Meta-analysis of new intervention measures for preventing side effects of artificial joint replacement

BACKGROUND Intertrochanteric fracture of the femur occurs mostly among older people,and seriously affects daily life and quality of life.At present,physical intervention,drug treatment,routine intervention and rehabilitation training are widely used for prevention of side effects,but it is still inconclusive which intervention has the best effect.AIM To compare the effects of new intervention measures for preventing side effects of artificial joint replacement.METHODS We searched the Chinese and English literatures for comparative studies on the prevention of side effects of new interventions for artificial joint replacement from July 2013 to June 2023 in China HowNet,PubMed,Wanfang,Weipu and other databases.Study quality was evaluated by improved Jadad scoring standard,and the effects of different interventions on preventing different complications were analyzed by meta-analysis of evidence-based medicine with Review Manager 5.0 software.RESULTS Ten articles,including 869 cases,were finally included.The preventive effects of different interventions on the side effects of artificial joint replacement were studied,and valid data were extracted.There were two articles on the preventive effects of drug intervention,four on comparison of the preventive effects of combined and single interventions,and three on the preventive effects of physical intervention,rehabilitation training and routine intervention.Meta-analysis showed that the preventive effect of rivaroxaban was significantly better than low molecular weight heparin calcium[mean difference(MD)=-0.16,95%CI:-0.28 to-0.04,P<0.05].The effect of combined intervention was significantly better than that of single intervention(MD=-0.08,95%CI:-0.16 to-0.01,P<0.001).Physical intervention was significantly better than routine intervention and rehabilitation training(MD=0.26,95%CI:0.16–0.36,P<0.001).CONCLUSION Rivaroxaban combined with rehabilitation training is preferred for preventing deep vein thrombosis after artificial joint replacement.In the prevention of pulmonary embolism,rivaroxaban drug intervention is given priority.The effect of combined intervention is better than that of single intervention.

Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

The outbreak of coronavirus disease 2019(COVID-19)is a global pandemic.Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality.The drugs of higher interest include umifenovir,bromhexine,remdesivir,lopinavir/ritonavir,steroid,tocilizumab,interferon alpha or beta,ribavirin,fivapiravir,nitazoxanide,ivermectin,molnupiravir,hydroxychloroquine/chloroquine alone or in combination with azithromycin,and baricitinib.Gastrointestinal(GI)symptoms and liver dysfunction are frequently seen in patients with COVID-19,which can make it difficult to differentiate disease manifestations from treatment adverse effects.GI symptoms of COVID-19 include anorexia,dyspepsia,nausea,vomiting,diarrhea and abdominal pain.Liver injury can be a result of systemic inflammation or cytokine storm,or due to the adverse drug effects in patients who have been receiving different treatments.Regular monitoring of liver function should be performed.COVID-19 vaccines have been rapidly developed with different technologies including mRNA,viral vectors,inactivated viruses,recombinant DNA,protein subunits and live attenuated viruses.Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks.Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.

Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C

AIM: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon.METHODS: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 μgpeginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R).RESULTS: Therapy with pegylated interferon alfa-2bproduces comparable scores for depression (ANOVA:P = 0.875) as compared to conventional interferon.Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups.CONCLUSION: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.

Side Effects during Treatment of Advanced Gastric Carcinoma by Chemotherapy Combined with CIK-cell Transfusion in Elderly People

OBJECTIVE To study the side effects and therapeutic results of autologous cytokine-induced killer （CIK） cell treatment in elderly patients with advanced gastric cancer. METHODS CIK cells were induced and cultured using biotechnics in vitro, and then the cells were infused back into the patients. Sixty elderly gastric cancer patients treated by chemotherapy （FOLFOX4 protocol） were followed-up. Among them, 29 patients were treated with CIK cells during application of chemotherapy. Short-term curative effects and adverse events from the CIK transfusion and chemotherapy were observed. RESULTS Eight cases developed partial remission （PR）, 9 cases moderate remission （MR）, 7 cases stable disease （SD） and 5 cases progressive disease （PD）. Out of a total of 29 patients who received chemotherapy combined with autologous CIK therapy, the total remission rate （PR ＋ MR） was 58.6%. The total remission rate following chemotherapy alone was 45.2%, including 5 PR cases, 9 MR cases, 7 SD cases, and 10 PD cases. There was a relatively lower rate of severe chemotherapic toxicities in the CIK-cell transfusion group. Side effects of autologous CIK transfusion included chills （13 cases）, fever （9 cases）, nausea and vomiting （1 case） and general malaise （3 cases）. Side effects were treated with conventional therapy resulting in their amelioration. No patients developed shock, blood capillary leakage syndrome, or abnormalities in routine blood, urine, liver and renal function tests.CONCLUSION Adoptive immunotherapy with autologous CIK cells may decrease the clinical signs and symptoms of elderly patients who suffer from advanced gastric cancer. Adverse reactions of patients can be alleviated by conventional therapy. Autologous CIK-cell transfusion may improve endurance to chemotherapy.

Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma

AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti-tumor effects.CONCLUSION: Avidin chase can effectively reduce the side effects of RIT, and improve therapeutic efficacy.

Side Effects of Pfizer-BioNTech COVID-19 Vaccine among Libyan Young Adults: Observational Study

Purpose: Since the mRNA technology used to manufacture Pfizer-BioNTech COVID-19 Vaccine is new, it is still difficult to predict its consequences. However, many young people, especially in developing countries, think that they are less susceptible to severe infection with the Coronavirus 2 (SARS-CoV-2), Therefore, they do not prefer to take the COVID-19 vaccines. Accordingly, studies in this aspect are necessary to increase people’s awareness of the acceptance of vaccination, especially for the youth. Patients and Methods: This study was conducted on healthy young adults of both sexes. Participants (n = 81) were received two doses of the Pfizer-BioNTech COVID-19 Vaccine. A paper questionnaire was prepared, the survey asks about the side effects related to receiving the Vaccine. All participants completed the questionnaire twice, once after the first dose and again after the second dose. Data were collected and statistically analyzed. Results: The most common side effects were Muscle pain, Tiredness, Headache, and Fever. Less common side effects were Chills, Fainted, Breathlessness, and Coughing. Rare side effects include nausea and vomiting, Diarrhea, Anaphylactic Reaction, and Swollen Lymph Nodes. Side effects that are strongly associated with females are Headache, and Joint pain, for males, Anaphylactic reaction. The study revealed a significant difference between the number of females (96.5%) and males (85%) who suffered from the side effects of the Pfizer-BioNTech COVID-19 Vaccine (P = 0.033). Conclusion: Most of the side effects reported in our study were consistent with Pfizer’s fact sheet for recipients and caregivers. Through our follow-up to the participants in the study, we noticed that the reported side effects were not too bad, and they were able to carry out their daily activities, so we recommend taking the vaccine, especially for young people.

Progestogen-Only Injectable Contraceptives: The Profile of the Acceptors, Side Effects and Discontinuation in a Low Resource Setting, Nigeria

Progestogen-only injectable contraceptive is a highly effective, long lasting and reversible agent of fertility control. The objective is to determine the profile of the acceptors, side effects and indication for discontinuation of progestogen-only injectable contraceptives at UCTH, Calabar. This was a retrospective study of the clients who used progestogen-only injectable contraceptives at the family planning unit between 1st January 2008 and 31st December 2014. A total of 1392 clients used the injectable progestogen-only contraceptive out of 5986 total contraceptive users giving the prevalence rate of 23.3% over the period. Of these, 60.4% of the clients accepted the depot medroxyprogesterone acetate, while 39.6% accepted the norethisterone enanthate. It was mostly utilized by multiparous women, clients with tertiary education and those in their third decade of life. Secondary amenorrhea was the commonest side effect in 47.7% of the clients. Over the study period, 243 (19.8%) discontinued the method and 48.1% discontinued due to secondary amenorrhea while 31.4% was due to desire to get pregnant. Progestogen-only injectable contraceptive was associated with multiple side-effects, with secondary amenorrhea being the most common, and menstrual irregularity was the main reason for discontinuation. Providing adequate information to clients about this method of contraception and its probable side effects, supportive counseling during initiation of contraception and re-enforcement during follow-up visit can go a long way in enhancing patient satisfaction and hence continuation of progestogen-only injectable contraceptive despite minor side effects.

