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PloS One 2022Glucocorticoids are often used illegally in food-producing animals for the growth promotion of livestock animals. In accordance to official chemical methods for...
Glucocorticoids are often used illegally in food-producing animals for the growth promotion of livestock animals. In accordance to official chemical methods for glucocorticoid detection, an animal is declared as non-compliant when a residue is identified in the sample. Neverthless, growth promoting molecules can often escape identification due to their rapid elimination or due to the use of non-detectable new generation drugs. Therefore, an indirect screening method able to detect the biological effect of long-term administration of low doses of dexamethasone and prednisolone on livestock has been developed to support official methods. As already described, FKBP5 (FKBP prolyl isomerase 5) expression in bovine thymus is regulated by glucocorticoids, and this specific regulation can be exploited in an indirect screening assay. In the present study, male veal calves and young bulls were considered in three different trials in which estradiol, dexamethasone, and prednisolone were administered alone or in combination with Revalor-200 subcutaneous pellets. Thoracic thymus was sampled from all animals and molecular analysis was performed. A duplex droplet digital PCR assay with EvaGreen® was employed to detect the target gene expression using absolute quantification. The developed droplet digital PCR assay was precise, showing intra- and inter-assay mean coefficient of variation values of about 6.16% and 3.17%, respectively. It was also highly specific (100%) with Youden's index of 76.92% and 53.57% applied to veal calves and young bulls, respectively. The lowest detection limit in which the target gene expression level was kept constant, was 0.05 ng/μl of cDNA with 1 copies/μL and 0.5 copies/μL for target and reference gene, respectively. This study establishes the basis for using a digital PCR-based assay as an efficient test to identify animals illegally treated with glucocorticoids.
Topics: Animals; Biological Assay; Cattle; Dexamethasone; Glucocorticoids; Male; Polymerase Chain Reaction; Prednisolone
PubMed: 35839236
DOI: 10.1371/journal.pone.0271613 -
British Journal of Haematology Feb 2021We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097).... (Randomized Controlled Trial)
Randomized Controlled Trial
We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant-ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six-week cycle followed by eight five-week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1-4) or Arm B (nine four-week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1-4). The primary end-point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45·8 and 35·1 mg/m , CR rate was 18·6% [95% confidence interval (CI) 8·4-33·4] and 6·7% (95% CI 1·4-18·3), and the median progression-free survival (PFS) was 2·5 and 1·4 years in Arms A and B [hazard ratio (HR) 1·93 (95% CI 1·09-3·42)], respectively. Frequent grade ≥3 haematologic toxicities in Arms A and B were neutropenia (64·4% vs. 28·3%) and thrombocytopenia (35·6% vs. 10·9%). Grade 2/3 peripheral neuropathy was observed in 24·4/2·2% in Arm A and 8·7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Female; Humans; Male; Melphalan; Multiple Myeloma; Prednisolone; Survival Analysis; Treatment Outcome
PubMed: 32583431
DOI: 10.1111/bjh.16878 -
BMC Infectious Diseases Jan 2024After infection with SARS-CoV-2 a relevant proportion of patients complains about persisting symptoms, a condition termed Post-COVID-19-syndrome (PC19S). So far,...
Feasibility, safety and effectiveness of prednisolone and vitamin B1, B6, and B12 in patients with post-COVID-19-syndrome (PreVitaCOV) - protocol of a randomised, double-blind, placebo-controlled multicentre trial in primary care (phase IIIb).
BACKGROUND
After infection with SARS-CoV-2 a relevant proportion of patients complains about persisting symptoms, a condition termed Post-COVID-19-syndrome (PC19S). So far, possible treatments are under investigation. Among others, neurotropic vitamins and anti-inflammatory substances are potential options. Thus, the PreVitaCOV trial aims to assess feasibility, safety, and effectiveness of treating patients in primary care with prednisolone and/or vitamin B1, B6 and B12.
