Addition Of Prednisolone Research Articles

Integration of levofloxacin-loaded spanlastics and prednisolone into a buccal mucoadhesive sponge for combating severe pneumonia: In-vitro/ex-vivo assessment, qRT-PCR analysis, and quantification of the HMGB-1/NF-қB signaling pathway

Pneumonia induced by Klebsiella pneumoniae (K. pneumoniae) is a grave pathological state that bears profound implications for morbidity and mortality rates. It is marked by an exaggerated inflammatory response in the lung tissue, resulting in lung damage. Accordingly, combining Levofloxacin hemihydrate (LV) with Prednisolone (PD) could potentially reduce the inflammatory response associated with severe pneumonia and save patients’ lives. Therefore, this study aimed to develop LV-loaded spanlastics (SPs)/PD buccal mucoadhesive sponge for the treatment of severe pneumonia. For LV SPs fabrication and optimization, a full 32 factorial design was utilized to examine the impact of the type of edge activator (EA) and Span 60: EA ratio on vesicle size (VS) and encapsulation efficiency percent (EE%). The optimum formula was determined by recording the minimum VS and maximum EE%. It was then tested microbiologically, followed by integration into a mucoadhesive sponge with the addition of PD, forming LV SPs/PD sponge that was evaluated via in-vivo study. The optimum LV SPs was formulation 3 (F3), which was fabricated using Tween 80 as an EA with a Span 60: EA ratio of 80:20. F3 exhibited an EE% of 92.40 ± 0.01 %, a VS of 248.60 ± 2.05 nm, highly elastic spherically shaped nanovesicles with a controlled release profile, and enhanced drug permeation. The minimum inhibitory concentration (MIC) of F3 was reduced by a factor of 8 compared to Levoxin®. Moreover, F3 revealed superiority over Levoxin® by 10, 20, and 10 percentage points increase in downregulating gyrA, gyrB, and parC gene expression in K. pneumoniae, respectively. The LV SPs/PD sponge revealed a spongy structure with well-defined pores. It had a surface pH of 6.93 ± 0.06, a swelling index of 3.52 ± 0.35, an ex-vivo mucoadhesion residence time of 3.01 ± 0.61 h, and a drug content of 97.39 ± 1.82 % for LV and 98.06 ± 1.34 % for PD. As well, the release pattern of the LV SPs/PD sponge was significantly slower than that of the F3 for LV and the Epicopred® for PD. The in-vivo study of the LV SPs/PD sponge demonstrated a prevalence effect in restoring the typical lung histology in rats. Additionally, it returns high mobility group box (HMGB)-1 and nuclear factor-kappa B (NF-қB) biomarkers to their normal levels, surpassing the effects observed with Levoxin®/Epicopred®. Collectively, the LV SPs/PD sponge might hold great potential as a promising treatment approach for the management of severe pneumonia.

Effects of immunoglobulin plus prednisolone in reducing coronary artery lesions in patients with Kawasaki disease: study protocol for a phase III multicenter, open-label, blinded-endpoints randomized controlled trial

BackgroundKawasaki disease (KD) is an acute systemic vasculitis of unclear etiology that mainly affects infants and young children. Strategies to reduce the incidence and severity of coronary artery lesions (CALs), the determinant factor in the long-term prognosis of KD, are currently a focus of studies on KD. Corticosteroids, preferred in the treatment of the majority of vasculitides, are controversial in the treatment of acute KD. In this trial, we will evaluate whether the addition of prednisolone to standard intravenous immunoglobulin (IVIG) plus aspirin therapy can reduce the occurrence of CAL in Chinese patients with KD.MethodsThis is a multicenter, prospective, open-label, randomized controlled trial, which is expected to be conducted in more than 20 hospitals in China and aims to assess the efficacy and safety of IVIG + prednisolone treatment versus standard treatment. Patients with KD who fulfill the inclusion and exclusion criteria will be recruited and randomized (1:1) to receive either a large dose of IVIG (2 g/kg over 12–24 h with a maximum dose of 60 g) + aspirin 30 mg/kg/d or IVIG (2 g/kg over 12–24 h) + aspirin 30 mg/kg/d + prednisolone (2 mg/kg/d with a maximum dose of 60 mg tapered over 15 days after normalization of C-reactive protein concentration). The primary outcome will be the occurrence of CAL at 1 month of illness. The follow-up duration for each participant will be set as 1 year. Patients and treating physicians will be unmasked to group allocation.DiscussionThis will be the first multicenter randomized controlled trial to evaluate the efficacy of IVIG + aspirin + prednisolone in Chinese pediatric patients with KD, which may provide high-level evidence for improving the initial treatment for acute KD.Trial registrationClinicalTrials.govNCT04078568. Registered on 16 August 2018.

