PURPOSE:To evaluate the activitv of protein kinase C(PKC) in response to retinal photochemical insult in rat. Furthermore, to investigate the effect of dexamethasone(DXM ) on PKC activity.
METHODS :The experiments were performed on 48 SI') rats whieh were separated into two groups,control and treated groups,and the latter received daily intraperitoneal injections of DXM (1 mg/kg)for 5 consecutive days,starting 3 days before light exposure. The animals were continually exposed to green fluorescent light (510nm~560nm) with an illuminance level of (1 900plusmn;106.9)lx for 24 hrs.The retinal enzyme activity of PKC was tested at 6 hrs,1 day,3 days,7 days,and 14 days after light exposure respectively.
RESULTS:In animal models,PKC activity showed a transient increase in both groups at 6 hrs after light exposure and then decrease persistently there alter. The activity of PKC was unresponsive to DXM intervention. CONCLUSIONS :These results suggested that the persistent lower PKC activity might result in disturbance of retinal function in rat retinal photochemical injury.
（Chin J Ocul Fundus Dis,1997,13: 78-80）
Objective To investigate the clinical significance of low dose corticosteroid applied in early period after lung volume reduction surgery（LVRS）. Methods From Apr. 2001 to Mar. 2004, 27 patients with chronic obstructive pulmonary disease were undergone video-assisted unilateral LVRS assisted with mini-incision in our department were retrospectively reviewed. According to whether dispensed with postoperative corticosteroid or not, patients were divided into corticosteroid group and non-corticosteroid group. Corticosteroid group received dexamethasone 10mg iv tid for 3 days and then declined to prednisone 5mg qd for 7 days. Both groups were measured and compared the quantity of thoracic drainage flow, duration of chest tube drainage, the time of air leaks and fever, and so on. At same time, blood gas analysis and blood routine test were performed at 1, 3, 7 and 30 d after operation. Results Corticosteroid and non-corticosteroid groups had no statistically differences in the air leaks time （P 〉 0.05）, but the quantity of thoracic drainage flow of corticosteroid group was lower than that of non-corticosteroid group evidently （700±210ml vs. 950±150ml, P = 0.001）. There was significant difference in average duration of chest tube drainage between both groups （9±3 d vs. 12±2 d, P = 0. 05）. Compared with non-corticosteroidgroup, PaO2 of corticosteroid group was higher at 1, 3d after operation （P〈0.05）. The amount of blood leukocyte of corticosteroid group was lower than that of non-corticosteroid group at 3, 7d after operation, there was no statistically significant in two groups （P 〉 0. 05）. At early period after surgery, both groups had no significant infection and death patient. Conclusion The low dose corticosteroid applied in early period after LVRS for short time（10 days in this research） could shorten the duration of chest tube drainage, decrease the quantity of thoracic drainage flow and the extent of inflammation in pleural cavity. In the mean time, this treatment does not increase the occurrence of significant complications during the early postoperative period, and there is no negative influence to the blood gas analysis.
Objective To examine the levels of nitrite /nitrate( NO2 /NO3 ) , IL-4 and IFN-γin exhaled breath condensates( EBCs) in patients with asthma, and to investigate the effect of corticosteroid treatment. Methods Forty patients diagnosed as mild to moderate asthma were recruited. Among them, twenty were newly diagnosed and steroid naive( non-treatment group) . The other 20 patients had been treated with corticosteroid treatment( treatment group) . Twenty healthy volunteers were enrolled as normal control.EBC samples were taken for measurement of NO2 /NO3, IL-4 and IFN-γlevels. Serum IL-4 and IFN-γ concentrations were also measured. Results NO2 /NO3 level in EBC of the non-treatment group was significantly higher than that of the normal controls and the treatment group[ ( 48. 55 ±27. 37) μmol / L vs( 24. 51 ±18. 22) μmol /L, ( 36. 06 ±25. 13) μmol /L, respectively, both P lt; 0. 05] , and no significant difference was found between the treatment group and the normal controls( P gt;0. 05) . The IL-4 and IFN-γ levels in both EBC and serum had no significant difference between the three groups ( all P gt; 0. 05) . Conclusion NO2 /NO3 in EBCs increases in asthmatic patients, and decreases after corticosteroid treatment. Whether IL-4 and IFN-γlevels can be used for reflecting airway inflammation need further study.
