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1.
The Immunomodulatory Properties of Extracellular Vesicles Derived from Probiotics: A Novel Approach for the Management of Gastrointestinal Diseases.
Molina-Tijeras, JA, Gálvez, J, Rodríguez-Cabezas, ME
Nutrients. 2019;(5)
Abstract
Probiotics, included in functional foods, nutritional supplements, or nutraceuticals, exhibit different beneficial effects on gut function. They are extensively used to improve the digestive processes as well as reduce the symptoms and progression of different diseases. Probiotics have shown to improve dysbiosis and modulate the immune response of the host by interacting with different cell types. Probiotics and the host can interact in a direct way, but it is becoming apparent that communication occurs also through extracellular vesicles (EVs) derived from probiotics. EVs are key for bacteria-bacteria and bacteria-host interactions, since they carry a wide variety of components that can modulate different signaling pathways, including those involved in the immune response. Interestingly, EVs are recently starting to be considered as an alternative to probiotics in those cases for which the use of live bacteria could be dangerous, such as immunocompromised individuals or situations where the intestinal barrier is impaired. EVs can spread through the mucus layer and interact with the host, avoiding the risk of sepsis. This review summarizes the existing knowledge about EVs from different probiotic strains, their properties, and their potential use for the prevention or treatment of different gastrointestinal diseases.
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Current therapies and therapeutic decision making for childhood-onset movement disorders.
Mohammad, SS, Paget, SP, Dale, RC
Movement disorders : official journal of the Movement Disorder Society. 2019;(5):637-656
Abstract
Movement disorders differ in children to adults. First, neurodevelopmental movement disorders such as tics and stereotypies are more prevalent than parkinsonism, and second, there is a genomic revolution which is now explaining many early-onset dystonic syndromes. We outline an approach to children with movement disorders starting with defining the movement phenomenology, determining the level of functional impairment due to abnormal movements, and screening for comorbid psychiatric conditions and cognitive impairments which often contribute more to disability than the movements themselves. The rapid improvement in our understanding of the etiology of movement disorders has resulted in an increasing focus on precision medicine, targeting treatable conditions and defining modifiable disease processes. We profile some of the key disease-modifying therapies in metabolic, neurotransmitter, inflammatory, and autoimmune conditions and the increasing focus on gene or cellular therapies. When no disease-modifying therapies are possible, symptomatic therapies are often all that is available. These classically target dopaminergic, cholinergic, alpha-adrenergic, or GABAergic neurochemistry. Increasing interest in neuromodulation has highlighted that some clinical syndromes respond better to DBS, and further highlights the importance of "disease-specific" therapies with a future focus on individualized therapies according to the genomic findings or disease pathways that are disrupted. We summarize some pragmatic applications of symptomatic therapies, neuromodulation techniques, and some rehabilitative interventions and provide a contemporary overview of treatment in childhood-onset movement disorders. © 2019 International Parkinson and Movement Disorder Society.
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Cepharanthine: An update of its mode of action, pharmacological properties and medical applications.
Bailly, C
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019;:152956
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Abstract
BACKGROUND Cepharanthine (CEP) is a drug used in Japan since the 1950s to treat a number of acute and chronic diseases, including treatment of leukopenia, snake bites, xerostomia and alopecia. It is the only approved drug for Human use in the large class of bisbenzylisoquinoline alkaloids. This natural product, mainly isolated from the plant Stephania cephalantha Hayata, exhibits multiple pharmacological properties including anti-oxidative, anti-inflammatory, immuno-regulatory, anti-cancer, anti-viral and anti-parasitic properties. PURPOSE The mechanism of action of CEP is multifactorial. The drug exerts membrane effects (modulation of efflux pumps, membrane rigidification) as well as different intracellular and nuclear effects. CEP interferes with several metabolic axes, primarily with the AMP-activated protein kinase (AMPK) and NFκB signaling pathways. In particular, the anti-inflammatory effects of CEP rely on AMPK activation and NFκB inhibition. CONCLUSION In this review, the historical discovery and development of CEP are retraced, and the key mediators involved in its mode of action are presented. The past, present, and future of CEP are recapitulated. This review also suggests new opportunities to extend the clinical applications of this well-tolerated old Japanese drug.
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Rice Components with Immunomodulatory Function.
