Hjorthastings3815
Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and MPO activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations.
Pretreatment with Mg protects the liver from the acute injury which occurs shortly after septicemia.
Pretreatment with Mg protects the liver from the acute injury which occurs shortly after septicemia.
We investigated the possible non-lipid effects of simvastatin (SIMV) on paraoxonase 1 (PON1) and butyrylcholinesterase (BuChE) activity, as well as on malondialdehyde (MDA) levels in normolipidemic rats.
Two experimental groups of Wistar rats (10mg/kg/day of SIMV) and two control groups (saline) underwent a 21-day treatment period (TP). On the 22nd day one experimental and one control group of rats were sacrificed. Remaining groups of animals were sacrificied on the 32nd day of the study (10-day after-treatment period (AT)). Blood samples and slices of liver, heart, kidney, and brain tissue were obtained for the measurement of PON1 and BuChE activity and levels of MDA. Data were analyzed by means of t-test for independent samples. p values≤0.05 were considered as statistically significant.
SIMV caused a significant decrease of serum and liver PON1 activity (18-24%, p≤0.05) and MDA concentrations in the plasma, heart, liver, kidney, and brain (9-40%, p≤0.05), while plasma and liver BuChE activity increased by 29% (p≤0.05) and 18%, respectively. All effects of SIMV were largely diminished following AT. The exception was MDA, which remained significantly decreased in plasma and all tissues analyzed.
SIMV significantly decreased PON1 activity and MDA levels and increased BuChE activity. We suggest that the decrease of MDA levels is a beneficial therapeutic effect of SIMV, for example in cardiovascular disorders, while the increase of BuChE activity, especially in brain, may be a potential adverse effect in patients with Alzheimer disease.
SIMV significantly decreased PON1 activity and MDA levels and increased BuChE activity. We suggest that the decrease of MDA levels is a beneficial therapeutic effect of SIMV, for example in cardiovascular disorders, while the increase of BuChE activity, especially in brain, may be a potential adverse effect in patients with Alzheimer disease.
Recent growing consensus introduced thiazolidinediones, agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma as promising candidates in the management of ischemia in various organs. Thereby, interest was raised to investigate the neuroprotective effects of pioglitazone against transient ischemia/reperfusion (I/R) injury in diabetic rats targeting mainly the oxidative-inflammatory-apoptotic cascades which are involved in this insult.
Forebrain ischemia was induced in streptozotocin-diabetic rats by occlusion of the bilateral common carotid arteries for 15min followed by 1h reperfusion. Pioglitazone (10mg/kg; po) was administered daily for 2 weeks prior to I/R.
The drug alleviated hippocampal injury inflicted by diabetes and/or I/R injury where it suppressed nuclear factor kappa (NFκB), and consequently the downstream inflammatory cytokines tumor necrosis factor-α and interleukin-6. In parallel, the anti-inflammatory cytokine interleukin-10 was elevated. Antioxidant potential of pioglitazone was depicted, where it reduced neutrophil infiltration, lipid peroxides, nitric oxide associated with replenished reduced glutathione. Decline of excitatory amino acid glutamate content is a main finding which is probably mediated by the NFκB signaling pathway as well as improved oxidant status. Pioglitazone exerted an anti-apoptotic effect as reflected by the reduction of the cytosolic cytochrome c and the key downstream executioner caspase-3.
Pioglitazone is endowed with neuroprotective properties which are probably mediated by its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms hence may provide a successful agent for the management of ischemic stroke.
Pioglitazone is endowed with neuroprotective properties which are probably mediated by its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms hence may provide a successful agent for the management of ischemic stroke.
Radiotherapy within pelvis is a vital component of curative therapy for urological, gynecological and rectal malignances. EGFR targets Rectum is especially vulnerable to secondary radiation injury resulting in proctitis. The most common and life-threatening symptom is rectal hemorrhage. Formalin application into the rectum causes local cauterization of telangiectatic mucosal vessels. The aim of our study was to assess the efficacy of local formalin application in patients with hemorrhagic radiation proctitis.
A solution of 4.0% formalin was used in the treatment of 20 patients with clinical and proctoscopic evidence of radiadion proctitis. Treatment involved direct application of 4.0% formalin into the rectum. All patients were followed-up in terms of complete resolution of symptoms or recurrences of bleeding.
A total of 20 patients with a mean age of 69.7 (range, 57-80) years were followed for 51.2 (range, 1-93) months. The mean duration of symptoms was 4.5 (range, 1-10) months and the interval between the end of radiotherapy and symptoms was mostly between 5 and 30 months. Patients required an average of 2 (range, 1-5) formalin treatments. Of the 20 patients, 10 had complete resolution of their symptoms after their first treatment. In 10 patients bleeding recurred and they were offered another formalin instillation and/or 5-ASA suppositories and argon therapy. Complete resolution of symptoms was achieved in all patients.
