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Structural studies on inhibitory mechanisms of antibiotic, corticosteroid and catecholamine molecules on lactoperoxidase.
Sheikh, IA, Jiffri, EH, Ashraf, GM, Kamal, MA, Beg, MA
Life sciences. 2018;:412-419
Abstract
AIM: Lactoperoxidase (LPO) is an essential protein with broad spectrum antimicrobial activity present in mammalian milk. It imparts immunity to infants against wide range of pathogenic infections. Several in vitro studies have shown inhibition of LPO activity by pharmaceutical compounds including commonly used antibiotics such as ampicillin and gentamicin, and molecules like prednisolone, norepinephrine, etc. Prescription of such drugs to lactating mothers might have adverse health effects on infants. The aim of our study was the elucidation of the structural aspects of the inhibitory mechanism of ampicillin, gentamicin, amoxicillin, prednisolone and norepinephrine on LPO. MATERIAL AND METHODS Three dimensional structure of camel LPO (cLPO) was developed using homology modeling and used for in silico experimental studies. The Schrödinger induced fit docking along with binding affinity estimation experiments were performed. The cLPO and Ligands were prepared using Protein Preparation Wizard and Ligprep modules available in Schrodinger suite. For estimating Binding affinity Prime Molecular Mechanics with Generalized Born and Surface Area (MMGB-SA) module was used. KEY RESULTS The five drug ligands formed three to five hydrogen bonding interactions with cLPO. Amino acids Arg-231, Asp-232, Ser-370, Arg-371 and Glu-374 of cLPO were crucial for these interactions. The binding affinity values for gentamicin were highest and for norepinephrine were the lowest. SIGNIFICANCE This study concludes that the five drug molecules show potential ability to inhibit the LPO activity. Further, a very high sequence similarity of cLPO with human LPO imparts high significance to these conclusions in relation to human health especially in new born infants.
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Diagnostic and Therapeutic Long-term Management of Eosinophilic Esophagitis- Current Concepts and Perspectives for Steroid Use.
Greuter, T, Alexander, JA, Straumann, A, Katzka, DA
Clinical and translational gastroenterology. 2018;(12):e212
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Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which requires short- and long-term treatment. In addition, patients under long-term treatment for any chronic condition should have a structured follow-up. The mainstays in EoE treatment are drugs (such as swallowed topical corticosteroids [STC] and proton pump inhibitors), dietary exclusions, and endoscopic dilations. STC are the most widely used treatment and have proven efficacy in inducing clinical, endoscopic and histological remission in active EoE. However, data regarding maintaining disease remission and long-term management are limited. Ongoing disease activity and relapses despite STC treatment are frequently observed. This sheds light on the urgent need for adequate maintenance strategies, which have not been well defined. In terms of follow-up concepts, to date neither guidelines nor consensus recommendations have been published. To summarize the current knowledge on long-term diagnostic and therapeutic STC management of EoE, we conducted a literature search using PubMed and Embase applying the following key search items: Eosinophilic esophagitis, eosinophils, esophagus, swallowed topical corticosteroids, fluticasone, budesonide, long-term, treatment, therapy, and follow-up. In addition, we present empirically developed long-term management concepts applied at two large EoE centers, with a special focus on STC treatments. Finally, we highlight areas of future research and perspectives regarding the long-term management of EoE.
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Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD: A Randomized Clinical Trial.
Devereux, G, Cotton, S, Fielding, S, McMeekin, N, Barnes, PJ, Briggs, A, Burns, G, Chaudhuri, R, Chrystyn, H, Davies, L, et al
JAMA. 2018;(15):1548-1559
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IMPORTANCE Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD. OBJECTIVE To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD. DESIGN, SETTING, AND PARTICIPANTS The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites. INTERVENTIONS Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787). MAIN OUTCOMES AND MEASURES The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period. RESULTS Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, -0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%). CONCLUSIONS AND RELEVANCE Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN27066620.
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Effect of Antioxidant Vitamins as Adjuvant Therapy for Sudden Sensorineural Hearing Loss: Systematic Review Study.