The Effect of Immunomodulatory Treatments on Anti-Dystrophin Immune Response After AAV Gene Therapy in Dystrophin Deficient mdx Mice.

AAV-based gene therapy is an attractive approach to treat Duchenne muscular dystrophy (DMD) patients. Although the long-term consequences of a gene therapy approach for DMD are unknown, there is evidence in both DMD patients and animal models that dystrophin replacement by gene therapy leads to an anti-dystrophin immune response that is likely to limit the long-term use of these therapeutic strategies. Our objective is to test whether the anti-dystrophin immune response is affected by immunomodulatory drugs in mdx mice after rAAV gene therapy. mdx mice were treated with rAAV microdystrophin alone or in combination with immunomodulatory drugs. Dystrophin expression in skeletal muscle was assessed by mass spectrometry. Immune responses were assessed by immunophenotyping, western blot for anti-dystrophin antibodies and flow cytometry assays for antigen-specific T-cell cytokine expression. The impact on muscle was measured by grip strength assessment, in vivo torque, optical imaging for inflammation and H&E staining of sections to assess muscle damage. We found that AAV-9-microdystrophin gene therapy induced expression of microdystrophin, anti-dystrophin antibodies, and T-cell cytokine responses. Immunomodulatory treatments, rituximab and VBP6 completely abrogated the anti-dystrophin antibody response. Prednisolone, CTLA4-Ig, and eplerenone showed variable efficacy in blocking the anti-dystrophin immune response. In contrast, none of the drugs completely abrogated the antigen specific IFN-γ response. AAV-microdystrophin treatment significantly reduced inflammation in both forelimbs and hindlimbs, and the addition of prednisolone and VBP6 further reduced muscle inflammation. Treatment with immunomodulatory drugs, except eplerenone, enhanced the beneficial effects of AAV-microdystrophin therapy in terms of force generation. Our data suggest that AAV-microdystrophin treatment results in anti-dystrophin antibody and T-cell responses, and immunomodulatory treatments have variable efficacy on these responses.

Evolution of Mixed Connective Tissue Disease in 7 Years Old Child: Clinical Case

Background. Mixed connective tissue disease (Sharp syndrome) is the rare chronic autoimmune pathology combining various features of systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis, dermatomyositis and high antibody titer to nuclear ribonucleoprotein. The mixed connective tissue disease may evolve into other systemic diseases over time. Description of any cases of mixed connective tissue disease and its evolution in Russian patients has not been published previously.Clinical Case Description. The results of observations of the child with clinical and immunological signs of the mixed connective tissue disease followed by the progression of systemic scleroderma symptoms and development of Sjogren's syndrome in the short period of time are presented in the article. Improvement (such as pain attenuation, increase in volume of movements in affected joints, decrease of Raynaud syndrome manifestations duration) was observed on treatment (methotrexate 10 mg/week with subsequent addition of prednisolone 0.75 mg/kg/day).Conclusion. Timely diagnostics of clinical signs of the systemic diseases debut is crucial for correct patient routing and for achieving of disease improvement.

