DXM Group Research Articles

Cyasterone has a protective effect on steroid-induced Osteonecrosis of the femoral head.

Cyasterone alleviated the apoptosis of BMSCs induced by Dexamethasone via the PI3K/AKT signaling pathway. In addition, Cyasterone had a protective effect on SIONFH model rats by reducing the percentage of empty bone lacunae. To study the effect of Cyasterone on apoptosis of rat BMSCs and its function on the SIONFH rat model. Rat BMSCs were cultured and divided into Control, DXM and Cyasterone (DXM+Cyasterone) groups. The apoptosis of each group was detected by flow cytometry, the expressions of Caspase-3 and Caspase-9 were detected by immunofluorescence staining, and the mRNA and protein expressions of AKT, BAX, P53, P85, Bcl-2 and Cytochrome C were detected by qPCR and WB. In animal experiments, the femoral head of rats were subjected to HE staining and Micro-CT to observe the necrosis and repair conditions. The apoptosis rate of DXM and Cyasterone groups increased compared with Control group, and the apoptosis rate of Cyasterone group decreased compared with DXM group. Compared with DXM group, the mRNA expression of BAX, P53, P85 and Cytochrome C in Cyasterone group were increased, while the protein expression of AKT and Bcl-2 decreased. The histopathological and morphological analysis showed that Cyasterone promoted the trabecular bone structure in rat, which evenly benefit for the repair of SIONFH. Cyasterone can reduce the apoptosis of rat BMSCs induced by Dexamethasone, and help promoting the bone repair in SIONFH rats.

Cost effectiveness and long-term outcomes of dexamethasone administration in major non-cardiac surgery

Study objectivesPostoperative administration of dexamethasone has been proposed to reduce morbidity and mortality in patients undergoing major non-cardiac surgery. In this ancillary study of the PACMAN trial, we aimed to evaluate the cost effectiveness of dexamethasone in patients undergoing major non-cardiac surgery. MethodsPatients included in the multicentric randomized double-blind, placebo-controlled PACMAN trial were followed up for 12 months after their surgical procedure. Patients were randomized to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Cost effectiveness between the dexamethasone and placebo groups was assessed for the 12-month postoperative period from a health payer perspective. ResultsOf 1222 randomized patients in PACMAN, 137 patients (11%) were followed up until 12 months after major surgery (71 in the DXM group and 66 in the placebo group). Postoperative dexamethasone administration reduced costs per patient at 1 year by €358.06 (95%CI -€1519.99 to €803.87). The probability of dexamethasone being cost effective was between 12% and 22% for a willingness to pay of €100,000 to €150,000 per life-year, which is the threshold that is usually used in France and was 52% for willingness to pay of €50,000 per life-year (threshold in USA). At 12 months, 9 patients (13.2%) in the DXM group and 10 patients (16.1%) in the placebo group had died. In conclusion, our study does not demonstrate the cost effectiveness of perioperative administration of DXM in major non-cardiac surgery.

Dexametasona frente a metilprednisolona ajustada al peso en pacientes con neumonía moderada-grave por SARS-CoV-2

ObjectivesTo compare the 30-day outcome (mortality and/or ICU admission) of patients admitted for moderate-severe SARS-CoV-2 pneumonia treated with dexamethasone after the Recovery study versus those treated with weight-adjusted methylprednisolone. MethodsRetrospective cohort study of 65 patients with moderate-severe pneumonia who received dexamethasone 6 mg/day (DXM group) versus 80 treated with weight-adjusted methylprednisolone (MTPN group). ResultsTwenty-one (32.3%) patients in the DXM group died vs. 8 (10%) in the MTPN group (p-value < 0.001) and 29 (44.6%) in the DXM group required ICU admission vs. 2 (2.5%) of the MTPN group (p-value < 0.001). There were no baseline differences regarding sociodemographic characteristics with a higher mean qSOFA in the MTPN group. The hazard ratio for mortality and ICU admission adjusted for age, sex, and admission CRP was 2.189 (1.082–4.426; 95% CI) and 10.589 (2.139–48.347; 95% CI) for the DXM group, respectively, vs. MTPN group. ConclusionsMortality and admission to the ICU were lower in patients treated with weight-adjusted methylprednisolone compared to those treated with dexamethasone.