Ibrahim, I, Zeitouni, A, da Silva, SD
Audiology & neuro-otology. 2018;(1):1-7
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IMPORTANCE Sudden sensorineural hearing loss (SSNHL) is an otological emergency of unknown etiology. Recent reports showed that antioxidant drugs can benefit patients with SSNHL. This study attempted to evaluate the effect of adding antioxidant vitamins as an adjuvant therapy alongside with corticosteroids. OBJECTIVE To evaluate the effects of the 3 major antioxidant vitamins (A, C, and E) as an adjuvant therapy, administered with corticosteroids, for the treatment of SSNHL in adult patients (≥18 years). DATA SOURCES MEDLINE, EMBASE, PubMed, Web of Science and Cochrane electronic databases from January 1, 1995, through September 25, 2017. STUDY SELECTION Published studies of adult patients who received antioxidant vitamins (A, C, E, or any combination of these vitamins) as an adjuvant therapy in addition to the regular treatment (corticosteroids) for SSNHL. Quality assessment was performed using the Cochrane Collaboration Tool for Assessing Risk of Bias. DATA EXTRACTION Each study had a control group (conventional treatment + placebo) and a trial group (antioxidant vitamin(s) + conventional treatment). RESULTS From 446 manuscripts identified in the literature, 3 studies were included in the review with 279 patients. The most common vitamins used to treat SSNHL were the 3 major antioxidant vitamins A, C, and E, combined sometimes with other antioxidants such as selenium. CONCLUSIONS AND RELEVANCE The success of the treatment is increased in patients who received antioxidant vitamins in combination with conventional therapy.
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Inhaled magnesium sulfate in the treatment of acute asthma in children.
Normansell, R, Knightly, R, Milan, SJ, Knopp-Sihota, JA, Rowe, BH, Powell, C
Paediatric respiratory reviews. 2018;:31-33
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Comparison of the Effects of Curcumin Mucoadhesive Paste and Local Corticosteroid on the Treatment of Erosive Oral Lichen Planus Lesions.
Nosratzehi, T, Arbabi-Kalati, F, Hamishehkar, H, Bagheri, S
Journal of the National Medical Association. 2018;(1):92-97
Abstract
INTRODUCTION Lichen planus is a prevalent chronic mucocutaneous condition, whose exact pathogenesis has not been elucidated yet and its standard treatment at present involves the use of local corticosteroids. Curcumin is a colored material extracted from Curcuma longa plant species and is used as an appetizer and for medical purposes. It has anti-inflammatory, antioxidative and anti-cancerous properties. In the present study, the effect of mucoadhesive pastes containing curcumin and local corticosteroids was evaluated for the treatment of erosive lichen planus lesions. MATERIALS AND METHODS In this case‒control study, 40 patients with oral lichen planus were evaluated. Twenty patients, as the cases, were given mucoadhesive pates containing curcumin and 20 patients, as the controls, were given local corticosteroids. The lesion sizes were recorded in the first session and during the follow-up sessions. Pain severities were measured and recorded using the visual analogue scale (VAS) on the first session and during the follow-up sessions. Data were analyzed with SPSS 19, using Student's t-test and Mann-Whitney test. Data are significant P < 0.05. RESULTS The lesion sizes, pain severities and changes in classification of the lesions exhibited significant differences at different follow-up sessions (weeks 1, 2, 4, 8 and 12) in the two groups (P < 0.05). However, there were no significant differences between the group treated with curcumin and the group treated with local corticosteroids (P > 0.05). CONCLUSION Curcumin was effective in the treatment of oral lichen planus lesions and resulted in decreases in lesion sizes, pain and burning sensation severities and changes in classification of the lesions without any complications.
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Corticosteroids for Preventing Caustic Esophageal Strictures: Systematic Review and Meta-analysis.
Katibe, R, Abdelgadir, I, McGrogan, P, Akobeng, AK
Journal of pediatric gastroenterology and nutrition. 2018;(6):898-902
Abstract
OBJECTIVES Caustic ingestion can have a complicated clinical course. Corticosteroids are widely used but there is uncertainty about its role in preventing esophageal stricture formation following caustic ingestion. This systematic review and meta-analysis assessed the available clinical evidence regarding the efficacy and safety of corticosteroids for preventing esophageal strictures following caustic injury. METHODS We assessed randomized controlled trials (RCTs) that compared corticosteroids versus no corticosteroids in the prevention of esophageal stricture formation following caustic ingestion. We searched the following databases from inception to March 2017: PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers retrieved eligible articles, assessed risk of bias, and performed data extraction. The main outcome measure was the prevention of esophageal stricture formation. RESULTS The search identified 763 citations. Three RCTs involving 244 participants met the inclusion criteria. There was no benefit of corticosteroids in the prevention of esophageal strictures following the ingestion of caustic materials (risk ratio [RR] = 0.63, 95% CI = 0.29-1.37). CONCLUSIONS The available evidence does not support the use of corticosteroids for the prevention of esophageal strictures following caustic ingestion. The overall quality of the evidence is limited because of methodological weaknesses and small sample sizes in the primary studies.
