ABSTRACT
Paracetamol (P), one of the most popular and commonly used analgesic and antipyretic agents, causes hepatotoxicity in overdoses. Amlodipine (AML), an L-type calcium channel blocker, has been shown to have anti-inflammatory activity by reversing the effect of calcium in the inflammation pathogenesis. In this study, the hepatoprotective activity of AML on P-induced hepatotoxicity was evaluated. Thirty male albino Wistar rats were divided into five groups: (1) control, (2) 2 g/kg of P, (3) 2 g/kg of P + 5 mg/kg of AML, (4) 2 g/kg of P + 10 mg/kg of AML, and (5) 10 mg/kg of AML. Some liver enzymes, oxidative parameters, cytokine mRNA expressions, histopathology, and immunohistochemical studies were performed in liver and blood samples. The serum levels of alanine aminotransferase and aspartate aminotransferase and the mRNA expression of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta in the liver tissues were significantly increased in the group treated with P. The superoxide dismutase and glutathione parameters decreased and malondialdehyde levels increased in the livers of the rats treated with P. All these parameters were increased with both doses of the AML similar to the control group. A histopathological examination of the liver showed that AML administration ameliorated the P-induced inflammatory liver damage. In immunohistochemical staining, the expression of TNF-α in the cytoplasm of the hepatocytes was increased in the P group but not in other treatment groups when compared to the control. In conclusion, AML treatment showed significant protective effects against P-induced hepatotoxicity by increasing the activity of antioxidants and reducing inflammatory cytokines.
Subject(s)
Acetaminophen , Amlodipine/pharmacology , Calcium Channel Blockers/pharmacology , Calcium Channels, L-Type/drug effects , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Calcium Channels, L-Type/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Cytokines/metabolism , Cytoprotection , Disease Models, Animal , Inflammation Mediators/metabolism , Liver/metabolism , Liver/pathology , Male , Oxidative Stress/drug effects , Rats, WistarABSTRACT
Our purpose is to evaluate the complications of open hip dislocation, which is used as a helpful technique in hip surgery. We have retrospectively reviewed 45 hips of 44 cases who applied open hip dislocation with various indications in our institute between the years 2006-2013. There were 27 males and 17 females whose mean age was 31,9 (range, 11-58) years with mean follow-up time of 56,9 months (range, 13-106). The number of cases with at least one complication related to open hip dislocation was 27. Within our series 14 hips have developed only 1 complication, 1 hip have 2, 10 hips have 3 and 2 hips have 4 different complications. Regarding Dindo-Clavien classification 17 hips were evaluated as Grade I (38%), 3 hips were Grade IIa (7%), 2 hips were Grade IIb (4%) and 5 hips were Grade III (11%). In conclusion, the absence of major complications after open hip dislocation does not make it absolutely safe. Open hip dislocations can only be indicated when trochanteric complications are considered. The patients need to be well informed on potential issues and risks.
Subject(s)
Disarticulation/adverse effects , Hip Dislocation/complications , Hip Joint/surgery , Postoperative Complications/etiology , Adolescent , Adult , Child , Female , Follow-Up Studies , Hip Dislocation/physiopathology , Hip Joint/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. METHODS: The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each. Diabetes model was created with the use of streptozotocin, and blood glucose levels of the rats were measured after 72 hours. Thirty days after the transplantation, blood samples were obtained from the rats, and then pancreas, kidney, and ovary specimens were fixed in 10% formaldehyde and the experiment completed. After staining with hematoxylin and eosin, the tissue samples were morphologically evaluated by a specialist histopathologist. RESULTS: Changes in mean blood glucose and C-peptide levels were statistically significant in the ovary and kidney subcapsule groups. Histologic examination revealed that granulosus insulin-bearing cells were detected in the islet grafts of both ovary and kidney subcapsule groups. The renal subcapsule group had inflammation signs on histologic examination. The islet cells of both ovary and renal subcapsule groups had no vacuolization. CONCLUSIONS: We showed that the ovary might be a new site for islet transplantation. Further research should be done on whether the initial results of this study can be reproduced in larger numbers of animal models and eventually in humans.
