Management Of Chronic Inflammatory Diseases Research Articles

Mediterranean Diet Favors Vitamin K Intake: A Descriptive Study in a Mediterranean Population.

The Mediterranean diet (MD) is associated with improved longevity and the prevention and management of chronic inflammatory diseases (CIDs). Vitamin K, which is present in MD core components such as leafy green vegetables, is also known as a protective factor for CIDs. Estimates of vitamin K intake in Mediterranean settings are still scarce, and the association between MD and vitamin K intake is yet to be established. This study analyzed vitamin K intake and MD adherence in the Algarve region, in Portugal. We conducted a cross-sectional study in a nonrandom sample of adults using an online questionnaire which included a validated food-frequency questionnaire and a screener for MD adherence. A total of 238 participants were recruited (68% women and 32% men). Adherence to the MD was low (11%). Only 10% of the participants had vitamin K intake below the adequate intake. Adherence to the MD was positively correlated with vitamin K intake (r = 0.463; p < 0.001) and age (r = 0.223; p < 0.001). Our findings underscore the importance of promoting adherence to the MD for optimal vitamin K intake, and future research should focus on developing effective interventions to promote this dietary pattern, particularly among younger individuals and men.

Effectiveness and safety in the management of chronic inflammatory diseases with etanercept and infliximab biosimilars in Colombian patients

ObjectiveTo determine the effectiveness and safety of infliximab and etanercept biosimilar drugs in patients diagnosed with rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and psoriasis in a specialized institution in Colombia, between 2015 and 2019. MethodsA retrospective study in patients treated with infliximab and etanercept biosimilar drugs treated in an institution specializing in the management of rheumatological diseases, to verify the clinimetric indicators of effectiveness and reports of adverse drug reactions. Clinical, sociodemographic, and pharmacological variables were identified over 5 years of follow-up. Results207 patients were identified with a mean age of 48.7±15.1 years, 61.4% were women. Of the patients, 58.0% (n=120) used infliximab and 42.0% (n=87) etanercept. It was found that 46 (22.2%) patients had adverse drug reactions. At the end of the observation period, 61.6% (n=72) of the patients with RA had achieved control of the disease (mild activity or remission), and 57.9% (n=117) had problems with access to and persistence with therapy. ConclusionIn a group of patients treated in Colombia, the biosimilars of infliximab and etanercept showed proportions of effectiveness and safety comparable to the reference drugs, but lack of adherence to treatment was quite common.

Rediscovering the Therapeutic Potential of Agarwood in the Management of Chronic Inflammatory Diseases.

The inflammatory response is a central aspect of the human immune system that acts as a defense mechanism to protect the body against infections and injuries. A dysregulated inflammatory response is a major health concern, as it can disrupt homeostasis and lead to a plethora of chronic inflammatory conditions. These chronic inflammatory diseases are one of the major causes of morbidity and mortality worldwide and the need for them to be managed in the long term has become a crucial task to alleviate symptoms and improve patients’ overall quality of life. Although various synthetic anti-inflammatory agents have been developed to date, these medications are associated with several adverse effects that have led to poor therapeutic outcomes. The hunt for novel alternatives to modulate underlying chronic inflammatory processes has unveiled nature to be a plentiful source. One such example is agarwood, which is a valuable resinous wood from the trees of Aquilaria spp. Agarwood has been widely utilized for medicinal purposes since ancient times due to its ability to relieve pain, asthmatic symptoms, and arrest vomiting. In terms of inflammation, the major constituent of agarwood, agarwood oil, has been shown to possess multiple bioactive compounds that can regulate molecular mechanisms of chronic inflammation, thereby producing a multitude of pharmacological functions for treating various inflammatory disorders. As such, agarwood oil presents great potential to be developed as a novel anti-inflammatory therapeutic to overcome the drawbacks of existing therapies and improve treatment outcomes. In this review, we have summarized the current literature on agarwood and its bioactive components and have highlighted the potential roles of agarwood oil in treating various chronic inflammatory diseases.

Combination of Vitamin C and Curcumin Safeguards Against Methotrexate-Induced Acute Liver Injury in Mice by Synergistic Antioxidant Effects.

