Prednisolone inhibits SaOS2 osteosarcoma cell proliferation by activating inducible nitric oxide synthase

AIM:To investigate the effect of prednisolone,a synthetic glucocorticoid used in inflammatory diseases,on the growth of cultured osteosarcoma cells.METHODS:Two osteosarcoma cell lines with different degree of differentiation were used.SaOS2 show a rather mature phenotype,while U2 OS are negative for almost all osteoblastic markers.The cells were exposed to different concentrations of prednisolone(1-9 μmol/L) with or without antioxidants or the inhibitor of inducible nitric oxide synthase(i NOS) l-N6-(iminoethyl)-lysine-HCl(L-NIL).Cell growth was assessed by counting viable cells.The production of nitric oxide(NO) was measured in the conditioned media by the Griess method.The production of reactive oxygen species was quantified using 2'-7'-dichlorofluorescein diacetate.Western blot with specific antibodies against NOSs was performed on cell extracts.RESULTS:Prednisolone inhibited SaOS2 cell growth in a dose dependent manner.No significant effects were observed in U2OS.The inhibition of SaOS2 growth is not due to oxidative stress,because antioxidants do not rescue cell proliferation.Since high concentrations of NO inhibit bone formation,we also measured NO and found it induced in SaOS2,but not in U2 OS,exposed to prednisolone,because of the upregulation of i NOS as detected by western blot.Therefore,we treated SaOS2 with prednisolone in the presence or in the absence of L-NIL.L-NIL prevented NO release induced by prednisolone at all the concentrations apart from 9 μmol/L.At the same concentrations,we found that L-NIL rescued SaOS2 growth after exposure to prednisolone.In U2 OS cells,prednisolone did not induce NO production nor affected cell growth.All together,these data indicate that a link exists between increased amounts of NO and growth inhibition in response to prednisolone in SaOS2.CONCLUSION:Prednisolone inhibited SaOS2 proliferation by increasing the release of NO through the upregulation of i NOS,while no effect was exerted on U2OS.

Prednisolone induced pneumatosis coli and pneumoperitoneum

Pneumatosis intestinalis(PI)is defined as the presence of gas within the submucosal or subserosal layer of the gastrointestinal tract.It is a radiologic sign suspicious for bowel ischemia,hence non-viable bowel must be ruled out in patients with PI.However,up to 15%of cases with PI are not associated with bowel ischemia or acute abdomen.We described an asymptomatic patient with prednisolone-induced PI and modified the Naranjo score to aid in a surgeon’s decision-making for emergency laparotomy vs non-operative management with serial assessment in patients who are immunocompromised due to long-term steroid use.

Comparison of the Effects of Kinesio Taping to Local Injection of Methyl Prednisolone in Treating Brachial Biceps Tendonitis

Objectives: This study compared the effect of Kinesio Taping (KT) with local Methyl Prednisolone injection in patients with biceps tendonitis based on visual analog scale (VAS) and range of motion (ROM). Methods: Thirty-eight patients (15 females and 23 males;mean age: 29.87 ± 6.31, years) with biceps tendonitis were participated in this study during 2014-2015. The patients were randomly assigned into two groups: 19 patients in KT group and 19 patients in injection group. In the first group, KT was used three times for 24 hours sequentially with four-day intervals;in the second group, one dose of Methyl Prednisolone (40 mg) plus 1% lidocaine was injected in the bicipital fissure around the long head of the biceps muscle. The injections and KT therapy were performed by the same physician. The patients were investigated for VAS and ROM in the first, second, seventh and twelfth days. Results: VAS and ROM indices were significantly improved in the second and seventh days (p 0.05). Conclusion: Regarding the more immediate effect of KT on ROM and VAS and the fast restoring of the patient to normal life, it could be used as a noninvasive alternative to injection and as the first line of treatment specially in patients who need the immediate effect of treatment.