Gynecological Side Effects of Tamoxifen among Sudanese Women, Khartoum, Sudan, 2020

Background: In Sudan, the common endocrine therapy tamoxifen is prescribed to HR-positive patients, which is associated with a variety of complications such as hot flashes, vaginal discharge, and vaginal dryness. Objective: This study aimed to determine the gynecological side effects of tamoxifen among Sudanese women who have been diagnosed with breast cancer in Khartoum, Sudan. Methods: A retrospective cross-sectional study was conducted at Alzara Hospital in Al Amal Toure Revere, Sudan. A convenience sample of individuals previously diagnosed with breast cancer attended refer clinic. From October 2020 to September 2021, all patients attending were checked for eligibility. Results: A total of 100 patients were enrolled in the study;60% of patients reported increased vaginal secretions after taking the drug, 28% reported normal vaginal secretions with no change, and 11% reported decreased secretions after taking the medication, while 22% developed vaginal bleeding, and 22% of the ultrasound results revealed endometrial masses among the study patients. Also, 54 percent of female patients experienced hot flashes after taking the medication, and 12% of women missed some doses of treatment. Conclusion: Tamoxifen results in several gynecological side effects in women with breast cancer. A high percentage of women in the study developed hot flashes, vaginal bleeding, and discharge, in addition to having ultrasound results showing endometrial masses among them.

CLINICAL STUDY ON THE TIME OF TREATING CHEMOTHERAPY INDUCED TOXIC AND SIDE EFFECTS IN MALIGNANT TUMOR PATIENTS BY ACUPOINT INJECTION OF ASTRAGALUS ROOT INJECTION

Objective: To investigate the suitable time of treating virulent and side effects of chemotherapy for malignant tumor by acupoint injection of Astragalus Root injection. Methods: Sixty three patients with malignant tumor were divided into three groups: prevention treatment (PT) group (n=23 cases),post chemotherapy treatment (PCT) group( n=22 cases), Western medicine (WM) group ( n=18 cases). The patients in PT, PCT and WM groups were treated respectively from the fifth day on before chemotherapy and from the first day on after chemotherapy, 18 days in all. The patients in WM group were administered Batilol and Leucogen from the first day on after chemotherapy. Changes of leukocytes and immunoglobulin before and after treatment were observed. Results: 1) Acupoint injection of Astragalus Root injectio could increase the number of leukocytes and immunoglobulin content and its effect was better than that of Western medicine (P<0.05); 2) The effect of PT group was better than that of PCT group in preventing and treating virulent and side effects of chemotherapy (P<0.05). Conclusion: It should be stressed on prevention of malignant tumor by using acupoint injection of Astragalus Root for relieving virulent and side effects of chemotherapy.

Effects of glucocorticoids on leukocytes:Genomic and non-genomic mechanisms

Glucocorticoids(GCs)have been widely used as immunosuppressants and antiinflammatory agents to treat a variety of autoimmune and inflammatory diseases,and they fully exert their anti-inflammatory and immune-regulating effects in the body.The effect of GCs on white blood cells is an important part of their action.GCs can cause changes in peripheral blood white blood cell counts by regulating the proliferation,differentiation,and apoptosis of white blood cells.Although the total number of white blood cells,neutrophil counts,lymphocytes,and eosinophils increases,the counts of basic granulocytes and macrophages decreases.In addition,GCs can regulate the activation and secretion of white blood cells,inhibit the secretion of a variety of pro-inflammatory cytokines,the expression of chemokines,and promote the production of anti-inflammatory cytokines.For patients on GC therapy,the effects of GCs on leukocytes were similar to the changes in peripheral blood caused by bacterial infections.Thus,we suggest that clinicians should be more cautious in assessing the presence of infection in children with long-term use of GCs and avoid overuse of antibiotics in the presence of elevated leukocytes.GCs work through genomic and non-genomic mechanisms in the human body,which are mediated by GC receptors.In recent years,studies have not fully clarified the mechanism of GCs,and further research on these mechanisms will help to develop new therapeutic strategies.

Arava Treatment,between Beneficial Action on Joint Inflammation and Side Effects on Liver,Myocardium and Kidney in Experimental Murine Arthritis

The purpose of the experiment was the follow-up in time of the course of joint inflammation phenomena in laboratory animals (white female adult Wistar rats) by determining particular biological, hematological, radiological, osteodensitometric, immunological and anatomic-pathological parameters and by assessing the effects of Leflunomide (Arava) on the course of the disease. ARAVA&reg;(Leflunomide) is a pyrimidine synthesis inhibitor. The experimental study was conducted for 8 weeks. We have also assessed the side effects of the therapy on their liver, myocardium and kidney. Leflunomide therapy improved the course of the clinical and paraclinical parameters, but it did not cure the condition. The positive results in the joints were accompanied by many histological alterations. The experiment revealed the toxic visceral effects of Leflunomide on the liver, heart and kidney.

