Antibiotic Resistance Pattern in Intensive Care Units in a Large Referral Hospital in Iran.

Background & Objective: Antibiotic resistance, especially in the form of multidrug-resistant (MDR), is a big problem, especially in intensive care units (ICUs). This study aimed to evaluate antibiotic resistance and MDR patterns among patients hospitalized in the ICUs in one of the large referral centers in Iran. Methods: The present study was conducted at Imam Khomeini Hospital in Tehran (a great referral hospital), which admits critically ill patients requiring ICU services. To determine the rate of positive cultures for resistant strains, the patient's blood specimens were sent to the laboratory of the hospital for inoculation on proper culture media within 2 hours of extraction. Antimicrobial susceptibility tests were done using the Bauer-Kirby disk diffusion method. Results: A total of 1,755 samples were collected from the patients to assess microbial strains and antibiotic resistance. The most common microbial strains detected in the cultures extracted from peripheral blood samples were Klebsiella pneumonia (22.1%), Staphylococcus epidermidis (7.9%) and another coagulase-negative Staphylococcus (15.0%). The antibiogram test showed antibiotic resistance in 1,509 cases, leading to a resistance prevalence rate of 85.9%. The most common antimicrobial resistance observed was against cotrimoxazole (61.7%), ciprofloxacin (51.3%), imipenem (50.0%), and ampicillin (49.6%). The rate of MDR was found to be 96.3%. Conclusion: In Iran's ICUs, a significantly high level of antibiotic resistance may be seen especially the MDR pattern, which indicates the need to change the pattern of prescribing and managing these drugs in ICU centers.

Effect of Papaver rhoeas hydroalcoholic extract on blood corticosterone and psychosocial behaviors in the mice model of predator exposure-induced post-traumatic stress disorder.

The function of hypothalamic-pituitary-adrenal (HPA) axis and psychosocial behaviors are affected in post-traumatic stress disorder (PTSD). Based on presence of several beneficial alkaloids in Papaver rhoeas (PR) plant, we assessed the effects of PR hydroalcoholic extract on blood corticosterone and psychosocial behaviors in the mice model of predator exposure-induced PTSD. Male NMARI mice were assigned into two main groups (control or PTSD) according to stress exposure (presence or absent of the predator). Each main group was divided into four subgroups according to treatment with the different doses of PR extract. Mice were treated intraperitoneally by PR extract at three different doses (1,5&10 mg/kg) 30 min before the beginning of test on days 1, 2&3. Corticosterone concentration determined in the blood samples on days 1, 3&21, and mice examined for the psychosocial behaviors on the third day. PTSD induction in mice by exposing to hungry predator increased blood corticosterone and changed the psychosocial and physiological behaviors. PR extract decreased blood corticosterone in PTSD mice on the third day as well as 21st day. Also, PR extract improved the psychosocial and physiological behaviors in PTSD mice. Moreover, PR extract increased blood corticosterone in control mice at a dose-response manner. PR extract is able to decrease blood corticosterone in PTSD condition and probably prevent the HPA hyperactivity in PTSD mice when exposed to the stress stimuli. Accordingly, decreased blood corticosterone by PR extract might be involved in improvement of the physiological and psychosocial behaviors in PTSD mice.

Safety of megadose meropenem in the empirical treatment of nosocomial sepsis: a pilot randomized clinical trial.

Objective: To evaluate the safety of megadose meropenem as empirical treatment of nosocomial sepsis. Materials & methods: Critically ill patients diagnosed with sepsis received either high-dose (2 g every 8 h) or megadose (4 g every 8 h) meropenem as an intravenous infusion over 3 h. Results: A total of 23 patients with nosocomial sepsis were eligible and included in the megadose (n = 11) or high-dose (n = 12) group. No treatment-related adverse events were observed during a 14-day follow-up. Clinical response was also comparable between the groups. Conclusion: Megadose meropenem may be considered for empirical treatment of nosocomial sepsis without serious concern regarding its safety.

