This study reports a new procedure for utilizing 5fluorouracil (5-Fu)-loaded polycaprolactone (PCL)/chitosan-covered magnetite nanographene oxide (5-Fu/SPION/NGO@PCL−LMWC) as a platform for synergistic thermo−chemotherapy. In fact, superparamagnetic iron oxide nanoparticles/nanographene oxide (SPION/ NGO) nanoparticles can be coated with copolymers PCL/chitosan to attain better colloidal stability in the biological environment. Nanoparticles were synthesized and characterized for their size, surface charge, X-ray patterns, polymer content, and in vitro heat-triggered release. In vitro cytotoxic effects of nanoparticles on CT-26 cells were assessed with an MTT assay and real-time polymerase chain reaction. In vivo tumor growth inhibition was evaluated on an allograft mouse model of CT-26 cells. Tumor-bearing mice were injected with 5-Fuloaded nanoparticles intravenously, and then, the targeted delivery was amplified using a magnetic field and finally exposed to an alternating magnetic field (AMF) (40 A/m, 13.56 MHz), during which the tumor site temperature increased to 43 °C. By using an infrared camera, we managed to heat the nanoparticles up to a constant temperature between 42.5 and 43.5 °C, with a tolerance ±0.03 °C. Finally, in vitro results showed that 5-Fu-loaded nanoparticles combined with AMF hyperthermia significantly reduced the plating efficiency of the cells (P < 0.01) and increased the Bax/Bcl-2 ratio (1.42 times, P < 0.01) compared with those achieved with each one alone. Furthermore, in vivo results demonstrated that the treatment of 5-Fu-loaded nanoparticles combined with the AMF diminished the growth of CT-26 tumor cells and increased the life span of the tumor-bearing mice (P < 0.001) by thermal energy deposition compared to that of the free 5-Fu drug. Also, the high level of accumulation of the nanoparticles within the tumor site was easily monitored with magnetic resonance imaging. It was concluded that the multifunctional magnetic nanoparticles could be used as a promising nanocarrier platform for achieving concurrent goals, drug delivery, magnetic targeting, thermal-sensitizing, cell death induction, and real-time monitoring of response to treatment.
Introduction: Ischemic stroke is still a leading cause of death and long-term disability all around the world. Restoration of blood flow with thrombolytic agents like tissue plasminogen activator (t-PA) is the only way that may rescue patients exposed to cerebral ischemia. Complications of these agents are commonly related to hemorrhage, arterial reocclusion, anaphylaxis, or reperfusion damage. Recurrence of stroke in the same or other cerebral arteries only rarely causes early deterioration during or shortly after thrombolytic administration. We report a patient who experienced a second stroke despite intravenous thrombolytic therapy. Case Presentation: A 68-year-old man with the history of uncontrolled hypertension and diabetes mellitus presented with acute ischemic stroke in the territory of vertebrobasilar system to the emergency department. Atrial fibrillation (AF) rhythm, high blood sugar and uncontrolled hypertension were recorded on admission. Echocardiography performed before thrombolysis, did not identify any embolic sources. Five Hours after intravenous injection of tissue Plasminogen Activator (t-PA), the patient became comatose and developed a recurrent infarction in the territory of right middle cerebral artery (MCA). Discussion: It seems that thrombolysis therapy in patients with the risk factors of recurrent stroke, must be done with more preparation and readiness for concurrent processing. Regardless of normal trans-thoracic echocardiography, in patients with AF rhythm, transesophageal echocardiography may be helpful. Also performing appropriate randomized trial to compare the incidence of recurrent stroke in patients under t-PA therapy and controls were still needed.
Background: Cerebrovascular accident (CVA), as a debilitating neurological impairment, is one of the most common causes of death in adults. It is observed that CVA is less well-documented in the developing countries compared to the developed ones and most of the available data are based on case series. Objectives: The current study aimed to evaluate the effectiveness, feasibility, outcome, and safety of intravenous recombinant tissue plasminogen activator (IV rt-PA) administration in patients with acute ischemic cerebrovascular accident (CVA). Patients and Methods: All CVA patients referred three hours after onset of symptoms to the emergency department (ED) of Shohadaye Tajrish Hospital, Tehran, Iran, from February 2012 to March 2014 were included. The following data were collected using specific check list: demographic data, chief complaint, signs and symptoms, medical history, risk factors, focused neurologic examination, and the National Institutes of Health CVA Scale (NIHSS). Then, all patients received 0.9 mg/kg of rt-PA as a bolus intravenous dose and intravenous infusion under close monitoring in the ED. Outcomes were categorized as good (complete reversal of focal neurologic deficit), not bad (partial reversal of focal neurologic deficit), death, and unknown (missed follow up). Data were analyzed by STATA software version 11. Results: Fifteen patients with the mean age of 56.7 ± 18.9 years included in the study (male 66.7%). The most common chief complaints were left side hemiplegia (46.67%), right side hemiplegia (40%), and decreased level of consciousness (13.33%), respectively. The most common affected vascular territory was medial cerebral artery (MCA) (86.67%). There was no significant relationship between age (P = 0.06), gender (P = 0.08), NIHSS score (P = 0.07), location of infarct (P > 0.99) and mean time from admission to beginning the drug administration (P = 0.55) with the outcomes. The outcome in 26.7% of the patients was favorable and death (two of four) happened due to intra cranial hemorrhage (ICH) as rt-PA side effects. Conclusions: It seems that intravenous rt-PA administered three hours after CVA is bemeficial in patients with CVA and by reducing the early evaluation time and brain imaging can overcome the CVA complications. However, any conclusion from this study is limited by the small population under study.
Introduction:Wernicke encephalopathy (WE) is a medical emergency characterized by ataxia, confusion, nystagmus and ophthalmoplegia resulting from thiamin deficiency. Alcoholism is the common cause for this disease.Case Presentation:A 41 year old man was brought to our emergency department (ED) complaining of confusion. One week earlier he had started to experience severe nausea and vomiting followed by diplopia, dysarthria and also dysphagia. One day later he had experienced gait disturbance and progressive ataxia accompanied with confusion, apathy and disorientation. He had no history of alcoholism, drug abuse or previous surgery but had history of untreated Crohn disease. Just before arrival to our emergency department, he had been hospitalized in another center for about a week but all investigations had failed to provide a conclusive diagnosis. Upon admission to our ED, he was dysarthric and replied with inappropriate answers. On physical examination, bilateral horizontal nystagmus in lateral gaze, left abducens nerve palsy and upward gaze palsy were seen. Gag reflex was absent and plantar reflexes were upwards bilaterally. After reviewing all the previously performed management measures, MRI was performed and was consistent with the diagnosis of WE. Treatment with thiamine led to partial resolution of his upward gaze palsy and nystagmus on the first day. At the end of the third day of treatment, except for gate ataxia, all other symptoms completely resolved and he was fully conscious. After the fifth day his gait became normal and after one week he was discharged in good general condition.Discussion:After reviewing the current literature, it seems that brain MRI can be helpful in the diagnosis of WE in patients with the classic clinical trial in the absence of clear risk factors.
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