Surgery After Primary Dexamethasone Treatment for Patients with Chronic Subdural Hematoma—A Retrospective Study

We aimed to quantify the need for additional surgery in patients with chronic subdural hematoma (CSDH) primarily treated with dexamethasone and to identify patient characteristics associated with additional surgery. Data were retrospectively collected from 283 patients with CSDH, primarily treated with dexamethasone, in 3 hospitals from 2008 to 2018. Primary outcome was the need for additional surgery. The association between baseline characteristics and additional surgery was analyzed with univariable and multivariable logistic regression analysis and presented as adjusted odds ratios (aOR). In total, 283 patients with CSDH were included: 146 patients (51.6%) received 1 dexamethasone course (DXM group), 30 patients (10.6%) received 2 dexamethasone courses (DXM-DXM group), and 107 patients (37.8%) received additional surgery (DXM-SURG group). Patients who underwent surgery more often had a Markwalder Grading Scale of 2 (as compared with 1, aOR 2.05; 95% confidence interval [CI] 0.90-4.65), used statins (aOR 2.09; 95% CI 1.01-4.33), had a larger midline shift (aOR 1.10 per mm; 95% CI 1.01-1.21) and had larger hematoma thickness (aOR 1.16 per mm; 95% CI 1.09-1.23), had a bilateral hematoma (aOR 1.85; 95% CI 0.90-3.79), and had a separated hematoma (as compared with homogeneous, aOR 1.77; 95% CI 0.72-4.38). Antithrombotics (aOR 0.45; 95% CI 0.21-0.95) and trabecular hematoma (as compared with homogeneous, aOR 0.31; 95% CI 0.12-0.77) were associated with a lower likelihood of surgery. More than one-third of patients with CSDH primarily treated with dexamethasone received additional surgery. These patients were more severely affected amongst others with larger hematomas.

556. Ruxolitinib for the Management of Severe Pneumonia Caused by SARS-CoV-2. Exploring the Combination with dexamethasone

BackgroundMexico is one of the top five countries with a higher mortality rate of hospitalized patients of 30.1%. Since COVID-19 has been associated with immune dysregulation and hyper inflammation, JAK-12 inhibitors have been tested to reduce IL6 production. Studies have shown improvements when using ruxolitinib (rxb) in severely hospitalized patients with COVID-19. These have included patients in combination with corticosteroids such as dexamethasone (dxm). This work aims to test the response of hospitalized patients with severe or critical COVID-19 treated with rxb with or without dxm. MethodsAn experimental, open, prospective study in a single third-level hospital in Mexico was performed. The primary outcome was favorable clinical response defined as withdrawal or decline of supplementary oxygen. Secondary outcomes such as mean hospital stay, improvement in systemic inflammatory response parameters, and mortality were also evaluated. Statistical differences for baseline and final measure and the use and not use of dxm were estimated. The study included adults with SARS-CoV-2 infection confirmed with polymerase chain reaction, radiological pneumonia, and oxygen saturation less than 90%. Rxb was administered 5mg/12hrs/15days, IV dxm 6mg/day/10days. ResultsThe final sample was 108 adults with complete information and informed consent. Sixty-two patients (57%) received only rxb. There were no differences between groups for any parameter at the beginning of treatment, and all patients were receiving supplemental oxygen. After 28-day follow-up, 70% reduce supplemental oxygen requirement (74% rxb and 71% rxb+dxm; p=0.628), 18% remained, and 2% increases support (1% with rxb, and 5% rxb+dxm; p< 0.001); 87% of patients were discharged (89% rxb and 85% rxb+dxm; p=0.603). In both groups, there was a significant reduction of CRP, LDH, and Ferritin on day 15. The mortality rate was 9% (no difference in groups; p=0.453), and a higher proportion died for Pseudomonas aeruginosa superinfection in the rxb+dxm group (p< 0.001). Differences for support oxygen at baseline and discharge Final health outcomes of patients with severe or critical COVID-19 in a third-level hospital in Mexico ConclusionThe use of rxb could be considered as a treatment helping clinical improvement in hospitalized patients with severe COVID-19. Combination with dxm apparently did not add clinical benefits. It should be further evaluated.Disclosures All Authors: No reported disclosures