PF707 INCIDENCE AND OUTCOMES OF REFRACTORY IMMUNE THROMBOCYTOPENIC PURPURA IN CHILDREN; A SINGLE INSTITUTION EXPERIENCE

Background:The treatment of refractory immune thrombocytopenic purpura (ITP) in children is challenging. Although various medical approaches have been used to treat refractory ITP, few data are available on the long‐term incidence of outcomes in children with refractory ITP.Aims:In this study, we aimed to reveal the outcomes of 87 children with ITP in our institution during the last 19 years.Methods:We retrospectively reviewed the clinical data of children who were newly diagnosed with ITP from April 1998 to March 2017 at the Nihon University Itabashi Hospital. Patients aged below 16 years were included in this study. Patients with follow‐up duration of less than 3 months were excluded. In this study, refractory ITP was defined as a platelet count of <50 × 109 /L, which did not respond to intravenous immunoglobulin (IVIG) and prednisolone (PSL). The definition of the treatment response was as follows: complete response (CR) or partial response (PR), platelet count sustaining more than 100 × 109/L or between 50 and 100 × 109/L at 6 months after change in the treatment approach, respectively. Since 2009, we have introduced cyclosporine (CSA) for refractory ITP; we have diagnosed refractory ITP as refractory thrombocytopenia, which is a subtype of refractory cytopenia of childhood, and then we have used CSA for such patients. In this study, we compared the incidence of CR plus PR in refractory ITP at 3 years after diagnosis in the 1998–2008 group and in the 2009–2017 group. This retrospective study was approved by the institutional review board.Results:A total of 87 children with ITP were identified (50 males and 37 females): 42 children (48%) in the 1998–2008 group and 45 children (52%) in the 2009–2017 group. There were 9 patients (21%) with refractory ITP in the 1998–2008 group and 8 patients (18%) in the 2009–2017 group. Treatment chart in 17 patients with refractory ITP are shown in Figure 1. We changed the diagnosis of ITP to refractory thrombocytopenia in the all patients with refractory ITP in the 2009–2017 group, and initiated treatment with CSA. CSA was started at a dose of 4–6 mg/kg/day (per oral), and the trough level was adjusted between 100 and 150 ng/ml. Two patients achieved CR by CSA therapy alone at 16 and 119 days after starting CSA therapy, respectively. One patient achieved PR with the addition of PSL. Five patients did not respond to CSA therapy alone and then received IVIG at the CSA trough level of more than 100 ng/ml. With this approach, 4 patients achieved CR at a median time of 21 days (range, 13–38) after starting CSA therapy. Overall, 7 out of the 8 patients with refractory ITP in the 2009–2017 group maintained CR plus PR at 3 years after diagnosis. No severe CSA‐associated adverse event was seen in any patients. In contrast, only 2 out of 9 patients with refractory ITP in the 1998–2008 group achieved CR spontaneously (without additional treatment) at 3 years after diagnosis. Moreover, 2 patients obtained CR after splenectomy, and the other 5 patients remained with thrombocytopenia.Summary/Conclusion:CSA with or without IVIG therapy was effective in most cases (88%) of childhood refractory thrombocytopenia. These findings indicate that childhood thrombocytopenia is partially mediated by T cells. Although splenectomy was a conventional treatment for refractory ITP, it surely increases the long‐term risks of venous and arterial thrombosis as well as sepsis from Streptococcus pneumoniae. Therefore, CSA with or without IVIG therapy is feasible in children with refractory ITP to avoid splenectomy.image

High Efficacy of Prednisolone in a Complicated Case of Weil Disease.