Methotrexate (MTX), an antineoplastic and immunosuppressive drug, widely used in the treatment of different types of cancers and the management of chronic inflammatory diseases. However, its use is associated with hepatotoxicity. Vitamin C (VC) and curcumin (CUR) exhibit anti-inflammatory and antioxidant effects. Thus, we aimed to investigate the potential hepatoprotective effects of VC and CUR pretreatment alone and in combination against MTX-induced hepatotoxicity. Albino mice were randomly divided into 7 groups: the control group, which received only normal saline; MTX group; VC group, pretreated with VC (100 or 200 mg/kg/day orally) for 10 days; CUR group, pretreated with CUR (10 or 20 mg/kg/day orally); and combination group, which received VC (100 mg/kg) and CUR (10 mg/kg). MTX was administered (20 mg/kg, intraperitoneally) to all the groups on the tenth day to induce hepatotoxicity. Forty eight hours after MTX administration, the mice were anesthetized. Blood samples were collected, the liver was removed for biochemical analysis, and a part of the tissue was preserved in formalin for histopathological analysis. The results indicated that pretreatment with a combination of VC and CUR induced a more significant decrease in the serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, and lactic dehydrogenase and a significant increase in the tissue level of superoxide dismutase and glutathione; furthermore, it induced a significant decrease in malondialdehyde levels and improvement in histopathological changes in the liver tissues, confirming the potential hepatoprotective effects of the combination therapy on MTX-induced liver injury. To conclude, MTX-induced hepatotoxicity is mediated by induction of oxidative stress as evident by increased lipid peroxidation and reduction of antioxidant enzyme activity. Pretreatment with VC, CUR or their combination reduces the MTX-induced hepatotoxicity by antioxidant and anti-inflammatory effects. However, the combined effect of VC and CUR provided a synergistic hepatoprotective effect that surpasses pretreatment with CUR alone but seems to be similar to that of VC 200 mg/kg/day. Therefore, VC and CUR combination or a large dose of VC could be effective against MTX-induced hepatotoxicity. In this regard, further studies are warranted to confirm the combined hepatoprotective effect of VC and CUR against MTX-induced hepatotoxicity.

Infliximab anti-drug antibody (ADA) detection by homogenous mobility shift assay (HMSA): Potential clinical utility of neutralising (NADA) vs non-neutralising binding ADA (BADA)

Detection of ADA to therapeutic large molecule tumour necrosis factor (TNF) inhibitors has established utility in the management of chronic inflammatory diseases.1 ADA are of two types: neutralising (nADA) and binding (bADA).2 HMSA differentiates between dimer and multimer drug-ADA complexes. We describe a 52-year-old male with psoriatic arthritis who was switched to infliximab infusions every 8 weeks with good therapeutic response. However, by the third to fourth maintenance infusion he reported ‘wear-off’ at around 4–6 weeks post-infusion and this pattern persisted.

Glucocorticoid Resistance: Interference between the Glucocorticoid Receptor and the MAPK Signalling Pathways.

Endogenous glucocorticoids (GCs) are steroid hormones that signal in virtually all cell types to modulate tissue homeostasis throughout life. Also, synthetic GC derivatives (pharmacological GCs) constitute the first-line treatment in many chronic inflammatory conditions with unquestionable therapeutic benefits despite the associated adverse effects. GC actions are principally mediated through the GC receptor (GR), a ligand-dependent transcription factor. Despite the ubiquitous expression of GR, imbalances in GC signalling affect tissues differently, and with variable degrees of severity through mechanisms that are not completely deciphered. Congenital or acquired GC hypersensitivity or resistance syndromes can impact responsiveness to endogenous or pharmacological GCs, causing disease or inadequate therapeutic outcomes, respectively. Acquired GC resistance is defined as loss of efficacy or desensitization over time, and arises as a consequence of chronic inflammation, affecting around 30% of GC-treated patients. It represents an important limitation in the management of chronic inflammatory diseases and cancer, and can be due to impairment of multiple mechanisms along the GC signalling pathway. Among them, activation of the mitogen-activated protein kinases (MAPKs) and/or alterations in expression of their regulators, the dual-specific phosphatases (DUSPs), have been identified as common mechanisms of GC resistance. While many of the anti-inflammatory actions of GCs rely on GR-mediated inhibition of MAPKs and/or induction of DUSPs, the GC anti-inflammatory capacity is decreased or lost in conditions of excessive MAPK activation, contributing to disease susceptibility in tissue- and disease- specific manners. Here, we discuss potential strategies to modulate GC responsiveness, with the dual goal of overcoming GC resistance and minimizing the onset and severity of unwanted adverse effects while maintaining therapeutic potential.

