Is ultrafiltration volume a predictor of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass?

INTRODUCTION: Intraoperative ultrafiltration (UF) is a procedure used during cardiopulmonary bypass (CPB) to reduce haemodilution and prevent excessive blood transfusion. However, the effect of UF volume on acute kidney injury (AKI) is not well established, and the results are conflicting. Additionally, there are no set indications for applying UF during CPB. METHODS: This retrospective study analysed 641 patients who underwent coronary artery bypass graft (CABG) surgery with CPB. Perioperative parameters were extracted from the patients' records, and the UF volume was recorded. Acute Kidney Injury Network classification was used to define AKI. Univariable and multivariable logistic regression models were used to predict AKI while controlling for confounding factors. RESULTS: The study enrolled patients with a mean age of 58.8 ± 11.1 years, 39.2% of whom were female. AKI occurred in 22.5% of patients, with 16.1% (103) experiencing stage I and 6.4% (41) experiencing stage II. The results showed a significant association between UF volume and the risk of developing AKI, with higher UF volumes associated with a higher risk of AKI. In the multivariable analysis, the other predictors of AKI included age, lowest mean arterial pressure (MAP), and red blood cell (RBC) transfusion during CPB. CONCLUSION: The predictors of postoperative AKI in coronary CABG patients were the volume of UF, age, MAP, and blood transfusion during CPB.

The analgesic effects of insulin and its disorders in streptozotocin-induced short-term diabetes.

Evidence suggests that insulin resistance plays an important role in developing diabetes complications. The association between insulin resistance and pain perception is less well understood. This study aimed to investigate the effects of peripheral insulin deficiency on pain pathways in the brain. Diabetes was induced in 60 male rats with streptozotocin (STZ). Insulin was injected into the left ventricle of the brain by intracerebroventricular (ICV) injection, then pain was induced by subcutaneous injection of 2.5% formalin. Samples were collected at 4 weeks after STZ injection. Dopamine (DA), serotonin, reactive oxygen species (ROS), and mitochondrial glutathione (mGSH) were measured by ELISA, and gene factors were assessed by RT-qPCR. In diabetic rats, the levels of DA, serotonin, and mGSH decreased in the nuclei of the thalamus, raphe magnus, and periaqueductal gray, and the levels of ROS increased. In addition, the levels of expression of the neuron-specific enolase and receptor for advanced glycation end genes increased, but the expression of glial fibrillary acidic protein expression was reduced. These results support the findings that insulin has an analgesic effect in non-diabetic rats, as demonstrated by the formalin test. ICV injection of insulin reduces pain sensation, but this was not observed in diabetic rats, which may be due to cell damage ameliorated by insulin.

Effects of intracerebroventricular administration of calcitonin gene-related peptide (CGRP) on sex hormones and sperm quality in rats.

Background: Therapeutic strategies with calcitonin gene-related peptide (CGRP) or its receptor have been investigated, but there are few studies regarding the possible harmful effects of CGRP in other body organs. Objective: This study aimed to investigate the effect of intracerebroventricular (ICV) injection of CGRP on sex hormones and sperm quality in rats. Methods: Twelve male rats were divided into two groups (n=6 per group). The first group (control) rats were injected with 5 µl artificial cerebrospinal fluid intra-ICV; the second group rats, 5 µl (1.5 nmol) CGRP. The levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured. Epididymal sperms were used to determine the sperm parameters. Results: The levels of testosterone, LH and FSH in CGRP group was significantly lower than in artificial cerebrospinal fluid (ACSF) group (P<0.05). The concentration and motility of sperm in CGRP group was significantly lower than in ACSF group (P<0.05). In CGRP group live spermatozoa and intact acrosome significantly reduced compared to the ACSF group (P<0.05). In addition, in CGRP group dead spermatozoa and lose acrosome significantly increased compared to the ACSF group (P<0.05). Conclusion: ICV injection of CGRP may reduce sperm quality, probably through induction of an imbalance in FSH and LH production as well as testosterone.