METHODS
The phase IIIb, multi-centre randomised, double-blind, and placebo-controlled PreVitaCOV trial has a factorial design and is planned as a two-phase approach. The pilot phase assessed feasibility and safety and was transformed into a confirmatory phase to evaluate effectiveness since feasibility was proven. Adult patients with PC19S after a documented SARS-CoV-2 infection at least 12 weeks ago are randomly assigned to 4 parallel treatments: prednisolone 20 mg for five days followed by 5 mg for 23 days (trial drug 1), B vitamins (B1 (100 mg OD), B6 (50 mg OD), and B12 (500 µg OD)) for 28 days (trial drug 2), trial drugs 1 and 2, or placebo. The primary outcome of the pilot phase was defined as the retention rate of the first 100 patients. Values of ≥ 85% were considered as confirmation of feasibility, this criterion was even surpassed by a retention rate of 98%. After transformation, the confirmatory phase proceeds by enrolling 240 additional patients. The primary outcome for the study is the change of symptom severity from baseline to day 28 as assessed by a tailored Patient Reported Outcomes Measurement Information System (PROMIS) total score referring to five symptom domains known to be typical for PC19S (fatigue, dyspnoea, cognition, anxiety, depression). The confirmatory trial is considered positive if superiority of any treatment is demonstrated over placebo operationalised by an improvement of at least 3 points on the PROMIS total score (t-score).
DISCUSSION
The PreVitaCOV trial may contribute to the understanding of therapeutic approaches in PC19S in a primary care context.
TRIAL REGISTRATION
EudraCT: 2022-001041-20. DRKS: DRKS00029617.
CLINICALTRIALS
gov: F001AM02222_1 (registered: 05 Dec 2022).
Topics: Adult; Humans; Thiamine; Prednisolone; Feasibility Studies; COVID-19; SARS-CoV-2; Vitamins; Double-Blind Method; Syndrome; Primary Health Care; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 38184567
DOI: 10.1186/s12879-023-08925-2 -
Respiratory Research Sep 2021We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens.
METHODS
Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir.
RESULTS
The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098).
CONCLUSION
The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.
Topics: Adult; Aged; Antiviral Agents; COVID-19; Drug Therapy, Combination; Female; Glucocorticoids; Hospital Mortality; Humans; Intensive Care Units; Intubation, Intratracheal; Iran; Length of Stay; Male; Middle Aged; Prednisolone; Severity of Illness Index; Time Factors; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34526033
DOI: 10.1186/s12931-021-01833-6 -
International Journal of Molecular... Feb 2023The prognosis for patients with relapsed childhood acute lymphoblastic leukaemia (cALL) remains poor. The main reason for treatment failure is drug resistance, most...
Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Childhood Acute Lymphoblastic Leukaemia Cells.
The prognosis for patients with relapsed childhood acute lymphoblastic leukaemia (cALL) remains poor. The main reason for treatment failure is drug resistance, most commonly to glucocorticoids (GCs). The molecular differences between prednisolone-sensitive and -resistant lymphoblasts are not well-studied, thereby precluding the development of novel and targeted therapies. Therefore, the aim of this work was to elucidate at least some aspects of the molecular differences between matched pairs of GC-sensitive and -resistant cell lines. To address this, we carried out an integrated transcriptomic and metabolomic analysis, which revealed that lack of response to prednisolone may be underpinned by alterations in oxidative phosphorylation, glycolysis, amino acid, pyruvate and nucleotide biosynthesis, as well as activation of mTORC1 and MYC signalling, which are also known to control cell metabolism. In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-α-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs. Among other druggable targets that were identified in this study, inhibition of glutamine metabolism presents a potential therapeutic approach in GC-sensitive, but more importantly, in GC-resistant cALL cells. Lastly, these findings may be clinically relevant in the context of relapse-in publicly available datasets, we found gene expression patterns suggesting that in vivo drug resistance is characterised by similar metabolic dysregulation to what we found in our in vitro model.
Topics: Humans; Child; Prednisolone; Glutamine; Drug Resistance, Neoplasm; Glucocorticoids; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36834787
DOI: 10.3390/ijms24043378 -
BMJ Case Reports Apr 2021We report a case of a 55-year-old man presenting with diplopia, masticatory weakness and dysarthria several weeks post multitrauma. The clinical suspicion of myasthenia...
We report a case of a 55-year-old man presenting with diplopia, masticatory weakness and dysarthria several weeks post multitrauma. The clinical suspicion of myasthenia gravis (MG) was supported with positive acetylcholine receptor antibodies and abnormal repetitive stimulation study. He responded well to pyridostigmine, intravenous immunoglobulin and oral prednisolone. In this report, we describe the timing and progression of MG in our patient, and review the literature pertaining to the relationship between trauma and MG. The search for definitive evidence of causation may be impractical, but should not delay the recognition and management of a treatable condition.
