171009036661N2. Registered 27 May 2018-Retrospectively registered, © 2020 The Author(s)