A comparative study of intrathecal clonidine VS dexmedetomidine in caesarean patients

Introduction: Spinal anaesthesia is the most commonly employed technique for Caesarean section. Many drugs such as opioids as intrathecal additives such have been widely studied found to be associated with respiratory depression, pruritis, etc. Upcoming studies on alpha-2 agonists as intrathecal additives have been found promising and will replace opioids soon. Knowledge on the efficacy of the individual a2 agonists over one another is lacking. So the aim of the study is to compare the spinal additive effect of dexmedetomidine and clonidine in pregnant patients for caesarean section. Materials and Methods: Ninety patients belonging to ASA group I and II of age group of 20 – 40 years were included in the study. Patients with PIH, Diabetes, Body weight above 100kg, Height less than 145 cm, Post spinal surgeries, spinal deformity, and known history of Coagulopathy and allergic to study drugs, documented IUGR, intrauterine anomaly and patients those who are not willing for spinal anaesthesia were excluded from the study. They were randomly allocated into three groups of 30 patients each, Group D where the patients received dexmedetomidine 5µg with bupivacaine 10mg, Group C where the patients received clonidine 15µg with bupivacaine 10mg and Group B where the patient received bupivacaine 10mg with 0.9% saline 0.5ml. The duration of the sensory and the motor blockade, two segment regression times, duration of the postoperative analgesia, sedation and neonatal wellbeing with maternal hemodynamic changes were studied. Results: Demographic characteristics and hemodynamic parameters were comparable between the three groups. The onset and maximal sensory block was faster in Dxm and clonidine groups (162±41.40;166±37.57) than control group (254.67±28.73) which was statistically significant. The two segment regression time was significantly shorter in control group (67.53±5.94) than Dxm and clonidine group (103.47±8.08;108±6.90). Dxm and clonidine group showed shorter

Effects of danshensu on the transforming growth factor-β1/smads signaling pathway in rats with lung injury

Observe the therapeutic effect of Danshensu on lung injury for rats, as well as explore the mechanism of Danshensu in TGF-β1/Smads signaling. Thirty Sprague-Dawley (SD) rats were intratracheally instilled with bleomycin to induce lung injury and interstitial fibrosis. Divided Thirty rats into three groups. DA group (η = 10): Inject 15 mg/kg Danshensu into the abdominal cavity; DXM group (η = 10): Inject 1 mg/kg dexamethasone into the abdominal cavity; BLM group (η = 10): Inject 2 mL physiological saline into the abdominal cavity. Then ten SD rats were intratracheally instilled with physiological saline as normal control group, NC group: Inject 2 mL physiological saline into the abdominal cavity. After a period of 28 days, the degree of pulmonary alveolitis was evaluated using hematoxylin-eosin (HE) staining, and the degree of lung fibrosis was evaluated using Masson?s trichrome (MT) staining. The immunohistochemistry was used to determine the expression of α-SMA. Magnetic nanoparticles+rtQ-PCR was used to determine the mRNA expressions for TGF-β1, Smad3, and Smad7. The alveolitis and pulmonary fibrosis in DA rats were obviously less than those in BLM rats and DXM rats. The expression of α-SMA in DA rats was obviously less than that of in BLM rats and DXM rats; the mRNA expression of TGF-β1 and Smad3 in DA rats were obviously reduced; the Smad7 mRNA expression was obviously up-regulated. DA can alleviate rat lung injury caused by bleomycin. Inhibiting the TGF-β1 and Smad3 mRNA expression, as well as boosting the Smad7 mRNA expression is one of the mechanisms by which Danshensu reduces lung injury.