Topics: Blepharoptosis; Diplopia; Humans; Male; Middle Aged; Myasthenia Gravis; Prednisolone; Pyridostigmine Bromide; Wounds and Injuries
PubMed: 33811091
DOI: 10.1136/bcr-2020-238415 -
The Journal of Clinical Endocrinology... Sep 2020Glucocorticoids (GCs) are commonly prescribed, but their use is associated with adverse metabolic effects. 5α-reductase inhibitors (5α-RI) are also frequently... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Glucocorticoids (GCs) are commonly prescribed, but their use is associated with adverse metabolic effects. 5α-reductase inhibitors (5α-RI) are also frequently prescribed, mainly to inhibit testosterone conversion to dihydrotestosterone. However, they also prevent the inactivation of GCs.
OBJECTIVE
We hypothesized that 5α-RI may worsen the adverse effects of GCs.
DESIGN
Prospective, randomized study.
PATIENTS
A total of 19 healthy male volunteers (age 45 ± 2 years; body mass index 27.1 ± 0.7kg/m2).
INTERVENTIONS
Participants underwent metabolic assessments; 2-step hyperinsulinemic, euglycemic clamp incorporating stable isotopes, adipose tissue microdialysis, and biopsy. Participants were then randomized to either prednisolone (10 mg daily) or prednisolone (10 mg daily) plus a 5α-RI (finasteride 5 mg daily or dutasteride 0.5 mg daily) for 7 days; metabolic assessments were then repeated.
MAIN OUTCOME MEASURES
Ra glucose, glucose utilization (M-value), glucose oxidation, and nonesterified fatty acids (NEFA) levels.
RESULTS
Co-administration of prednisolone with a 5α-RI increased circulating prednisolone levels (482 ± 96 vs 761 ± 57 nmol/L, P = 0.029). Prednisolone alone did not alter Ra glucose (2.55 ± 0.34 vs 2.62 ± 0.19 mg/kg/minute, P = 0.86), M-value (3.2 ± 0.5 vs 2.7 ± 0.7 mg/kg/minute, P = 0.37), or glucose oxidation (0.042 ± 0.007 vs 0.040 ± 0.004 mmol/hr/kg/minute, P = 0.79). However, co-administration with a 5α-RI increased Ra glucose (2.67 ± 0.16 vs 3.05 ± 0.18 mg/kg/minute, P < 0.05) and decreased M-value (4.0 ± 0.5 vs 2.6 ± 0.4 mg/kg/minute, P < 0.05), and oxidation (0.043 ± 0.003 vs 0.036 ± 0.002 mmol/hr/kg, P < 0.01). Similarly, prednisolone did not impair insulin-mediated suppression of circulating NEFA (43.1 ± 28.9 vs 36.8 ± 14.3 μmol/L, P = 0.81), unless co-administered with a 5α-RI (49.8 ± 8.6 vs 88.5 ± 13.5 μmol/L, P < 0.01).
CONCLUSIONS
We have demonstrated that 5α-RIs exacerbate the adverse effects of prednisolone. This study has significant translational implications, including the need to consider GC dose adjustments, but also the necessity for increased vigilance for the development of adverse effects.
Topics: 5-alpha Reductase Inhibitors; Adipose Tissue; Adolescent; Adult; Aged; Disease Progression; Drug Interactions; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Dutasteride; Energy Metabolism; Finasteride; Glucocorticoids; Glucose Clamp Technique; Healthy Volunteers; Humans; Male; Middle Aged; Prednisolone; Prescription Drugs; Proof of Concept Study; Young Adult
PubMed: 32594135
DOI: 10.1210/clinem/dgaa408 -
BMJ Open Oct 2022Multiple myeloma is a malignancy of plasma cells with around 6000 new cases per year in the UK. Cyclophosphamide plus prednisolone is considered a standard of care for...
MUKtwelve protocol: a phase II randomised, controlled, open, parallel group, multicentre trial of selinexor, cyclophosphamide and prednisolone (SCP) versus cyclophosphamide and prednisolone (CP) in patients with relapsed or refractory multiple myeloma.
INTRODUCTION
Multiple myeloma is a malignancy of plasma cells with around 6000 new cases per year in the UK. Cyclophosphamide plus prednisolone is considered a standard of care for disease and symptom control in the advanced relapsed or refractory myeloma setting within the UK NHS. The selective nuclear export inhibitor, selinexor, has been relatively well tolerated in previous clinical trials and offers promise when used in combination with a wide range of other anti-cancer treatments. Here, we investigate if the addition of selinexor can improve responses to cyclophosphamide plus prednisolone without adding prohibitive toxicity.