Subject(s)
Diabetes Mellitus, Experimental/surgery , Islets of Langerhans Transplantation/methods , Kidney , Ovary , Animals , Blood Glucose/analysis , C-Peptide/analysis , Diabetes Mellitus, Experimental/pathology , Female , Insulin-Secreting Cells/metabolism , Islets of Langerhans/cytology , Kidney/cytology , Ovary/cytology , Pancreas/metabolism , Rats , Rats, Sprague-Dawley , StreptozocinABSTRACT
The PharmacoGenomic Mutation Database (PGMD) is a comprehensive manually curated pharmacogenomics database. Two major sources of PGMD data are peer-reviewed literature and Food and Drug Administration (FDA) and European Medicines Agency (EMA) drug labels. PGMD curators capture information on exact genomic location and sequence changes, on resulting phenotype, drugs administered, patient population, study design, disease context, statistical significance and other properties of reported pharmacogenomic variants. Variants are annotated into functional categories on the basis of their influence on pharmacokinetics, pharmacodynamics, efficacy or clinical outcome. The current release of PGMD includes over 117 000 unique pharmacogenomic observations, covering all 24 disease superclasses and nearly 1400 drugs. Over 2800 genes have associated pharmacogenomic variants, including genes in proximity to intergenic variants. PGMD is optimized for use in annotating next-generation sequencing data by providing genomic coordinates for all covered variants, including Single Nucleotide Polymorphisms (SNPs), insertions, deletions, haplotypes, diplotypes, Variable Number Tandem Repeats (VNTR), copy number variations and structural variations.
Subject(s)
Databases, Factual , Pharmacogenetics , Databases, Genetic , Mutation , Pharmacokinetics , Pharmacological PhenomenaABSTRACT
The present study assessed the advantages and disadvantages of growth-friendly spinal instrumentation surgery for early-onset scoliosis in 17 patients who underwent this surgery with a minimum 2-year follow-up. The mean number of lengthening procedures was three, initial age at which surgery was performed was 108.1 ± 30.2 months, and follow-up duration was 40.6 ± 16.6 months. Spinal height (T1-S1 and T1-T12), lung space available, major Cobb angle for scoliosis, maximum thoracic kyphosis, lumbar lordosis, shoulder and pelvic balance, and coronal and sagittal balance were assessed preoperatively and at the last follow-up. Treatment with growth-friendly spinal instrumentation showed evident increases in the spinal height and space available for the lungs, and significant improvement in scoliosis and thoracic kyphosis. The most commonly observed complications were proximal anchor problems and proximal junctional kyphosis. To avoid proximal junctional kyphosis in treatments with growing rods, excessive thoracic kyphosis correction should not be performed.
Subject(s)
Orthopedic Procedures/methods , Scoliosis/surgery , Spine/surgery , Age of Onset , Child , Female , Humans , Male , Orthopedic Procedures/instrumentation , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: The aim of this study is to show the effect of a new mechanism on endothelin (ET) receptors in the physiopathology of diabetes-related pulmonary injury. We tested the hypothesis that dual ET-1 receptor antagonism via bosentan can reverse diabetes-induced lung injury. METHODS: The rats (24 male) were separated into four groups: group 1 (HEALTHY): Control group; group 2 (DM): Streptozotocin 60 mg/kg (i.p.); group 3 (DM + BOS-1): Diabetes + bosentan 50 mg/kg per-os; group 4 (DM + BOS-2): Diabetes + bosentan 100 mg/kg per-os. The bosentan treatment was initiated immediately after the onset of STZ-induced diabetes and continued for 6 weeks. RESULTS: In the treatment group, SOD activity was significantly increased, although GSH and MDA levels and TNF-α and TGF-ß gene expression were decreased. Bosentan 50 mg/kg and bosentan 100 mg/kg showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA expression. CONCLUSIONS: In conclusion, increased endothelin levels in the lung associated with diabetes may be one cause of endothelial dysfunction, cytokine increase, and oxidant/antioxidant imbalance in the pathogenesis of complications that may develop during diabetes. With its multiple effects, bosentan therapy may be an effective option against complications that may develop in association with diabetes.