Effect of insulin and cinnamon extract on spatial memory and gene expression of GLUT1, 3, and 4 in streptozotocin-induced Alzheimer's model in rats.

Objectives: Since diminished hippocampal insulin signaling leads to memory impairment, insulin resistance and hyperinsulinemia are probably associated with Alzheimer's disease (AD). The effect of intracerebroventricular injection of insulin (Ins) and oral cinnamon extract (Cinn) on glucose transporter (GLUT) 1, 3, and 4 gene expressions in the hippocampus and spatial memory in a streptozotocin (STZ)-induced AD rat model was investigated in the present study. Materials and Methods: Fifty-six adult male Sprague-Dawley rats (280±20 g) were allocated into eight distinct groups (n=7) of five controls (negative, Ins, Cinn, Ins+Cinn, and STZs) and three treatments (STZ+ Ins, STZ+ Cinn, and STZ+ Ins + Cinn). Single dose STZ 4 mg/kg (icv), Cinn at a dose of 200 mg/ kg (orally for 14 days), and Ins 5 mIU/5 µl (icv for 14 days) were administered in the defined groups. To evaluate the behavioral performance the animals were subjected to the Morris Water Maze (MWM) test. The level of mRNA expression of GLUTs was evaluated by the Real time-PCR method. Results: In the STZ+Cinn+Ins group, the performance of animals in the MWM test was improved and the over-expression of GLUTs genes in hippocampal tissue was observed. The results of Ins and Cinn synergist treatment groups revealed improvement in the behavioral tests and gene expression compared with Ins and Cinn treatment groups (P<0.001). Conclusion: Administration of Ins and Cinn has a positive effect on the function of the AD rat model. To clarify the effect of Ins and Cinn extract on the GLUTs investigated in this study, it is essential to evaluate their influence on the protein levels.

The effects of metformin on the hippo pathway in the proliferation of melanoma cancer cells: a preclinical study.

YAP and TAZ, two closely related transcriptional regulators, have crucial roles in tissue repair upon injury, organ size control, and cancer treatment. Some drugs, such as metformin, that alter cell metabolism can play a role in the regulation of the Hippo pathway. The cells were treated with various concentrations of metformin, dacarbazine (IC50), and both of them. The evaluation of the biomarker and proteins was performed by FACS and immunoblotting, respectively. Cell viability was reduced by 50% after 24 h. Data showed that metformin treatment down-regulated YAP and TAZ (p = .002) expressions and enhanced YAP phosphorylation (p < .001). Metformin, alone and in combination, inhibited the growth and viability of melanoma cells in vitro. The increase in the phosphorylation of YAP renders it a potential target in the development of anticancer drugs. This study showed the effects of metformin on the inhibition of oncogenic YAP and TAZ in the proliferation of melanoma cells.

The effect of maternal exposure to titanium dioxide nanoparticles on the pain response in offspring mice using formalin test.

This study was conducted to evaluate the effect of maternal exposure to TiO2 nanoparticles on the pain response in offspring mice. 30 female mice with a mean ± SD weight of 30 ± 5 g were randomly divided into three groups: the control group (group 1) received only the basal diet; the sham group (group 2) received saline plus as a carrier (100 µL/mice) subcutaneously on days 3, 7, 10, and 14 post-mating; and the test group (group 3) received 100 µL/mice TNPs subcutaneously on days 3, 7, 10, and 14 post-mating. Offspring were divided into 6 groups 21 days after birth and underwent formalin test. Blood samples were taken to evaluate possible oxidative changes in total antioxidant capacity (TAC) and malondialdehyde (MDA). Exposure to TNPs significantly (p < 0.05) decreased pain perception. Except for a significant difference between the sham group and the control group, MDA and TAC were not significantly different among the studied groups. Injection of TNPs to pregnant mice would affect the pain perception in their offspring. This may be attributable to the ability of these particles to pass through the placenta to produce free radicals.

Effects of ethanolic extracts of Quercus, Cirsium vulgare, and Falcaria vulgaris on gastric ulcer, antioxidant and inflammatory indices, and gene expression in rats.