Single doses of p38 MAP kinase inhibitors or prednisolone affect CRP and IL-6 in patients with active Rheumatoid Arthritis (RA)

Purpose: To investigate the effects of single doses of losmapimod, dilmapimod (inhibitors of p38 MAPK) and prednisolone on biomarkers of systemic inflammation (serum C-reactive protein (CRP) and interleukin (IL)-6) in subjects with active rheumatoid arthritis (RA). Methods: Two randomized, double blind, placebo controlled, parallel group, single dose studies investigated the CRP and IL-6 dose-response relationships for losmapimod (study A) and dilmapimod and prednisolone (study B) in patients with active RA on stable weekly doses of methotrexate. CRP, IL-6 and other exploratory biomarkers were measured in blood at baseline and up to 72 hours post-dosing. Results: In study A, 51 subjects were randomized to receive losmapimod (7.5, 20 and 60 mg) or placebo and in study B, 77 subjects were randomized to receive dilmapimod (7.5, 15 and 25 mg) or prednisolone (10, 20 and 50 mg) or placebo. Single doses of prednisolone caused a decrease in circulating IL-6 detectable at 3 and 24 hours post-dose as well as a CRP single-dose relationship at 48 hours post-dose in patients with active RA. All doses of losmapimod produced a statistically significant reduction in serum IL-6, 3 hours post-dose but had no effect on CRP. Dilmapimod had no effect on IL-6 or CRP at any dose or time. Conclusion: This single-dose response clinical study design could be useful in the early clinical development of anti-inflammatory agents for the treatment of rheumatoid arthritis. Inhibition of both circulating IL-6 and CRP would increase confidence that a new chemical entity may have the potential to deliver clinical benefit in RA. Trial registration: [clinicaltrials.gov: NCT00256919 and NCT00134693].

Improvement of Live Birth Rate Following Frozen-Thawed Blastocyst Transfer by Combination of Prednisolone Administration and Stimulation of Endometrium Embryo Transfer

The endometrial condition is a significant factor for successful pregnancy. To regulate endometrial function in fertility treatment, prednisolone (PSL) is administered for suppression of increased natural killer cells and stimulation of endometrium embryo transfer (SEET) to enhance communication between embryo and maternal tissues. We attempted to improve the endometrial condition by PSL administration and SEET during frozen–thawed blastocyst transfer (FBT). Patients took PSL (5 mg) 3 times daily for 3 days after ovulation during the FBT cycle. To analyse effects of PSL combined with SEET, we determined rates of chemical pregnancy, clinical pregnancy, foetal heart movement (FHM) and live birth. Rates of chemical pregnancy, clinical pregnancy and FHM were significantly higher in the PSL(+)/SEET(+) (57.7%, 50.0% and 46.2%, respectively) and PSL(+)/SEET(-) (53.3%, 46.7% and 46.7%, respectively) groups than in the PSL(-)/SEET(+) (30.3%, 18.2% and 18.2%, respectively) and PSL(-)/SEET(-) (22.4%, 22.4% and 18.4%;P = 0.0043, 0.0081 and 0.0055, respectively) groups. The live birth rate was significantly higher in the PSL(+)/SEET(+) group than in the PSL(+)/SEET(-), PSL(-)/SEET(+) and PSL(-)/SEET(-) groups (42.3%, 26.7%, 18.2% and 12.2%, respectively;P = 0.0237). PSL combined with SEET may be a useful adjunct to assisted reproductive technology in women who repeatedly fail to conceive by infertility treatment.

Prednisolone therapy accelerates recovery of severe drug-induced liver injury: A prospective, randomized controlled study

Background and aims:Drug-induced liver injury(DILI)is one of the most serious adverse drug reactions and its incidence has been increasing rapidly.Accumulating evidence suggests that immune activation and systemic inflammatory responses are very important in the progression of DILI.Corticosteroids are often used in DILI,but their clinical usefulness remains controversial.We therefore conducted a prospective,randomized controlled study to investigate whether corticosteroid therapy can accelerate recovery and reduce mortality in severe DILI(SDILI).Methods:SDILI patients with total bilirubin?171μmol/L who presented to the Fifth Medical Center of Chinese PLA General Hospital,Beijing from 2016 to 2019 were randomly allocated to prednisolone and control groups.The endpoints were resolution of SDILI,defined as a decrease in total bilirubin of at least 35μmol/L to<171μmol/L,and overall survival at 6 months.Patients in the prednisolone group received prednisolone 60 mg/day therapy for the first 7 days.Patients with a decrease in total bilirubin of more than 35μmol/L on day 8 continued on tapering doses of prednisolone;otherwise,prednisolone was discontinued.Results:On day 8,50.75%(34/67)and 26.47%(18/68)of the participants in the prednisolone and control groups,respectively,achieved the primary endpoint(p¼0.002).However,there was no significant difference in overall survival at 6 months:95.52%(64/67)vs.91.18%(62/68)in the prednisolone and control groups,respectively(p¼0.3).All deaths in both groups occurred in patients who failed to achieve SDILI resolution on day 8.Conclusion:Prednisolone therapy may accelerate the recovery of SDILI.