Effects of intrathecal dexmedetomidine vs intrathecal magnesium sulfate as adjuvants in spinal anesthesia

Aim Intrathecal adjuvants are used for prolongation of duration of subarachnoid block and provide adequate analgesia. This study was designed to evaluate the onset, duration, and regression of sensory and motor block of intrathecal dexmedetomidine vs magnesium sulfate as an adjuvant to 0.5% hyperbaric bupivacaine for spinal anesthesia. Materials and methods Sixty patients aged 21–50 years, with American Society of Anesthesiologists status I, II scheduled for elective lower abdominal and lower limb surgeries, were divided into three equal groups in a randomized-controlled manner: the control group (S: n=20) received 15 mg hyperbaric bupivacaine (3 ml) and 1 ml saline, the dexmedetomidine group (DXM: n=20) received15 mg hyperbaric bupivacaine (3 ml) and 10 µg of dexmedetomidine, and the magnesium sulfate group (Mg: n=20) received 15 mg hyperbaric bupivacaine (3 ml) and 50 mg of magnesium sulfate. Hemodynamic variables such as heart rate, systolic and diastolic blood pressure, onset of sensory and motor block, regression time, time to first analgesic request, and adverse effects were recorded for each patient. Results The onset time of sensory and motor block was rapid in the DXM group in comparison with the Mg and control groups. The onset time of sensory and motor blockade were delayed in the Mg group in comparison with the S group. The regression time of sensory and motor blockade was prolonged in the DXM group and in the Mg group compared with the S group. Demand for analgesia was significantly late in the DXM group compared with the Mg and control groups, but early in the control group. Conclusion Dexmedetomidine had faster onset of sensory and motor blocks, and provided prolonged postoperative analgesia compared with the magnesium sulfate and control groups

S231. THE ROLE OF DOPAMINERGIC AND GLUTAMATERGIC NEUROTRANSMISSION IN DELUSIONAL IDEATION AND SENSORY INFORMATION PROCESSING OF PATIENTS WITH SCHIZOPHRENIA IN COMPARISON TO HEALTHY HUMAN PARTICIPANTS

BackgroundThe primary aim of this study was to generate neurobiological evidence regarding the impact of dopaminergic and glutamatergic neurotransmission on reasoning biases related to delusional ideation in patients with schizophrenia associated with impaired processing of sensory information. The proposed respective roles of these neurotransmitter systems have been encapsulated in the so-called dopamine- and glutamate-hypotheses of schizophrenia. From a behavioural perspective both reduced glutamate and enhanced dopamine levels are currently discussed as critical contributing factors to generate aberrant beliefs (glutamate) during information sampling and to generate confidence or expected precision (dopamine) during action selection. Hence, by modulating levels of glutamate and dopamine in the brain we hypothesized to induce reported impairments of patients with schizophrenia related todelusional ideation.MethodsThe study consisted of three aligned experiments: In the first two experiments a prospective interventional drug study was conducted with n=192 participants employing a randomized, placebo-controlled, double-blinded design on two parallel testing-groups, receiving either dopaminergic or glutamatergic neuromodulators: Experiment I: either 2.5mg haloperidol (D1/D2-receptor antagonist; HAL), 2.5mg bromocriptine (D2-receptor agonist; BRO), or placebo (PLC-1). Experiment II: either 120mg Dextromethorphan (NMDA-receptor antagonist, DXM), 250mg D-Cycloserine (NMDA-receptor agonist, CYC), or placebo (PLC-2). In the third experiment n=45 patients with schizophrenia (SZ) and n=45 healthy control participants (HC) matched for gender, age and IQ were investigated. All experiments employed a computerized (Matlab, Cogent) version of the Beadstask (Huq, Garety et al. 1988). In total participants processes 60 Beadstask trials subdivided into three levels of difficulty: (I) easy trials with a bias of 80–90% for one predominant bead color in a sequence, (II) difficult trials (60–70% bias), and (III) ambiguous trials (no bias, 50% likelihood). Additionally, the task consisted of three parts that were presented in a fixed order: an easy draws-to-decision condition, an easy probability estimates condition, and a difficult draws-to-decision condition.ResultsIn accordance with foregoing studies, SZ patients showed significantly less draws to decision compared to HC (all p≤0.038). Explorative analysis across experimental conditions further revealed no significant differences for participants receiving DXM (NMDA-receptor antagonist) compared SZ patients (all p≥0.090), but obtained less draws to decision in the DXM group than all other groups. Whereas following HAL intervention the number of draws increased significantly compared to any other experimental group (all p≤0.048). Analyzing the probability estimates condition we quantified changes of probability estimates on an individual subject level whenever there was a change of bead color in a sequence (so called disconfirmatory evidence score, DES). In case of easy and difficult trial types we observed significantly higher DES scores in participants with SZ compared to HC (p≤0.003) and again obtained no differences between SZ and DXM (p=0.037).DiscussionOur findings are supportive for a hypothesized relationship between neurotransmitter state alterations of glutamate and dopamine in patients with schizophrenia and the delusional ideation. Future analysis will focus on developing a computational behavioral model of cognitive processing of the Beadstask, implementing our neurobiological findings in order to further disentangle the neurobiological underpinnings of delusional ideation in patients with schizophrenia.