To the Editor, Leptospirosis is a self-limited zoonotic disease in mild cases, but the more severe form, known as Weil disease, can progress to multi-organ failure (1). Clinical signs and routine laboratory tests are non-specific. Therefore, in clinically suspected cases, antibiotic treatment must be immediately initiated. However, the antibiotic treatment may not be sufficient in Weil disease. Supportive treatment may be life-saving at this point. A 19 year-old male presented with fever, nausea, vomiting, generalized jaundice, and reduced urinary output. Laboratory investigations revealed severe thrombocytopenia, elevated total bilirubin, and increased urea and creatinine levels. The history revealed that he had worked in a wooden fruit crate production facility. He resigned from his job and returned to his city 15 days before the clinical onset. He frequently scratched his hands and there were mice infestations where he used to work. He was initially diagnosed with Weil disease and treatment with ampicillinsulbactam (Ampisid, Mustafa Nevzat Medical; Istanbul, Turkey) was initiated at 3gr/day. On the third day of the follow-up, his platelet count decreased to 19,000 and his total bilirubin level rose to 14.7 mg/dL; he had epistaxis. Since we could not perform plasmapheresis, prednisolone (Prednisolon, Actavis Medical; Istanbul, Turkey) was initiated at 1 mg/kg on the third day of admission. With the initiation of prednisolone, his platelet count began to rise and epistaxis regressed. Prednisolone was stopped on the fifth day and ampicillin-sulbactam course was completed after 14 days. At his outpatients’ control after 15 days, total biliruin level regressed to 6.0 mg/dL and all other laboratory results normalized (Table 1). Microagglutination test (MAT) for serodiagnosis was later determined to be positive (L. icterohaemorrhagiae, titer: 1:200; serum was taken on the first day). TABLE 1. Laboratory results before and after prednisolone therapy (The prednisolone was started on Day 3) Our patient had a history of highly probable contact with mouse urine. He was initially diagnosed with Weil disease and antibiotic treatment was initiated immediately. His renal functions partially improved following intensive hydration and antibiotic treatment; however, thrombocytopenia worsened and total bilirubin level increased further. It has been reported that 50–80% of leptospirosis patients had thrombocytopenia, frequently accompanying renal failure (1,2). Although its pathophysiology is not exactly clear, the following explanations were asserted: 1- direct toxicity of leptospira on the bone marrow, 2- thrombocyte consumption caused by DIC, 3- immune-mediated thrombocyte destruction due to capillary vasculitis and inflammation (most favored mechanism), and 4- increased thrombocyte consumption secondary to vascular endothelial activation (3,4). The presence of thrombocytopenia indicates severe disease; therefore, it should be closely monitored with regard to bleeding. After the addition of prednisolone, the platelet count rise and epistaxis regressed, supporting the idea that thrombocytopenia in leptospirosis appears secondary to vasculitis and inflammation. There are limited data evaluating the use of prednisolone in Weil disease (2,5,6). These reports showed that anti-inflammatory drugs like corticosteroids can reverse vasculitis by suppressing inflammation triggered by the disease and, as a result, reduce mortality. Similarly, we also found an effective response to corticosteroid therapy in a short period of time in our case. Based on this, we would like to emphasize that considering Weil disease in differential diagnosis of patients with fever, icterus, azotemia or hematological abnormalities is of significance. Antibiotic treatment should be initiated immediately upon suspicion of Weil disease in order to prevent mortality. Early administration of steroids helps to improve renal functions and prevents mortality in cases with thrombocytopenia. This approach could be important for centers where resources and patient transfer chances are limited.

The effects of 1% prednisolone acetate on pupil diameter and intraocular pressure in healthy dogs treated with 0.005% latanoprost.

Prostaglandin analogs contribute to blood-aqueous barrier breakdown and may exacerbate uveitis. As these analogs induce de novo synthesis of endogenous prostaglandins, their therapeutic, hypotensive effect could potentially be inhibited by anti-inflammatory treatment. We therefore evaluated whether topical 1% prednisolone acetate alters the effects of 0.005% latanoprost on pupil diameter (PD) and intraocular pressure (IOP). Ten healthy Labrador retriever dogs from the Israel Guide Dog Center for the Blind. Pupil diameter and IOP were measured hourly, 8 AM-4 PM, with the right and left eyes serving as control (CE) and treated (TE) eyes, respectively. Measurements were conducted during four sessions: (1) without treatment (n = 10), (2) following latanoprost treatment (n = 10) at 8 AM, (3) following prednisolone treatment (n = 7) at 8 AM, and (4) bilateral latanoprost treatment at 8 AM, prednisolone treatment in TE at 11 AM (n = 8). The different number of dogs in sessions 3 and 4 is because some dogs were matched with their new owners earlier than expected. Pupil diameters were not affected by the addition of prednisolone and, at 4 PM, were 3.82 ± 0.47 and 3.97 ± 0.36 mm in TE and CE, respectively (P = 0.175, Wilcoxon). IOPs were not affected by the addition of prednisolone and, at 4 PM, were 9.0 ± 0.8 and 9.3 ± 0.8 mm Hg in TE and CE, respectively (P = 0.339, Wilcoxon). Prednisolone did not alter latanoprost's miotic and hypotensive effects in normal dogs during this study period.

Pneumocystis pneumonia in children in Calabar, Nigeria

Pneumocystis pneumonia (PJP), initially thought to be rare in this part of the world, has over the years, been diagnosed and treated in our center. PJP should be considered in a young child 3 to 6 months of age with very severe pneumonia, known or suspected to be HIV infected. It should be suspected when severity of illness is out of proportion with the chest findings and chest x-ray is normal or shows minimal or bilateral interstitial infiltrates. Treatment is oral or intravenous high dose cotrimoxazole given 6-8 hourly for 3 weeks and the addition of prednisolone. The objective of this report is to describe the presentation, challenges of diagnosing and management of PJP in children in a developing country. Report of 3 cases aged 3, 4 and 41/2 months, exposed to the HIV. All developed severe pneumonia characteristic of PJP and all responded to treatment with high dose cotrimoxazole and Prednisolone. A high index of suspicion is needed to diagnose PJP in a resource poor setting like ours. It is common in HIV positive children but can also occur in HIV negative individuals as shown by these case reports. A presumptive diagnosis can be made in a young child, usually below 6 months of age, very ill with severe pneumonia and minimal chest findings who responds to cotrimoxazole. Addition of prednisolone has been found to improve the outcome. Antibiotics should continue to cover for co-existing bacterial pneumonia.

