Intravenous Injection Of Saline Research Articles

Parecoxib reduced ventilation induced lung injury in acute respiratory distress syndrome

BackgroundCyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS). The objective of present study was to observe the therapeutic effect of parecoxib on VILI in ARDS.MethodsIn this parallel controlled study performed at Harbin Medical University, China between January 2016 and March 2016, 24 rats were randomly allocated into sham group (S), volume ventilation group/ARDS (VA), parecoxib/volume ventilation group/ARDS (PVA). Rats in the S group only received anesthesia; rats in the VA and PVA group received intravenous injection of endotoxin to induce ARDS, and then received ventilation. Rats in the VA and PVA groups were treated with intravenous injection of saline or parecoxib. The ratio of arterial oxygen pressure to fractional inspired oxygen (PaO2/FiO2), the wet to dry weight ratio of lung tissue, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and histopathologic analyses of lung tissue were examined. In addition, survival was calculated at 24 h after VILI.ResultsCompared to the VA group, in the PVA group, PaO2/FiO2 was significantly increased; lung tissue wet to dry weight ratio; macrophage and neutrophil counts, total protein and neutrophil elastase levels in BALF; tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 levels in BALF and serum; and myeloperoxidase (MPO) activity, malondialdehyde levels, and Bax and COX-2 protein levels in lung tissue were significantly decreased, while Bcl-2 protein levels were significantly increased. Lung histopathogical changes and apoptosis were reduced by parecpxib in the PVA group. Survival was increased in the PVA group.ConclusionsParecoxib improves gas exchange and epithelial permeability, decreases edema, reduces local and systemic inflammation, ameliorates lung injury and apoptosis, and increases survival in a rat model of VILI.

Metabolomics analysis of anaphylactoid reaction reveals its mechanism in a rat model.

Anaphylactoid reactions, accounting for more than 77% of all immune-mediated immediate hypersensitivity reactions, have become a serious threat to public health, but their effect mechanism is not clear and diagnostic tests are limited. Comprehensive metabolite analysis may reveal the anaphylactoid effect mechanism systematically and provide reference for future diagnostic purposes. Plasma from Brown Norway rats given intravenous injection of saline, compound 48/80 (2.5 mL/kg) or ovalbumin (20 mL/kg) in 20 s for the first time was used to study the effect mechanism of anaphylactoid reactions through metabolomics (UPLC-qTOF-MS/MS). Metabolomics integrated with proteomics data were used to analyze the anaphylactoid pathways by MetaboAnalyst followed by integrated pathway analysis. Thirty metabolites were identified through the METLIN database by MS/MS and 18 of them were confirmed by authentic standards. The results showed that adenosine, histamine, N-acetylhistamine, N(α)-γ-glutamylhistamine, malate and xanthine are important indices for anaphylactoid reactions. It could be concluded that the effect mechanism is mainly composed of histidine metabolism, arachidonic acid metabolism, energy metabolism, purine metabolism and other small molecules through 30 metabolites. Multiple linear regression analysis indicated that not only histamine but also N(α)-γ-glutamylhistamine and arachidonic acid could be used to evaluate anaphylactoid symptoms of animals. Furthermore, the citrate cycle, histidine metabolism and arachidonic acid metabolism could be the main pathways of anaphylactoid reactions as determined by MetaboAnalyst. The results may provide a reference to improve diagnostic accuracy and predict and monitor treatment efficacy in anaphylactoid reactions in the clinical setting.

Effect of Low-dose Atracurium on Laryngeal Mask Airway Insertion Conditions: A Randomized Double-blind Clinical Trial.

Background:The amount of sedation and muscle relaxation of the jaw may have an impact on complications caused by laryngeal mask airway (LMA). The aim of this study is to evaluate the effect of low-dose Atracurium on conditions of insertion, complications, and hemodynamic responses to LMA insertion following induction of anesthesia with propofol, in patients undergoing cataract surgery.Patients and Methods:In this double-blind randomized clinical trial study, 60 patients were randomly divided into two groups. Initially, the patients in the study group received 0.15 mg/kg intravenous injection of atracurium, and the patients in the control group received 2 ml of intravenous injection of normal saline, after which anesthesia in both groups were induced with midazolam, fentanyl, lidocaine, and propofol. The amount of jaw relaxation, ease of insertion, and the time needed for insertion, hemodynamic responses and complications of LMA insertion were evaluated.Results:Jaw relaxation and ease of LMA insertion in the study group was significantly better than that of the control group (P = 0.02). Average time needed for LMA placement in the study group (5/06 ± 0.52 second) was significantly lower than the control group (5/76 ± 0.67 second) (P = 0.001). Hemodynamic response to LMA insertion was similar in both groups. Sore throat at recovery and 24 h after surgery in the control group was significantly higher than that of the study group (3/30 vs. 10/30) (P = 0.01).Conclusions:Using low doses of atracurium decreases the time needed for LMA insertion and sore throat after the operation. Atracurium also increases jaw relaxation and facilitates the placement of LMA.