Impact of calorie restriction and intermittent fasting on periodontal health.

The scientific evidence indicates that calorie restriction and intermittent fasting are among the appropriate strategies targeting factual causative factors of various inflammatory and lifestyle-related disorders. Periodontitis is a common oral inflammatory disease leading to bone loss that is associated with various systemic problems. Previous studies suggest that calorie restriction may dampen inflammation and concomitant tissue damage under inflammatory conditions, such as periodontal diseases in nonhuman primates. However, insufficient research has been carried out to assess the effects of a calorie-restricted diet on the initiation and progression of periodontal disease in humans. This review of the literature aims to describe the general concepts of calorie restriction, its clinical implications, and related therapeutic potential in controlling periodontal inflammation. The review shows that fasting regimen groups have shown lesser bone loss because of an increase in osteoprogenitor cells than non-fasting groups. Calorie restriction dampens the inflammatory response and reduces circulating inflammatory mediators like tumor necrosis factor-alpha, interleukin-6, matrix metalloproteinase-8, matrix metalloproteinase-9, and interleukin-1-beta in gingival crevicular fluid. However, the incorporation of this form of dietary intervention continues to be challenging in our current society, in which obesity is a major public concern. Calorie restriction and intermittent fasting can play a key role in the cost-effective resolution of periodontal inflammation as a primary prevention strategy for the management of chronic inflammatory diseases, including periodontal diseases.

Barriers to shared decision-making with women of reproductive age affected by a chronic inflammatory disease: a mixed-methods needs assessment of dermatologists and rheumatologists

ObjectivesThe main study objective was to identify challenges and barriers experienced by dermatologists and rheumatologists when engaging women of reproductive age in shared decision-making (SDM) related to treatment and management...

Novel cell-based therapies in inflammatory bowel diseases: the established concept, promising results.

Inflammatory bowel diseases (IBDs) are chronic and relapsing disorders that affect the quality of life in many individuals around the world. Over the past few years, the prevalence of IBDs is substantially rising which might pose a considerable social and economic burden on health systems. Progresses in the management of chronic inflammatory diseases lead to prolonged remission phase and decreased hospitalization rate. However, during treatment, many patients become refractory to conventional therapies. Recently, advanced approaches using somatic cell therapy medicinal products (SCTMPs) including immune and stem cell-based therapies have drawn many researchers’ attentions. Promising results from recent trials, alongside with the emerging market indicated that these therapeutic approaches could be an alternative and promising treatment to conventional therapies. In this review, we will discuss recent advances in cell-based therapies, which have been developed for treatment of IBDs. In addition, the global emerging market and the novel products in this field are highlighted.

The Role of Leukotrienes Inhibitors in the Management of Chronic Inflammatory Diseases.