Addition of prednisolone and heparin in patients with failed IVF/ICSI cycles: a preliminary report of a clinical trial

Through a non-randomized clinical trial, we examined the theoretical benefit of the coadministration of low molecular weight heparin (LMWH) and prednisolone on pregnancy outcomes in women with previously failed IVF/ICSI cycles. Fifteen women constituted the study group, and were compared with 19 women receiving LMWH alone and another 18 women with no drugs. Our finding that the combination of the two drugs produced positive differences in terms of embryo quality, pregnancy and live birth rates points to the necessity for adequately powered randomized trials.

Early treatment with addition of low dose prednisolone to methotrexate improves therapeutic outcome in severe psoriatic arthritis

Psoriatic arthritis (PsA) is increasingly being recognized to cause progressive joint damage and disability. PsA unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs), the conventional first-line choice of treatment, is usually managed with disease-modifying antirheumatic drugs (DMARDs) especially methotrexate. An 18-year-old HIV-negative male had progressively severe PsA of 4-month duration that was nearly confining him to a wheel chair. He did not respond to multiple NSAIDs, alone or in combination with methotrexate (15 mg/week), given for 4 weeks. Addition of prednisolone (10 mg on alternate days) controlled his symptoms within a week. The NSAIDs could be withdrawn after 4 weeks as the treatment progressed. The doses were tapered for methotrexate (5 mg/week) and prednisolone (2.5 mg on alternate days) every 8 weekly subsequently during 15 months of follow-up without recurrence/deformities or drug toxicity. For years, the use of corticosteroids in psoriasis has been criticized for their propensity to exacerbate the skin disease on withdrawal. However, monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in early stage of the PsA rather than ‘steroid rescue’ later. This will help in early control of joint inflammation, prevent joint damage and maintain long-term good functional capacity and quality of life. This may be useful when the cost or availability of biologics precludes their use. However, we discourage the use of corticosteroids as monotherapy.

A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell's palsy: the BELLS study

To determine whether oral prednisolone or aciclovir, used separately or in combination, early in the course of Bell's palsy, improves the chances of recovery at 3 and 9 months. A 2 x 2 factorial randomised double-blind trial. Patients were randomly assigned to treatment by an automated telephone service using a permuted block randomisation technique with block sizes of four or eight, and no stratification. Mainland Scotland, with referrals mainly from general practice to 17 hospital trial sites. Adults (aged 16 years or older) with unilateral facial nerve weakness of no identifiable cause presenting to primary care, the emergency department or NHS24 within 72 hours of symptom onset. Patients were randomised to receive active preparations or placebo for 10 days: (1) prednisolone (50 mg per day, 2 x 25-mg capsules) and aciclovir (2000 mg per day, 5 x 400-mg capsules); (2) prednisolone and placebo (lactose, indistinguishable); (3) aciclovir and placebo; and (4) placebo and placebo. The primary outcome was recovery of facial function assessed by the House-Brackmann scale. Secondary outcomes included health status, pain, self-perceived appearance and cost-effectiveness. Final outcomes were available for 496 patients, balanced for gender; mean age 44 years; initial facial paralysis moderate to severe. One half of patients initiated treatment within 24 hours of onset of symptoms, one-third within 24-48 hours and the remainder within 48-72 hours. Of the completed patients, 357 had recovered by 3 months and 80 at 9 months, leaving 59 with a residual deficit. There were significant differences in complete recovery at 3 months between the prednisolone comparison groups (83.0% for prednisolone, 63.6% for no prednisolone, a difference of + 19.4%; 95% confidence interval (CI): + 11.7% to + 27.1%, p < 0.001). The number needed to treat (NNT) in order to achieve one additional complete recovery was 6 (95% CI: 4 to 9). There was no significant difference between the aciclovir comparison groups (71.2% for aciclovir and 75.7% for no aciclovir). Nine-month assessments of patients recovered were 94.4% for prednisolone compared with 81.6% for no prednisolone, a difference of + 12.8% (95% CI: + 7.2% to + 18.4%, p < 0.001); the NNT was 8 (95% CI: 6 to 14). Proportions recovered at 9 months were 85.4% for aciclovir and 90.8% for no aciclovir, a difference of -5.3%. There was no significant prednisolone-aciclovir interaction at 3 months or at 9 months. Outcome differences by individual treatment (the four-arm model) showed significant differences. At 3 months the recovery rate was 86.3% in the prednisolone treatment group, 79.7% in the aciclovir-prednisolone group, 64.7% in the placebo group and 62.5% in the aciclovir group. At 9 months the recovery rates were respectively 96.1%, 92.7%, 85.3% and 78.1%. The increase in recovery rate conferred by the addition of prednisolone (both for prednisolone over placebo and for aciclovir-prednisolone over aciclovir) is highly statistically significant (p < 0.001). There were no significant differences in secondary measures apart from Health Utilities Index Mark 3 (HUI3) at 9 months in those treated with prednisolone. This study provided robust evidence to support the early use of oral prednisolone in Bell's palsy as an effective treatment which may be considered cost-effective. Treatment with aciclovir, either alone or with steroids, had no effect on outcome.

