Academic literature on the topic 'Prednisolone in serum'

Prednisolone is a commonly prescribed corticosteroid used in the treatment of many diseases. Despite high doses of prednisolone, some patients appear to have subtherapeutic concentrations of the drug. It would be useful to measure prednisolone in this group to determine if they have poor absorption or compliance. Hence, we have developed a liquid chromatography-tandem mass spectrometry method for the determination of prednisolone in serum. Chromatography was performed using a C18 column, giving a retention time for both prednisolone and deuterated prednisolone (internal standard) of 1.6 min. Two transitions were monitored for both prednisolone and deuterated prednisolone. These were m/z 361.2>343.0 and m/z 361.2>146.9 for prednisolone, and m/z 367.2>349.0 and m/z 367.2>149.9 for the internal standard. The intra- and inter-batch imprecision was <7% in both cases over a concentration range of 62.5-750 μg/L. The imprecision at the lower limit was 8%, the lower limit of quantitation was determined to be 30 μg/L and the method was linear up to 5000 μg/L. The method allows rapid prednisolone analysis because of a simplified sample extraction step, and has a cycle time of 3.5 min.

Abstract Context Short-term glucocorticoid exposure increases serum insulinlike growth factor I (IGF-I) concentrations but antagonizes IGF-I tissue signaling. The underlying mechanisms remain unknown. Objective To identify at which levels glucocorticoid inhibits IGF-I signaling. Design and Methods Nineteen healthy males received prednisolone (37.5 mg/d) and placebo for 5 days in a randomized, double-blinded, placebo-controlled crossover study. Serum was collected on days 1, 3, and 5, and abdominal skin suction blister fluid (SBF; ~interstitial fluid) was taken on day 5 (n = 9) together with muscle biopsy specimens (n = 19). The ability of serum and SBF to activate the IGF-I receptor (IGF-IR) (bioactive IGF) and its downstream signaling proteins was assessed using IGF-IR–transfected cells. Results Prednisolone increased IGF-I concentrations and bioactive IGF in serum (P ≤ 0.001) but not in SBF, which, compared with serum, contained less bioactive IGF (~28%) after prednisolone (P < 0.05). This observation was unexplained by SBF concentrations of IGFs and IGF-binding proteins (IGFBPs) 1 to 4. However, following prednisolone treatment, SBF contained less IGFBP-4 fragments (P < 0.05) generated by pregnancy-associated plasma protein A (PAPP-A). Concomitantly, prednisolone increased SBF levels of stanniocalcin 2 (STC2) (P = 0.02) compared with serum. STC2 blocks PAPP-A from cleaving IGFBP-4. Finally, prednisolone suppressed post–IGF-IR signaling pathways at the level of insulin receptor substrate 1 (P < 0.05) but did not change skeletal muscle IGF-IR, IGF-I, or STC2 messenger RNA. Conclusion Prednisolone increased IGF-I concentrations and IGF bioactivity in serum but not in tissue fluid. The latter may relate to a STC2-mediated inhibition of PAPP-A in tissue fluids. Furthermore, prednisolone induced post–IGF-IR resistance. Thus, glucocorticoid may exert distinct, compartment-specific effects on IGF action.

Key Messages: (1) Standard treatment of autoimmune hepatitis in adults should be steroid based. In early trials, prednisolone +/- azathioprine was superior to the azathioprine mono-therapy (which was not significantly better than placebo). Prednisolone plus azathioprine has similar efficacy to, but is better tolerated than a higher-dose of prednisolone alone and therefore has become standard therapy. (2) In most treated patients, serum transaminases and globulin/IgG fall, but percentage attaining normal values within 6 months varies between 10 and 90%. Patients failing to do so have a worse longer-term outcome. (3) A higher initial prednisolone dose (1 mg/kg/day) plus azathioprine achieved 76% serum transaminase normalisation after 6 months but needs longer-term evaluation. (4) Histological remission (minimal hepatitis on re-biopsy) lags behind transaminase normalisation by 6-12 months and is achieved in 55-70% of patients after 24-36 months prednisolone. This lag and the inefficacy of azathioprine mono-therapy justifies continuing prednisolone (5-10 mg/day), even after transaminase normalisation, for a total of >2 years. (5) Repeat biopsy should be considered because 40-60% of patients still have (usually mild) persisting inflammation, despite normal serum transaminases and IgG. In such patients, fibrosis is less likely to regress and long-term mortality is higher. (6) In a large trial, non-cirrhotic treatment-naïve patients given budesonide (9 mg/day) plus azathioprine were more likely to achieve normal serum ALT after 6 months than those receiving prednisolone plus azathioprine and had less side effects. This trial was short term in nature and lacked follow-up histology. Budesonide is recommended in non-cirrhotic patients who develop prednisolone-related side effects. In an open study of mycophenolate plus prednisolone, 88% of treatment-naïve patients achieved normal serum transaminases. However, half relapsed during or after steroid withdrawal and only one of eight re-biopsied patients achieved histological remission. Mycophenolate is teratogenic, limiting its use in younger women. Conclusion: Despite its limitations, no regime has yet been shown clearly to be better than prednisolone and azathioprine-based therapy.