Dimethyl Sulfoxide Attenuates Acute Lung Injury Induced by Hemorrhagic Shock/Resuscitation in Rats

Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively (n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45mmHg for 60min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression.

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats.

Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension.

The influence of extracorporeal circulation on EV1000 monitor hemodynamic parameters at two sites of intravenous cold saline injection

The influence of extracorporeal circulation on EV1000 monitor hemodynamic parameters at two sites of intravenous cold saline injection

Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation.

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction.

Abstract 3779: Evaluation of efficacy of an RNA aptamer toward non-small cell lung cancer

Abstract A specific RNA aptamer (RA16) targeting non-small cell lung cancer (HCI-H460 cells) was previously selected by in vivo SELEX. In this study, we report subsequent studies that determined the effect of RA16 on HCI-H460 cell proliferation in vitro and xenogfrat tumor growth in vivo. Firstly, RA16 apatmer, but SCAP control, was capable of inhibiting cell proliferation in a dose-dependent manner. At 300 nM, RA16 apatmer suppressed cell proliferation by 80%. The IC50 for RA16 was determined at 116.7 nM. Intriguingly, RA16 exhibited no inhibitory effect on HeLa cells even at 600 nM. Moreover, inhibition of HCI-H460 cell growth by RA16 was also observed when it was non-covalently conjugated to Epirubicin(EPI)at the ratio of 1:8 (RA16:EPI). Cell inhibition of 93.6±1.48% was observed with RA16:EPI conjugate (0.375μM:3μM), whereas cell inhibition of 89.0±1.67% and 74.8±5.01% was observed with EPI at 3μM and RA16 alone at 0.375μM, respectively. No inhibition of cell proliferation was observed for the control group treated with cell culture medium. Secondly, an in vivo study was performed to investigate the inhibition of RA16 on HCI-H460 xenograft tumors in mice. Twelve mice with tumor sizes ranging from 50 to 100 mm3 were randomly divided into 2 groups (n = 6). The mice from each group were administrated via intravenous injections of saline (control) or 2 nM of RA16 on days 0, 3, 5, 7, and 9, respectively. Tumor sizes were measured every other day and tumor volumes were calculated by the formula V (mm3) = 1/2×a×b2. The average inhibition rate for mouse tumors of treated group was 54.26±5.87% on day 16 compared with the control group mice. Finally, an in vivo study was performed to evaluate the inhibition of RA16:EPI conjugates on xenograft tumors in mice. Thirty tumor-bearing mice (with tumor sizes about 200∼300 mm3) were randomly divided into 6 groups(n = 5)and treated with various combinations of RA16 and EPI weekly for 3 times. A strong inhibition (64.38±6.45%) of tumor growth was observed when the mice were treated with RA16:EPI conjugate with PEG (EPI at 1.5 mg/kg/week). A moderate inhibition (47.13±10.21%) was observed in mice treated with EPI alone at 1.5 mg/kg/week. Similarly, a moderate inhibition (39.07±5.65%) of tumor growth was observed in mice treated with RA16-EPI conjugate (EPI at 0.5 mg/kg/week) whereas a weak inhibition (28.76±5.65%) was noticed in mouse group treated with EPI alone at 0.5 mg/kg/week. Furthermore, RA16:EPI conjugate (EPI at 1.5 mg/kg/week) inhibited tumor growth by 32.80±6.99% where no PEG was linked to RA16, suggesting that PEGlyation prolongs the efficiency of RA16 in tumor inhibition in vivo. No any inhibition was observed with saline-treated mice. In conclusion, our studies demonstrate that RNA aptamer RA16 specifically inhibits proliferation of transformed HCI-H460 cells in vitro and xenograft tumor growth in vivo and that RA16 conjugated with EPI exhibits enhanced activities both in vitro and in vivo. Citation Format: Hanlu Wang, Haiping Yang, Xinxin Ding, Wei Dai, Yongping Jiang. Evaluation of efficacy of an RNA aptamer toward non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3779.

LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats.

Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

BMSCs transplantation improves cognitive impairment via up-regulation of hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion

Bone marrow mesenchymal stem cells (BMSCs) transplantation can ameliorate cognitive impairment in chronic ischemic brain injury, but the underlying mechanism is poorly understood. It is considered that the hippocampus holds the capabilities of memory consolidation and spatial navigation, and the gamma amino butyric acid (GABA)ergic system plays an important role in the control of learning and memory processes. Herein, we investigated whether transplantation of BMSCs could improve cognitive impairment via regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Animals treated with permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) (a rat model of chronic cerebral hypoperfusion) received intravenous injections of BMSCs or saline as experimental group and control group I, the sham-operated rats received intravenous injections of BMSCs or saline as the sham group and control group II. Four weeks later, the Morris Water Maze was employed to evaluate the cognitive changes of each group, immunohistochemistry and western blotting was used to investigate the GABAergic system expression including GABA, glutamic acid decarboxylase 67 (GAD67) or GABAB receptor 1 (GABABR1) in the hippocampus. Our results showed that the 2VO model presented decreased capacities of learning and memory and down-regulated the expression of GABA, GAD67 or GABABR1 in the hippocampal CA1 subfield in comparison to the sham group (P<0.05), while administration of BMSCs (experimental group) manifested increased performances of learning sessions and probe tasks, as well as up-regulated expression of GABA, GAD67 or GABABR1 compared with the control group I (P<0.05). Collectively, these findings suggest that transplantation of BMSCs is capable of improving cognitive impairment via up-regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Hence, BMSCs transplantation could serve as an important tool for cell therapy in chronic cerebral hypoperfusion disorders.

Pre-existent anxiety symptoms is associated with modified behavioral response during endotoxemia

Experimental endotoxin administration is a well-established model to analyze the effect of inflammation on the development of mood impairments. However, it remains unknown from previous studies in comparatively small samples whether pre-existing inter-individual differences modulate the behavioral response during endotoxemia. We addressed this question in the present study using a merged database combining data from multiple studies performed at two study sites. In 286 healthy volunteers who either received low-dose intravenous injection of lipopolysaccharide (LPS, 0.4–0.8 ng/kg, n = 168) or saline ( n = 118), plasma concentrations of TNF-alpha and IL-6 were analyzed before and 2, 3.5 and 6 hours post injection together with state anxiety symptoms (STAI). Pre-existent symptoms of anxiety and depression (HADS) were assessed before injection. LPS administration induced an increase in state anxiety 2 hours post injection that was positively correlated with increases in TNF-alpha and IL-6, but not with pre-existent HADS scores (when adjusted for age, sex, BMI, LPS dose, and study design). However, higher levels of pre-existent HADS anxiety symptoms predicted a stronger subsequent reduction in state anxiety at 3.5 and 6 hours post LPS injection. Taken together, these data suggest that although inter-individual differences in anxiety or depression symptoms do not appear to explain the extent of mood impairments during endotoxemia, at least in non-patient samples, they still lead to a modified mood response with a faster and stronger decline.

Efficacy of thymosin α1 and interferon α for the treatment of severe acute pancreatitis in a rat model.

The present study aimed to investigate the effects of treatment with thymosin α1 (TA1) or interferon α (IFNα) following the establishment of severe acute pancreatitis (SAP) in rats. A total of 144 Sprague-Dawley rats were randomly divided into four groups. The rats in all four groups were celiotomized, and the rats in the control group were administered with an intravenous injection of saline. The three other groups were administered with 5% 1 ml/kg sodium taurocholate via the cholangiopancreatic duct. SAP group rats were administered with an intravenous injection of saline; TA1 group rats received 26.7 µg/kg TA1; and interferon α (INFα) group rats received 4.0×105 U/kg IFNα. The rats were anesthetized and blood samples were collected from the animals 3, 12 and 24 h after surgery. The levels of T cell subsets, serum enzyme indicators, cytokines and procalcitonin (PCT) were measured. The general conditions of the rats were observed until sacrifice, and pancreatic and lung tissue samples were sampled for hematoxylin and eosin staining and histological scoring. The expression levels of aspartate transaminase, lactate dehydrogenase, α-amylase (AMY), P-type-amylase, lipase, PCT, tumor-necrosis factor α, interleukin (IL)-4, IL-5, and IL-18 in the TA1 and IFNα-treated rats were significantly lower, compared with those of the SAP rats within the first 24 h of model establishment (P<0.05). The TA1 and IFNα-treated rats exhibited significantly increased levels of CD3+, CD4+ and CD8+ T cells, and an increased ratio of CD4+/CD8+ cells, compared with SAP rats. Histological analysis revealed that the TA1 and IFNα-treated rats exhibited significantly ameliorated pancreas and lung damage, and mortality rates were reduced from 50.0% (6/12) to 25.0% (3/12) and 33.3% (4/12), respectively. The immunomodulatory agents TA1 and IFNα reduced acute inflammation, decreasing cell damage and enhancing immune function and survival rates in the SAP rats.

