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Clinical and Experimental Rheumatology 2017
Topics: Cataract; Diabetes Mellitus; Glaucoma; Glucocorticoids; Humans; Hypertension; Polymyalgia Rheumatica; Prednisolone; Withholding Treatment
PubMed: 28079505
DOI: No ID Found -
Diabetes Care Sep 2013The metabolic effects of low-dose prednisolone and optimal management of glucocorticoid-induced diabetes are poorly characterized. The aims were to investigate the acute... (Clinical Trial)
Clinical Trial
Effects of low-dose prednisolone on hepatic and peripheral insulin sensitivity, insulin secretion, and abdominal adiposity in patients with inflammatory rheumatologic disease.
OBJECTIVE
The metabolic effects of low-dose prednisolone and optimal management of glucocorticoid-induced diabetes are poorly characterized. The aims were to investigate the acute effects of low-dose prednisolone on carbohydrate metabolism and whether long-term low-dose prednisolone administration increases visceral adiposity, amplifying metabolic perturbations.
RESEARCH DESIGN AND METHODS
Subjects with inflammatory rheumatologic disease without diabetes mellitus were recruited. Nine subjects (age, 59 ± 11 years) not using oral glucocorticoids were studied before and after a 7- to 10-day course of oral prednisolone 6 mg daily. Baseline data were compared with 12 subjects (age, 61 ± 8 years) using continuous long-term prednisolone (6.3 ± 2.2 mg/day). Basal endogenous glucose production (EGP) was estimated by 6,6-(2)H2 glucose infusion, insulin sensitivity was estimated by two-step hyperinsulinemic-euglycemic clamp, insulin secretion was estimated by intravenous glucose tolerance test, and adipose tissue areas were estimated by computed tomography.
RESULTS
Prednisolone acutely increased basal EGP (2.44 ± 0.46 to 2.65 ± 0.35 mg/min/kg; P = 0.05) and reduced insulin suppression of EGP (79 ± 7 to 67 ± 14%; P = 0.03), peripheral glucose disposal (8.2 ± 2.4 to 7.0 ± 1.6 mg/kg/min; P = 0.01), and first-phase (5.9 ± 2.0 to 3.9 ± 1.6 mU/mmol; P = 0.01) and second-phase (4.6 ± 1.7 to 3.6 ± 1.4 mU/mmol; P = 0.02) insulin secretion. Long-term prednisolone users had attenuated insulin suppression of EGP (66 ± 14 vs. 79 ± 7%; P = 0.03) and nonoxidative glucose disposal (44 ± 24 vs. 62 ± 8%; P = 0.02) compared with nonglucocorticoid users, whereas basal EGP, insulin secretion, and adipose tissue areas were not significantly different.
CONCLUSIONS
Low-dose prednisolone acutely perturbs all aspects of carbohydrate metabolism. Long-term low-dose prednisolone induces hepatic insulin resistance and reduces peripheral nonoxidative glucose disposal. We conclude that hepatic and peripheral insulin sensitivity should be targeted by glucose-lowering therapy for glucocorticoid-induced diabetes.
Topics: Adiposity; Aged; Anti-Inflammatory Agents; Carbohydrate Metabolism; Female; Glucose; Glucose Clamp Technique; Humans; Insulin Resistance; Liver; Male; Middle Aged; Prednisolone; Rheumatic Fever
PubMed: 23670996
DOI: 10.2337/dc12-2617 -
Frontiers in Endocrinology 2023As a treatment for various immune-mediated diseases, the use of glucocorticoids as anti-inflammatory and immunosuppressive agents is common practice. However, their use...