Influence of concomitant prednisolone on trimethoprim-associated hyperkalaemia

Trimethoprim-sulfamethoxazole may cause hyperkalaemia by the amiloride-like effect of trimethoprim on sodium channels in the distal nephron. Hyperkalaemia usually occurs after 7-10 days and has been reported in 20%-50% of patients receiving trimethoprim-sulfamethoxazole. Patients with Pneumocystis jiroveci pneumonia and severe hypoxaemia benefit from the use of prednisolone as an adjuvant to trimethoprim-sulfamethoxazole. The addition of prednisolone may lower the incidence of trimethoprim-related hyperkalaemia due, in part, to its mineralocorticoid activity. We studied the effect of concomitant prednisolone on trimethoprim-related hyperkalaemia. Thirty patients qualified for inclusion and were reviewed. Patients were divided into two groups: one group received trimethoprim-sulfamethoxazole plus prednisolone (18 patients); and the other group received trimethoprim-sulfamethoxazole alone (12 patients). The two groups were comparable at baseline, except for the severity of the P. jiroveci pneumonia. Hyperkalaemia developed in seven patients: all in the prednisolone and trimethoprim-sulfamethoxazole group. The greater incidence of hyperkalaemia in this group is surprising and was counter to our expectation. Although it is possible that there is an unexplained interaction between trimethoprim and prednisolone, we postulate that our observation is a result of the catabolic effect of prednisolone. The patients treated with trimethoprim-sulfamethoxazole plus prednisolone appear to be more likely to develop hyperkalaemia than patients treated with trimethoprim-sulfamethoxazole alone.

Differential Effects of Prednisolone and Azathioprine on the Development of Human Cytomegalovirus Replication Post Liver Transplantation

We sought to investigate the impact of different immunosuppressive regimens on human cytomegalovirus (HCMV) incidence and replication dynamics in a cohort of 256 patients after liver transplantation. A time-updated approach was used to determine the risk of developing HCMV replication (>200 genomes/mL blood) within the first 100 days after liver transplantation according to the immunosuppressive regimen being received at specific time points. In patients receiving tacrolimus, the addition of prednisolone was associated with a significant increased risk of HCMV replication both at baseline (relative rate of infection [RRI]=4.34; P=0.0001) and in a time-updated analysis (RRI=4.68; P=0.0001). However, the addition of azathioprine substantially reduced the risk of HCMV replication to that observed with tacrolimus alone. As expected donor/recipient HCMV serostatus was also a risk factor for viraemia. Multivariable models showed that the tacrolimus plus prednisolone regimen and donor/recipient serostatus were independent risk factors for HCMV replication. Viral replication dynamics showed that the duration of HCMV viraemia, the peak viral load, and the growth rate of HCMV were greatest in patients receiving tacrolimus plus prednisolone although these differences did not reach statistical significance. The combination of prednisolone plus tacrolimus as baseline immunosuppression after liver transplantation is associated with a high risk of HCMV replication. This effect can be negated by the addition of azathioprine.