Leukotrienes are powerful mediators of inflammation and interact with specific receptors in target cell membrane to initiate an inflammatory response. Thus, Leukotrienes (LTs) are considered to be potent mediators of inflammatory diseases including allergic rhinitis, inflammatory bowel disease and asthma. Leukotriene B4 and the series of cysteinyl leukotrienes (C4, D4, and E4) are metabolites of arachidonic acid metabolism that cause inflammation. The cysteinyl LTs are known to increase vascular permeability, bronco-constriction and mucus secretion. To review the published data for leukotriene inhibitors of plant origin and the recent patents for leukotriene inhibitors, as well as their role in the management of inflammatory diseases. Published data for leukotrienes antagonists of plant origin were searched from 1938 to 2019, without language restrictions using relevant keywords in both free text and Medical Subject Headings (MeSH terms) format. Literature and patent searches in the field of leukotriene inhibitors were carried out by using numerous scientific databases including Science Direct, PubMed, MEDLINE, Google Patents, US Patents, US Patent Applications, Abstract of Japan, German Patents, European Patents, WIPO and NAPRALERT. Finally, data from these information resources were analyzed and reported in the present study. Currently, numerous anti-histaminic medicines are available including chloropheneremine, brompheniramine, cetirizine, and clementine. Furthermore, specific leukotriene antagonists from allopathic medicines are also available including zileuton, montelukast, pranlukast and zafirlukast and are considered effective and safe medicines as compared to the first generation medicines. The present study reports leukotrienes antagonistic agents of natural products and certain recent patents that could be an alternative medicine in the management of inflammation in respiratory diseases. The present study highlights recent updates on the pharmacology and patents on leukotriene antagonists in the management of inflammation respiratory diseases.

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium.

Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.

Increased risk of developing Crohn's disease or ulcerative colitis in 17018 patients while under treatment with anti-TNFα agents, particularly etanercept, for autoimmune diseases other than inflammatory bowel disease.

Anti-TNFα agents have revolutionised management of chronic inflammatory diseases. Paradoxically, these agents might provoke development of de novo autoimmune diseases. To examine whether there is an increased risk of developing Crohn's disease (CD) and ulcerative colitis (UC) while under treatment with anti-TNFα agents for diseases other than inflammatory bowel disease (IBD) METHODS: A nationwide cohort study, based on Danish health registries, of all patients who utilised anti-TNFα agents for non-IBD indications. Included were patients, who had diseases for which anti-TNFα agent is indicated (rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, others). The observation period for development of de novo IBD started from 2004. Exposed patients had received at least one dose of anti-TNFα. In total 17018 individuals with autoimmune diseases were exposed to anti-TNFα (the vast majority had infliximab, etanercept and adalimumab), and 63308 individuals were not. Patients treated with etanercept had an increased risk of being diagnosed with CD and UC while under treatment, adjusted hazard ratio 2.0 [95% CI: 1.4-2.8] and 2.0 [95% CI: 1.5-2.8], respectively. The corresponding hazards ratios for infliximab were 1.3 [95% CI: 0.8-2.2] and 1.0 [95% CI:0.6-1.6], and for adalimumab 1.2 [95% CI: 0.8-1.8] and 0.6 [95% CI: 0.3-1.0]. Patients treated for autoimmune diseases with anti-TNFα had an increased risk of being diagnosed with CD or UC while under treatment with etanercept. The nature of this association is uncertain. This finding has relevance to clinical care and insights into common mechanisms of the pathophysiology of these diseases.

Protective effects of Cotoneaster integerrimus on in vitro and ex-vivo models of H2 O2 -induced lactate dehydrogenase activity in HCT116 cell and on lipopolysaccharide-induced inflammation in rat colon.

The present study evaluated the biological potential of methanol and aqueous extracts of the twigs and fruits of Cotoneaster integerrimus Medik. Lethality bioassays performed on Artemia salina showed that aqueous and methanol C. integerrimus extracts were non-toxic in the concentration range (0.1-20mg/ml), with a LC50≥2.5mg/ml, for each single extract. The protective effect of the extracts was assessed in vitro against hydrogen peroxide-induced lactate dehydrogenase (LDH) activity and tumor necrosis factor (TNF)α gene expression in colon cancer HCT116 cell line. All the extracts downregulated (H2 O2 )-induced TNFα gene expression, in HCT116. By contrast, it was observed that the lipopolysaccharide (LPS)-induced increase in colon nitrite, prostaglandin E2 , and 8-iso-PGF2α levels were counteracted mostly by the methanol twig extract. The present study showed protective effects induced by C. integerrimus in vitro and ex vivo, thus supporting potential application in the management of chronic inflammatory diseases. PRACTICAL APPLICATIONS: In the present study, protective effects of C. integerrimus are highlighted using in vitro and ex-vivo models of hydrogen peroxide-induced LDH activity in HCT116 cell and on LPS-induced inflammation in rat colon. Based on our results, this edible and traditionally used species could be considered as a valuable source of natural agents to combat inflammatory diseases, particularly ulcerative colitis. Results amassed herein advocates for further bioprospection of this species that could open new avenues for the development of nutraceuticals and functional foods geared toward the management of chronic inflammatory diseases.