As a treatment for various immune-mediated diseases, the use of glucocorticoids as anti-inflammatory and immunosuppressive agents is common practice. However, their use is severely hampered by the risk of the development of adverse effects such as secondary osteoporosis, skin atrophy, and peptic ulcer formation. The exact molecular and cellular mechanisms underlying those adverse effects, which involve most major organ systems, are not yet fully understood. Therefore, their investigation is of great importance to improve treatment regimens for patients. Here, we investigated the effects of the glucocorticoid prednisolone on cell proliferation and Wnt signaling in homeostatic skin and intestinal tissue and compared them to the anti-regenerative effects in zebrafish fin regeneration. We also investigated a potential recovery from the glucocorticoid treatment and the impact of short-term treatment with prednisolone. We identified a dampening effect of prednisolone on Wnt signaling and proliferation in highly proliferative tissues, namely the skin and intestine, as well as reduced fin regenerate length and Wnt reporter activity in the fin. The presence of the Wnt inhibitor Dickkopf1 was enhanced in prednisolone treated skin tissue. A decreased number of mucous producing goblet cells was observed in the intestine of prednisolone treated zebrafish. Unexpectedly, proliferation in bone forming osteoblasts of the skull, homeostatic scales, as well as the brain was not decreased, opposite to the observed effects in the skin, fin, and intestine. Short-term treatment with prednisolone for a few days did not significantly alter fin regenerate length, skin cell proliferation, intestinal leukocyte number and proliferation of intestinal crypt cells. However, it affected the number of mucous-producing goblet cells in the gut. Likewise, discontinuation of prednisolone treatment for a few days saved the skin and intestine from a significant reduction of skin and intestinal cell proliferation, intestinal leukocyte number and regenerate length, but did not rescue goblet cell number. The suppressive effects of glucocorticoids in highly proliferative tissues may be relevant in the context of their therapeutic applications in patients with inflammatory diseases.
Topics: Animals; Zebrafish; Glucocorticoids; Wnt Signaling Pathway; Prednisolone; Homeostasis
PubMed: 37334313
DOI: 10.3389/fendo.2023.1122351 -
Basic & Clinical Pharmacology &... Dec 2021Because several steroid hormones are metabolized to their respective 6β-hydroxy forms by CYP3A4 and CYP3A5, these isoenzymes have been assumed to metabolize the...
Because several steroid hormones are metabolized to their respective 6β-hydroxy forms by CYP3A4 and CYP3A5, these isoenzymes have been assumed to metabolize the immunosuppressive drug prednisolone, with conflicting results in the literature with respect to their relative importance. A direct study of the metabolism of prednisolone by microsomal CYP3A4 and CYP3A5 is missing. The aim of this in vitro study was to investigate the relative importance of recombinant CYP3A4 and recombinant CYP3A5 in the metabolism of prednisolone and to compare the extent of formation of 6β-OH-prednisolone by the two enzymes. Through in vitro incubations using rCYP3A4 and rCYP3A5 enzymes, intrinsic clearance (CL ) of prednisolone was determined by the substrate depletion approach. Formation of the metabolite 6β-OH-prednisolone by rCYP3A4 and rCYP3A5, respectively, was compared. Prednisolone concentrations were measured, and its metabolite 6β-OH-prednisolone was identified using a HPLC-MS/MS in-house method. CL for prednisolone by rCYP3A5 was less than 26% relative to rCYP3A4. Formation of 6β-OH-prednisolone by rCYP3A5 was less than 11% relative to rCYP3A4. The study indicates that 6β-hydroxylation of prednisolone assessed in vitro in recombinant CYP enzymes depends on rCYP3A4 rather than rCYP3A5 and that CYP3A5 may be responsible for the formation of other prednisolone metabolite(s) in addition to 6β-OH-prednisolone.
Topics: Animals; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Glucocorticoids; Humans; Hydroxylation; Insecta; Microsomes; Prednisolone; Tandem Mass Spectrometry
PubMed: 34396687
DOI: 10.1111/bcpt.13645 -
Journal of Veterinary Internal Medicine Nov 2020Activity of 1,2-O-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase in serum shows good agreement with pancreatic lipase (cPL) in dogs....
BACKGROUND
Activity of 1,2-O-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase in serum shows good agreement with pancreatic lipase (cPL) in dogs. Although prednisolone therapy does not seem to affect serum cPL concentration, its influence on DGGR lipase is unclear.