Subject(s)
Acute Lung Injury/drug therapy , Diabetes Mellitus, Experimental/complications , Endothelin Receptor Antagonists/therapeutic use , Lung/metabolism , Sulfonamides/therapeutic use , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Animals , Bosentan , Diabetes Mellitus, Experimental/metabolism , Endothelin Receptor Antagonists/pharmacology , Glutathione/metabolism , Lung/drug effects , Male , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Rats , Rats, Wistar , Sulfonamides/pharmacology , Superoxide Dismutase/metabolism , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: A few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model. METHOD: Twelve-week-old BALB/c (H-2d/d) female rats (n = 18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n = 6), and (group III) asthma induced with OVA + treated with adalimumab (n = 6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed. RESULT: Severity of lung damage was found to be reduced significantly in the asthma induced with OVA + treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score = 1, p = 0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration. CONCLUSION: Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma
No disponible
Subject(s)
Animals , Rats , Antibodies, Monoclonal, Humanized/pharmacokinetics , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Inflammation/drug therapy , Asthma/drug therapy , Disease Models, Animal , Protective Agents/pharmacokinetics , Cytokines/analysis , Ovalbumin/pharmacokineticsABSTRACT
BACKGROUND: A few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model. METHOD: Twelve-week-old BALB/c (H-2d/d) female rats (n=18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab (n=6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed. RESULT: Severity of lung damage was found to be reduced significantly in the asthma induced with OVA+treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score=1, p=0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration. CONCLUSION: Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Asthma/drug therapy , Lung/drug effects , Respiratory Hypersensitivity/drug therapy , Adalimumab , Allergens/immunology , Animals , Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Asthma/immunology , Cell Movement/drug effects , Disease Models, Animal , Female , Humans , Lung/pathology , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Respiratory Hypersensitivity/immunology , Tumor Necrosis Factor-alpha/immunologyABSTRACT
Bone tissue engineering literature conveys investigations regarding biodegradable polymers where bioactive inorganic materials are added either before or after electrospinning process. The goal is to mimic the composition of bone and enhance the biocompatibility of the materials. Yet, most polymeric materials are hydrophobic in nature; therefore, their surfaces are not favorable for human cellular adhesion. In this sense, modifications of the hydrophobic surface of electrospun polymer fibers with hydrophilic and bioactive nanoparticles are beneficial. In this work, dispersion of hydroxyapatite (HAp), which is similar to the mineral component of natural bone, within biodegradable and biocompatible polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with the aid of a surfactant has been investigated. Non-ionic TWEEN20 and 12-hydroxysteric acid (HSA), cationic dodecyl trimethyl ammonium bromide (DTAB) and anionic sodium deoxycholate and sodium dodecyl sulfate (SDS) surfactants were used for comparison in order to prepare stable and homogenous nanocomposite suspensions of HAp/PHBV for the electrospinning process. Continuous and uniform composite nanofibers were generated successfully within a diameter range of 400-1,000 nm by the mediation of all surfactant types. Results showed that incorporation of HAp and any of the surfactant types strongly activates the precipitation rate of the apatite-like particles and decreases percent crystallinity of the HAp/PHBV mats. Mineralization was greatly enhanced on the fibers produced by using DTAB, HSA, and especially SDS on where also osteoblastic metabolic activity was similarly increased. The produced HAp/PHBV nanofibrous composite scaffolds would be a promising candidate as an osteoconductive bioceramic/polymer composite material for tissue engineering applications.