INTRODUCTION: Gastric ulcer is a multifaceted process and is usually caused by mucosal damage. Herbal medicines have received much attention considering the side effects of chemical drugs. Nowadays, the use of herbal medicines has received much attention considering the side effects of chemical drugs. Quercus brantii Lindl, Cirsium vulgare (Savi) Ten, and Falcaria vulgaris Bernh are plants used as traditional phytomedicine for gastric ulcer diseases. AIM OF THE STUDY: This study was aimed to investigate the protective effects of hydroalcoholic extracts of these herbs on ethanol-induced gastric ulceration, in addition, to investigate the antioxidant, anti-inflammatory, and gene expression. MATERIALS AND METHODS: Thirty Sprague Dawley rats, (200-250 g), were divided into six groups: Control: intact animals; sham: gavaged with distilled water (14 days); negative control: gavaged with 20 mg/kg of omeprazole (14 days); experimental groups I, II, and III: gavaged with 500 mg/kg of the extract of Falcaria vulgaris, Quercus brantii, and Cirsium vulgare, respectively, (14 days). The number of ulcers and pathological parameters were assessed. The serum superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, total antioxidant capacity, albumin, total protein, haptoglobin, alpha-1-acid glycoprotein, total globulin, alpha-2-macroglobulin, C-fos, C-myc, and Caspase-9 were measured by ELISA and RT-PCR. RESULTS: The extracts significantly reduced gastric ulcer (52.33%). The results showed that the Quercus brantii extract was more effective. There were significant differences between the serum levels of alpha-1-acid glycoprotein and those of alpha-2-macroglobulin. Also, there was a significant difference in the serum level of antioxidant parameters. Changes in the expression of the genes also confirmed the results suggested by other parameters. The expression levels of C-fos, C-myc, and caspase-9 were decreased, but the Bcl-2 expression increased. CONCLUSION: The hydro-alcoholic extracts revealed various protection and noticeable change in the expression of caspase-9, C-myc, C-fos, and Bcl-2 genes in rats.

Expression Pattern of MicroRNA-21 during the Liver Ischemia/Reperfusion.

Ischemia/reperfusion (I/R) injury in cadaveric liver transplantation is not avoidable. Liver I/R injury is an important phenomenon in hepatic damage. MicroRNA-21 (miR-21) plays an important role in I/R injury. The present study aimed to determine the expression pattern of miR-21 in liver I/R injury/recovery and its correlation with the immunologic transmission signals pathways several days post-reperfusion. In an animal model for I/R in the liver, 40 male Balb/c mice were divided into 3 groups. The animals were monitored for 3 and 24 hours, and also for 4, 7, 14, and 28 days post-reperfusion. Liver tissue damage was assessed by histopathology. The plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total antioxidant capacity (TAC) levels were measured with enzymatic assays. MiR-21, programmed cell death 4 (PDCD4) mRNA, T-cell-restricted intracellular antigen 1 (TIA1) mRNA, and fas ligand (FASL) mRNA expression levels were measured; using reverse transcription-polymerase chain reaction (RT-PCR) at different times after the reperfusion in liver tissue and blood. Histopathology and plasma ALT, AST, ALP, and TAC levels confirmed liver damage induced by I/R injury. MiR-21 increased by twofold in the liver tissue and on the inflammatory phase after 24 hours of reperfusion; it then continued to decrease up to day 7 post-reperfusion. Afterward, it continued to rise slightly up to day 14 post-reperfusion. This trend was in parallel with the recovery of the liver damage. MiR-21 expression level in the liver and blood is a predictor of the extent of I/R injury.

Effect of titanium dioxide nanoparticles administered during pregnancy on depression-like behavior in forced swimming and tail suspension tests in offspring mice.