As resistance to antibiotics is increasing among microbes, rational use of these drugs is important both in the community and in hospitals. Many infections with resistant microorganisms may be fatal. For a long time, carbapenems have been the last resort for treatment of resistant microorganisms. Unfortunately, resistance to these drugs is increasing. It appears that use of higher doses of antibiotics may help in some cases. However, the potential harm caused by higher doses is a problem. In this primary study, higher doses of meropenem, a common carbapenem, were found to be safe.

Investigation of how stimulation intensity of rTMS affects magneto permeabilization of the Blood-Brain Barrier (BBB).

The present study aimed to assess the effect of the rTMS (repetitive Transcranial Magnetic Stimulation) intensity on the permeability of the BBB for brain-targeted drug delivery. For this purpose, different rTMS intensities including 70%, 100%, and 130% of Resting Motor Threshold (RMT) assessed in three groups of rats (three groups of 5 rats). Stimulation applied over the right hemisphere of the animals. The first phase of the study was composed of intravenous administration of Evans Blue Dye (EBD), rTMS stimulation and EBD uptake measurement in both brain hemispheres. The second examination was included rTMS stimulation, injection of the MRI Contrast Agent (CA), and signal intensity measurement in post-contrast images. Each exam also included five rats in a sham group. Thus, the total of 40 male Wistar rats enrolled in this study. There was no significant difference in the amount of EBD accumulated between the right hemisphere of the brain in the sham group and the group with 70% RMT magnetic stimulation, while this figure was significantly higher than the sham group for both 100 and 130% RMT groups. There was also a significant difference in this index between 100 and 130% groups. All of the results from the first phase of the study were consistent with the second assessment representing an upward trend of induced permeability by rising rTMS intensity. The results of this study imply that to cause an effective temporary disruption in the BBB the intensity of 100% RMT or above should be used for stimulation.

Anti-diabetic effects of fullerene C60 nanoparticle mediated by its anti-oxidant activity in the pancreas in type 1 diabetic rats

Abstract The present study aims to examine the anti-diabetic effects of fullerene C60 nanoparticle, as an anti-oxidant compound, on serum glucose level, body weight, food and water intake, and pancreatic oxidative stress in the rats with type 1 diabetes. Diabetes mellitus was induced by single intravenous injection of streptozotocine (45 mg/kg) into the tail vein of the rats. Four groups of rats were divided as follow: normal, normal treatment, diabetic, and diabetic treatment groups. Normal treatment and diabetic treatment groups received intra-orally fullerene (1 mg/ kg/daily) up to day 60 following streptozotocine injection. Oxidative stress markers in the pancreas were evaluated on day 60 after inducing diabetes mellitus. Injection of streptozotocine significantly increased serum glucose level as well as food and water intake on all experimental days; it decreased body weight on day 60. Streptozotocine increased MDA level and decreased GSH level and SOD activity in the pancreas. Fullerene significantly decreased food and water intake and increased body weight as compared with the diabetic group. Fullerene also could normalize the pancreatic MDA and GSH markers. The present study suggested that fullerene can decrease diabetic symptoms via its anti-oxidant activity in the pancreas in the rats with type 1 diabetes mellitus.

Intracerebroventricular injection of propranolol blocked analgesic and neuroprotective effects of resveratrol following L5 spinal nerve ligation in rat.