Subject(s)
Biocompatible Materials/chemical synthesis , Durapatite/chemistry , Nanofibers/chemistry , Osteoblasts/cytology , Polyesters/chemistry , Surface-Active Agents/chemistry , Tissue Scaffolds , 3T3 Cells , Animals , Bone Substitutes/chemical synthesis , Cell Differentiation/physiology , Electroplating/methods , Equipment Design , Equipment Failure Analysis , Materials Testing , Mice , Nanocomposites/chemistry , Nanocomposites/ultrastructure , Nanofibers/ultrastructure , Osteoblasts/physiology , Osteogenesis/physiology , Rotation , Surface-Active Agents/classificationABSTRACT
PURPOSE: We evaluate the effect of stem cells to induce endometrial proliferation and angiogenesis on Asherman Syndrome (AS). METHODS: The experimental study was performed in stemcell research laboratory. Forty Wistar-Albino rats were divided according to groups. In group1 (n = 10) to establish the model; trichloroacetic acid was injected to right uterine horn. Two weeks later, intrauterine synechia was confirmed. In group2 (n = 10), 2 weeks later, 2 × 106 mesenchymal stem cells (MSC) were injected into right uterine horn followed by three intraperitoneal injections of MSCs. In group3 (n = 10), daily oral estrogen was initiated on the second week. In group4 (n = 10), MSC injections and oral estrogen was given together. The amount of fibrosis, vascularisation, inflammation and immunohistochemical staining with vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and Ki-67 were evaluated in the uterine tissues. RESULTS: In all treatment groups; fibrosis decreased but vascularisation and immunhistohemical stainings increased in the experimental side. The amount of fibrosis, vascularisation, Ki-67 and PCNA scores were similar between group2 and 3. In group4, comparing to group2, less fibrosis but more Ki-67, PCNA and VEGF staining was observed. CONCLUSION: Stem cells, when added to estrogen, are a highly effective alternative to induce regeneration of endometrium in Asherman Syndrome therapy.
Subject(s)
Adipose Tissue/cytology , Endometrium/cytology , Fibrosis/prevention & control , Gynatresia/pathology , Inflammation/prevention & control , Mesenchymal Stem Cells/cytology , Neovascularization, Physiologic , Adipose Tissue/metabolism , Animals , Biomarkers/metabolism , Cell Differentiation , Cells, Cultured , Endometrium/metabolism , Female , Fibrosis/metabolism , Fibrosis/pathology , Gynatresia/metabolism , Immunoenzyme Techniques , Inflammation/metabolism , Inflammation/pathology , Mesenchymal Stem Cells/metabolism , Rats , Rats, WistarABSTRACT
OBJECTIVES: Ischemic conditioning (IC) is a method of angiogenic stimulus for limb ischemia. Here, we aimed to investigate the effects of short-term repeated ischemic stimulus on critical lower limb ischemic injury. METHODS: Rats were divided into four groups consisting of 40 animals in each group: sham, ischemia, local IC, and remote IC groups. Right-leg critical limb ischemia was achieved through ligation of the iliac artery and vein in male Sprague-Dawley rats except the sham group. Repeated transient ischemia using the tourniquet method was used for IC of lower extremities in the local and remote groups. IC was performed on the right leg for the local group and on the left leg for the remote group. Ten rats in each group were sacrificed for evaluation on days 1, 7, 14, and 30. Endothelial progenitor cell (EPC) counts were measured. Gastrocnemius muscles were evaluated for the degree of ischemia. Laser Doppler blood flow measurements were performed in order to make comparison between the blood flows of the limbs of the groups. RESULTS: The blood flow in the right limb of rats in the sham (1.65 perfusion units [PU]) and local IC (1.67 PU) groups was significantly higher than the ischemic group (1.17 PU) (p = .001 and p = .022 respectively). The levels of EPCs in the ischemia (1.09 ± 0.5) and remote IC groups (1.36 ± 0.8) were significantly higher than the sham (0.38 ± 0.2) group on day 7 (p = .026 and p = .002 respectively). Remote IC and local IC groups exhibited increased histopathological ischemia on day 7 when compared with sham group (p = .001, p = .01 respectively). The angiogenic scores on the 7th, 14th and 30th days for local IC and remote IC groups were significantly higher than sham and ischemia groups. CONCLUSIONS: IC seems to be the potent activator of angiogenesis in ischemic tissue. This study provides preliminary data showing that repeated short ischemic stimuli may reduce critical ischemic injury by promoting angiogenesis.