Topical formalin instillation is effective, safe, and well-tolerated method for the patients with radiation proctopathy. This therapy may be repeated in case of recurrent bleeding and combined with other methods of treatment.
Topical formalin instillation is effective, safe, and well-tolerated method for the patients with radiation proctopathy. This therapy may be repeated in case of recurrent bleeding and combined with other methods of treatment.
Arjunolic acid (AA), a pentacyclic triterpenoidal saponin of Terminalia arjuna is well recognized for its antioxidant properties. We proposed to evaluate its antioxidant potential against focal cerebral ischemia reperfusion (I/R) injury in rats subjected to middle cerebral artery occlusion (MCAO).
In the present study, rats were randomly divided into a sham, MCAO, AA (10 and 20mg/kg) treated groups. Rats received their respective treatment orally by gavage for 7 days prior to MCAO. Rats were anaesthetized with ketamine (100mg/kg), xylazine (10mg/kg) and subjected to 2h occlusion and 22h reperfusion. Neurological deficit, brain water content and oxidative stress markers were measured after 22h of reperfusion.
Rats pretreated with AA showed significantly reduced neurological deficit score, infarct size. AA prevented neuronal damage induced by I/R by regulating the levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), protein carbonyl content and mitochondria generated reactive oxygen species. In addition, it also controlled the enzyme activities of Na(+)-K(+) ATPase, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR).
Pre-treatment with AA effectively prevented the cerebral I/R induced oxidative damage by virtue of its antioxidant potential. These results indicate that supplementation of AA may be beneficial in stroke prone population.
Pre-treatment with AA effectively prevented the cerebral I/R induced oxidative damage by virtue of its antioxidant potential. These results indicate that supplementation of AA may be beneficial in stroke prone population.
The mechanisms underlying memory functions during withdrawal from the chronic drug use are poorly understood.
We assessed learning and spatial working memory using the delayed alternation assay (T-maze) in rats, previously subjected to cocaine self-administration. The T-maze training was conducted 1-5 weeks after cocaine cessation; working memory efficacy was assessed at 5-8 weeks of drug withdrawal. After behavioral training and testing, the rats were sacrificed and the levels of p-CREB/CREB and p-ERK2/ERK2 in several brain areas were measured. The same molecular assessment was performed in rats with cocaine injections, but forced to drug abstinence in home cages.
After 5 weeks of cocaine withdrawal from self-administration, a significant impairment of working memory under increased working memory load (inter-trial delay extended to 30s), with no changes at baseline conditions (inter-trial delay 10s), was noticed. Neither acquisition phase nor working memory performance measured 6-8 weeks after the last drug intake differed between cocaine or saline pretreated rats. Upon T-maze training and 8-week withdrawal, cocaine-pretreated rats had higher levels of p-CREB/CREB in prefrontal cortex and dorsal striatum and lower in hippocampus compared to saline rats. Increased levels of p-ERK2/ERK2 were observed in dorsal striatum, hippocampus and decreased in nucleus accumbens. In cocaine-pretreated caged rats no changes in p-CREB/CREB levels were observed, while ERK2 levels either decreased (frontal cortex) or increased (nucleus accumbens).
Our results suggest that cocaine self-administration results in cognitive impairments and alterations in ERK/CREB signaling pathway long after discontinuation of drug use.
Our results suggest that cocaine self-administration results in cognitive impairments and alterations in ERK/CREB signaling pathway long after discontinuation of drug use.
From a theoretical point of view, cholecalciferol (vitamin D3) as a precursor of calcitriol, a representative of secosteroids, may have neuroprotective properties and affect seizure phenomena.
In the present study, interactions between cholecalciferol and three second generation antiepileptic drugs (oxcarbazepine, lamotrigine, and topiramate) were studied in the maximal electroshock test in mice. Effects of drugs on motor coordination, long-term memory and explorative behavior of animals were evaluated in the chimney test, passive-avoidance task and plus-maze test, respectively.
Cholecalciferol applied ip at doses of 37.5-75μg/kg significantly raised the electroconvulsive threshold. Cholecalciferol, administered at the subthreshold dose of 18.75μg, potentiated the anticonvulsant activity of oxcarbazepine and lamotrigine, but did not change their brain concentrations, therefore the revealed interactions seem to be pharmacodynamic. Furthermore, the action of cholecalciferol was not dependent on its conversion to calcitriol. The anticonvulsant effect of topiramate was enhanced by cholecalciferol applied at the higher dose of 37.5μg/kg, at which it also increased the brain level of topiramate. As regards adverse effects, cholecalciferol, antiepileptic drugs, and their combinations did not significantly impair motor coordination or long-term memory in mice. Moreover, cholecalciferol did not show either anxiolytic or anxiogenic properties.
Our findings show that cholecalciferol has not only its own anticonvulsant action but also enhances efficacy of certain antiepileptic drugs, at least in experimental conditions.
Our findings show that cholecalciferol has not only its own anticonvulsant action but also enhances efficacy of certain antiepileptic drugs, at least in experimental conditions.