Effects of glucocorticoids on the growth and chemosensitivity of carcinoma cells are heterogeneous and require high concentration of functional glucocorticoid receptors

AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors （GR） was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin cytotoxicity of two （H460 and Hep3B） cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX （5.2±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 （11.1%） breast cancer and 43 of the 85 （50.6%） non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines. CONCLUSION： The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of GC on individual patients are identified.

Effect of low-dose amitriptyline on globus pharyngeus and its side effects

AIM:To compare the efficacy and side effects of lowdose amitriptyline(AMT)with proton pump inhibitor treatment in patients with globus pharyngeus.METHODS:Thirty-four patients who fulfilled the RomeⅢcriteria for functional esophageal disorders were included in this study.Patients were randomly assigned to receive either 25 mg AMT before bedtime(AMT group)or 40 mg Pantoprazole once daily for 4 wk(conventional group).The main efficacy endpoint was assessed using the Glasgow Edinburgh Throat Scale(GETS).The secondary efficacy endpoints included the Medical Outcomes Study 36-item short form health survey[social functioning(SF)-36]and the Pittsburgh Sleep Quality Index.Treatment response was defined as a>50%reduction in GETS scores.All patients entering this study recorded side effects at days 1,8,15,22 and 29 using a visual analogue scale.RESULTS:Thirty patients completed the study.After 4 wk of treatment,the AMT group had a greater response than the conventional group(75%vs 35.7%,P=0.004).At day 3,the AMT group showed significantly more improvement than the Conventional group in GETS score(3.69±1.14 vs 5.64±1.28,P=0.000).After 4 wk of treatment,the AMT group showed significantly greater improvement in GETS score and sleep quality than the Conventional group(1.25±1.84 vs 3.79±2.33,4.19±2.07 vs 8.5±4.97;P<0.01 for both).Additionally,the AMT group was more likely than the Conventional group to experience improvement in the SF-36,including general health,vitality,social functioning and mental health(P=0.044,0.024,0.049 and 0.005).Dry mouth,sleepiness,dizziness and constipation were the most common side effects.CONCLUSION:Low-dose AMT is well tolerated and can significantly improve patient symptoms,sleep and quality of life.Thus,low-dose AMT may be an effective treatment for globus pharyngeus.

Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Tyrosine kinase inhibitors(TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors(GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence-and experience-based consensus to guide the management of TKI-associated side events in clinical practice.

Efficacy and side effects of praziquantel in the treatment of Schistosomiasis mansoni in schoolchildren in Shesha Kekele Elementary School,Wondo Genet,Southern Ethiopia

Objective:To evaluate the efficacy and side effects of praziquantel(PZQ) in the treatment of schistosomiasis in Ethiopia.Methods:In a cross-sectional study,stool specimens were collected from randomly selected 299 school children in Shesha Kekele Elementary School,Wondo Genet, Southern Ethiopia,in April 2010.Stool specimens were examined using a single Kato-Katz thick smear for Schistosoma mansoni(5.mansoni) ova.Children who were found positive for S.mansoni were treated with a single oral dose of PZQ at 40 mg/kg bw and interviewed for treatment-related symptoms 24 hours after drug administration.Four weeks post-treatment,stool specimens were collected from the same children and examined following the same procedure as in the pretreatment.Drug efficacy was determined based on cure and egg reduction rates.Results:Pretreatment prevalence of S.mansoni infection was 74.9%with geometric mean egg count of 268. The evaluated generic PZQ produced an overall cure rate of 73.6%(P<0.000 1,OR:8.33,CI:5.3-13.1) and egg reduction rate of 68.2%(P=0.03,F=0.64).The cure rate showed significant association with age(x^2=H,P=0.004),the highest rate being observed in the 15-22 age group.83%of S. mansoni infected children showed various treatment-related symptoms,the most frerjiient being headache,nausea,and abdominal pain.These symptoms were associated with age(P<0.001) and pre-treatment intensity of infection(P<0.05).Conclusions:The present observations revealed relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ brands in Ethiopia.Hence,in depth studies are recommended to clarify whether the present relatively lower cure rate is the actual cure rate of the praziquantel evaluated,treatment failure,or reduced susceptibility of the parasite.Treatment-related side effects observed were transient and tolerable.