ObjectiveTo evaluate the effect of low-to-moderate doses of corticosteroids on human infections with avian influenza A (H7N9) virus, and explore when to initiate the treatment of corticosteroids and the duration of corticosteroids administration.MethodsThe study collected clinical data of 8 cases with avian influenza A (H7N9) virus infection admitted from January 25, 2017 to May 12, 2017. The final analysis included 5 severe patients who had received adjuvant corticosteroid treatment. The variation curves of WBC, CRP, PCT, CK, HBDH, LDH, temperature, ratio of SpO2/FiO2 were depicted and analyzed. The progress of clinical improvements, deterioration and prognosis were observed and discussed.ResultsThere were 1 female and 4 males in the 5 included patients with a median age of 58.0 years, among them 3 survived. The median time of illness onset to hospitalization and diagnosis confirmed were 4 days and 8 days respectively; the median duration of hospitalization to admission to infective ICU were 3 days. The first course of adjuvant corticosteroid treatment was initiated 11 days (median) after admission with a duration of 4 days (median), during which, the serum levels of HBDH and LDH decreased remarkably except the patient 3, and the oxygenation (SpO2/FiO2) improved except the patient 3. The second course of systemic administration of corticosteroid was given at a median of 26.5 days after admission with a duration of 9 days (median), during which, the patients survived with improved oxygenation (SpO2/FiO2), and weaned from mechanical ventilation.ConclusionsFor patients suffered severe human infection with avian influenza A (H7N9) virus, low-to-moderate doses of corticosteroids may decrease the level of inflammation, regulate the aberrant immune response, improve the oxygenation, make an early unassisted breathing. And corticosteroids treatment can be initiated at the time of disease deterioration, after/at the peak inflammatory response, and within 10-14 days of ARDS. Also, the adjuvant corticosteroids may be administered when oxygenation is dificult to be improved by other ways, or dificult to be liberated from mechanical ventilation, suffering severe septic shock, and refractory fever. And the duration of corticosteroids may be prolonged to 10-14 days, or until the higher level of HBDH and LDH decreased again.
Objective
To evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) for treatment of macular edema associated with retinal vein occlusion (RVO).
Methods
This study was a six-month, randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial with a 2-month open-label study extension. Patients with branch or central RVO received DEX (n=129) or sham procedure (n=130) in the study eye at baseline; all patients who met re-treatment criteria received DEX at month 6. Efficacy measures included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA), and central retinal thickness (CRT) on optical coherence tomography.
Results
Time to ≥15-letter BCVA improvement from baseline during the first 6 months (primary endpoint) was earlier with DEX than sham (P＜0.001). At month 2 (peak effect), the percentage of patients with ≥15-letter BCVA improvement from baseline was DEX: 34.9%, sham: 11.5%; mean BCVA change from baseline was DEX: 10.6±10.4 letters, sham: 1.7±12.3 letters; and mean CRT change from baseline was DEX: ?407±212 μm, sham: ?62±224 μm (all P＜0.001). Outcomes were better with DEX than sham in both branch and central RVO. The most common treatment-emergent adverse event was in-creased intraocular pressure (IOP). Increase sin IOP generally were controlled with topical medication. Mean IOP normalized by month 4, and no patient required incisional glaucoma surgery.
Conclusions
DEX had a favorable safety profile and provided clinically significant benefit in a Chinese patient population with RVO. Visual and anatomic outcomes were improved with DEX relative to sham for 3 - 4 months after a single implant.
Objective To formulate an evidence-based treatment for a patient with pulmonary tuberculosis combined with tuberculous meningitis and tuberculous pericarditis. Methods According to the principles of evidencebased clinical practice, we searched The Cochrane Library (Issue 2, 2008), Ovid-Reviews (1991 to 2008), MEDLINE (1950 to 2008), and http://www.guideline.org. to identify the best evidence for treating a patient with pulmonary tuberculosis combined with tuberculous meningitis and tuberculous pericarditis. Results Nine guidelines, 2 systematic reviews, and 11 randomized controlled trials were included. The evidence showed that corticosteroids could help reduce the risk of death and disabling residual neurological deficiencies in patients with tuberculous meningitis. After adjusting for age and gender, the overall death rate of patients with tuberculous pericarditis was significantly reduced by prednisolone (P=0.044), as well as the risk of death from pericarditis (P=0.004). But for patients with pulmonary tuberculosis, there was still a controversy about the use of corticosteroids. Given the evidence, the patient’s clinical conditions, and his preferences, dexamethasone was used for the boy in question. After 7 weeks of treatment, his cerebrospinal fluid returned to normal and pericardial effusion disappeared. Conclusion Corticosteroids should be recommended in HIV-negative people with tuberculous meningitis or/and tuberculous pericarditis. The difference in the effectiveness of various corticosteroids such as dexamethasone, prednisolone, or methylprednisolone and the optimal duration of corticosteroid therapy is still unknown.
Objective
To evaluate the methodological and reporting quality of systematic reviews/meta-analyses related to the efficacy and safety of corticosteroid-assisted treatment for severe pneumonia.
