Influence Of Prednisolone Research Articles

Histological changes in the spleen of rats under the influence of prednisolone and its combination with vitamin D

The possibility of using vitamin D to normalize the histological structure of the spleen changed under the influence of prednisolone in rats was studied. The animals were subjected to the intragastric administration of saline and either prednisolone (5 mg/kg b. w.) or its combination with vitamin D (800 IU/kg) daily for 3 weeks. The results of morphometric analysis of spleen slices reveal that the administration of prednisolone leads to a significant decrease in spleen sizes, white pulp volume, and in sizes of germinal centers of lymphatic follicles within the white pulp, and to an increase in the number of megakaryocytes in the red pulp. Vitamin D alleviates histological changes due to the prednisolone treatment, in particular the substantial restoration in sizes of germinal centers in the spleen has been found. The data obtained suggest the benefits of further studies of possible mechanisms of vitamin D to normalize immunological and hematopoietic functions in subjects subjected to glucocorticoid treatment.

Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Δ6- desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial

Glucocorticoid treatment decreases liver insulin sensitivity and may modify fatty acid metabolism. We investigated the influence of oral prednisolone on indices for de novo lipogenesis (DNLi), stearoyl-CoA desaturase (SCDi) and Δ6-desaturase (D6Di) activity in healthy males. In addition, we explored whether the changes may be associated with prednisolone-induced changes in glucose and lipid metabolism and insulin sensitivity.Thirty-two healthy young males (mean ± SD age 22 ± 3 years, BMI 22.4 ± 1.7 kg/m2) were allocated to receive prednisolone 7.5 mg/day (PRED7.5; n = 12), prednisolone 30 mg/day (PRED30; n = 12), or placebo (n = 8) in a randomized double-blind fashion for 2 weeks. Fatty acid compositions of plasma cholesteryl esters (CE), phospholipids (PL) and triglycerides (TG) were measured at baseline and on day 14. DNLi, SCDi and D6Di were estimated from product/precursor ratios in CE, with DNLi primary deriving from 16:1ω7/18:2ω6, SCDi from 16:1ω7/16:0 and D6Di from 22:6ω3/20:5ω3. Ratios were also assessed in PL and TG.In CE, PRED30 increased DNLi by 51.2 [95%CI 14.8; 87.6]%, increased SCDi by 48.6 [18.7; 78.5]%, and decreased D6Di by 57.7 [-91.8; -23.5]% (p ≤ 0.01 for all, compared to placebo). The prednisolone-induced increases in DNLi and SCDi were positively correlated with insulin sensitivity (r = 0.35 and 0.50, respectively). Similar results were found in PL and TG.Prednisolone dose-dependently increases DNLi and SCDi and decreases D6Di in plasma CE, PL and TG in healthy males after 2 weeks. The observed unfavorable effects on fatty acid metabolism were related to the induction of glucocorticoid-induced insulin resistance.

Effect of long-term low dose prednisolone administration on bone mineral density: Relating to non-compliant women with rheumatoid arthritis.

Background:Long-term treatment of rheumatoid arthritis (RA) with prednisolone (PRED) is associated with bone mineral density (BMD) loss. This study aimed to determine the status of BMD in non-compliant women who used PRED alone for RA.Methods:Non-adherent RA taking < 7.5 mg daily PRED without DMARDs for > 6 months, and RA patients taking methotrexate +PRED (RA control) were compared with age-matched non-RA controls. BMD was measured by dual energy x-ray absorptiometry (DXA) method and osteoporosis (OP) was diagnosed by WHO criteria. Influence of PRED on RA bone mass, and the risk of OP in RA was assessed by comparing PRED users RA and RA control,versus non-RA controls.Results:Sixty-four PRED user RA, 39 RA controls and 111 non RA-controls, with respective mean (±SD) age of 52±11; 8, 51±11; and 52±7.5 years (P=0.91) were studied. Median duration of treatment in PRED users and RA control was 2.5 and 4 years, respectively. BMD g/cm2 at the femoral neck (FN-BMD) and lumber spine (LS-BMD) in PRED users and RA control was significantly lower than non-RA control (P=0.001). The prevalence of OP at either FN or LS in both RA groups was significantly higher than controls (P=0.001). In PRED users, the risk of OP increased by OR=4.9, P=0.001) and in RA controls by OR=1.7 (P=0.20). The risk of OP in PRED user RA was 2.89 times (P=0.014) greater than RA controls.Conclusions:These findings indicate significantly lower BMD, and higher prevalence of osteoporosis in non-compliant women with RA taking low-dose PRED alone for a median period of 2.5 years, as compared with patients taking standard treatment comprising methotrexate +PRED.