Effects of N-acetyl cysteine to improve acute lung injury in rats.

To study the mechanism of NAC to improve LPS induced acutelung lung injury. The 40 rats were divided into 4 groups included NC group, Model group, NAC group and DXM group. The rats of Model, NAC and DXM groups were injected LPS, NAC group and DXM group were resepectively injected NAC (200 mg/kg) or DXM (70 mg/kg). Collecting the bronchoalveolar lavage fluid (BALF) from lung, and measuring the TGF-β1 concentration of BALF and lung tissue in 4 groups; After executing the rats, taken the lung tissue to observant lung pathological morphology and evaluated TGF-β1 expression of difference groups. Measuring the TLR-4 and NF-κb in 4 groups by WB assay. Compared with Model group, The NAC and DXM groups were improved in H (et) E staining, the TGF-β1 concentration of NAC and DXM groups were significantly reduced in BALF and lung tissue (p < 0.05, respectively). TLR-4 and NF-κb proteins of NAC and DXM groups were lower than that of Model group in IHC and WB assays (p < 0.05, respectively). NAC had effects to protect LPS induced lung injury via TLR-4/NF-κb signaling pathway (Fig. 5, Ref. 19).

Intrathecal dexamethasone and methotrexate treatment of neoplastic meningitis from solid tumors

Aim: Neoplastic meningitis (NM) from solid tumors is an advanced malignancy with poor prognosis. Intrathecal chemotherapy is a reliable treatment, and we have obtained some experiences in the treatment of NM with intrathecal dexamethasone and methotrexate (IT DXM and MTX). Methods: Retrospective study of 23 patients with NM from lung cancer ( n = 11), breast cancer ( n = 3), gastric cancer ( n = 1), malignant melanoma ( n = 1), unknown cancer ( n = 7) was conducted. Among these patients, eight received IT DXM and MTX treatment, and 15 patients were placed into a palliative care group. Overall survival (OS) was compared, and the patients' characteristics, symptoms, and some laboratory examinations were analyzed to find the risk factors affecting OS. Results: OS of IT DXM and MTX group was significantly longer than that of the palliative care group ( P = 0.01). The median survival (MS) of palliative care group was 7.53 weeks (5.50-9.57; n = 15), and of the IT DXM and MTX group, 28.63 weeks (12.50-44.75; n = 8); IT DXM and MTX prolonged the OS of NM patients (regression coefficient = −2.923), with odds ratio (OR) being 0.054 (0.09-0.323). Spinal nerves damage decreased the OS (regression coefficient = 1.595), with OR being 4.928 (1.382-17.579). Conclusion: IT DXM and MTX have prolonged the patients' MS, which could be used as a fundamental treatment of NM. Time of induction treatment should be flexible and individualized, and induction treatment could restart when central nervous system relapse. Patients with spinal nerves damage are apt to live shorter.