Addition of prednisolone to IV immune globulin (IVIG) therapy for Kawasaki's syndrome in children improves the coronary artery outcome,

Addition of prednisolone to IV immune globulin (IVIG) therapy for Kawasaki's syndrome in children improves the coronary artery outcome,

Regulation of progesterone production in human term trophoblasts in vitro by CRH, ACTH and cortisol (prednisolone)

In most mammals, onset of labor is accompanied with progesterone withdrawal. In humans, cortisol blockade of progesterone is a possible mechanism involved in the initiation of labor. Therefore, aim of the study was to clarify the effect of CRH, ACTH and cortisol (prednisolone) on the release of progesterone by term trophoblast cells in vitro. Cytotrophoblast cells were prepared from human term placentas by standard dispersion of villous tissue followed by a percoll gradient centrifugation step. Trophoblasts were incubated with CRH, ACTH as well as with prednisolone. The release of progesterone is decreased in CRH- and ACTH-treated trophoblast cell cultures compared to untreated trophoblast cells. Addition of prednisolone in varying concentrations leads to an increase of trophoblast progesterone production. The results suggest that CRH and ACTH directly modulate the endocrine function of trophoblasts in culture by downregulating progesterone production. Prednisolone on the other hand showed a stimulating effect on progesterone production in term trophoblast cells in vitro. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that CRH and ACTH are directly involved in the auto- or paracrine regulation of this procedure.

Immunohistochemical and ultrastructural studies of the effects of prednisolone on transformation of fibroblast to regenerated mesothelial cells

We have proposed in the past that chest wall fibroblasts are transformed to regenerated mesothelial cells. This study was conducted to investigate the effects of prednisolone on the differentiation and migration of fibroblasts in their transformation to mesothelial cells. Rat fibroblasts harvested from intercostal thoracic wall specimens were cultured in culture medium until cell spheroids were formed. An experimental cell spheroid group to whose culture medium prednisolone had been added and a control spheroid group with no addition of prednisolone were then subjected to immunohistochemical and ultrastructural studies of the changes in the fibroblasts with the passage of time. On days 1 and 2 of culture, the fibroblasts in each group were cytokeratin negative. However, on day 3 the control group became cytokeratin positive, and ultrastructural observations revealed formation of macula adherens and microvilli. In contrast, the experimental group fibroblasts remained cytokeratin negative even on day 3, but became cytokeratin positive on day 5 of culture. Macula adherens and microvilli also manifested on day 5. Prednisolone inhibited the differentiation and migration of fibroblasts, but it was surmised that fibroblasts that have resisted from the effects of prednisolone finally differentiate into mesothelial cells which have formed macula adherens.

Effects of Acyclovir and Prednisolone on Acute Herpes Zoster

Acyclovir has been shown to be of clinical benefit in the treatment of acute herpes zoster when given for 7 to 10 days. Studies of its effectiveness in preventing postherpetic neuralgia, however, have produced conflicting results. Similarly, the use of corticosteroids as treatment for herpes zoster is extremely controversial. To address both of these issues, British investigators performed a double-blind controlled trial in patients with acute herpes zoster to determine whether a longer course of acyclovir therapy (21 days) or the addition of prednisolone offers any improvement over …

IL-2 responsiveness of lectin-induced lymphoblasts: soluble IL-2 receptor release and differential in vitro effects of immunosuppressants.

We examined the mode of action of different immunosuppressants on the responsiveness of phytohemagglutinin (PHA)-induced lymphoblasts further stimulated by recombinant interleukin-2 (rIL-2). The stimulation of PHA blasts with rIL-2 resulted in an enhancement of tritiated thymidine ([3H]TdR) incorporation and of soluble interleukin-2 receptor (sIL-2R) release. Cyclosporin A (CsA) and prednisolone inhibited in different ways the responsiveness of PHA pre-stimulated blood mononuclear cells (PBMC) to rIL-2, as measured by [3H]TdR incorporation. The addition of CsA resulted in considerable enhancement of the release of sIL-2R, whereas the addition of prednisolone was associated with a similar enhancement only when the higher concentrations of rIL-2 were employed. EGTA, a calcium (Ca2+) chelator, and verapamil, a Ca2+ channel blocker, inhibited [3H]TdR incorporation in a concentration-dependent manner. EGTA inhibited sIL-2R release in the same manner when used alone, and reversed the CsA- and prednisolone-induced enhancement of sIL-2R release by rIL-2 induced lymphoblasts, when used in combination with CsA or prednisolone. Verapamil had a similar but less striking effect. The effects of CsA and prednisolone were also studied in PHA-induced blasts originating from purified CD4+ or CD8+ lymphocytes. Stimulation of these blasts with rIL-2 resulted in higher [3H]TdR incorporation by CD8+ blasts than by CD4+ blasts: however, no sIL-2R release was detected in supernatants of either CD4+ or of CD8+ blasts. Both CsA and prednisolone inhibited the rIL-2-induced enhancement of [3H]TdR incorporation by both T-cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Monocyte zinc andIn vitro prostaglandin E2 and interleukin-1? production by cultured peripheral blood monocytes in patients with Crohn's disease