Beer with the pine needles extract addition toxic effect research

Topicality. Alcohol is one of the risk factors for many diseases, including coronary heart disease, stroke, type 2 diabetes mellitus and others. Common world ways in solving this problem in recent years has improved the preparatory technology quality of alcohol and their composition optimization, leading to lessening the negative alcohol effects on the body.Aim. To investigate the beer toxicological aspects and assess the feasibility of creating a new brewing technology with the addition of an aqueous pine needles extract, which partly replaced by hops.Material and methods. Beer prepared on the classical recipe with the addition of pine extract (600 ml/dl). The influence of beer with the pine needle extract addition on prooxidant-antioxidant status of the animals liver comparing with the beer produced by the classical recipe.Results and discussion. The animals were given the beer examples produced by classical technology at a dose of 15 g/kg for a period of 14 days significantly increased the content of oxidative markers in the liver homogenate (GC 20.4 %, TBA-reagents – 51.6 %) compared to animals that received placebo and reduced activity catalase – by 40.9 %. Biomarkers in liver homogenate of animals treated beer with an pine needles extract were within the physiological norm. Under the influence of prednisolone (50 mg/kg) dien conjugates content in the liver of animals treated with classical technologies beer by 23.8 % more than in animals that under conditions of oxidative stress used purified water. The content of TBA-reagents over 13.7 %, glutathione content less than 25.0 % compared to the placebo group. In animals treated with beer extract of pine needles all anti-oxidative markers of liver catalase activity are significantly differed from that of animals that used purified water. In animals treated with the classic beer technology under normobaric hypoxia model was likely reduce the average lifetime to 313.1 s in terms of lack of oxygen compared to animals treated with purified water. In animals administrated with beer extract of pine needles average lifetime remained intact at figures and had no probable deviations.Conclusions. According to biochemical markers research of anti-oxidative system in liver homogenate of animals, beer with pine needles extract, due to its antioxidative properties, minimizes the negative alcohol impact on the liverthat manifested in less oxidative stress. Beer with pine needles extract does not potentiate the adverse effects of alcohol in acute hypoxic condition and does not reduce the average lifetime of the animal, as opposed to the usual beer. A beer“Emerald” with an extract of pine needles, due to its antioxidant properties, may be an alternative to modern alcoholic beverages and significantly reduce the toxic effects of alcohol.

Influence of prednisolone on craniofacial and long bones in growing rats: A cephalometric and peripheral quantitative computed tomographic analysis

Glucocorticoids are used for treatment of a variety of diseases, although they are also known to have an effect on skeletal growth and induce osteoporosis. The aim of this study was to investigate whether exposure to prednisolone had an effect on craniofacial bone growth and the internal bone structure in young rats. Twenty 5-week-old growing male rats were divided into two equal groups. Prednisolone at 30 mg/kg/day (prednisolone group) or no drug (control group) was administered orally on alternate days for 6 weeks. Thereafter, growth of the total skull, neurocranium, maxilla, and mandible was determined on lateral cephalograms, while cortical bone density and strength strain index (SSI) of the femur diaphysis and mandible were determined using peripheral quantitative computed tomography (pQCT). In addition, the femur length was measured. In the prednisolone group, total body weight, femur length, mandibular corpus length and height, and coronoid process height were reduced. No effects of prednisolone administration on cortical bone density of the femur and mandible were detected, however, the SSI values, cortical bone cross-sectional area, and mineral content of the femur and mandible, and cortical thickness and periosteal circumference of the femur in the prednisolone group were significantly lower when compared with the control group. The findings indicate that glucocorticoid administration decreases longitudinal and mandibular bone growth, quality, and strength in growing rats, whereas it has no significant effect on cortical bone density.