The aim of this study was to investigate the effect of different doses of prednisolone in puppies experimentally induced with meconium aspiration syndrome (MAS). Meconium was collected from human babies in the first day of life and was released into the trachea of 11 newborn puppies to induce MAS. Puppies were treated with 2 mg/kg prednisolone (standard dose), 30 mg/kg prednisolone (megadose) or 0.9% saline, all administered intravenously. The study ended 20 h after meconium aspiration and the lungs were then scored for histopathology. Animals not treated with prednisolone deteriorated after 8 h while respiration rate, oxygenation, pH and partial pressure of carbon dioxide values were better in the prednisolone-treated groups. Histopathology scores were better in the treatment groups compared with the control group, with megadose giving the best result. At the end of the study, serum malondialdehyde levels were significantly higher in the megadose prednisolone group compared with the other two groups. In conclusion, we determined that prednisolone reduced physiological and histological changes in puppies with MAS and that a 30 mg/kg dose was more effective than 2 mg/kg.

Background: This study aimed to ascertain the effect of cannabidiol (CBD) oil and prednisolone on serum liver enzyme markers and hepatic oxidative stress markers on cadmium-induced toxicity in male Wistar rats. Forty (40) male Wistar rats weighing between 150g to 200g were assigned into 8 groups (A-H) of five animals each. Group 1 served as control, Groups 2-8 received 1mg/kg body weight of prednisolone; 1.5mg/kg bw of cadmium; 1mg/kg bw of prednisolone + 0.2mg/kg bw of CBD-oil; 0.2mg/kg bw of CBD-oil + 2mg/kg bw of cadmium; 3mg/kg bw of prednisolone + 2mg/kg of cadmium; 0.1mg/kg bw of CBD-oil and 0.2mg/kg bw of CBD-oil respectively. The administration was done using an orogastric tube (gavage) for 14 days. Results revealed a significant decrease in the concentration of aspartate aminotransferase (AST) in all treated groups compared to control. Furthermore, serum alanine aminotransferase (ALT) showed a significant (p<0.05) decrease in all treated groups compared to control. There was a significant decrease in the concentration of alkaline phosphatase (ALP) in treated groups compared to the control. Liver catalase significantly increased in rats fed with pred +cadmium compared to control and other treated groups. Liver superoxide dismutase (SOD) significantly decreased in (p<0.05) the group treated with cadmium compared to the control and prednisolone groups. Liver malondialdehyde concentration did not reveal any significant change (p>0.05). Liver glutathione peroxidase significantly decreased in treated groups than in control. Liver-reduced glutathione significantly decreased across treated groups than the control. Histology of the liver revealed degeneration of hepatocytes and vascular congestion in groups treated with prednisolone, prednisolone+ cadmium, and CBD oil (0.2mg/kg). We conclude that CBD oil, prednisolone, and Cadmium administration at different doses decreased the concentration of serum liver enzyme and oxidative stress markers but caused local inflammation of the liver. If this study is applicable to humans, CBD-oil and prednisolone should be cautiously taken as they may likely present adverse effects, especially in people with liver disease.

Background/Aims. Glucocorticoids may have adverse effects on carbohydrate and lipid metabolism. The present study was conducted to investigate possible effects on carbohydrate and lipid metabolism of inhaled and oral glucocorticoids in children with asthma. Methods. Two randomised controlled trials with blinded crossover designs were performed. Active treatment was 400 μg inhaled budesonide or 5 mg prednisolone orally daily during one week. The budesonide trial included 17 and the prednisolone trial 20 school children. Serum fructosamine, total cholesterol and high-density lipoprotein were assessed. Results. Serum fructosamine was increased during active treatment (prednisolone 252.3 μM versus placebo 247.3 μM; P = 0.03 and budesonide 228.1 μM versus no treatment 223.1 μM; P = 0.02). Total cholesterol and high-density lipoprotein were not statistically significantly increased. Conclusion. Short-term treatment with oral prednisolone and inhaled budesonide may adversely affect mean blood glucose concentration. Possible long-term consequences require further investigations.