OBJECTIVES
The aim of the study was to evaluate the effect of prednisolone therapy on DGGR lipase serum activity in dogs.
ANIMALS
Thirty-four dogs were used, of which 17 dogs received prednisolone (study group) and 17 healthy dogs did not receive treatment.
METHODS
A prospective cohort study measured DGGR lipase activity in both groups at 3 time points: T0, T1, and T2, corresponding to days 0, 7-10, and 21-30, respectively. Dogs from study group presented a medical reason that justified the use of prednisolone for at least 3 weeks. Initial prednisolone dose was .5-2.0 mg/kg/day PO with a reduction at T1 to a final dose that was maintained until T2. DGGR lipase activity >160 U/L was defined as clinically relevant.
RESULTS
In the study group, DGGR lipase activity increased significantly from T0 to T1 (P = .02) and decreased significantly from T1 to T2 (P = .02). Median DGGR activity at each time point (T0, T1, and T2) was 24.74 (14.45-31.48), 36.82 (23.8-80.16), and 29.52 (15.91-48.48) U/L, respectively. In the control group, no significant changes were observed over time (P = .93). The DGGR lipase activity and prednisolone doses were not correlated for both T0-T1 (r = .371, P = .14) and T1-T2 (r = 0.390, P = .12).
CONCLUSION AND CLINICAL IMPORTANCE
DGGR lipase activity was affected by prednisolone administered orally in dogs. However, this variation was not clinically important as values remained below the relevant upper limit.
Topics: Animals; Dog Diseases; Dogs; Esters; Glutarates; Lipase; Pancreatitis; Prednisolone; Prospective Studies
PubMed: 33146921
DOI: 10.1111/jvim.15946 -
BMJ Case Reports Oct 2020Sudden onset sensorineural hearing loss (SSNHL) is frequently seen by otolaryngologists. The exact pathophysiology of the disease is still unknown, with the most likely...
Sudden onset sensorineural hearing loss (SSNHL) is frequently seen by otolaryngologists. The exact pathophysiology of the disease is still unknown, with the most likely causative factor being following a viral infection. Immediate steroids are the best treatment to improve prognosis. Despite a plethora of papers in the literature describing SSNHL, there are only a few reported cases of hearing loss following COVID-19, none of which have been reported in the UK. This paper presents the first UK case of SSNHL following COVID-19. Physical examination and imaging excluded any other cause of hearing loss. A literature review showed that four other cases have been previously described. Hearing loss can be a significant cause of morbidity and can easily be missed in the intensive care setting. Being aware and screening for SSNHL following COVID-19 enables an early course of steroids, which offers the best chance of recovering hearing.
Topics: Administration, Oral; Betacoronavirus; COVID-19; Coronavirus Infections; Glucocorticoids; Hearing Loss, Sudden; Humans; Injections; Male; Methylprednisolone Hemisuccinate; Middle Aged; Pandemics; Pneumonia, Viral; Prednisolone; SARS-CoV-2
PubMed: 33051251
DOI: 10.1136/bcr-2020-238419 -
BMJ (Clinical Research Ed.) Feb 1994
Topics: Adolescent; Humans; Male; Pericarditis, Tuberculous; Prednisolone
PubMed: 8136687
DOI: 10.1136/bmj.308.6927.535b -
The British Journal of Ophthalmology Sep 1962
Topics: Adult; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Methylprednisolone; Methylprednisolone Acetate; Prednisolone; Uveomeningoencephalitic Syndrome; Visual Acuity
PubMed: 18170815
DOI: 10.1136/bjo.46.9.563 -
Proceedings of the Royal Society of... Dec 1971
Topics: Arthritis; Ear Deformities, Acquired; Humans; Male; Middle Aged; Polychondritis, Relapsing; Prednisolone; Sclera
PubMed: 5131258
DOI: No ID Found -
British Medical Journal Apr 1977
Topics: Adult; Aortic Arch Syndromes; Female; Humans; Prednisolone; Takayasu Arteritis; Time Factors
PubMed: 15703
DOI: 10.1136/bmj.1.6066.975-e