Local infiltration analgesia is not improved by postoperative intra-articular bolus injections for pain after total hip arthroplasty

Background and purpose — The effect of postoperative intra-articular bolus injections after total hip arthroplasty (THA) remains unclear. We tested the hypothesis that intra-articular bolus injections administered every 6 hours after surgery during the first 24 hours would significantly improve analgesia after THA.Patients and methods — 80 patients undergoing THA received high-volume local infiltration analgesia (LIA; 200 mg ropivacaine and 30 mg ketorolac) followed by 4 intra-articular injections with either ropivacaine (100 mg) and ketorolac (15 mg) (the treatment group) or saline (the control group). The intra-articular injections were combined with 4 intravenous injections of either saline (treatment group) or 15 mg ketorolac (control group). All patients received morphine as patient-controlled analgesia (PCA). The primary outcome was consumption of intravenous morphine PCA and secondary outcomes were consumption of oral morphine, pain intensity, side effects, readiness for hospital discharge, length of hospital stay, and postoperative consumption of analgesics at 3, 6, and 12 weeks after surgery.Results — There were no statistically significant differences between the 2 groups regarding postoperative consumption of intravenous morphine PCA. Postoperative pain scores during walking were higher in the treatment group from 24–72 hours after surgery, but other pain scores were similar between groups. Time to readiness for hospital discharge was longer in the treatment group. Other secondary outcomes were similar between groups.Interpretation — Postoperative intra-articular bolus injections of ropivacaine and ketorolac cannot be recommended as analgesic method after THA.

Intra-ventral tegmental area HIV-1 Tat1-86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats.

Cigarette smoking prevalence in the HIV-positive individuals is profoundly higher than that in the HIV-negative individuals. We have demonstrated that HIV-1 transgenic rats exhibit attenuated nicotine-mediated locomotor activity, altered cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the mesocorticolimbic regions. This study investigated the role of HIV-1 transactivator of transcription (Tat) protein in the alterations of nicotine-mediated behavior and the signaling pathway observed in the HIV-1 transgenic rats. Rats received bilateral microinjection of recombinant Tat1–86 (25 μg/side) or vehicle directed at ventral tegmental area (VTA) followed by locomotor testing in response to 13 daily intravenous injections of nicotine (0.05 mg/kg, freebase, once/day) or saline. Further, we examined the phosphorylated levels of CREB (pCREB) and ERK1/2 (pERK1/2) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and VTA. Tat diminished baseline activity in saline control rats, and attenuated nicotine-induced behavioral sensitization. Following repeated saline injection, the basal levels of pERK1 in the NAc and VTA and pERK2 in VTA were lower in the vehicle control group, relative to the Tat group. After repeated nicotine injection, pERK1 in NAc and VTA and pERK2 in VTA were increased in the vehicle group, but not in the Tat group. Moreover, repeated nicotine injections decreased pCREB in the PFC and VTA in the Tat group but not in the vehicle group. Thus, these findings indicate that the direct injection of Tat at the VTA may mediate CREB and ERK activity in response to nicotine-induced locomotor activity.