Effect of glucocorticoid administration on improving the outcomes of kidney and liver allografts has not been clearly elucidated. This study investigated the effect of prednisolone administration after onset of brain death (BD) on kidney and liver in a controlled rat model of BD. BD was induced in rats by inflating an epidurally placed balloon catheter. Animals were treated with saline or prednisolone (5, 12.5, or 22.5 mg/kg) one hour after the onset of BD. After 4 hours of BD, experiments were terminated and serum and tissues were collected. Tissue gene and protein expression were measured for markers of inflammation, apoptosis, and cellular stress response markers. Prednisolone caused a reduction of plasma levels of IL-6, while the tissue expression ofIL-6, IL-1β,andMCP-1in both kidney and liver were also reduced. Creatinine plasma levels, complement (C3) expression,HSP-70, HO-1, Bcl2/BAXratio, and PMN influx did not significantly change in kidney nor liver. Plasma AST and LDH levels were increased in the prednisolone treated group. Our results demonstrate prednisolone can has an anti-inflammatory effect mediated through reducing serum circulating cytokines. However, this anti-inflammatory effect does not translate into improved kidney function and indeed was associated with increased liver injury markers.

Background: Nephrotic syndrome is a medical problem clinically characterized by proteinuria, generalized body edema and hypercholesterolemia. We did this study to compare the effectiveness of single dose versus split dose prednisolone in achieving remission in patients with nephrotic syndrome in children.Patients and methods: This open-ended randomized control trial was done in pediatric unit of tertiary care hospital from January to December 2019.We included one hundred Patients of nephrotic syndrome in the study who met the inclusion criteria. We divided total Patients into 2 groups (group A & B) 50 patients in each group. Group A was given single dose prednisolone, while group B was given split dose prednisolone therapy. Both groups were compared with respect of achievement of remission.Results: Out of 50 patients of group A who were given single dose prednisolone 37 (74%) were male, while in group B who were given split dose prednisolone 22 (44%) were male (p-value=0.137). Mean age of patients of study group A and B was 4.5 ±1.67 years and 4.9 ±1.49 years respectively (p-value=0.1876). Mean serum creatinine level in study group A and B was 0.744±0.189 and 0.736±0.167 (p-value=0.823). Similarly mean serum albumin level in study group A and B was 2.34±0.358 and 2.39±0.33 (p-value=0.473). When both groups were compared with regard to response to treatment, in group A mean remission duration was 16.48 ±3.69. In group B mean remission duration was 19.42 ±3.11 days (p-value<0.05).Conclusion: From our study we concluded that single dose prednisolone is more effective in achieving remission in steroid sensitive nephrotic syndrome as compared to split dose prednisolone.

Objective. To test the hypothesis that an anti-inflammatory corticosteroid drug enhances spinal motor plasticity induced by acute intermittent hypoxia (AIH) in persons with chronic incomplete spinal cord injury (iSCI). Methods. Fourteen subjects with incomplete spinal cord injury (ASIA level C or D; mean age = 46 years) participated in a randomized, double-blinded, crossover, and placebo-controlled study. Subjects received either 60 mg oral prednisolone or a matching placebo, 1 hour before administration of AIH (15, 60-second hypoxic exposures; fraction of inspired oxygen [FiO2] = 0.09). Changes in voluntary ankle strength, lower extremity electromyograms (EMG), and serum inflammatory biomarkers were quantified. Results. Maximal ankle plantarflexion torque was significantly higher following prednisolone + AIH versus placebo + AIH (mean difference [MD] 9, 11, and 7 newton meter [N∙m] at 30, 60, and 120 minutes post-AIH, respectively; all Ps <.02). Soleus surface EMG during maximal voluntary contraction was also significantly increased following prednisolone + AIH (MD 3.5, P = .02 vs placebo + AIH), while activity of other leg muscles remained unchanged. Individuals had significantly higher levels of the anti-inflammatory serum biomarker interleukin-10 after prednisolone versus placebo ( P = .004 vs placebo + AIH). Conclusions. Pretreatment with prednisolone increased the capacity for AIH-induced functional motor plasticity, suggesting that suppression of inflammation enhances the efficacy of AIH administration in individuals with spinal cord injury. Clinical trial registration number: NCT03752749.