INTRODUCTION: Applications of engineered nanoparticles are rapidly increasing. Titanium dioxide nanoparticles (TiO2 NPs) are used in many products including those produced by pigment and cosmetic manufacturers. The objective of this study was to investigate the effects of maternal exposure during pregnancy to TiO2 NPs on depressive-like behavior in the first and second generation offspring. MATERIALS AND METHODS: Forty female albino mice were placed into four groups for 2 weeks. Fertile males were then added to each cage by a ratio of two males to five females. After detection of pregnancy, the mice were transferred to separate cages. The study groups were divided into four groups: the first group, served as control, did not receive any treatment; the second group received injections of normal saline; groups 3 and 4 received, respectively, 50 and 100 µl of TiO2 NP solution injections subcutaneously on days 3, 7, 10, and 14 after mating. Behavioral tests were conducted on postnatal days 21 and 40. FINDINGS: Subcutaneous injection of 50 and 100 µl of TiO2 NPs significantly (p < 0.05) increased the immobility time in the forced swimming test and tail suspension test (TST). No significant difference was observed in measured variables between groups receiving 50 and 100 µl of TiO2 NPs. No significant difference was also found between male and female offspring. Depression-like behavior increased in the second generation of mice in the forced swim test and TST. CONCLUSION: Prenatal exposure of mothers to TiO2 NPs would increase depression-like behavior in neonatal mice.

The effect of intra-cerebroventricular injection of insulin on the levels of monoamines on the raphe magnus nucleus of non-diabetic and short-term diabetic rats in the formalin test.

OBJECTIVES: Systemic and intracerebroventricular (ICV) injection of insulin possess analgesic effects. The raphe magnus nucleus (RMN) is part of the endogenous analgesia system. The objective of the present study was to evaluate the effects of ICV injection of insulin on the levels of monoamines and their related metabolites in the RMN during the formalin test in non-diabetic and short-term diabetic rats. MATERIALS AND METHODS: Sixty four adult male rats were used. Diabetes was induced by Streptozotocin (STZ) (60 mg/kg, IP); insulin (5 mU/animal, 5 µl) was injected into the left ventricle. Microdialysis was performed in each rat. Samples were collected at 15 min intervals. After taking the base sample of microdialysis, 50 µl of 2.5% formalin was injected into the plantar surface of the hind paw, and the level of nociception was recorded every 15 sec for 1 hr. Monoamines and their metabolites concentrations were measured using the HPLC-ECD method. RESULTS: Findings showed that ICV injection of insulin in non-diabetic rats increased the concentration of monoamines and their related metabolites in the RMN. In diabetic rats, injection of insulin decreased the concentrations of monoamines and their related metabolites in the RMN (P<0.05). Our results determined that, at least in part, insulin is associated with antinociceptive effect in non-diabetic rats. CONCLUSION: Based on the results, it seems that ICV injection of insulin in non-diabetic rats increased the activity of the central pain control pathways leading to antinociceptive response, but this condition was not seen in diabetic rats.

Effects of Salmon Calcitonin on the Concentrations of Monoamines in Periaqueductal Gray in Formalin Test

Background: The receptors of salmon calcitonin, located on certain areas of the brain such as the periaqueductal gray matter, are responsible for pain modulation. Aims: The effects of intracerebroventricular injection of salmon calcitonin on the behavioral response to pain and on the levels of monoamines in the periaqueductal gray were explored using a biphasic animal model of pain. Study Design: Animal experiment. Methods: A total of 45 male rats were divided into four groups (n=6). Salmon calcitonin was injected into the lateral ventricle of the brain (1.5 nmol, with a volume of 5 µL). After 20 min, 2.5% formalin was subcutaneously injected into the right leg claw, and pain behavior was recorded on a numerical basis. At the time of the formalin test, the periaqueductal gray area was microdialized. High-performance liquid chromatography method was used to gauge the levels of monoamines and their metabolites. Results: Intracerebroventricular injections of salmon calcitonin resulted in pain reduction in the formalin test (p<0.05). The dialysate concentrations of serotonin, dopamine, norepinephrine, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic, and 4-hydroxy-3-methoxyphenylglycol increased in the periaqueductal gray area in different phases of the formalin pain test (p<0.05). Conclusion: Salmon calcitonin reduced pain by increasing the concentrations of monoamines and the metabolites derived from them in the periaqueductal gray area.