Subject(s)
Ischemia/therapy , Ischemic Preconditioning , Muscle, Skeletal/blood supply , Neovascularization, Physiologic , Animals , Biomarkers/metabolism , Blood Flow Velocity , Critical Illness , Disease Models, Animal , Endothelial Cells/metabolism , Extremities , Iliac Artery/physiopathology , Iliac Artery/surgery , Iliac Vein/physiopathology , Iliac Vein/surgery , Ischemia/etiology , Ischemia/metabolism , Ischemia/physiopathology , Ischemic Preconditioning/instrumentation , Laser-Doppler Flowmetry , Ligation , Male , Rats , Rats, Sprague-Dawley , Regional Blood Flow , Stem Cells/metabolism , Time Factors , TourniquetsABSTRACT
BACKGROUND: N-acetylcysteine (NAC) is an antioxidant agent that has been shown to have beneficial effects when treating various diseases. The aim of this study was to investigate the effects of NAC on spinal cord injury in an experimental rat model. METHODS: A total of 48 adult male wistar albino rats were divided into six groups. Group C included the control rats, group L included the rats that underwent laminectomy, and group T included the rats in which spinal cord trauma was induced by the weight-drop method after laminectomy. Groups M (the methylprednisolone group), N (the NAC group), and MN (the methylprednisolone + NAC group) were the treatment groups. In the fourth group (group M), 30 mg/kg methylprednisolone (MP) was administered as a bolus intraperitoneally (IP), and a standard MP treatmentat a dose of 5.4 mg/kg was applied for 24 h. In the fifth group (group N), only 300 mg/kg NAC was administered as a bolus IP. In the sixth group (group MN), the standard MP treatment and a single 300 mg/kg dose of NAC were administered as a bolus IP. The motor functions of the rats were evaluated on the 1st, 7th, and 14th days using the inclined plane test defined by Rivlin and Tator and the motor scale defined by Gale et al. Spinal cord samples were obtained on the 14th day. The samples were evaluated using pathological and biochemical analysis. RESULTS: In the neuroclinical assessment, no differences were observed between groups T and M in terms of motor improvement. However, statistically significant differences were observed between group T and groups N and MN (p < 0.001, p = 0.01, respectively). Statistically significant differences were also seen between group M and groups N and MN on the 1st and 7th days (p < 0.017, p < 0.01, respectively). Additionally, when groups N and MN were compared with groups T and M,the pathological and biochemical analyses were found to be statistically different (p < 0.05, p < 0.001, respectively). CONCLUSION: It was concluded that NAC treatment and the combined NAC + MP treatment may be more useful for healing in rats with experimental spinal cord injury in terms of neuroclinical, pathological, and biochemical results than MP-only therapy.
ABSTRACT
BACKGROUND AND AIM: Statins are HMG-CoA reductase inhibitors within the framework of cholesterol biosynthesis and used to lower the low-density lipoprotein (LDL). There are other aspects of statins can deploy a protective effect, even without the LDL's lowering. The aim of this study is to investigate the effects of different type of statins on proliferative and migrative behaviors of Hepatocyte Growth Factor (HGF) induced human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Human umbilical vein endothelial cells were isolated and cultured. Groups were designed in order to observe the effects of every individual substance. HUVECs were stimulated with HGF, statins and farnesylpyrophosphat ammonium salt (FPP) or geranylgeranyl-pyrophosphate (GGPP), respectively. Cell proliferations were counted 48 hours after initial stimuli and distances between migration fronts were used in migration analyses. RESULTS: All types of statins showed significant anti-migrative and anti-proliferative characters. Simvastatin and fluvastatin but not cerivastatin, were able to inhibit the HGF-depending migration and showed a significant effect on the inhibition of the isoprenylation (GGPP). Only simvastatin influenced the HGF-depending migration via inhibiting the isoprenylation process through GGPP. Cerivastatin significantly decreased the proliferation and Fluvastatin significantly enhanced the migration behaviors of HUVECs when they were co-incubated with methyl-8-cyclodextrin (MCD). CONCLUSIONS: Statins countermand the proproliferative and as well as the promigrative effect of HGF on HUVECs. The mechanisms which provoke this effect are dependent on the type of statin. Direct interactions of statins with lipid rafts play a significant role in the endothelial cell mechanisms.