OBJECTIVES: Resveratrol as a natural polyphenolic agent can alleviate neuropathic pain symptoms. The mechanism of analgesic activity of resveratrol is far from clear. The current study examine whether analgesic activity of resveratrol is mediated by its neuroprotective and anti-oxidant activity in the neuropathic pain. We further examine whether analgesic activity of resveratrol is mediated by ß-adrenoceptors in the brain. METHODS: Neuropathic pain induced by L5 spinal nerve ligation (SNL). Male Wistar rats assigned into sham, SNL, SNL + resveratrol (40 µg/5 µL), and SNL + resveratrol + propranolol (a non-selective ß-adrenoceptor antagonist, 30 µg/5 µL) groups. Drugs injected intracerebroventricular (ICV) at day SNL surgery and daily for 6 days following SNL. Thermal allodynia and anxiety examined on days of -1, 2, 4, and 6 following SNL. Electrophysiological study performed on day 6 following SNL for evaluation of resveratrol effects on sciatic nerve conduction velocity (NCV). The activity of catalase (Cat) and superoxide dismutase (SOD) enzymes in the brain assessed on days 6 following SNL. RESULTS: Resveratrol significantly decreased thermal allodynia (and not anxiety) in all experimental days. Additionally, resveratrol significantly increased NCV, and also normalized the disrupted Cat and SOD activities following neuropathic pain. Furthermore, propranolol significantly blocked the analgesic and neuroprotective effects of resveratrol. CONCLUSIONS: It is suggested that the analgesic effects of resveratrol is mediated by its neuroprotective and antioxidant activities in the neuropathic rats. Furthermore, propranolol blocked the analgesic and neuroprotective effects of resveratrol.

Fenofibrate protects the neurovascular unit and ameliorates plasma corticosterone levels in pentylenetetrazole-induced kindling seizure in mice.

Epileptic seizures are the most common neurological diseases that change the function of neurovascular unit at molecular levels accompanied by activation of a wide variety of neurodegenerative cascades. Based on the pleiotropic functions of peroxisome proliferator-activated receptor-alpha (PPARα), the current study evaluated the neuroprotective effects of fenofibrate (an effective PPARα agonist) on the brain injuries induced by pentylenetetrazole (PTZ)-induced kindling seizure. Adult male NMRI mice were randomly assigned into four groups (n = 14) as follows; control, untreated kindled mice (PTZ) and two fenofibrate-treated kindled groups. Repeated intraperitoneal injections of PTZ (45 mg/kg) were used to develop kindling seizure every 48 h for 21 days. Treated mice were administered orally fenofibrate at doses of 30 and 50 mg/kg/day during the study. Plasma corticosterone and brain levels of brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA) and mRNA transcription of p53, as well as blood-brain barrier (BBB) permeability, were determined at termination of the study. Fenofibrate considerably improved seizure latency and anxiety-like behaviors in treated kindled mice. Fenofibrate at doses of 30 and 50 mg/kg significantly (P < 0.001) decreased plasma corticosterone (56.88 ± 0.80 and 54.81 ± 0.29 ng/mL, respectively) compared to PTZ group (74.96 ± 1.60 ng/mL). It also significantly (P < 0.05) decreased BDNF levels in both treatment groups (8.13 ± 0.14 and 8.74 ± 0.09 ng/mL, respectively) compared to PTZ group (9.68 ± 0.20 ng/mL). Fenofibrate particularly at higher dose significantly (P < 0.01) decreased MDA content and mRNA expression levels of p53 in treated kindled mice by 67% and 28%, respectively, compared to PTZ group. Similarly, 50 mg/kg fenofibrate significantly (P < 0.05) decreased Evans blue extravasation into brain in treated kindled mice (8.72 ± 0.96 µg/g) compared to PTZ group (15.31 ± 2.18 µg/g). Our results revealed the anticonvulsive and neuroprotective effects of fenofibrate in PTZ-induced kindling seizure in mice. Fenofibrate also improved the neurovascular functions at molecular levels in kindling seizure that might be associated with ameliorating the seizure behaviors.

Crocin Improves Diabetes-Induced Oxidative Stress via Downregulating the Nox-4 in Myocardium of Diabetic Rats.