Management of autoimmune hepatitis induced by hepatitis delta virus

Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.

Synthesis and in vivo distribution of 2-deoxy-2-aminodiglucose-prednisolone conjugate(DPC)

In order to develop a novel kidney-targeted drug delivery system,a small molecular carrier（2-deoxy-2-aminodiglucose） was synthesized,and then the 2-deoxy-2-aminodiglucose-prednisolone conjugate（DPC） was synthesized to verify the kidney targeting capability of the carrier.Both 2-deoxy-2-aminodiglucose and DPC were confirmed by NMR and MS spectrum.The tissue distribution studies showed that DPC presented an excellent kidney targeting property in vivo,compared with prednisolone group, 4.9-fold of drug concentration in kidney was observed in the DPC group.Thus,it indicated that 2-deoxy-2-aminodiglucose could be a potential carrier for kidney-targeted drug delivery.

Prednisolone succinate-glucosamine conjugate:Synthesis,characterization and in vitro cellular uptake by kidney cell lines

Prednisolone succinate-glucosamine（PSG） conjugate,a prodrug for prednisolone,was synthesized and confirmed by NMR and MS spectrum.The stabilities of the prodrug in PBS（pH 2.50,5.00,7.20,and 7.89） were studied.Cytotoxicity and uptake assay of the prodrug were perfomed on HK-2 and MDCK cell lines.The results showed that compared with prednisolone,the PSG not only did not increase the cytotoxicity but also improved the uptake to 2.2 times of prednisolone by the cells.Thus,it indicated that glucosamine might be a potential carrier for kidney-targeting delivery of prednisolone.

Efficacy and Safety of Prednisolone Monotherapy Versus Prednisolone Plus Methotrexate in Erythema Nodosum Leprosum (Type 2 Lepra Reaction)

Objective:This study was performed to compare the efficacy and safety of methotrexate(MTX)plus prednisolone versus prednisolone monotherapy in patients with erythema nodosum leprosum(ENL).Methods:This comparative clinical study was performed in the Chittagong Medical College Hospital,Bangladesh from June 2018 to December 2019.Nineteen patients were selected according to inclusion criteria and randomly allocated to either the MTX plus prednisolone group(Group A,n=10)or the prednisolone monotherapy group(Group B,n=9).All patients were followed up until the end of the 6-month duration of therapy to observe the clinical outcomes and adverse effects.Results:All patients in both groups showed significant improvement(P=0.005 and P=0.008 in Group A and B,respectively).However,prednisolone-related adverse events were more frequent in Group B.Conclusion:The present study has demonstrated that a combination of prednisolone and MTX is a safer and more effective treatment than steroid monotherapy in ENL patients including the healing of nodules.However,this combination therapy did not appear to have a significant steroid-sparing effect,possibly because of the small sample size and short study period.Therefore,a well-designed multicenter randomized controlled trial is recommended for validation of MTX with prednisolone for the management of ENL.

Percutaneous Puncture Biopsy and Treatment Using Lo-cal Injection of Prednisolone for Solitary Esosinophilic Granuloma of the Skull.

The authors reported 8 cases of solitaty eosinophilic granuloma of the skull proved by percutaneous aspiration biopsy and treated with local prednisolone injection under fluoroscopic guidance and palpation with excellent results.