METHODS AND ANALYSIS
MUKtwelve is a UK-based, randomised, controlled, open, parallel group, multicentre phase II trial designed to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisolone (SCP) in patients with relapsed or refractory multiple myeloma. A calibration arm will receive cyclophosphamide and prednisolone alone (CP). Participants who experience disease progression on the CP arm may, if eligible, receive SCP.The MUK trial results will be the first to assess clinical efficacy of selinexor with low-dose CP in relapsed/refractory multiple myeloma. It is widely accepted that the relapsing-remitting nature of the disease is accompanied by cellular changes that often result in the requirement for novel agents and drug combinations to regain disease control. Patients also often experience cumulative toxicities throughout their treatments, limiting the treatment intensity that can be given at relapse. Thus, there is a need for novel effective combination therapies with acceptable toxicity profiles.
ETHICS AND DISSEMINATION
Ethics approval is obtained. Results will be submitted for publication in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
ISRCTN15028850.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Cyclophosphamide; Dexamethasone; Multicenter Studies as Topic; Multiple Myeloma; Neoplasm Recurrence, Local; Prednisolone; Randomized Controlled Trials as Topic
PubMed: 36288835
DOI: 10.1136/bmjopen-2022-062504 -
BMC Veterinary Research Sep 2019The recognition of illegal administration of synthetic corticosteroids in animal husbandry has been recently challenged by the case of prednisolone, whose occasional...
BACKGROUND
The recognition of illegal administration of synthetic corticosteroids in animal husbandry has been recently challenged by the case of prednisolone, whose occasional presence in the urine of bovines under strong stressful conditions was attributed to endogenous biosynthesis, not to exogenous administration. The study of the natural stress sources possibly inducing endogenous prednisolone production represents a stimulating investigation subject. The biochemical effects of transportation and slaughtering were verified in untreated cows by studying the possible occurrence of prednisolone and its metabolites in urine, liver and adrenal glands, and the cortisol/cortisone quantification.
RESULTS
Cortisol, cortisone, prednisolone and its metabolites were measured in urine, collected at farm under natural micturition and then at the slaughterhouse. The study was performed on 15 untreated cows reared in different farms at the end of their productive cycle. 2-3 days after the first urine collection, the animals were transported by trucks to the abattoir, slaughtered, and subjected to a second urine sampling from the bladder. Specimens of liver and adrenal gland were also collected and analysed by means of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) validated method. The stressful conditions of transportation and slaughtering proved to increase considerably the urinary levels of cortisol and cortisone as compared to those collected at farm. Prednisolone was detected in the urine collected at the slaughterhouse of two cows only, at a concentration level (≈0.6 μg L) largely below the official cut off (5.0 μg L) established to avoid false non-compliances. These two animals exhibited the highest urinary cortisol levels of the series. Prednisolone and prednisone were also detected in the adrenal glands of a different cow. Prednisolone metabolites were not detected in any urine, liver, and adrenal gland sample.
CONCLUSION
Within the constraints of the condition adopted, this study confirms the sporadic presence of prednisolone traces (2 samples out of 15) and the consistently increased concentration of cortisone and cortisol in the urines collected from cows subjected to truck transportation and subsequent slaughtering. No prednisolone metabolites were detected in any liver and adrenal gland samples, nor in urine specimens, unlike what was previously reported for cows artificially stressed by pharmacological treatment.
Topics: Abattoirs; Adrenal Glands; Animals; Cattle; Cortisone; Female; Hydrocortisone; Liver; Prednisolone; Stress, Physiological; Transportation
PubMed: 31533706
DOI: 10.1186/s12917-019-2069-4 -
Annals of Medicine 2023Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial.
INTRODUCTION
Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients.
PATIENTS AND METHODS
This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884.
RESULTS
The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (p = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups.
CONCLUSIONS
The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain.KEY MESSAGESLow initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis.Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.
Topics: Adult; Humans; Prednisolone; Thyroiditis, Subacute; Anti-Inflammatory Agents, Non-Steroidal; Hypothyroidism; Pain
PubMed: 38048390
DOI: 10.1080/07853890.2023.2288941