Side Effects of Chemotherapy in Cancer Patients and Evaluation of Patients Opinion about Starvation Based Differential Chemotherapy

Side-effects associated with the cancer chemotherapy limit the scope of chemotherapeutic drugs and no data was available about these side effects in Pakistan. Moreover starvation based differential chemotherapy has been proved to greatly reduce the side effects of chemotherapy depending on starvation time. The current study was conducted to survey the common side effects of the chemotherapeutic drugs and the role of starvation to reduce them. The study included total 100 subjects with multiple carcinomas. A comprehensive questionnaire about starvation inquiry, chemotherapy side effects and their basic information was filled by interviewers as told by patients. There were 48% patients with breast cancer and 11% with uterine cancer. Out of these patients 30%, 28%, 9% and 9% patients were agreed to starve for 12, 24, 36 and 48 hours respectively. The survey regarding the side effects of chemotherapy showed that 43% patients were suffering from headache, fatigue 90%, weakness 95%, hair loss 76%, nausea 77%, vomiting 75%, diarrhea 31%, abdominal cramps 40%, mouth sores 47%, dry mouth 74%, memory impairment 14%?and numbness 49%. Breast cancer is the most common cancer in Pakistan. Only 18% of the total patients were agreed to starve for more than one day. Chemotherapy-associated side effects vary greatly and it does not depend upon cancer type. But these side effects depend on multiple factors such as the type and dose of chemotherapeutic drug, patient’s health status and stage of cancer.

Escin enhances anti-rheumatoid arthritis effects of low dose glucocorticoids through up-regulation of glucocorticoid receptor

OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro.In vivo experiment:rats were randomly divided into model group(AIA),dexamethasone high dose(Dex,0.2 mg·kg^-1)group,dexamethasone low dose(Dex,0.05 mg·kg^-1)group,Escin 10 mg·kg^-1 group,Dex 0.05+Escin group,10 rats in each group,another 10 were used as normal control group.The vehicle and the corresponding drug were administered intragastrically(ig)daily for 14 d.In vitro experiment:LPS was used to stimulate RAW 264.7 macrophages for inflammatory models,which were divided into control group,LPS group,Dex with high dose(50 nmol·L^-1)group,and Dex with low dose(12.5 nmol·L^-1)group.In the Escin 10μmol·L^-1 group and the Dex+Escin(12.5 nmol·L^-1+10μmol·L^-1)group,the corresponding drugs were added to each well.After 2 h,LPS was added to induce inflammation.RESULTS Escin combined with low dose Dex significantly decreased arthritic index,serum IL-6 and TNF-α,improved paw swelling,and ameliorated the joint pathology immune organ pathology significantly.Gene chip results revealed that Nr3c1(GR)altered significantly.And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro.Furthermore,Escin combined with low dose Dex also significant increase GR mRNA expression.However,when suppression of GR by its specific inhibitor,the anti-RA effect of Escin combined with low dose Dex was abolished.CONCLUSION Escin combined with Dex reduces the dose of Dex,and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex.This combination might be attributed to GR activation.This study might provide a new combination drugs for the treatment of RA.

Forskolin augments the effects of glucocorticoids on proliferation and differentiation of a human osteosarcoma cell line by up-regulation of glucocorticoid receptor

The effect of forskolin, an activator of adenylate cyclase, on glucocorticoid-induced modulation of proliferation and differentiation of a human osteosarcoma cell line(HOS-8603) was iniually studied. It was found that forskolin could significantly augment

Side effects of different doses of ephedrine in rats with cerebral ischemia/reperfusion injury

Ephedrine has a protective effect against cerebral ischemia,but its side effects limit its clinical application.Results from a previous study showed that 1.5 mg/kg per day ephedrine can promote motion recovery in rats following cerebral ischemia/reperfusion without significant side effects.In the present study,ephedrine at doses of 3.0,2.5 and 2.0 mg/kg was used to treat rats with cerebral ischemia/reperfusion and the effects of ephedrine on the heart,liver,kidney and cerebrum were observed.Results showed that the blood pressure of rats with cerebral ischemia/reperfusion injury following ephedrine treatment was lower than in rats that recovered naturally from cerebral ischemia/reperfusion,but the pressure decreased with increasing doses of ephedrine.In addition,serum aspartate transaminase,alkaline phosphatase and creatinine concentration in rats with cerebral ischemia/reperfusion injury following ephedrine treatment were greater than in rats that recovered naturally from cerebral ischemia/reperfusion.The concentrations of these enzymes were decreased with increasing doses of ephedrine.Ephedrine-treated rats displayed hyperemia,degeneration and edema in the cerebrum,liver,heart and kidney.Results demonstrated that ephedrine exhibited side effects on the cerebrum,heart,liver and kidney in rats following cerebral ischemia/reperfusion in a dose-dependent manner.