BACKGROUND: Oxidative stress has a crucial role in the pathophysiology of cardiac dysfunction in the diabetic milieu. Crocin is a natural compound that acts as an antioxidant which could potentially ameliorate oxidative damages in various tissues. The potential role of crocin in the myocardial tissue is not clear yet. This study was aimed to evaluate the possible antioxidative properties of crocin in the myocardium of diabetic rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into four groups as normal, normal-treated, diabetic, and diabetic-treated. Diabetes was induced by a single intravenous injection of STZ (40 mg/kg). Two treated groups of animals (diabetic and non-diabetic) were treated with crocin daily for 8 weeks (40 mg/kg/IP). At the end of day 56, animals were sacrificed under deep anesthesia, and blood and tissue samples were collected. After tissue preparation, the level of nitrate, malondialdehyde, and glutathione and the activity of superoxide dismutase and catalase enzymes were measured via standard protocols. In addition, the level of Nox-4 mRNA expression was examined by RT-PCR method. The data were analyzed via one-way ANOVA, and P < 0.05 was considered as a significant difference. RESULTS: Diabetes induces oxidative damages by upregulating the Nox-4 enzyme and increasing nitrate and malondialdehyde levels in the myocardium. Diabetes reduced the superoxide dismutase, catalase, and glutathione activities in the myocardial tissues. Treatment with crocin reversed these changes, reduced Nox-4 mRNA expression, and reduced the nitrate and malondialdehyde content in the myocardium of diabetic rats. CONCLUSION: Diabetes induces oxidative stress in myocardium via the upregulating Nox-4 enzyme, and the treatment with crocin reversed these changes. Thus, crocin could be considered as a novel agent for potentially protecting myocardial tissues against diabetes-induced oxidative damages.

Prevalence of nosocomial infections in Covid-19 patients admitted to the intensive care unit of Imam Khomeini complex hospital in Tehran.

BACKGROUND AND OBJECTIVES: Nosocomial infections (NIs) are an important cause of mortality and morbidity in intensive care units (ICU). Pneumonia is the most common serious manifestation of infection in Covid-19 patients. The aim of this study was to investigate the prevalence of pneumonia in Covid-19 patients admitted to the ICU. MATERIALS AND METHODS: In this cross-sectional study, 1240 Covid-19 patients admitted for more than 48 h in the ICUs of Imam Khomeini Complex Hospital (IKCH) in Tehran for seven months in 2020 were included in the study with initial diagnosis of Covid-19 (PCR test and chest imaging). Data were collected regarding severity of the illness, primary reason for ICU admission, presence of risk factors, presence of infection, length of ICU and hospital stay, microbial type and antibiotic resistance. In this study, the pattern of antibiotic resistance was determined using the disk difusion method. RESULTS: In this study, 289 (23.3%) out of 1320 patients experienced NIs. 221 (76.4%) out of 289 patients had underlying diseases and the most common of which were hypertension, diabetes and heart disease, respectively. 163 patients (56.4%) were RT-PCR COVID-19 positive and 200 patients (69%) died. The majority of patients with NIs (71%) were over 55 years old. The most common type of nosocomial infection (66%) was ventilator-associated pneumonia (VAE). The most common microorganisms that cause pneumonia were Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa, respectively. CONCLUSION: Pneumonia infection is high in Covid-19 patients admitted to the ICU, it needs to be planned with the diagnosis and measures related to the control and prevention of this infection.

PPAR-α Agonist Fenofibrate Ameliorates Oxidative Stress in Testicular Tissue of Diabetic Rats.