Effects of different doses of 5-HT receptor ligands on genioglossus discharge in chronic intermittent hypoxia rats

To explore the effects of different doses of 5-HT2A/2CR agonist or 5-HT2AR antagonist on genioglossus discharge in chronic intermittent hypoxia rats. Thirty adult male Sprague-Dawley rats, each 180-200 g, were randomly divided into the normoxia group (group A, n=5) and the chronic intermittent hypoxia group (CIH group, n=25) by the random number table. The rats in the CIH group were fed in the intermittent hypoxia animal chambers, while the normoxia control group was placed in the normoxia animal chambers for 8 h per day for 4 consecutive weeks. After 28 days, 5 min×3 times of stimulation with acute intermittent hypoxia (AIH) were given and the genioglossus muscle activity were then recorded and compared before and after intravenous injection of saline (group B, n=5), the 5-HT2A/2CR agonist 30 µg/3 µl (group C, n=5) or 50 µg/5 µl group (group D, n=5), 5-HT2AR antagonist 10 µg/1 µl (group E, n=5) or 70 µg/7 µl (group F, n=5). The average peak amplitude in 60 min of genioglossus muscle activity in the CIH saline control group (group B) was significantly higher than that in the normoxia group (group A), while the genioglossus discharge in the 2 groups were (42.29 ± 1.78) µV, (25.38 ± 0.89) µV respectively (P<0.01). The 5-HT2A/2CR agonist (30 µg/3 µl or 50 µg/5 µl) caused the amplitude of genioglossus muscle activity firstly to increase and then to decrease, with the peak changes showing statistical difference (P<0.05). 10 µg/1 µl 5-HT2AR antagonist did not influence genioglossus muscle activity (P>0.05), however, after intravenous injection of 70 µg/7 µl 5-HT2AR antagonist, the amplitude of genioglossus discharge firstly decreased and then gradually returned to baseline level, the difference being statistically significant, P<0.01. Our results indicate that CIH strengthens the genioglossus discharge in CIH rats. The 5-HT2A/2CR agonist can strengthen the genioglossus discharge but the 5-HT2AR antagonists can weaken the effect, both of which have dose-related effects.

Local application of ibandronate/gelatin sponge improves osteotomy healing in rabbits.

Delayed healing or non-union of skeletal fractures are common clinical complications. Ibandronate is a highly potent anti-catabolic reagent used for treatment of osteopenia and fracture prevention. We hypothesized that local application of ibandronate after fracture fixation may improve and sustain callus formation and therefore prevent delayed healing or non-union. This study tested the effect of local application of an ibandronate/gelatin sponge composite on osteotomy healing. A right-side distal-femoral osteotomy was created surgically, with fixation using a k-wire, in forty adult male rabbits. The animals were divided into four groups of ten animals and treated by: (i) intravenous injection of normal saline (Control); (ii) local implantation of absorbable gelatin sponge (GS); (iii) local implantation of absorbable GS containing ibandronate (IB+GS), and (iv) intravenous injection of ibandronate (IB i.v.). At two and four weeks the affected femora were harvested for X-ray photography, computed tomography (CT), biomechanical testing and histopathology. At both time-points the results showed that the calluses in both the ibandronate-treated groups, but especially in the IB+GS group, were significantly larger than in the control and GS groups. At four weeks the cross sectional area (CSA) and mechanical test results of ultimate load and energy in the IB+GS group were significantly higher than in other groups. Histological procedures showed a significant reduction in osteoclast numbers in the IB+GS and IB i.v. groups at day 14. The results indicate that local application of an ibandronate/gelatin sponge biomaterial improved early osteotomy healing after surgical fixation and suggest that such treatment may be a valuable local therapy to enhance fracture repair and potentially prevent delayed or non-union.

Ozone preconditioning attenuates contrast-induced nephropathy in rats

BackgroundContrast-induced nephropathy (CIN) is an important complication of vascular interventions. Ozone therapy can induce tolerance to ischemic insults, a phenomenon known as ozone oxidative preconditioning (OOP). The aim of this study was to investigate the effects of OOP on CIN. Materials and methodsThirty-two Wistar rats were randomized into four groups (n = 8). The control group had intravenous saline injection. The contrast media (CM) group had intravenous meglumine/sodium diatrizoate injection to form CIN. The ozone (O3) group received intraperitoneal ozone for 5 d before the induction of CIN. The oxygen (O2) group was given an equal amount of oxygen for 5 d before the induction of CIN. The animals were sacrificed 48 h after the administration of contrast agent or saline. Kidneys were harvested, and blood samples were obtained. Renal function tests, serum and renal tissue malondialdehyde (MDA), and nitric oxide (NO) levels and renal oxidant system parameters were determined. Histologic examination was performed for renal injury. ResultsSerum blood urea nitrogen (BUN), creatinine, and serum and renal MDA were increased after contrast exposure. Renal NO was decreased, and there was prominent tubular necrosis in the CM group. Serum BUN, creatinine, serum and renal MDA, and grade of tubular necrosis were decreased in the O3 group as compared with those in the CM group. The levels of serum and renal NO and renal total antioxidant system in O3 group were higher than the levels in the CM group. ConclusionsOOP attenuates experimental CIN. This effect is suggested to be mediated by reinforcement of renal antioxidant defenses and maintenance of renal NO levels.