Dissertação de Mestrado Integrado em Medicina Veterinária<br>ABSTRACT - 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase is a widely available biomarker, increasingly used in the investigation of canine pancreatitis mainly due to its low cost compared to pancreatic lipase immunoreactivity (cPLI). A previous study showed a good agreement between cPLI and DGGR lipase concentration. While the effect of corticotherapy on cPLI quantification has been studied, its influence on DGGR lipase is unknown. This study aims to evaluate the effect of prednisolone therapy in canine DGGR lipase serum levels. A prospective cohort study was conducted, including the measurement of DGGR lipase in two groups: the study group (SG) composed of dogs treated with oral prednisolone for a medical reason, at the initial dosage of 0.5-1.7 mg/kg/day for at least 3 weeks, and the control group (CG) composed of healthy untreated dogs. As an inclusion criterion, animals had basal DGGR lipase within the reference range (<80 U/L). DGGR lipase was measured at three time points (Day 0(T0), Day 7-10(T1), and Day 21-30(T2)) in both groups. The analysis was performed using a previously validated kit (Randox® DGGR lipase). Thirty-four dogs were included (17 dogs for each group, which were age and sex-matched). At T0, there was no significant difference in DGGR lipase concentrations between groups (p=0.868). Mean starting dosage of prednisolone was 0.94 (±0.85) mg/kg/day, decreasing to 0.45 (±0.05) mg/kg/day after T1. The median DGGR lipase concentration in SG at each time point (T0, T1, and T2) was: 24.74 (14.45-31.48) U/L, 36.82 (23.8-80.16) U/L and 29.52 (15.91-48.48) U/L, respectively. There was a statistically significant effect of prednisolone on DGGR lipase values (p=0.007) over T0, T1, and T2. A poor correlation was verified between the variations of DGGR lipase and the correspondent prednisolone dosage of T0-T1 and T1-T2 (rs=0.371 e rs=0.121, respectively). In CG, DGGR lipase did not significantly change over the three time points (p=0.926). This study suggests that DGGR lipase levels are affected by oral prednisolone therapy in dogs treated for a medical reason. However, as values remained below the considered significant upper limit (160 U/L), this variation does not seem to be clinically relevant.<br>RESUMO - O EFEITO DA PREDNISOLONA NO DOSEAMENTO DA 1,2-O-DILAURYL-RAC- -GLYCERO GLUTARIC ACID-(6′-METHYLRESORUFIN) ESTER (DGGR) LIPASE - 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase é um biomarcador recentemente disponível, que tem vindo a ser cada vez mais utilizado na exploração clínica de pancreatite em cães, sobretudo pelo seu custo acessível face à lipase pancreática específica (cPLI). Foi demonstrada uma boa concordância entre a cPLI e a DGGR lipase. Estudos prévios avaliaram a influência da corticoterapia no doseamento de cPLI. Contudo, a influência na DGGR lipase ainda não é conhecida. Este estudo visa avaliar o efeito da prednisolona nos níveis sérios de DGGR lipase em cães. Foi efetuado um estudo prospetivo de coorte, que incluiu a medição da DGGR lipase em dois grupos: o grupo de estudo (GE) constituído por cães aos quais foi administrada prednisolona por via oral com justificação médica na dose inicial de 0.5-1.7mg/kg/dia durante pelo menos 3 semanas e o grupo controlo (GC) composto por cães saudáveis sem tratamento concomitante. Como critério de inclusão consideraram-se cães com valores de DGGR lipase abaixo do valor de referência (<80 U/L). A DGGR lipase foi quantificada em três pontos temporais (Dia 0 (T0), Dia 7-10 (T1) e Dia 21-30 (T2)). A análise foi efetuada com recurso a um kit previamente validado (Randox® DGGR lipase). Foram incluídos 34 cães (17 cães em cada grupo, emparelhados relativamente ao género e idade). Em T0 não se observou diferença estatisticamente significativa entre grupos (p=0.868). A dose inicial média de prednisolona foi de 0.94 (±0.85) mg/kg/dia, tendo decrescido para 0.45 (±0.05) mg/kg/dia após T1. A concentração mediana de DGGR lipase no GE em cada ponto temporal (T0, T1 e T2) foi: 24.74 (14.45-31.48) U/L, 36.82 (23.8-80.16) U/L e 29.52 (15.91-48.48) U/L, respetivamente. Observou-se um efeito estatisticamente significativo da prednisolona nos valores de DGGR lipase ao longo de T0, T1 e T2 (p=0.007). Foi verificada uma baixa correlação entre as variações de DGGR lipase e a dose de prednisolona correspondente em T0-T1 e T1-T2 (rs=0.371 e rs=0.121, respetivamente). Em relação ao GC não se observaram diferenças estatisticamente significativas ao longo de T0, T1 e T2 (p=0.926). Sugere-se que a DGGR lipase seja afetada pela administração oral de prednisolona por justificação médica. No entanto, como os valores permanecem abaixo do limite máximo considerado (160 U/L), esta variação não aparenta ser clinicamente relevante.<br>N/A