BACKGROUND: Oxidative stress has the potential to induce impotence, especially in diabetic patients. Peroxisome proliferator-activated receptor alpha (PPAR-α) agonists can potentiate antioxidants in a wide variety of tissues. However, no available evidence exists showing a direct antioxidant effect on testicular tissue in the setting of diabetes. Therefore, the aim of this study was to evaluate whether PPAR-α agonists can act directly to protect testicular tissue from oxidative damage. METHODS: Male Wistar rats (180-200 g) were randomly allocated into four groups: normal control (N), normal treated (NF), diabetic (D), and diabetic treated (DF) (n = 6 for each group). Diabetes was induced by a single intravenous injection of streptozotocin STZ (40 mg/kg). Two treatment groups (diabetic and nondiabetic) were treated with fenofibrate daily for 8 weeks (80 mg/kg orally). At the end of 8 weeks, the animals were sacrificed and blood and testicular tissue samples collected. Nitrate, malondialdehyde, and glutathione levels, and the activity of superoxide dismutase and catalase enzymes were evaluated. The data were analyzed via two-way analysis of variance (ANOVA), with P < 0.05 taken as significant. RESULTS: Diabetes significantly augmented free radicals, as attested by an increase in nitrate levels in testicular tissue, reduced activity of superoxide dismutase and catalase enzymes, and enhanced malondialdehyde content. These changes lead to oxidative stress in testicular tissues. Treatment with fenofibrate in the diabetic group improved oxidative stress by potentiation of antioxidant elements and a reduction in nitrate and malondialdehyde production. CONCLUSION: Diabetes has a potent effect in promoting the development of oxidative damage in testicular tissue. The PPAR-a agonist fenofibrate improves the redox state and may prevent oxidative stress in the setting of diabetes-induced oxidative stress.

Crocin treatment decreased pancreatic atrophy, LOX-1 and RAGE mRNA expression of pancreas tissue in cholesterol-fed and streptozotocin-induced diabetic rats.

Objective Oxidative stress in diabetic mellitus is a consequence of oxidative stress, which plays a critical role in the pathogenesis of diabetic tissue damage. Receptors for advanced glycation end products and for oxidized low-density lipoproteins (LDL) have critical contribution in oxidative tissue damage. The present study investigated whether anti-diabetic effects of Crocin via modulation of mRNA expression of RAGE and LOX-1 receptors in diabetic rats. Methods In the current study, high-fat cholesterol (HFC) and streptozotocin (40 mg/kg) used to induce type II diabetes. Experimental groups as follows: (Group 1: control); (Group 2: control treatment [Crocin]); (Group 3: DM [STZ]); (Group 4: DM treatment [STZ + Crocin]); (Group 5; DM + HFC [STZ + HFC]); (Group 6; DM + HFC treatment [STZ + HFC + Crocin]). Crocin (20 mg/kg/day, i.p.) administered in treatment groups for 60 days. Serum glucose and cholesterol levels evaluated on days 5, 30 and 60 after induction of DM. Pancreatic tissue from all group removed on day 60 for histological and RT-PCR analysis. Results Application of Crocin significantly decreased serum cholesterol levels on day 60 after induction of DM in diabetic + HFC rats. Moreover, Crocin significantly decreased serum glucose levels on days 30 and 60 both in diabetic and diabetic + HFC rats. Crocin partially prevented the atrophic effects of STZ on both exocrine and endocrine parts of pancreas. Additionally, Crocin significantly decreased LOX-1 and RAGE mRNA expression OF pancreas in diabetic rats. Conclusion The current study suggested that Crocin suppressed atrophic change of the pancreas by decrease of LOX-1 and RAGE mRNA expression in diabetic rats.

Crocin Improves Oxidative Stress by Potentiating Intrinsic Anti-Oxidant Defense Systems in Pancreatic Cells During Uncontrolled Hyperglycemia.