This study investigated the relationship between zinc status and prostaglandin E2 and interleukin-1 beta production by cultured monocytes in patients with Crohn's disease. Monocyte zinc was significantly decreased in both 12 inpatients and 22 outpatients compared with controls (P less than 0.001) but lymphocyte and polymorphonuclear cell zinc were normal. When cultured monocytes from 10 outpatients with Crohn's disease were stimulated with lipopolysaccharide, prostaglandin E2 production increased markedly, coupled with a fall in monocyte zinc. In matched controls, prostaglandin E2 production was significantly less and monocyte zinc remained stable. No difference in interleukin-1 release was noted between patients and controls. The addition of prednisolone to cell cultures suppressed prostaglandin E2, interleukin-1 synthesis, and monocyte zinc did not change. Zinc chloride augmented prostaglandin E2 production in patients, but not controls, and interleukin-1 remained stable. These results demonstrate a link between low monocyte zinc concentration and excessive prostaglandin production in patients with Crohn's disease.

Corticosteroids inhibit the generation of lymphokine-activated killer activity in vitro.

In phase-I clinical trials of adoptive immunotherapy using lymphokine-activated killer (LAK) cells plus recombinant interleukin-2 (rIL-2) (Cetus) for the treatment of malignant glioma, we observed that blood mononuclear cells (MNC) from patients dependent on dexamethasone for management of cerebral edema produced substantially less LAK activity as compared to MNC of normal blood donors or glioma patients not receiving steroid therapy. Therefore, we examined the in vitro effects, brought about by therapeutically attainable concentrations of various corticosteroids, on the proliferative response, production of gamma interferon (IFN-gamma), and induction of LAK activity from blood MNC of normal donors. Incubation in media containing rIL-2 (1000 U/ml) with either dexamethasone, hydrocortisone, methylprednisolone, or prednisolone profoundly affected all of these parameters. First, while 0.01 micrograms/ml of either dexamethasone or hydrocortisone caused a slight enhancement of the mitogenic response of lymphocytes to phytohemagglutinin, a dose-dependent decline occurred as concentrations increased to 10 micrograms/ml. The addition of prednisolone and methylprednisolone elicited a dose-dependent inhibition of lymphocyte proliferation over the entire concentration range tested. At 0.1 microgram/ml or higher, dexamethasone, hydrocortisone, methylprednisolone and prednisolone significantly (P less than 0.02) inhibited the production of IFN-gamma: respectively 18.9%, 4.4%, 2.2%, and 12.3% of the IFN-gamma produced by MNC in the absence of steroids. All four corticosteroids inhibited the induction of LAK activity. Compared to MNC that had been incubated with 1000 U/ml rIL-2 alone, MNC cultured with rIL-2 and 10 micrograms/ml either dexamethasone or prednisolone demonstrated significantly lower cytotoxicity (P less than 0.05) for the natural-killer-cell-resistant cell line, Daudi. Culturing MNC with hydrocortisone had a more dramatic result, causing a significant decline (P less than 0.01) in lytic activity at both 1.0 micrograms/ml and 10 micrograms/ml, while incubation with methylprednisolone produced a significant drop (P less than 0.02) in LAK-mediated cytotoxicity at 0.1 micrograms/ml as well as 1.0 micrograms/ml and 10 micrograms/ml. When cytotoxicity was expressed as lytic units per million effectors, a dose-response decline in lytic activity was once again apparent, with hydrocortisone, methylprednisolone and prednisolone showing significant inhibition (P less than 0.05) at both 1.0 micrograms/ml and 10 micrograms/ml and dexamethasone at 10 micrograms/ml (P less than 0.01). These results indicate that corticosteroids commonly used in the management of cere