Acute neck tendonitis with dyspnea:A case report

BACKGROUND Longus colli tendinitis(LCT)with dyspnea is a relatively less-reported condition in the literature,and physicians should be aware of its existence.Misdiagnosis of this condition may cause unnecessary treatment for dyspnea.CASE SUMMARY Herein,we report the case of a 40-year-old man with acute neck tendonitis.The patient presented to the pneumology department clinic with a complaint of acute neck tendonitis with dyspnea.An emergency cervical magnetic resonance examination was performed,and the preliminary diagnosis was“acute longus cervicalis tendinitis.”After aggressive medical treatment,the symptoms obviously improved.CONCLUSION LCT is a self-limiting disease that usually improves after three to seven days of conservative treatment following a definite diagnosis.However,owing to its insidious onset and complex clinical manifestations,most relevant personnel are not fully understood.The definite diagnosis of LCT is based on a comprehensive understanding of the triad,rare symptoms,and the clear identification of cervical 1 and 2 levels calcification and prevertebral edema by medical imaging examination,especially magnetic resonance imaging and computed tomography.

气相色谱-离子阱二级质谱法测定猪肉中的氢化泼尼松和甲基氢化泼尼松残留

建立了固相萃取-气相色谱-离子阱二级质谱（GC-MS/MS）测定猪肉中氢化泼尼松和甲基氢化泼尼松残留量的分析方法。待测药物用乙腈提取,C18柱净化,K2Cr2O7氧化,GC-MS/MS测定。采用DB-5毛细管柱分离,电子轰击电离源二级质谱监测模式检测,外标法定量。方法的线性关系良好,线性相关系数均大于0.99,线性范围为2-50μg/kg;氢化泼尼松和甲基氢化泼尼松的回收率为56%-84%。两种药物的检测限和定量限均分别为1μg/kg和2μg/kg。

Use of corticosteroids during acute phase of Kawasaki disease

In spite of initial intravenous immunoglobulin(IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, havebeen considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids- the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary.

Jisuikang, a Chinese herbal formula, increases neurotrophic factor expression and promotes the recovery of neurological function after spinal cord injury

The Chinese medicine compound, ]isuikang, can promote recovery of neurological function by inhibiting lipid peroxidation, scavenging oxygen free radicals, and effectively improving the local microenvironment after spinal cord injury. However, the mechanism remains unclear. Thus, we established a rat model of acute spinal cord injury using a modified version of Allen＇s method. Jisuikang （50, 25, and 12.5 g/kg/d） and prednis- olone were administered 30 minutes after anesthesia. Basso, Beattie, and Bresnahan locomotor scale scores and the oblique board test showed improved motor function recovery in the prednisone group and moderate-dose Jisuikang group compared with the other groups at 3-7 days post-injury. The rats in the moderate-dose Jisuikang group recovered best at 14 days post-injury. Hematoxylin-eosin staining and transmis- sion electron microscopy showed that the survival rate of neurons in treatment groups increased after 3-7 days of administration. Further, the structure of neurons and glial cells was more distinct, especially in prednisolone and moderate-dose Jisuikang groups. Western blot assay and immunohistochemistry showed that expression of brain-derived neurotrophic factor （BDNF） in injured segments was maintained at a high level after 7-14 days of treatment. In contrast, expression of nerve growth factor （NGF） was down-regulated at 7 days after spinal cord injury. Re- al-time fluorescence quantitative polymerase chain reaction showed that expression of BDNF and NGF mRNA was induced in injured segments by prednisolone and Jisuikang. At 3-7 days after injury, the effect of prednisolone was greater, while 14 days after injury, the effect of moder- ate-dose Jisuikang was greater. These results confirm that Jisuikang can upregulate BDNF and NGF expression for a prolonged period after spinal cord injury and promote repair of acute spinal cord injury, with its effect being similar to prednisolone.