Subject(s)
Cell Movement/drug effects , Cell Proliferation/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Fatty Acids, Monounsaturated/pharmacology , Fluvastatin , Hepatocyte Growth Factor/pharmacology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Indoles/pharmacology , Membrane Microdomains/drug effects , Membrane Microdomains/metabolism , Polyisoprenyl Phosphates/pharmacology , Pyridines/pharmacology , Sesquiterpenes/pharmacology , Simvastatin/pharmacology , beta-Cyclodextrins/pharmacologyABSTRACT
Paracetamol was shown to induce hepatotoxicity or more severe fatal acute hepatic damage. Agomelatine, commonly known as melatonin receptor agonist, is a new antidepressant, which resynchronizes circadian rhythms with subjective and objective improvements in sleep quality and architecture, as melatonin does. In the present study, it was aimed to evaluate the hepatoprotective activity of agomelatine on paracetamol-induced hepatotoxicity and to understand the relationship between the hepatoprotective mechanism of agomelatine and antioxidant system and proinflammatory cytokines. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kg agomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly. In conclusion, agomelatine administration protects liver cells from paracetamol-induced hepatotoxicity via antioxidant activity and reduced proinflammatory cytokines, such as TNF-α and IL-6.
Subject(s)
Acetamides/therapeutic use , Antidepressive Agents/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Protective Agents/therapeutic use , Acetamides/pharmacology , Acetaminophen , Alanine Transaminase/blood , Animals , Antidepressive Agents/pharmacology , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Dinoprost/analogs & derivatives , Dinoprost/metabolism , Glutathione/metabolism , Interleukin-6/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Protective Agents/pharmacology , Rats , Rats, Wistar , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/bloodABSTRACT
We investigated the potential protective effects of Nigella sativa (NS) on mortality, serum levels of proinflammatory cytokines, oxidative stress and histopathological changes in lung tissues, in cecal ligation and puncture (CLP)-induced sepsis model in rats. Sepsis induction by CLP, determination of serum cytokine levels by ELISA, spectrophotometric determination of oxidative stress parameters, and histological examination of lung tissues. The rat groups were: 1) CLP group, 2) sham group, 3) NS500-sham group, 4) NS125, 5) NS250, 6) NS500 groups. NS treatment significantly decreased proinflammatory cytokine levels in serum; LPO level, MPO activity, and pathological changes in lung tissues, in CLP-induced sepsis, while significantly increasing GSH levels and SOD activity in the lung tissue. NS treatment after CLP potentially reduced mortality and may exert effects through the reduction in tissue oxidative stress and serum cytokines. The histopathological changes were minimized in lung tissue by NS, under sepsis conditions. We can suggest that NS reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure. It may be suggested that role of the NS ethanolic extract in preventing formation of CLP induced sepsis, is due to the anti-inflammatory and antioxidant effects of the different compounds of the black seeds.
Subject(s)
Lung Injury/drug therapy , Nigella sativa/chemistry , Plant Extracts/therapeutic use , Sepsis/complications , Animals , Cecum , Cytokines/blood , Disease Models, Animal , Glutathione/metabolism , Ligation , Lipid Peroxidation/drug effects , Lung Injury/etiology , Lung Injury/metabolism , Lung Injury/pathology , Male , Peroxidase/metabolism , Plant Extracts/pharmacology , Punctures , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
We aimed to investigate how Diabetes Mellitus (DM) affects myeloperoxidase activity, antioxidant status, and lipid peroxidation using biochemical approaches in heart, liver, and lung and serum cytokine analyses, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in rat with sepsis induced by a cecal ligation and puncture-induced (CLP) sepsis. The rats were divided into four groups: control group, diabetic group, sepsis group, and diabetic+sepsis group. DM was induced in the male Wistar albino rats by administration of alloxan. Polymicrobial sepsis was induced by cecal ligation and two-hole puncture. After alloxan administration, all groups of rats were allowed to recover for 1 month. CLP model was applied after 1 month recovery to group 3 and 4. IL-6 and TNF-α, were measured. Effects of antioxidant defenses on the DM and/or sepsis process, the antioxidant levels superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) were evaluated in heart, lung and liver tissues. The oxidant levels, such as lipid peroxidation (LPO) and myeloperoxidase (MPO) levels were also evaluated in tissues. We demonstrated DM to augment the level of oxidant and proinflammatory cytokines in lung, liver, and heart and also to exacerbate oxidative injury as assessed by increased LPO and MPO, and decreased GSH and SOD levels in a sepsis model. DM increased levels of proinflammatory cytokines while DM also resulted in significantly increased levels of proinflammatory cytokines following CLP. DM-increased plasma proinflammatory cytokines levels correlated positively with tissue oxidant levels, such as MPO and LPO levels in a rat abdominal sepsis model, based on CLP, which resulted in the exacerbation of oxidative organs injury.