Methods
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WanFang Data and VIP databases were searched by computer, and the systematic reviews/meta-analyses of corticosteroid hormone as an auxiliary means for the treatment of severe pneumonia which were published from establishment of the databases to October 25th, 2018 were searched. A Measurement Tool to Assess Systematic Review-2 (AMSTAR-2) was used to assess the methodological quality of the included studies, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to evaluate the quality of literature reports.
Results
A total of 16 systematic reviews/meta-analyses were included, all of which were non-Cochrane systematic reviews. In terms of methodological quality assessed by AMSTAR-2, there was no plan in all studies; only one study explained the reasons for inclusion in the study type; eight studies did not describe the dose and follow-up time of the intervention/control measures in detail; three studies did not indicate the evaluation tools and did not describe the risk bias; six studies did not explicitly examine publication bias. In terms of reporting quality assessed by PRISMA, all studies had no pre-registered study protocol or registration number; thirteen studies did not describe the specific amount of articles retrieved from each database; three studies did not present their retrieval strategies or excluded reasons in detail; no funding sources were identified in included studies; eight studies reported both whether the study was funded and whether there was a conflict of interest.
Conclusions
At present, there are many systematic review/meta-analysis studies on the efficacy and safety of corticosteroid-assisted treatment for severe pneumonia, and the overall quality of the study has been gradually improved. However, the common problems in the study are relatively prominent. The follow-up period and dose of intervention in the study of severe pneumonia are different, so the baseline is difficult to be unified. Suggestions: strengthening the training of researchers, standardize the research process, and report articles in strict accordance with the PRISMA statement; subgroup analysis being conducted according to the dose and duration of the hormone.
ObjectiveTo prepare curcumin loaded monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolicacid) (mPEG-PLGA) nanopaticles (CUR-NPs), investigate the effect of curcumin (CUR) and CUR-NPs on reversing corticosteroid resistance induced by cigarette smoke extract (CSE), and compare biological function between CUR and CUR-NPs in macrophages RAW264.7.
MethodsmPEG-PLGA nanoparticles loaded with CUR were prepared via emulsion solvent evaporation.In lipopolysaccharide (LPS) stimulated macrophages RAW264.7, budesonide (BUD) was used to treat macrophages RAW264.7.In LPS and CSE stimulated macrophages RAW264.7, BUD (10-10-10-5 mol/L), CUR(10-10-10-5 mol/L), CUR(10-7 mol/L)+BUD(10-9-10-5 mol/L), CUR(10-9-10-5 mol/L)+BUD(10-7 mol/L), and CUR-NPs(10-9-10-5 mol/L)+BUD(10-7 mol/L) were respectively used to treat macrophages RAW264.7 activated.The level of IL-8 in cell culture supernatant was measured by ELISA.In CSE stimulated macrophages RAW264.7, CUR(10-7 and 10-6 mol/L) and CUR-NPs(10-7 and 10-6 mol/L) were used to treat macrophages RAW264.7.The mRNA level of HDAC2 was measured by real-time PCR, the protein level of HDAC2 was measured by Western blot.Cellular uptake of CUR and CUR-NPs in macrophages RAW264.7 was determined by cellular fluorescence intensity observed and detected by laser confocal microscopy imaging.
ResultsThe morphology of CUR-NPs was spherical and the mean particle size was (356.4±146.6)nm.Compared with LPS stimulation, co-stimulation of LPS and CSE led to a significant decrease in the maximum inhibitory rate of BUD on IL-8 (P < 0.05) and a significant increase in the 50% inhibitory concentration (IC50) of BUD on IL-8 (P < 0.05).When using LPS+CSE to stimulate, compared with BUD (10-10-10-5 mol/L) group, the maximum inhibitory rate of BUD in CUR (10-7 mol/L)+BUD (10-9-10-5 mol/L) group on IL-8 was significantly higher (P < 0.05) and the IC50 of BUD decreased significantly (P < 0.05).When using LPS+CSE to stimulate, CUR and CUR-NPs in 10-9, 10-8 and 10-7 mol/L concentration, the inhibitory rate of CUR-NPs+BUD (10-7 mol/L) on IL-8 was significantly higher than that of CUR+BUD (10-7 mol/L) (P < 0.05). CSE stimulation induced a significant decrease in the mRNA and protein expression of HDAC2. Compared with CSE group, the mRNA and protein levels of HDAC2 of CUR(10-7 and 10-6 mol/L) group and CUR-NPs(10-7 and 10-6 mol/L) group were significantly higher (P < 0.05).In 10-7 mol/L concentration, the mRNA and protein levels of HDAC2 in CUR-NPs group were significantly higher than those in CUR group.In 10-7 mol/L concentration, cellular uptake of CUR in CUR-NPs was significantly higher than the native CUR.
ConclusionsCUR and CUR-NPs can reverse the corticosteroid resistance induced by CSE.CUR-NPs can improve the cellular uptake of CUR.In the case of low concentration, CUR-NPs have more biological activity than CUR.