Toda, M
Journal of nutritional science and vitaminology. 2019;(Supplement):S9-S12
Abstract
Rice (Oryza sativa) is one of the most important food crops in the world, and the effect of its consumption on human health is of great concern. Evidence has accumulated that rice contains several components, such as γ-oryzanol and rice bran fibers, which modulate the immune system. In addition, rice has other immunologically beneficial characteristics. It has a low allergenic potential and is gluten-free, reducing the risk of development of food allergies and diseases related to gluten sensitivity such as coeliac disease. This review presents the recent advances in our understanding of the immunomodulatory function of rice components.
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Novel drugs and early polypharmacotherapy in status epilepticus.
Amengual-Gual, M, Sánchez Fernández, I, Wainwright, MS
Seizure. 2019;:79-88
Abstract
PURPOSE Rescue medications for status epilepticus (SE) have a relatively high rate of failure. The purpose of this review is to summarize the evidence for the efficacy of novel drugs and early polypharmacotherapy for SE. METHOD Literature review. RESULTS New drugs and treatment strategies aim to target the pathophysiology of SE in order to improve seizure control and outcomes. Changes at the synapse level during SE include a progressive decrease in synaptic GABAA receptors and increase in synaptic NMDA receptors. These changes tend to promote self-sustaining seizures. Current SE guidelines recommend a rapid stepwise treatment using benzodiazepines in monotherapy as the first-line treatment, targeting GABAA synaptic receptors. Novel treatment approaches target GABAA synaptic and extrasynaptic receptors with allopregnanolone, and NMDA receptors with ketamine. Novel rescue treatments used for SE include topiramate, brivaracetam, and perampanel, which are already marketed in epilepsy. Some available drugs not marketed for use in epilepsy have been used in the treatment of SE, and other agents are being studied for this purpose. Early polytherapy, most frequently combining a benzodiazepine with a second-line drug or an NMDA receptor antagonist, might potentially increase seizure control with relatively minor increase in side effects. Although many preclinical studies support novel drugs and early polytherapy in SE, human studies are scarce and inconclusive. Currently, evidence is lacking to recommend specific combinations of these new agents. CONCLUSIONS Novel drugs and strategies target the underlying pathophysiology of SE with the intent to improve seizure control and outcomes.
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6.
Pregnancy and Family Planning in Multiple Sclerosis.
Langer-Gould, AM
Continuum (Minneapolis, Minn.). 2019;(3):773-792
Abstract
PURPOSE OF REVIEW This article provides practical guidance on successful management of women with multiple sclerosis (MS) through pregnancy and the postpartum period. RECENT FINDINGS Recent studies indicate that most women diagnosed with MS today can have children, breast-feed, and resume beta interferons or glatiramer acetate per their preferences without incurring an increased risk of relapses during the postpartum period. More than 40% of women with mild MS do not require any treatment before conception or in the postpartum period. Women with highly active MS can now become well-controlled before, throughout, and after pregnancy via highly effective treatments. Unfortunately, pregnancy does not protect against relapses following the cessation of fingolimod or natalizumab, and some women experience severe rebound relapses during pregnancy. Accidental first-trimester exposure to teriflunomide or fingolimod increases the risk of fetal harm. SUMMARY Most women with MS can have normal pregnancies and breast-feed without incurring harm. Clinicians should avoid prescribing medications with known teratogenic potential (teriflunomide, fingolimod), known risk of severe rebound relapses (fingolimod, natalizumab), or unclear but plausible risks (dimethyl fumarate, alemtuzumab) to women of childbearing age who desire pregnancy or are not on reliable birth control. If a treatment needs to be resumed during breast-feeding, clinicians should opt for glatiramer acetate, interferon beta, natalizumab, or rituximab/ocrelizumab, as biologically plausible risks to the infant are exceedingly low.
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Management Algorithm for Interrupting Mother-to-Child Transmission of Hepatitis B Virus.