Effects of Intracerebroventricular and Intra-Arcuate Nucleus Injection of Ghrelin on Pain Behavioral Responses and Met-Enkephalin and ß-Endorphin Concentrations in the Periaqueductal Gray Area in Rats.

Ghrelin is an endogenous ligand for orphan growth hormone secretagogue receptors. Ghrelin receptors have been found in central nervous system (CNS) areas responsible for pain modulation and transmission. This study investigated the effects of intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin on pain behavioral responses and levels of ß-endorphin (ß-EP) and met-enkephalin (MENK) in the periaqueductal gray area (PAG) during the formalin test in rats. Thirty-five male rats were studied in five groups. Ghrelin was injected into the left lateral ventricle (ICV, 5 µL) or into the ARC (1 µL). After 15 min, formalin (2.5%) was subcutaneously injected into the left hind paw. Behavioral nociceptive scores were recorded for 60 min. MENK and ß-EP were collected by microdialysis in the PAG and determined by high-performance liquid chromatography (HPLC). ICV and ARC injection of ghrelin significantly reduced pain in all phases of the formalin test (p < 0.001). Dialysate concentrations of MENK and ß-EP in the PAG increased in all the phases (p < 0.01). In conclusion, the present study shows that the ARC nucleus and the endogenous opioid system are involved in ghrelin-induced pain modulation.

Effect of Probiotics Bacillus coagulans and Lactobacillus plantarum on Lipid Profile and Feces Bacteria of Rats Fed Cholesterol-Enriched Diet.

The aim of this study was to investigate the effect of Lactobacillus plantarum and Bacillus coagulans on serum lipid profile and lowering potential of probiotic in hypercholesterolemic rats. Twenty-eight male Wistar rats were divided into four groups as follows: (1) control group, fed standard commercial diet; (2) HC group, fed high-cholesterol diet; (3) HC + LP group, fed high-cholesterol diet and gavaging of L. plantarum; and (4) HC + BC group fed high-cholesterol diet and gavaging of B. coagulans. After 28 and 50 days, serum lipid profile; serum ALT and AST; the body and organ weights; fecal total count; Enterobacteriaceae, L. plantarum, and B. coagulans counts; and blood glucose tolerance were measured. We observed that levels of triglyceride, cholesterol, LDL, VLDL, and atherogenic index in serum were significantly lower in the HC + probiotic groups. Also, serum ALT and AST were significantly decreased in probiotic-treated groups. In addition, we found that feeding of a high-cholesterol diet for 50 days produced significant increases in the body weight, in addition to the fact that the administration of L. plantarum and B. coagulans has considerably reduced the body weight gain. B. coagulans and L. plantarum can survive passing through the upper-gastrointestinal tract after oral feeding to the rats and colonized in their colon. These bacteria could be exploited as a potential biotherapeutic remedy to reduce TC, TG, LDL, VLDL, and atherogenic index in hypercholesterolemic condition.

The effect of intracerebroventricular injection of CGRP on pain behavioral responses and monoamines concentrations in the periaqueductal gray area in rat.

OBJECTIVES: Calcitonin gene related peptide (CGRP) receptors are widely distributed in the central nervous system. The aim of this study was to investigate the effects of intracerebroventricular (ICV) injection of CGRP on pain behavioral responses and on levels of monoamines in the periaqueductal gray area (PAG) during the formalin test in rats. MATERIALS AND METHODS: Twenty-four male rats were studied in four groups (n=6). CGRP was injected into the left cerebral ventricle (1.5 nmol, 5 µl). After 20 min, formalin (2.5%) was subcutaneously injected into the right hind paw. Behavior nociceptive score was recorded up to 60 min. During the formalin test, the PAG was subjected to microdialysis and levels of norepinephrine, 3-methoxy-4-hydroxyphenyl-glycol (HMPG), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin and 5-hydroxyindole-acetic acid (HIAA) were measured by HPLC. RESULTS: ICV injection of CGRP lead to a significant pain reduction in acute, middle and chronic phases of the formalin test. Dialysate concentrations of norepinephrine, HMPG, dopamine, DOPAC, serotonin and HIAA in the PGA area showed an increase in acute phase, middle phase and beginning of the chronic phase of the formalin test. CONCLUSION: CGRP significantly reduced pain by increased concentrations of monoamines and their metabolites in dialysates from PAG when injected ICV to rats.