Subject(s)
Diabetes Mellitus, Experimental/complications , Lipid Peroxidation , Liver/pathology , Lung/pathology , Myocardium/metabolism , Oxidative Stress , Sepsis/complications , Animals , Catalase/biosynthesis , Catalase/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Glutathione/biosynthesis , Glutathione/metabolism , Interleukin-6/blood , Liver/metabolism , Lung/metabolism , Male , Myocardium/pathology , Peroxidase/metabolism , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Sepsis/pathology , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/bloodABSTRACT
BACKGROUND: There are several reports on the application of variable degrees of vacuum pressure to hardshell venous reservoirs. The aim of the current study was to compare the hemolytic effects of vacuum-assisted venous drainage (VAVD) at two different vacuum levels with the classical gravity siphon method. METHODS: A prospective, equally randomized (1: 1: 1), parallel group study was performed in elective coronary artery bypass grafting (CABG) operations. PATIENTS: (n = 162) were divided into three groups: gravity siphon (group 1, n = 55), VAVD at -40 mmHg (group 2, n = 55) and VAVD at -80 mmHg (group 3, n = 52). Hemolysis tests were performed at 2, 24 and 48 h following the operations. RESULTS: There were no deaths in this study. Plasma-free hemoglobin (PfHb) levels showed a difference at 2 h (p < 0.001) compared to 24 h (p = 0.02) between the groups. Haptoglobin (Hp) levels also revealed hemolysis in groups 2 and 3 at all sampling times. CONCLUSIONS: Constant negative suction at -80 mmHg during elective coronary bypass operations caused more hemolysis. We do not recommend a constant suction of -80 mmHg for VAVD.
Subject(s)
Cardiopulmonary Bypass/adverse effects , Coronary Artery Bypass/adverse effects , Drainage/adverse effects , Hemolysis , Aged , Biomarkers/blood , Cardiopulmonary Bypass/methods , Chi-Square Distribution , Coronary Artery Bypass/methods , Elective Surgical Procedures , Female , Haptoglobins/metabolism , Hemoglobins/metabolism , Humans , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Time Factors , Turkey , Vacuum , VeinsABSTRACT
This paper evaluates the effect of ergonomic factors on task performance and trainee posture during laparoscopic surgery training. Twenty subjects without laparoscopic experience were allotted into 2 groups. Group 1 was trained under the optimal ergonomic simulation setting according to current ergonomic guidelines (Condition A). Group 2 was trained under non-optimal ergonomic simulation setting that can often be observed during training in a skills lab (Condition B). Posture analysis showed that the subjects held a much more neutral posture under Condition A than under Condition B (p<0.001). The subjects had less joint excursion and experienced less discomfort in their neck, shoulders, and arms under Condition A. Significant difference in task performance between Conditions A and B (p<0.05) was found. This study shows that the optimal ergonomic simulation setting leads to better task performance. In addition, no significant differences of task performance, for Groups 1 and 2 using the same test setting were found. However, better performance was observed for Group 1. It can be concluded that the optimal and non-optimal training setting have different learning effects on trainees' skill learning.
Subject(s)
General Surgery/education , Laparoscopy/education , Adult , Ergonomics , Female , Humans , Male , Muscle Fatigue , Posture , Task Performance and Analysis , Upper Extremity/physiology , Young AdultABSTRACT
Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)-induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD-treated CLP group; (ii) 20 mg/kg SLD-treated CLP group; (iii) CLP group; and (iv) sham-operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil-treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham-operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF)-α level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLP-induced sepsis via maintenance of the oxidant-anti-oxidant status and decrease in the level of TNF-α.