Autoimmune hepatitis is an idiopathic inflammation of the liver attributed to immune responses against self-antigens presumed to be of hepatocyte origin. It is typically a relapsing and remitting corticosteroid-responsive condition associated with hepatitic serum liver tests, elevated gammaglobulins, and positive immune serology. Histological features are not specific but often include expanded portal tracts with a lymphoplasmacytic infiltrate. Epidemiology: predominantly affects women, may occur throughout life, has some heritable component, and 60% of patients have other autoimmune diseases. Clinical features: many patients are asymptomatic and identified through investigation of abnormal serum liver tests. Presentation may be with anorexia, nausea, hepatic discomfort, and jaundice, but others may have nonspecific malaise or extrahepatic manifestations such as arthralgia, arthritis, or fever. Clinical signs vary greatly, ranging from none to jaundice and tender hepatomegaly to fulminant hepatic failure. One-third of patients present as cirrhotic. Diagnosis: characteristic laboratory findings include elevated serum transaminase activities, hypergammaglobulinaemia (as IgG), and circulating autoantibodies (e.g. antismooth muscle antibodies, anti-liver–kidney microsomal antibodies, and antinuclear antibodies). Diagnosis depends on the combination of clinical features and biochemical, immunological, and liver biopsy abnormalities, with exclusion of viral and other aetiologies. There may be overlap features with other autoimmune liver diseases (primary sclerosing cholangitis or primary biliary cholangitis). Treatment and prognosis: the condition tends to progress to hepatic fibrosis and cirrhosis. Most cases should be treated with an immunosuppressive regimen, typically prednisolone with azathioprine in the first instance, and most require long-term immunosuppression. Crude 10-year survival rate is 65% for those presenting with cirrhosis and greater than 95% for those presenting without. End-stage decompensated cirrhosis and acute nonresponsive autoimmune hepatitis with liver failure can be indications for liver transplantation.

Liver transplantation is an established treatment for liver conditions that broadly fall into the categories of acute liver failure, end-stage chronic liver disease, primary hepatic malignancy, and metabolic disease. The expected 1-year survival rate is over 90% and some patients are alive more than 40 years after transplantation. Disease severity scores for cirrhosis heavily influence selection of patients with cirrhosis for transplantation. The prototype is the MELD (Model for End-Stage Liver Disease) score, based on serum bilirubin, serum creatinine, and INR: a score of 16 is considered the threshold that confers benefit from liver transplantation. Hepatocellular carcinoma accounts for most of the malignancy group and selection is largely determined by tumour bulk assessed by the number and size of lesions. Immunosuppression strategies based on tacrolimus, with or without other drugs including mTOR (mechanistic target of rapamycin) inhibitors, antiproliferative agents, or prednisolone, are highly effective in preventing loss of the graft through classical rejection processes. Recurrence of original disease is the main cause of loss of graft function, with recurrence of hepatitis C a particularly challenging problem, although new direct-acting antiviral agents are likely to radically improve outcomes. Technical problems can also result in graft loss due to hepatic artery thrombosis or diffuse ischaemic cholangiopathy, especially in livers harvested from donors after cardiac death. Anastomotic biliary strictures are the commonest technical complication, with 15 to 20% of patients requiring some form of endoscopic or surgical intervention. There is a considerably increased risk of myeloproliferative disease and skin cancers in transplant recipients, as well as aetiology-specific risk. Many patients die having achieved a normal life expectancy, and death with a functioning graft is the commonest terminal scenario.