Influence of prednisolone on craniofacial and long bones in growing rats: A cephalometric and peripheral quantitative computed tomographic analysis

Influence of prednisolone on craniofacial and long bones in growing rats: A cephalometric and peripheral quantitative computed tomographic analysis

Glucocorticoid therapy: Concentrated urine after thirsting despite pronounced suppression of vasopressin

Glucocorticoids exert tonic suppression of ADH secretion. Hypocortisolism in secondary adrenocortical insufficiency can result in a clinical picture similar to the Syndrome of Inappropriate ADH Secretion (SIADH). On the other hand, in vitro and in vivo results provide evidence for ADH suppression in states of hypercortisolism. 25–45% of the patients with Cushings-Syndrome show symptoms of polyuria/polydipsia. Many patients treated with glucocorticoids for immunosuppression after kidney transplantation also transiently develop polyuria. In both conditions, suppression of ADH may be an important pathogenic factor in addition to direct renal effects. To test the hypothesis that ADH suppression is of relevance during glucocorticoid therapy, we investigated the influence of prednisolone on the osmotic stimulation of ADH. Seven healthy men were subjected to water deprivation tests with the measurement of plasma ADH (pADH), urine aquaporin-2 (uAQUA-2) and osmolality in plasma and urine (pOsm and uOsm)). Before and after glucocorticoid treatment (five days 30mg prednisolone per day) they were water deprived for eight hours. Before glucocorticoid treatment the volunteers showed a normal test with an adequate increase of pADH (basal <0.4 to 1.9±0.72 pg/ml [mean±SD]) in relation to pOsm (basal 283.3±8.5 to 293.7±6 mosm/kg). After prednisolone intake, pADH was not stimulated (<0.4pg/ml) in spite of an increase of pOsm from 289.6±4.4 to 296.9±4.7 mosm/kg (p=0.001 for pADH after fluid deprivation with vs. without glucocorticoids). Thus, the relation of pADH to pOsm after glucocorticoid intake resembles the situation in patients with central diabetes insipidus although urinary concentrating ability was not impaired. uAQUA-2 secretion tended to increase after thirsting following prednisolone treatment compared to thirsting without steroid treatment (166.2±48.6 and 114.9±20.4 aquaporin-2/creatinine [ng/mmol] respectively). This may suggest an effect of glucocorticoids on aquaporin-2 water channels not mediated by ADH.

Influence of prednisolone on the secretion of mucin from the HT29-MTX cell line.

Glucocorticoids have been used in the treatment of otitis media with effusion with promising but inconsistent results. The HT29-MTX cell line is a completely differentiated and almost exclusively mucus-secreting goblet cell line. To assess the potential of steroids in suppressing mucin secretion, we have studied the response of this cell culture to prednisolone. Confluent cell cultures were trypsinized, subcultured in six-well plates and incubated with five doses of prednisolone from 10-3 M to 10-11 M and over a varying time course from 6 to 36 h. Analysis was performed using a monoclonal mouse antibody to human gastric mucin by dot-blot ELISA. Prednisolone caused a consistent reduction in mucin production from this cell line. Increasing concentrations of prednisolone resulted in increasing suppression of MUC5AC secretion. There is a dose-dependent suppression of mucin secretion by prednisolone, with a maximum effect of 21% over control seen at the highest steroid concentration used.

The influence of prednisolone on the secretion of MUC5AC from TH29-MTX cell culture

INTRODUCTION: Glucocorticoids have been used in the treatment of otitis media with effusion with promising but inconsistent resluts. The HT29-MTX cell line is a completely differentiated and almost exclusively mucous secreting cell line, which therefore has the potential to act as an ideal model for the study of mucus-secreting epithelia. To assess this potential of steroids in suppressing mucin secretion we have studied the response of the cell culture to prednisolone. METHODS: Confluent cell cultures were trypsinized, subcultured in six-well plates and incubated with four doses of prednisolone from 10-5 M to 10-11 M and over varying time courses from 12 to 36 h. ELISA was performed using a monoclonal mouse antibody to human gastric mucin by dot-blot ELISA. RESULTS: Prednisolone caused a reduction in mucin production from the cell line consistently. Media control values ranged from 3495 to 3559 compared with untreated controls of 18 998-27 176 and steroid treatment values of 12 244-27 792. Increasing concentrations of prednisolone result in increasing suppression of MUC5AC (P = 0.005). There was no independent time-related effect. CONCLUSION: There does appear to be a genuine suppression of mucus production by prednisolone and this appears to be dose-dependent but not time-dependent at the times studied. The effect size was small.