INTRODUCTION: Oxidative stress (OS) during uncontrolled hyperglycemia has a pivotal role in pancreatic dysfunction. Our study aimed to demonstrate that crocin can potentiate anti-oxidant defense systems of pancreatic cells to improve oxidative stress. METHODS: Male Wistar rats were divided randomly into four groups: a normal group, a normal-treated group, a diabetic group and a diabetic-treated group (n = 6 rats per group). Diabetes was induced by a single dose of streptozotocin (45 mg/kg/IV). The treated groups received crocin daily for 8 weeks (40 mg/kg/IP). At the end of the experiment, rats were sacrificed and pancreas tissue was obtained. Subsequently, the concentrations of malondialdehyde (MDA), nitrate and glutathione as well as the enzymatic activities of catalase and superoxide dismutase (SOD) were determined in all animals. Data were analyzed by two-way ANOVA with appropriate post hoc testing and a probability value of P < 0.05 was considered to represent a statistically significant difference in mean values. RESULTS: Uncontrolled hyperglycemia weakened the anti-oxidant system by decreasing SOD and catalase enzyme activity in pancreatic tissues and induced OS by increasing the MDA content in diabetic non-treated animals. Crocin potentiated the anti-oxidant defense system by increasing the activity of both SOD and catalase, and improved OS by diminishing MDA production in pancreatic cells of rats contained in the diabetic-treated group. CONCLUSION: Based on our results, it is concluded that uncontrolled hyperglycemia can weaken the anti-oxidant defense system and cause the development of OS. Also, crocin can improve OS in pancreatic cells by potentiating the anti-oxidant defense system.

Fullerenol Nanoparticles Decrease Blood-Brain Barrier Interruption and Brain Edema during Cerebral Ischemia-Reperfusion Injury Probably by Reduction of Interleukin-6 and Matrix Metalloproteinase-9 Transcription.

BACKGROUND: The present study aimed to examine the protective role of fullerenol nanoparticles against blood-brain barrier (BBB) interruption and brain edema during cerebral ischemia-reperfusion injury probably by reduction of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) transcription. METHODS: The male Wistar rats (weighting 280-320 g) were randomly assigned into four groups as follows: sham, control ischemic, pretreated ischemic, and posttreated ischemic groups. Cerebral ischemia-reperfusion (IR) injury was performed by occlusion of middle cerebral artery (MCA) for 90 minutes followed by twenty-four hours reperfusion. Rats were administered fullerenol 5mg/kg, intraperitoneally, 30 minutes before induction of IR in pretreated ischemic group and immediately after termination of MCA occlusion in posttreated ischemic group. After twenty-four hours reperfusion, the method of Evans blue dye extravasation (EBE) and RT-PCR were used for determination of BBB permeability and mRNA expression levels of MMP-9 and IL-6, respectively. Neuronal deficit score (NDS) and edema of the ischemic hemispheres were also evaluated. RESULTS: MCA occlusion increased NDS in control ischemic rats (3.16 ± 0.16) with concomitant increase in EBE (15.30 ± 3.98µg/g) and edema (3.53 ± 0.50%). Fullerenol in both pretreated and posttreated ischemic groups reduced NDS (36% and 68%, respectively), EBE (89% and 91%, respectively) and edema (53% and 81%, respectively). Although MCA occlusion increased the mRNA expression levels of MMP-9 and IL-6 in ischemic hemispheres, fullerenol in both treatment groups noticeably decreased the mRNA expression levels of these genes. CONCLUSION: In conclusion, fullerenol nanoparticles can protect BBB integrity and attenuate brain edema after cerebral ischemia-reperfusion injury possibly by reduction of IL-6 and MMP-9 transcription.

PPAR-α Agonist Improves Hyperglycemia-Induced Oxidative Stress in Pancreatic Cells by Potentiating Antioxidant Defense System.

BACKGROUND: Diabetes-induced oxidative stress has an essential role in pancreatic cells dysfunction. The present study aimed to evaluate whether peroxisome proliferator activated receptor- alpha (PPAR-α) induction by fenofibrate counterbalances oxidative stress in pancreatic cells. METHODS: In this in vivo study, male Wistar rats were randomly divided into four groups as normal, normal treated, diabetic and diabetic treated groups (n=6 in each group). Diabetes was induced by a single intravenous injection of streptozotocin (45 mg/kg). Treated animals received fenofibrate for 8 weeks (80 mg/kg/day) orally. At the end of the 8th week, rats were sacrificed and blood samples and pancreas tissues were collected. Then, the content of malondialdehyde (MDA), nitrate (Nox) and glutathione (GLT) and enzymatic activities of catalase (CAT) and superoxide dismutase (SOD) were assessed. D ata were analyzed using two-way ANOVA. RESULTS: Diabetes deteriorated anti-oxidant defense capacity in pancreatic cells by reducing SOD and CAT activities and induced oxidative stress as reflected by increased MDA content and free radicals production (Nox content). Treatment by fenofibrate increased SOD and CAT activities and improved oxidative stress by decreasing pancreatic MDA and Nox levels. CONCLUSION: Uncontrolled hyperglycemia weakens anti-oxidant defense capacity in pancreatic cells and contributes to oxidative stress. PPAR-α induction by fenofibrate can restore anti-oxidant defense systems and improve diabetes-induced oxidative stress.

Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats.

BACKGROUND: Diabetes-induced oxidative stress has an essential role in hepatic dysfunction. The current study was aimed to potentiate the impact of crocin treatment on the anti-oxidant defenses system of hepatic tissue following un-controlled hyperglycemia. METHODS: Male Wistar rats were randomly divided into four experimental groups as normal, normal treated, diabetic and diabetic treated (n = 6). Diabetes was induced by a single intravenous dose of streptozotocin into tail vein (40 mg/kg). Treated animals received crocin daily for 8 weeks intraperitoneally (40 mg/kg). At the end of the 8th week, animals were sacrificed and liver tissues were collected. After tissue preparation, malondialdehyde (MDA), nitrate and glutathione (GLT) contents and also catalase (CAT) and superoxide dismutase (SOD) enzymes activities were evaluated in all experimental animals. RESULTS: Un-controlled diabetes weakened anti-oxidant system by decreasing SOD and CAT enzymes activities and increasing MDA production. Crocin potentiated anti-oxidant defense system by increasing SOD and CAT enzymes activities and improved oxidative damage by lessening nitrate content and MDA production in hepatic tissues of diabetic animals. CONCLUSION: Crocin maybe a potential therapeutic candidate against diabetes-induced hepatic dysfunction by attenuating oxidative damage in the hepatic tissue.

Anticonvulsant and Antioxidant Effects of Pitavastatin Against Pentylenetetrazol-Induced Kindling in Mice.

Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation) have been reported by previous studies. Therefore, we aimed to determine whether pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin improves the brain antioxidant capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty-four mice were randomly divided into four groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day twenty-one. Animals received daily oral pitavastatin for twenty-one days. Latency, score and duration of the seizures were recorded. The activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all rats. Results: There was a progressive reduction in latency of the kindled rats in the next injections of PTZ. Pitavastatin reduced this value (latency) particularly at higher dose. Seizures duration and score also decreased in treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not significantly change the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ-kindling group by 53% and 30%, respectively. Pitavastatin at higher dose significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45% and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can improve the behavioral expression of the PTZ-kindling rats and attenuate the seizure-induced oxidative/nitrosative damage.

Fullerenol nanoparticles decrease ischaemia-induced brain injury and oedema through inhibition of oxidative damage and aquaporin-1 expression in ischaemic stroke.

BACKGROUND: We examined the possible protective effects of fullerenol nanoparticles on brain injuries and oedema in experimental model of ischaemic stroke through inhibition of oxidative damage and aquaporin-1 (AQP-1) expression. METHODS: Experiment was done in three groups of rats (N = 66): sham, control ischaemia and ischaemic treatment. Ischaemia was induced by 90-minutes middle cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion. Rats received a dose of 10 mg/kg of fullerenol 30 minutes before MCAO. Infarction, brain oedema, malondialdehyde (MDA) and nitrate contents as well as mRNA level of AQP-1 were determined 24 hours after termination of MCAO. RESULTS: Administration of fullerenol before MCAO significantly reduced the infarction of cortex and striatum by 72 and 77%, respectively. MCAO induced brain oedema in control ischaemic rats (3.83 ± 0.53%), whereas, fullerenol significantly reduced it (0.91 ± 0.55%). The contents of MDA and nitrate increased in ischaemic hemispheres by 86 and 41%, respectively. Fullerenol considerably reduced the MDA and nitrate contents by 83 and 48%, respectively. Moreover, MCAO noticeably increased the mRNA level of AQP-1 in ischaemic hemispheres by 22%, whereas fullerenol significantly decreased it by 29%. DISCUSSION: Fullerenol is able to reduce ischaemia-induced brain injuries and oedema possibly through inhibition of oxidative damage and AQP-1 expression in ischaemic stroke.