Protective effects of synbiotic diets of Bacillus coagulans, Lactobacillus plantarum and inulin against acute cadmium toxicity in rats.

BACKGROUND: Cadmium is a heavy metal that causes oxidative stress and has toxic effects in humans. The aim of this study was to investigate the influence of two probiotics along with a prebiotic in preventing the toxic effects of cadmium in rats. METHODS: Twenty-four male Wistar rats were randomly divided into four groups namely control, cadmium only, cadmium along with Lactobacillus plantarum (1 × 109 CFU/day) and inulin (5% of feedstuff) and cadmium along with Bacillus coagulans (1 × 109 spore/day) and inulin (5% of feedstuff). Cadmium treated groups received 200 µg/rat/day CdCl2 administered by gavage. During the 42-day experimental period, they were weighed weekly. For evaluation of changes in oxidative stress, the levels of some biochemicals and enzymes of serum including SOD, GPX, MDA, AST, ALT, total bilirubin, BUN and creatinine, and also SOD level of livers were measured at day 21 and 42 of treatment. The cadmium content of kidney and liver was determined by using atomic absorption mass spectrophotometry. Data were analyzed using analysis of variance (ANOVA) followed by Duncan's post hoc test. RESULTS: Treatment of cadmium induced rats with synbiotic diets significantly improved the liver enzymes and biochemical parameters that decreased AST, ALT, total bilirubin, BUN and metal accumulation in the liver and kidney and increased body weight, serum and liver SOD values in comparison with the cadmium-treated group. No significant differences were observed with MDA and GPX values between all groups (p > 0.05). CONCLUSIONS: This study showed that synbiotic diets containing probiotics (L. plantarum and B. coagulans) in combination with the prebiotic (inulin) can reduce the level of cadmium in the liver and kidney, preventing their damage and recover antioxidant enzymes in acute cadmium poisoning in rat.

Effect of Probiotic Bacillus Coagulans and Lactobacillus Plantarum on Alleviation of Mercury Toxicity in Rat.

The objective of this study was to evaluate the efficiency of probiotics (Lactobacillus plantarum and Bacillus coagulans) against mercury-induced toxicity using a rat model. Mercury (Hg) is a widespread heavy metal and was shown to be associated with various diseases. Forty-eight adult male Wistar rats were randomly divided into six groups (control, mercury-only, each probiotic-only, and mercury plus each probiotic group). Hg-treated groups received 10 ppm mercuric chloride, and probiotic groups were administrated 1 × 109 CFU of probiotics daily for 48 days. Levels of mercury were determined using cold vapor technique, and some biochemical factors (list like glutathione peroxidase (GPx), superoxide dismutase (SOD), creatinine, urea, bilirubin, alanine transaminase (ALT), and aspartate transaminase (AST)) were measured to evaluate changes in oxidative stress. Oral administration of either probiotic was found to provide significant protection against mercury toxicity by decreasing the mercury level in the liver and kidney and preventing alterations in the levels of GPx and SOD. Probiotic treatment generated marked reduction in the levels of creatinine, urea, bilirubin, ALT, and AST indicating the positive influence of the probiotics on the adverse effects of Hg in the body.

The effects of orally administered Bacillus coagulans and inulin on prevention and progression of rheumatoid arthritis in rats.