THE EFFECT OF STEROIDS ON THE REGULATION OF MAJOR NONLYMPHOID TISSUE1 HISTOCOMPATIBILITY COMPLEX-CLASS I1 EXPRESSION ON

The induction of MHC-class II antigens on human nonlymphoid tissues plays an essential role during the inhibition and augmentation of the immune response. Steroids have long been shown to possess strong immunosuppressive properties and successful steroid treatment has been associated with the absence of MHC-class II antigens on grated tissues. In this study we more specifically investigated the effect of steroids on the regulation of MHC-class II expression on nonlymphoid tissue. First, the influence of prednisolone on the induction process of the MHC-class II antigens on nonlymphoid tissue was determined. For this purpose vascular endothelial cells, kidney epithelial cells, fibroblasts, and a human colon tumor cell line were incubated with rIFN-gamma or primary MLC supernatant in the absence or presence of different concentrations of prednisolone. It was demonstrated that the induction process of MHC-class II antigens on these cell types was not affected by the drug at the different concentrations tested (1, 10, and 100 micrograms/ml). Next, the effect of prednisolone on the production of MHC-class II inducing factors was investigated. The drug was added at initiation of culture to primary MLC and the MHC-class II-inducing capacity of the supernatants was determined on day 7. Prednisolone at concentrations of 0.5-100 micrograms/ml clearly inhibited the overall production of factors responsible for MHC-class II induction on nonimmunological cells. The drug inhibited the production of IFN-gamma as well as non-IFN-gamma MHC-class II-inducing mediators. At a concentration of 1 microgram/ml the production of IFN-gamma and non-IFN-gamma MHC-class II-inducing mediators was reduced by, respectively, 85 per cent and 75 per cent. At a concentration of 10 micrograms/ml the production of both IFN-gamma and non-IFN-gamma mediators was almost completely inhibited. It is concluded that steroids downregulate the expression of MHC-class II antigens on nonlymphoid tissue by the inhibition of the production of MHC-class II-inducing mediators. However, once these mediators are present, the induction process itself is not affected by the drug.

The nonlinear pharmacokinetics of prednisone and prednisolone. II. Plasma protein binding of prednisone and prednisolone in rabbit and human plasma.

The protein binding characteristics of prednisone and prednisolone were determined in human and rabbit plasma and in a 4.7 per cent human serum albumin (HSA) solution. The influence of prednisolone on prednisone binding in human plasma was also examined. Prednisolone exhibited nonlinear binding and prednisone linear binding characteristics in both human and rabbit plasma. Prednisone binding was not influenced by the presence of prednisolone. Prednisone binding to HSA was linear but to a degree substantially lower than observed in human plasma, suggesting the possibility that prednisone binds to other proteins in human plasma. The results support the hypothesis that the protein binding characteristics of prednisone and prednisolone do not explain the reported nonlinear pharmacokinetics of prednisone.

Influence of prednisolone on antipyrine elimination in patients with obstructive lung disease.

The influence of prednisolone on the elimination of antipyrine has been investigated. The one-sample antipyrine clearance was estimated in 23 outpatients with obstructive lung disease before and after treatment with prednisolone 30 or 50 mg/day for 7 days. During prednisolone administration antipyrine clearance decreased from 54.9 +/- 14.8 to 51.7 +/- 14.6 ml/min (mean +/- SD; p less than 0.05). The results indicate that prednisolone decreases the rate of antipyrine elimination, but not to an extent suggesting a clinically important change in hepatic drug metabolism.

Influence of prednisolone on gastric alkaline response in rat stomach. A possible explanation for steroid-induced gastric lesion.

Exposure of the rat stomach for 10 min to 1 M NaCl produced an increase of luminal pH (alkaline response) with a concomitant reduction of the transmucosal potential difference (PD) and an increased generation of mucosal prostaglandins of E2 and 6-keto F1 alpha. Prednisolone (3-50 mg/kg), given subcutaneously 4 hr before exposure to 1 M NaCl, dose-dependently inhibited alkaline response without affecting the PD reduction, and at 50 mg/kg completely prevented the increased production of mucosal prostaglandins after exposure to 1 M NaCl. The inhibitory effect of prednisolone on alkaline response was significantly antagonized by pretreatment with 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) (3 micrograms/kg) or cycloheximide (1.5 mg/kg). A repeated administration of prednisolone (3-50 mg/kg), once daily for 4 days, produced gastric lesions dose-dependently. At 50 mg/kg, gastric lesions appeared after administration of this drug for more than 2 days, and the inhibition of alkaline response caused by 1 M NaCl became more potent as the days of treatment increased. Either 16,16-dmPGE2 (10-100 micrograms/kg) or cycloheximide (1 or 3 mg/kg), given daily in two divided doses for 4 days, dose-dependently inhibited formation of gastric lesions in response to prednisolone (50 mg/kg). These results indicate that prednisolone inhibits gastric alkaline response caused by 1 M NaCl by reducing generation of endogenous prostaglandins. The weakened self-defense mechanisms caused by prednisolone may be involved in the pathogenesis of steroid-induced gastric lesions.