170. Experimental endotoxemia alters neural processing of visceral stimuli: A brain imaging study in healthy volunteers

Recent studies documented that experimentally-induced endotoxemia leads to hyperalgesia in healthy subjects. It remains unclear whether and to what extent these effects are reflected by altered pain processing within the brain. Herein, we analyzed behavioral and neural responses to visceral painful stimuli during endotoxin-induced systemic immune activation using functional magnetic resonance imaging (fMRI). Implementing a randomized, placebo-controlled design, healthy males received an intravenous injection of either lipopolysaccharide (LPS group; 0.4 ng/kg) or saline (control group). Blood samples were collected before and up to 6 h post-injection to analyze changes in cytokine levels. Visceral pain thresholds and blood-oxygen-level-dependent (BOLD) responses to repeated painful rectal stimuli were assessed at baseline (prior to injection) and 2 h post-injection. LPS-administration increased TNF-α and IL-6 plasma levels as well as body temperature, reflecting systemic immune activation. Visceral pain thresholds were significantly decreased in response to LPS. Visceral stimuli led to significantly greater activation of the somatosensory cortex, insula, anterior cingulate (ACC), and dorsolateral prefrontal (DLPFC) cortices during endotoxemia. Within LPS-treated subjects, greater peak cytokine increases were associated with greater pain-induced activation of the ACC and DLPFC. Together, this study provides first evidence of altered central pain processing during experimental endotoxemia. Visceral hyperalgesia in response to systemic immune activation is reflected by greater activation of the “pain-matrix”, which supports the relevance of neuro-immune pathways in the pathophysiology of human visceral hyperalgesia.

The effect of single-dose administration of dexamethasone on postoperative pain in patients undergoing laparoscopic cholecystectomy.

Background:Postoperative pain is considered as a reason of patient’s delay in discharge and disability aggravation. Therefore, multimodal approaches have been suggested in order to mitigate pain and decrease postoperative side effects.Objectives:The aim of this study was to evaluate analgesic effect of a single dose injection of dexamethasone on reducing postoperative pain in laparoscopic cholecystectomy.Patients and Methods:In this double-blind, prospective study, 122 patients aged 18-60 years old, whom were selected for laparoscopic cholecystectomy, were classified into two case and control groups, and 61 patients were included in each group. The case (D) group underwent general anesthesia and a single- dose intravenous injection of dexamethasone. The Control (C) group received general anesthesia and intravenous injection of normal saline. Total dose of consumed meperidine and pain intensity during first 24 hours were evaluated in both groups.Results:No significant difference existed between two groups regarding age, sex, weight and operation time. Pain intensity in group D was significantly less than group C (P < 0.01) after two, six and 12 hoursof surgery. No significant difference existed in pain intensity between two groups at the beginning of and 24 hours after the surgery (P > 0.05). Meperidine consumption in group D was significantly less than group C (P < 0.05).Conclusions:Findings of present study showed that single dose of intravenous dexamethasone, led to less pain intensity and amounts of meperidine consumption, in comparison with placebo.

Improvement of cardiac function by short-term enzyme replacement therapy in a murine model of cardiomyopathy associated with Hunter syndrome evaluated by serial echocardiography with speckle tracking 2-D strain analysis

Cardiac systolic function is significantly decreased in a proportion of patients with Hunter syndrome. This study was performed to evaluate the change in myocardial function associated with enzyme replacement therapy (ERT) in a mouse model of cardiomyopathy associated with Hunter syndrome. Thirty 9-week-old iduronate-2-sulfatase (IDS) knockout mice received either intravenous injection of human recombinant IDS (ERT group, N=15) or saline (control group, N=15) for 5weeks. Echocardiography was performed at baseline and after treatment. Echocardiographic parameters of left ventricular (LV) systolic function and 2-dimensional radial and circumferential strain were assessed. At follow-up, there was a significant increase in LV fractional shortening and radial and circumferential strain in the ERT group only. Notable myocardial fibrosis was observed in the control group only. In the murine model of Hunter syndrome, ERT exerts beneficial effects on cardiac function, which can be evaluated by serial echocardiographic evaluation including 2-dimensional strain analysis.