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Clinical and ultrasonographic features associated to response to intraarticular corticosteroid injection. A one year follow up prospective cohort study in knee osteoarthritis patient with joint effusion.
Calvet, J, Orellana, C, Galisteo, C, García-Manrique, M, Navarro, N, Caixàs, A, Larrosa, M, Gratacós, J
PloS one. 2018;(1):e0191342
Abstract
OBJECTIVES Intraarticular injection is used for pain relief in knee osteoarthritis (OA), but there is not a well defined profile of patient who could get more benefit from it. The purpose of this study was to evaluate the frequency of pain relief at one year after corticosteroids intraarticular injection and to identify clinical factors associated to response in patients with knee osteoarthritis with joint effusion. METHODS One-year prospective cohort study of patients with knee OA with joint effusion confirmed by ultrasound. An intraarticular injection was performed following a clinical protocol. Anthropometric measurements, laboratory parameters, clinical severity, ultrasound parameters and radiological severity were collected. Response regarding pain and presence of synovial fluid on ultrasound at one month and at one year were evaluated. Clinical responder were consider in subjects with enough improvement to carry out normal daily activities with pain VAS<40mm. RESULTS One hundred and thirty-two patients were included.A significant number of patients (61.4%) improved pain at one year following the protocol established in this study. Pain and ultrasound synovial fluid at one month appeared to predict the response at one year. The Lequesne index and the percentage of body fat were independently associated to pain at one year while the Lequesne index and ultrasound synovial hypertrophy were independently related to the presence of synovial fluid at one year. CONCLUSIONS The status regarding pain or ultrasound synovial fluid at one month after an intraarticular joint injection appeared to predict the status at one year in patients with knee osteoarthritis and synovial effusion.
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Effect of Different Volumes on Pain Relief in Patient Receiving Fluoroscopic Guided Interlaminar Lumbar Epidural Steroid Injection.
Makkar, JK, Kumar, B, Jain, K, Dhutt, SS, Batra, YK, Singh, PM
Pain physician. 2018;(3):243-250
Abstract
BACKGROUND Epidural steroids injections (ESI) are frequently used to treat lumbar radicular pain. Although different volume have been used for interlaminar ESI in adults, there is no controlled trial comparing the effect of different volumes on pain relief for the same dose of steroid . OBJECTIVE To compare the effect of increase in volume of epidural drug on pain relief in lumbar ESI. STUDY DESIGN Randomized double blind trial SETTING Pain OR of a tertiary care centre METHODS Sixty patients were randomly allocated to 1 of 3 groups: Group A (4 mL), Group B (6 mL), and Group C (8 mL). Pain was evaluated using visual analog scale (VAS) and improvement in disability using modified Oswestry Disability Questionnaire scores (MODQS) at 2, 4, 8, 12, and 24 weeks. Patients having less than 50% pain relief from baseline received an additional epidural injection of the same volume with a maximum of 3 injections at least 15 days apart. The primary objective of the study was incidence of patients attaining more than 50% pain relief at 6 months. Secondary outcome included MODQS and pattern of spread of iodinated contrast on fluoroscopy. RESULTS At the end of 6 months, there was no significant difference in the effective pain relief between the 3 groups (Group A-16/22 (72.7%), Group B-15/20 (75%), Group C-13/18 (72.2%); P = 0.98, chi- square test). All groups demonstrated a significant reduction in mean VAS scores. There was no significant intergroup difference in VAS sores and MODQS at all the time intervals. The pattern of contrast spread did not differ between the 3 groups. LIMITATION Not a placebo controlled trial. CONCLUSIONS An increase in volume of the injectate from 4 mL to 8 mL did not increase the efficacy of interlaminar ESI. KEY WORDS Epidural steroid, volume, low back pain, interlaminar.
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Interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery.