Hou, J, Cui, F, Ding, Y, Dou, X, Duan, Z, Han, G, Jia, J, Mao, Q, Li, J, Li, Z, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(10):1929-1936.e1
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Abstract
In areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Four aspects (screening, antiviral intervention during pregnancy, immunoprophylaxis, and postvaccination serologic testing) are the core components of preventing MTCT. Although the combination of passive and active immunization in newborns of hepatitis B surface antigen-positive mothers reduces MTCT of HBV, this immunoprophylaxis cannot completely eradicate MTCT. In the past decade, administration of antiviral agents to pregnant women has been shown to be safe and effective in reducing MTCT of HBV in combination with immunoprophylaxis. Aiming to achieve zero MTCT, this algorithm recommends the use of antivirals during pregnancy by women with high viral loads. Preventing MTCT is key to achieving the goal of eliminating HBV as a public health threat by 2030. Implementation and enhancement of the standardized algorithm for pregnant women with chronic HBV infection and their infants is urgently needed to prevent MTCT.
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Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases.
Li, X, Chen, Y, Tang, Y, Ding, Y, Xu, Q, Sun, L, Qian, W, Qian, G, Qin, L, Lv, H
European journal of pediatrics. 2018;(8):1279-1292
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Abstract
UNLABELLED The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017. Eligible studies were retrieved by manual review of the references. Stata 12 was used for the meta-analysis. Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices. Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group. The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant. CONCLUSION The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease. What is Known: • Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance. What is New: • This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease.
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Interleukin-1 blockade in cardiovascular diseases: a clinical update.
Buckley, LF, Abbate, A
European heart journal. 2018;(22):2063-2069
Abstract
Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine. IL-1 was implicated as a cardiodepressant factor in septic shock, and subsequent pre-clinical and clinical research has defined important roles for IL-1 in atherosclerosis, acute myocardial infarction (AMI), and heart failure (HF). IL-1 promotes the formation of the atherosclerotic plaque and facilitates its progression and complication. In a large phase III clinical trial of stable patients with prior AMI, blocking IL-1 activity using a monoclonal antibody prevented recurrent atherothrombotic cardiovascular events. IL-1 also contributes to adverse remodelling and left ventricular dysfunction after AMI, and in phase II studies, IL-1 blockade quenched the inflammatory response associated with ST-segment elevation AMI and prevented HF. In patients with established HF, IL-1 is thought to impair beta-adrenergic receptor signalling and intracellular calcium handling. Phase II studies in patients with HF show improved exercise capacity with IL-1 blockade. Thus, IL-1 blockade is poised to enter the clinical arena as an additional strategy to reduce the residual cardiovascular risk and/or address inflammatory cardiovascular conditions refractory to standard treatments. There are several IL-1 blockers available for clinical use, which differ in mechanism of action, and potentially also efficacy and safety. While IL-1 blockade is not immunosuppressive and not associated with opportunistic infections or an increased risk of cancer, fatal infections may occur more frequently while on treatment with IL-1 blockers likely due to a blunting of the inflammatory signs of infection leading to delayed presentation and diagnosis. We discuss the practical use of IL-1 blockade, including considerations for patient selection and safety monitoring.
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Vitamin D for the treatment of multiple sclerosis: a meta-analysis.
McLaughlin, L, Clarke, L, Khalilidehkordi, E, Butzkueven, H, Taylor, B, Broadley, SA
Journal of neurology. 2018;(12):2893-2905
Abstract
OBJECTIVE There is an association between latitude, relative vitamin D deficiency and risk of multiple sclerosis (MS), and an association between vitamin D and disease progression. We have performed a meta-analysis with the aim of investigating the role of therapeutic vitamin D in MS. METHODS A systematic search of databases was performed to identify clinical trials assessing vitamin D in patients with relapsing-remitting MS. Studies were selected based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3 software. RESULTS Twelve studies involving 950 patients were included in the final analysis. Studies were divided into four groups because of heterogeneity in study design. Studies were judged to be at low or unclear risk of bias, except in three studies, and this was confirmed by funnel plots. No statistically significant difference was seen for any of the outcome measures. There were non-significant trends in favour of vitamin D for all outcome measures, particularly when only placebo-controlled studies were included. Dose comparison studies showed a significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01-0.30]) and non-significant trends of increased Expanded Disability Status Scale and gadolinium-enhancing lesions for the higher-dose arms. CONCLUSION These findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. However, there is uncertainty with regard to the most appropriate dose, with high doses potentially being associated with worse outcomes. There remains the need for further well-performed randomised, dose-ranging, placebo-controlled trials of vitamin D in MS.