A study of the effects of 25wssw on anti‐endotoxemia (1056.4)

OBJECTIVES: The aim of this study is to investigate the anti‐endotoxemia effect of 25wssw. METHODS: 25WSSW was dissolved in water. Then collected the supernatant. 24 SD rats(200g‐240g)were divided into four groups randomly: NS group, high 25wssw dosage group(HDG), low 25wssw dosage group(LDG), dexamethasone group (DXM). DXM Intraperitoneal injection(2mg/Kg) for dxm group. 25wssw Introgastric administration 1 time per day for 5 days to HDG and LDG. Then each group was invaded by endotoxin. 3h after, venous blood was collected, and the endotoxin concentration in serum was tested by Endotoxin tester. NEUT and WBC concentration were tested by automatic biochemistry analyzer. RESULTS: 3h after endotoxin injection, compared with NS group, the endotoxin concentration in serum at HDG and LDG was deseased(p&lt;0.05), the endotoxin concentration in serum at DXM group was deseased either,but compared with NS group, P&gt;0.05. And the amount of WBC at DXM group was obviously increased, but the amount of WBC at HDG tended to be decreased. There’s no significant difference to the amount of NEUT . CONCLUSION: 25wssw has the anti‐endotoxemia effects by neutralizing endotoxin in serum, and by decreasing the process of inflammation.Grant Funding Source: Supported by 2011 Natural Science Fund Project of Tibet science and technology department

Inhibitory effect of dexamethasone on expression of cysteine-rich 61 protein in airway epithelial cells of allergic mouse models

In order to study whether cysteine-rich 61 protein (cyr61) is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone (Dxm) on the expression of cyr61 in the lung tissues of asthmatic mice was investigated. Forty BALB/c mice were divided into asthma group (n=15), control group (n=10) and Dxm group (n=15). The asthma group was sensitized and challenged by ovalbumin (OVA). The mice in Dxm group were intraperitoneally administered with Dxm after OVA challenge. The expression of cyr61 in the lung tissues was detected by using immunohistochemistry, and that of eotaxin protein in the bronchoalveolar lavage fluid (BALF) by using enzyme-linked immunosorbent assay (ELISA). The number of inflammatory cells in BALF was also analyzed. The results showed that the cyr61 expression was highest in asthma group (P<0.05), followed by Dxm group (P<0.05) and control group. The cyr61 had a positive correlation with the total nucleated cells (r=0.867, P<0.05), especially eosinophils (r=0.856, P<0.05), and eotaxin level (r=0.983, P<0.05) in the BALF. Our findings suggested that cyr61 is expressed in airway epithelial cells and has a positive correlation with eotaxin and number of airway infiltrating eosinophils.

Tripterygium polyglycosid attenuates the established airway inflammation in asthmatic mice