BACKGROUND: Probiotics have been considered as an approach to addressing the consequences of different inflammatory disorders. The spore-forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic inulin also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. OBJECTIVE: In the present study, an in vivo model was conducted to investigate the possible influences of probiotic B. coagulans and prebiotic inulin, both in combination and/or separately, on the downregulation of immune responses and the progression of rheumatoid arthritis (RA), using arthritis-induced rat model. DESIGN: Forty-eight healthy male Wistar rats were randomly categorized into six experimental groups as follows: 1) control: normal healthy rats fed with standard diet, 2) disease control (RA): arthritis-induced rats fed with standard diet, 3) prebiotic (PRE): RA+ 5% w/w long-chain inulin, 4) probiotic (PRO): RA+ 10(9) spores/day B. coagulans by orogastric gavage, 5) synbiotic (SYN): RA+ 5% w/w long-chain inulin and 10(9) spores/day B. coagulans, and 6) treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with the listed diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund's adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by the biochemical parameters and paw thickness. Biochemical assay for fibrinogen (Fn), serum amyloid A (SAA), and TNF-α and alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28, and 35 (7, 14 and 21 days post RA induction), respectively. RESULTS: Pretreatment with PRE, PRO, and SYN diets significantly inhibits SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, was seen in the PRE, PRO, and SYN groups (P < 0.001), which was similar to the anti-inflammatory effect of indomethacin. Furthermore, no significant anti-inflammatory effects were observed following different treatments using α1 AGp as an RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). CONCLUSION: The results of this study indicate that the oral intake of probiotic B. coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat.

Factors associated with extubation time in coronary artery bypass grafting patients.

Background and Objectives. Cardiovascular diseases are the leading cause of death worldwide, with coronary artery disease being the most common. With increasing numbers of patients, Coronary Artery Bypass Grafting (CABG) has become the most common operation in the world. Respiratory disorder is one of the most prevalent complications of CABG. Thus, weaning off the mechanical ventilation and extubation are of great clinical importance for these patients. Some post-operative problems also relate to the tracheal tube and mechanical ventilation. Therefore, an increase in this leads to an increase in the number of complications, length of hospital stay, and treatment costs. Since a large number of factors affect the post-operative period, the present study aims to identify the predictors of extubation time in CABG patients using casualty network analysis. Method. This longitudinal study was conducted on 800 over 18 year old patients who had undergone CABG surgery in three treatment centers affiliated to Shiraz University of Medical Sciences. The patients' information, including pre-operative, peri-operative, and post-operative variables, was retrospectively extracted from their medical records. Then, the data was comprehensively analyzed through path analysis using MPLUS-7.1 software. Results. The mean of extubation time was 10.27 + 4.39 h. Moreover, extubation time was significantly affected by packed cells during the Cardiopulmonary Bypass (CPB), packed cells after CPB, inotrope use on arrival at ICU, mean arterial pressure 1st ICU, packed cells 1st ICU, platelets 1st ICU, Blood Urea Nitrogen 1st ICU, and hematocrit 1st ICU. Conclusion. Considering all of the factors under investigation, some peri-operative and post-operative factors had significant effects. Therefore, considering the post-operative factors is important for designing a treatment plan and evaluating patients' prognosis.

The effects of tramadol on norepinephrine and MHPG releasing in locus coeruleus in formalin test in rats: a brain stereotaxic study.

OBJECTIVES: The relationship between tramadol, as an antinociceptive drug, and locus coeruleus (LC), the main noradrenergic nucleus of the brain that affects regulation and modulation of pain through descending noradrenergic pathways was investigated. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into four groups of 10 rats. The rats were fixed in stereotaxic instrument and then a probe was inserted into LC. Pain was induced by subcutaneous injection of 50 µl of 2.5% formalin 40 minutes after initiation of microdialysis in right hind paw, and nociceptive pain scores were calculated every 5 minutes. Subsequently noradrenaline (NA) and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were collected and measured by microdialysis of locus coeruleus in freely moving rats every 15 minutes during formalin injection. RESULTS: Nociceptive pain scores observed in formalin test had the highest nociceptive sensation 5 minutes after injection. Significant rises in concentrations of NA and MHPG, in samples taken between 30 and 45 min after initiation of the locus coeruleus microdialysis, coincided with the peak of the pain after injection of formalin. CONCLUSION: According to concurrency of the highest nociceptive sensation and peak of NE and MHPG concentrations, tramadol can indirectly affect the LC by blocking the pain signals from different parts of the brain such as periaqueductal gray mater, central nucleus of amygdale or the spinal cord.