Influence of prednisolone on ethanol-induced gastric injury in the rat

The purpose of the present study was to investigate the effect of prednisolone on gastric injury induced by ethanol in the rat. Gastric damage was produced by oral administration of 1 ml of absolute ethanol to rats previously fasted for 24 hr and deprived of water for 19 hr. The severity of the ethanol-induced gastric damage varied considerably within the vehicle-treated group of rats which served as controls. Prednisolone, administered orally as a single dose 15 min before alcohol challenge, significantly decreased the number of rats which developed severe lesions. Prednisolone was effective in increasing the resistance of the gastric mucosa to ethanol when given from 1 to 60 min before alcohol. The steroid proved ineffective when 90 min elapsed between prednisolone and ethanol administration, or when the steroid was given at the same time (0 min) as alcohol. The dose-response curve for prednisolone plateaued at high doses. Our results suggest that a prostaglandin-mediated endogenous cytoprotective potential exists in the rat gastric mucosa. Prednisolone may enhance the degree of mucosal protection afforded by this mechanism.

Induction kinetics of human suppressor cells in the mixed lymphocyte reaction and influence of prednisolone on their genesis

The induction kinetics of human suppressor cells in mixed lymphocyte cultures (MLC) and the influence of prednisolone on the genesis of these suppressor cells is reported. We induced over 1 to 6 days suppressor cells in one-way MLC (MLC-1), the inhibitory activity of which was tested on a secondary MLC (MLC-2), and on responder cells alone, where lymphocytes were obtained from the same lymphocyte donors as for the MLC-1. In four experiments the degree of inhibition ( x ̄ ± SE ) when suppressor cells were induced for 2, 4, or 6 days was 38.5 ± 11.8, 79.5 ± 7, and 85 ± 6%, respectively, compared to 50.5 ± 9.4, 83.3 ± 7.8, and 85.3 ± 9.8% when 500 ng/ml prednisolone was added to the MLC-1. A similar inhibition pattern was observed when the generated suppressor cells were incubated with responder cells only. The inhibitory activity of these MLC-induced suppressor cells was abrogated by irradiation with 3000 R. Suppressor cells apparently are generated in MLCs between Days 1 and 4; furthermore, their genesis is not affected by usual therapeutic concentrations of prednisolone.

Effect of long-term corticosteroid therapy on monocyte chemotaxis in man.

The influence of prednisolone on monocyte chemotactic activity in vitro at prednisolone concentrations comparable with those achieved in man following oral dosage has been investigated. Chemotactic activity of monocytes from each of sixteen normal subjects was suppressed by concentrations of prednisolone as low as 25 ng/ml (suppression of chemotaxis, 20%). Maximal suppression occurred at 100 ng/ml (suppression of chemotaxis, 48%) and no significant increase in suppression was produced by increasing the concentration to 200 ng/ml (suppression of chemotaxis, 53%). In contrast, monocytes isolated from ten patients receiving corticosteroid therapy showed no significant suppression of chemotactic activity when exposed to these concentrations of prednisolone, even though they exhibited a normal ability to respond to a chemotactic stimulus. The lack of suppression of monocyte chemotaxis in patients receiving corticosteroid therapy is unexplained, but may represent a change in the circulating monocyte or lymphocyte populations.

The influence of prednisolone on hepatic function in normal subjects. Effects on galactose elimination capacity, sulfobromophthalein transport maximum and storage capacity, and D-glucaric acid output.

In view of the importance of liver tests in the follow-up of patients under treatment with corticosteroid hormones, 20 mg of prednisolone were given by mouth to normal volunteers for 4 days and hepatic function was assessed before and during treatment. Despite significant falls in plasma cortisol and serum bilirubin concentrations, the galactose elimination capacity, the BSP tests, and the urinary D-glucaric acid output remained essentially unchanged. Consequently no pharmacological effect of this corticosteroid hormone on the examined tests could be detected.

Influence of Prednisolone on Mitotic Index in Synchronized Lymphocytes Culture

Influence of Prednisolone on Mitotic Index in Synchronized Lymphocytes Culture

Influence of prednisolone and ACTH on the formation of insulin-binding antibodies.

Influence of prednisolone and ACTH on the formation of insulin-binding antibodies.