To investigate the effect of Tripterygium polyglycosid on establishing airway eosinophil infiltration and related airway hyperresponsiveness of asthmatic mice. A mature murine asthmatic model was made with ovabulmin sensitized and challenged C57BL/6 mice. Forty mice were divided into four groups with 10 mice in each group: mice sensitized and challenged with saline (WS group), mice sensitized and challenged with ovalbumin (WO group), mice sensitized and challenged with ovalbumin and treated with Tripterygium polyglycosid (TP group) and Dexamethasone (DXM group). The mice were intraperitoneally injected with 20 μg chicken ovabulmin emulsified in injected alum on days 0 and 14, then were challenged with an aerosol generated from 1% ovabulmin on days 24, 25 and 26. Tripterygium polyglycosid was injected intraperitoneally at 50 mg/kg on days 25, 26 and 27 after ovabulmin challenge. Dexamethasone was administrated to mice at 2 mg/kg on day 21, 23 before ovabulmin challenge. The airway hyperresponsiveness, mucus production, eosinophils in parabronchial area and bronchoalveolar lavage fluid and the level of interleukin-5, granulo-macrophage clone stimulating factor in bronchoalveolar lavage fluid were measured as indexes of inflammation. Tripterygium polyglycosid treatment after ovabulmin challenge completely inhibited eosinophil infiltration in bronchoalveolar lavage fluid [(0.63 ± 0.34)× 10(4) vs. (75.0 ± 14.8)× 10(4), P<0.05] and the peribrochial area (12.60 ± 3.48 mm(2) vs. 379.0 ± 119.3 mm(2), P<0.05), mucus overproduction in airway (2.8 ± 1.7 vs. 7.1±5.6, P<0.05), and increased interleukin-5 levels in bronchoalveolar lavage fluid (28.8 ± 2.8 pg/mL vs. 7.5 ± 3.5 pg/mL, P<0.05). Meanwhile, Tripterygium polyglycosid treatment after ovabulmin challenge also partially inhibited airway hyperresponsiveness. The level of granulo-macrophage clone stimulating factor in bronchoalveolar lavage fluid didn't change with drugs intervention. The administration of Tripterygium polyglycosid could inhibit the established airway inflammation and reduce the airway hyperresponsiveness of allergic asthmatic mice. It provides a possible alternative therapeutic for asthma.

Preventive effect of IL-18 gene modified mature dendritic cells vaccine on airway inflammation in mouse asthma model

To investigate the preventive effect of interleukin-18 (IL-18) gene modified mature dendritic cells (mDC) vaccine on airway inflammation in mouse asthma model. The asthma model was induced by injection of ovalbumin (OVA) in BALB/c mice. IL-18 gene modified mouse mature dendritic cells (mDC) were detected by flow cytometry and its capacity of inducing allogeneic T cell responses was examined by mixed lymphocyte reaction (MLR). The OVA-induced asthmatic mice were randomly divided into 6 groups: PBS group, DXM group, mDC group, Ad-LacZ-mDC group, Ad-IL-18-mDC group and control group. The pathological changes in lung tissues were assayed by HE and AB-PAS staining. The numbers of inflammatory cells and percentage of eosinophils (EOS) in bronchoalveolar lavage fluid (BALF) were counted. The levels of IFN-γ IL-4 and IL-13 in culture supernatant of splenocytes were measured by ELISA method. The percentage of CD4(+)CD25(+)Foxp3(+) Treg was assessed by flow cytometry analysis. The vaccine was effective in decreasing the infiltration of EOS and accumulation of airway goblet cells in lung tissues, the numbers of inflammatory cells and percentage of EOS in BALF, and the levels of IL-4 and IL-13 in culture supernatant of splenocytes, and in increasing the levels of IFN-γ in culture supernatant of splenocytes and the percentage of CD4(+)CD25(+)foxP3(+) reg. IL-18 gene modified mDC vaccine has a preventive effect on airway inflammation in OVA-induced asthmatic mice.

Regulatory effect of diammonium glycyrrhizinate on Th1/Th2 deviation in bronchial asthma: experiment with rats