Multi-Modal Preemptive Analgesia With Pregabalin, Acetaminophen, Naproxen, and Dextromethorphan in Radical Neck Dissection Surgery: A Randomized Clinical Trial.

BACKGROUND: Preemptive analgesia may be considered as a method not only to alleviate postoperative pain but also to decrease analgesic consumption. Different regimens are suggested, but there is currently no standard. OBJECTIVES: The aim was to measure the efficacy of preemptive analgesia with pregabalin, acetaminophen, naproxen, and dextromethorphan in radical neck dissection surgery for reducing the intensity of pain and morphine consumption. PATIENTS AND METHODS: This study was conducted as a randomized double-blind clinical trial. Eighty adult patients (18 to 60 years of age) under the American society of anesthesiologists (ASA) physical status I and II undergoing elective radical neck dissection were enrolled. Patients were randomized into two groups of 40 with a simple randomization method. The case group received a combination of 15 mg/kg acetaminophen, 2.5 mg/kg pregabalin, 7 mg/kg naproxen, and 0.3 mg/kg dextromethorphan administered orally one hour prior to surgery. Postoperative pain was assessed with the universal pain assessment tool (UPAT) at 0, 2, 4, 6, 12, and 24 hours after surgery. Subjects received morphine based on postoperative pain control protocol. Total administered morphine doses were noted. RESULTS: Postoperative pain rates at 0, 2, 4, 6, 12, and 24 hours after surgery were significantly lower for the case group than the control group (P values = 0.014, 0.003, 0.00, 0.00, and 0.00, respectively). Total morphine doses for the preemptive analgesia group were 45% lower than those of the other group. Side effects were similar for both groups. CONCLUSIONS: A single preoperative oral dose of pregabalin, acetaminophen, dextromethorphan, and naproxen one hour before surgery is an effective method for reducing postoperative pain and morphine consumption in patients undergoing radical neck dissection.

Overproduction of nitric oxide intensifies brain infarction and cerebrovascular damage through reduction of claudin-5 and ZO-1 expression in striatum of ischemic brain.

Nitric oxide (NO) overproduction has been demonstrated from different NO-synthase overexpression or hyperactivity after brain ischemia. Here, we examined the effects of inhibition of NO overproduction on brain infarction, cerebrovascular damage and expression of claudin-5 and zonula occludens-1 (ZO-1) in striatum of ischemic brain. The experiment was performed in three groups of rats; sham, control ischemia and ischemic treatment. Brain ischemia was induced by 60min of middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Treated rats received L-NAME 30min before induction of ischemia (1mg/kg, i.p.). Infarct volume and histopathological changes of ischemic striatum were assessed by TTC and LFB staining methods, respectively. Ultimately, quantitative RT-PCR was used for assessment of claudins-5 and ZO-1 expression. MCAO in the control group induced infarction (135±25mm3) at large areas of striatum in accompany with neuronal damages, whereas L-NAME significantly reduced infarction (87±16mm3) and neuronal injuries. The mRNA of ZO-1 and claudin-5 decreased in ischemic striatum, whereas inhibition of NO overproduction by L-NAME attenuated this reduction for these genes. Our findings indicated that NO overproduction after brain ischemia plays a crucial role in neuronal damage especially at striatal regions. Hence, inhibition of excessive NO production may save striatal cerebrovascular integrity of ischemic brain.