Chung, C, Bryant, A, Brown, PD
The Cochrane database of systematic reviews. 2018;(7):CD011492
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BACKGROUND Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality of life (QoL) and function. The underlying pathophysiological mechanism remains unclear for this condition, which makes establishing effective treatments challenging. OBJECTIVES To assess the effectiveness of interventions used for the treatment of brain radionecrosis in adults over 18 years old. SEARCH METHODS In October 2017, we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for eligible studies. We also searched unpublished data through Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials for ongoing trials and handsearched relevant conference material. SELECTION CRITERIA We included randomised controlled trials (RCTs) of any intervention directed to treat brain radionecrosis in adults over 18 years old previously treated with radiation therapy to the brain. We anticipated a limited number of RCTs, so we also planned to include all comparative prospective intervention trials and quasi-randomised trials of interventions for brain radionecrosis in adults as long as these studies had a comparison group that reflects the standard of care (i.e. placebo or corticosteroids). Selection bias was likely to be an issue in all the included non-randomised studies therefore results are interpreted with caution. DATA COLLECTION AND ANALYSIS Two review authors (CC, PB) independently extracted data from selected studies and completed a 'Risk of bias' assessment. For dichotomous outcomes, the odds ratio (OR) for the outcome of interest was reported. For continuous outcomes, treatment effect was reported as mean difference (MD) between treatment arms with 95% confidence intervals (CIs). MAIN RESULTS Two RCTs and one prospective non-randomised study evaluating pharmacological interventions met the inclusion criteria for this review. As each study evaluated a different drug or intervention using different endpoints, a meta-analysis was not possible. There were no trials of non-pharmacological interventions that met the inclusion criteria.A very small randomised, double-blind, placebo-controlled trial of bevacizumab versus placebo reported that 100% (7/7) of participants on bevacizumab had reduction in brain oedema by at least 25% and reduction in post-gadolinium enhancement, whereas all those receiving placebo had clinical or radiological worsening or both. This was an encouraging finding but due to the small sample size we did not report a relative effect. The authors also failed to provide adequate details regarding the randomisation and blinding procedures Therefore, the certainty of this evidence is low and a larger RCT adhering to reporting standards is needed.An open-label RCT demonstrated a greater reduction in brain oedema (T2 hyperintensity) in the edaravone plus corticosteroid group than in the corticosteroid alone group (MD was 3.03 (95% CI 0.14 to 5.92; low-certainty evidence due to high risk of bias and imprecision); although the result approached borderline significance, there was no evidence of any important difference in the reduction in post-gadolinium enhancement between arms (MD = 0.47, 95% CI - 0.80 to 1.74; low-certainty evidence due to high risk of bias and imprecision).In the RCT of bevacizumab versus placebo, all seven participants receiving bevacizumab were reported to have neurological improvement, whereas five of seven participants on placebo had neurological worsening (very low-certainty evidence due to small sample size and concerns over validity of analyses). While no adverse events were noted with placebo, three severe adverse events were noted with bevacizumab, which included aspiration pneumonia, pulmonary embolus and superior sagittal sinus thrombosis. In the RCT of corticosteroids with or without edaravone, the participants who received the combination treatment were noted to have significantly greater clinical improvement than corticosteroids alone based on LENT/SOMA scale (OR = 2.51, 95% CI 1.26 to 5.01; low-certainty evidence due to open-label design). No differences in treatment toxicities were observed between arms.One included prospective non-randomised study of alpha-tocopherol (vitamin E) versus no active treatment was found but it did not include any radiological assessment. As only one included study was a double-blinded randomised controlled trial, the other studies were prone to selection and detection biases.None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements.A limited number of prospective studies were identified but subsequently excluded as these studies had a limited number of participants evaluating different pharmacological interventions using variable endpoints. AUTHORS' CONCLUSIONS There is a lack of good certainty evidence to help quantify the risks and benefits of interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. In an RCT of 14 patients, bevacizumab showed radiological response which was associated with minimal improvement in cognition or symptom severity. Although it was a randomised trial by design, the small sample size limits the quality of data. A trial of edaravone plus corticosteroids versus corticosteroids alone reported greater reduction in the surrounding oedema with combination treatment but no effect on the enhancing radionecrosis lesion. Due to the open-label design and wide confidence intervals in the results, the quality of this data was also low. There was no evidence to support any non-pharmacological interventions for the treatment of radionecrosis. Further prospective randomised studies of pharmacological and non-pharmacological interventions are needed to generate stronger evidence. Two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.