To study the regulatory effect of diammonium glycyrrhizinate (GL) on the Th1/Th2 deviation in bronchial asthma. Thirty Wistar rats were injected intraperitoneally with antigen solution including ovalbumin (OVA), inactivated pertussis vaccine, and aluminum hydroxide for the purpose of sensitization. Fourteen days later OVA was sprayed 20 min everyday for a consecutive 5 days to evoke sensitization, thus models of asthma were established. Then the 30 rats were randomly divided into 3 equal groups: asthma model group, model+GL group, and model+DXM group. Another 10 rats were used as control group. All rats underwent tracheal intubation to perform the breathing curves. By the end of the experiment the rats were killed with their lungs taken out to undergo pathological examination. Suspension of splenocytes was prepared, the level of interferon (IFN)-gamma, a cytokine mainly secreted by Th1 cells, was detected by L929-VSV system, and the IL-4 level was detected by ELISA. The amplitude of the breathing curve of the GL group was similar to that of the DXM group, both significantly lower than that of the model group [(0.139+/-0.011) mV, both P<0.01] and higher than that of the control group. The respiratory rates of all groups became faster than normal. Pathology showed infiltration of inflammatory cells and proliferation of cup-shaped cells in the pneumonic tissues in the model group, and such damages were much slighter in the GL and DXM groups. The IFN-gamma level of the model group was (1.6+/-0.4) U, significantly lower than that of the control group [(3.7+/-1.0) U, P<0.05]. The IFN-gamma level of the GL group was (18.7+/-5.5) U, significantly higher than those of the DXM group [(2.1+/-0.3) U], model group and control group (all P<0.01). The IL-4 level of the model group was (305+/-36) pg, significantly higher than those of the GL group [(168+/-10) pg, P<0.01], DXM group [(213+/-47) pg], and control group [(54+/-6) pg, P<0.01], however, there was no significant difference between the GL and DXM groups. GL increases the IFN-gamma level and decreases the IL-4 level, thus promoting the polarization of Th1 cells, regulating the Th1/Th2 deviation, and alleviating asthma.

Preventive effects of nitroglycerine on glucocorticoid-induced osteoporosis in growing rats

The preventive effects of nitroglycerine (NG) on glucocorticoid-induced osteoporosis in growing rats were studied. Three-month-old female Wistar rats were randomly divided into control group (CON), dexamethasone group (DXM), DXM plus a low dose NG group (NG-L), DXM plus a middle dose NG group (NG-M) and DXM plus a high dose NG group (NG-H), 8 rats in each group. The rat model of osteoporosis was developed by intramuscular injection of dexamethasone twice a week. NG 0.2, 0.4 and 1.0 mg/kg was administered by oral gavages to the treatment groups every day for 12 weeks. Rats in CON group and DXM group were treated with normal saline of the same amount. After the treatment, the bone mineral density (BMD) and bone metabolism-associated biochemical markers were determined. Compared with CON group, BMD of lumbar spine and femur in DXM group was decreased significantly (P<0.05 and P<0.01 respectively), blood BGP levels and NO levels reduced (both P<0.01), and TRAP level increased (P<0.05). As compared with DXM group, BMD, serum BGP and NO were increased, and TRAP decreased in NG-L group and NG-M group, but had no significant difference in comparison to CON group. All the markers other than serum NO and TRAP levels had no significant difference between NG-H group and DXM group. It was concluded that low or middle doses of NG could prevent glucocorticoid-induced bone loss in growing rats, but high dose of NG could not. Supplement with NO donor could be considered as a preventive treatment for glucocorticoid-induced osteoporosis in a developing skeleton.

Does Antiinflammatory Therapy Attenuate the Lung Injury Caused by Ischemia/Reperfusion of the Lower Extremities in the Rabbit

It is known that acute transient aortic occlusion predispose to lung injury. The aim of this study was to determine whether dexamethasone and tenoxicam could have any protective effect on lung injury in an animal model. Thirty-five white rabbits were randomized into four groups. IR group (n=10), ischemia reperfusion (IR) injury was induced by infrarenal aortic clamping for 3 hours and reperfusion for 2 hour. Dxm group (n=10) was pretreated with 1 mg/kg dexamethasone; Tnx group (n=10) with 10 mg/kg tenoxicam, before clamping. Five animal were in the control group, operated without aortic occlusion. Ischemia reperfusion resulted in a significant increase in lung injury scores (mean 2.6+ in IR group and 2.5+ in Tnx group). The animals pretreated with dexamethasone had significantly lower score (1.7+, p<0.05). Dexamethasone can attenuate the lung injury, but the nonsteroidal antiinflammatory drug, tenoxicam, does not.