Combined glucocorticoid and antiviral therapy of hepatitis B virus-related liver failure

Acute hepatic failure due to hepatitis B virus(HBV)can occur both during primary infection as well as after reactivation of chronic infection.Guidelines recommend considering antiviral therapy in both situations,although evidence supporting this recommendation is weak.Since HBV is not directly cytopathic,the mechanism leading to fulminant hepatitis B is thought to be primarily immunemediated.Therefore,immunosuppression combined with antiviral therapy might be a preferred therapeutic intervention in acute liver failure in hepatitis B.Here wereport our favourable experience in three hepatitis B patients with fulminant hepatic failure who were treated by combining high-dose steroid therapy with standard antiviral treatment,which resulted in a rapid improvement of clinical and liver parameters.

Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature

BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the cases.For the better understanding of PTTM in HCC,the information of our recent case and reported cases have been summarized.CASE SUMMARY A patient with HCC exhibited acute and severe respiratory failure.Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious pneumonia.We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus.Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings.An autopsy showed the typical pattern of PTTM in the lung with multiple metastases.CONCLUSION PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients.Therefore,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.

Effect of hydroalcoholic extract of Hibiscus rosa sinensis Linn.leaves in experimental colitis in rats

Objective:To elucidate the ameliorative effect of liydrualcuholic extract of leaves of Hibiscus rosa sinensis(HRS) in acetic acid induced experimental colitis in male wistar rats.Methods: The animals were administered with 2 mL acetic acid(4%) via intra rectal.The animals were divided into various treatment groups(n=6).Prednisolone was used as standard drug and HRS was administered at a dose of 50,100 and 200 mg/kg p.o.The control group of animals received 1 mL of vehicle(distilled water).Ulcer area,ulcer index,spleen weight,colon weight to length ratio, macroscopic score,haemalological parameters,colonic superoxide dismutase(SOD),glutathione(GSH),myeloperoxidase(MPO),malondialdchyde(MDA),tumor necrosis factor-α(TNK- α), nitric oxide(NO) and histological changes were recorded after the treatment regimen of 11 days. Results:Intrarectal instillation of acetic acid caused enhanced ulcer area,ulcer index,spleen weight,colon weight to length ratio,colonic MPO,MDA,NO and TNF-α It caused significant decreased level of SOD and GSH.Pretreatment with HRS for 7 days exhibited significant effect in lowering of oxidative stress,colonic NO,TNF- α and elevation of SOD and GSH at a dose of 100 and 200 mg/kg in acetic acid induced colilis.Conclusions:The present investigation demonstrates HRS is of potent therapeutic value in the amelioration of expcrimenlal colilis in laboralory animals by inhibiting the proinflammatory mediator like NO and TNK-α.

Pneumonia and seizures due to hypereosinophilic syndrome—organ damage and eosinophilia without synchronisation:A case report

BACKGROUND Hypereosinophilic syndrome(HES)is a condition characterized by increased eosinophil proliferation in the bone marrow,as well as tissue eosinophilia,often causing organ damage.The cause of the disease is unknown.Initial symptoms include fatigue,cough,shortness of breath,myalgia,angioedema,fever,and pneumonia.In addition to the respiratory symptoms,damage to the central nervous system can lead to severe seizures.Here,we report a case with pneumonia and complex partial seizures secondary to HES.CASE SUMMARY A 94-year-old woman was admitted to our hospital for heart failure and bloody stools.After admission,she also showed symptoms of pneumonia.Non-contrast computed tomography of the chest showed pleural effusion and infiltrative shadows.Lower gastrointestinal endoscopy showed multiple ulcers in the sigmoid colon.Blood analyses showed marked eosinophilia(eosinophils 1760/mm3,total leukocytes 6850/mm3).Initial treatment with furosemide 20 mg/d and prednisolone 25 mg/d relieved these symptoms.However,the patient subsequently experienced localised epileptic seizures characterized by bilateral eyelid twitching and eyes rolling upwards,without generalized convulsions,and respiratory arrest occurred.Electroencephalography showed spikes and waves.Non-contrast magnetic resonance imaging of the brain showed extensive periventricular hyperintensity.With administration of levetiracetam 1000 mg/d the epileptic seizures disappeared.However,the patient’s consciousness remained impaired,and her pneumonia worsened again.Two weeks later,she died of pneumonia.CONCLUSION HES symptoms are variable and atypical,and the level and timing of eosinophilia and organ damage are often discordant.