Biosimilars in the management of chronic inflammatory diseases: The Dutch experience.

These days, the use of biosimilars for the treatment of bio-naive patients is well established. However, the transition of patients being treated with a bio-originator to its biosimilar is still a topic of discussion. The main issue is which approach to use when initiating the non-medical transition. The first real-world examples contain both mandatory and non-mandatory approaches, resulting in a variety of acceptance and discontinuation rates. At this moment a non-mandatory approach, based on shared decision making, is preferred by international guidelines and the Task Force on the Use of Biosimilars to Treat Rheumatological Diseases. However, clear definitions of mandatory and non-mandatory are lacking, as a result of which these terms may be wrongly used in some studies. This article aims to provide an overview of transition approaches used in the Netherlands, and how the approach used relates to acceptance and discontinuation rates of the biosimilar.

388. Characteristics and outcomes of prospectively reported pregnancies exposed to certolizumab pegol from a safety database

Introduction Anti-tumour necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNFs are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF approved for treatment of rheumatic diseases and/or Crohn’s disease, has no active placental transfer. Objective/Hypothesis To provide information on pregnancy outcomes in women receiving CZP, especially those with early pregnancy exposure. Methods Prospective and retrospective data on maternal CZP exposure, including timing and duration, outcomes, comorbidities, and major malformations were extracted from the UCB Pharma safety database through 6 March 2017. This analysis was limited to prospective reports to avoid bias associated with retrospective submissions. Numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained. Results From a total of 1541 maternal CZP-exposed pregnancies, 1137 were reported prospectively, of which 528 pregnancies (including 10 twins) had 538 known outcomes: 459 live births (85%), 47 miscarriages (9%), 27 elective abortions (5%), and 5 stillbirths (1%). Of the 459 live births, 8 (2%) cases of major congenital malformations were reported. Of the 528 prospective pregnancies with known outcomes, 436 (83%) were exposed to CZP during the 1st trimester, when most organogenesis occurs; 201 (45%) pregnancies were exposed during all 3 trimesters. Discussion This analysis represents the largest published cohort of pregnant women exposed to an anti-TNF for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a malformative effect of CZP compared to the EU general population (2–3%), nor an increased risk of foetal death. These data are reassuring for women of childbearing age considering treatment with CZP, however, the ongoing collection of post-marketing surveillance data, including the ongoing MotherToBaby study from the Organization of Teratology Information Specialists, will provide further important information.

Therapeutic drug monitoring of tumour necrosis factor inhibitors in the management of chronic inflammatory diseases.

Tumour necrosis factor inhibitor therapy has drastically changed the management of chronic inflammatory diseases. Some important drawbacks that can cause loss of response during treatment with these drugs are related to their large individual variability, the disease burden and the formation of antidrug antibodies that increase its clearance. Therapeutic drug monitoring of these drugs is not yet recommended by all scientific societies, and if so, only in patients with inflammatory symptoms. Proactive therapeutic drug monitoring represents a new strategy with many potential clinical benefits, including the prevention of immunogenicity, a reduction in the need for rescue therapy and greater durability of tumour necrosis factor inhibitor treatment. The review is based on a systematic search of the literature for controlled trials, systematic reviews, experimental studies, guideline papers and cohort studies addressing the best practice in tumour necrosis factor inhibitor therapeutic drug monitoring. Although there is ample evidence supporting the use of therapeutic drug monitoring in clinical practice to achieve better outcomes, some challenges have been detected. Many studies are focused on finding solutions for the lack of standardization of analytical methods to measure tumour necrosis factor inhibitor and antidrug antibodies concentrations. Other challenges are development of effective cost-saving proactive algorithms to identify optimal drug concentrations and the research on the role of antidrug antibodies, especially in the management and prevention of loss of response. Therapeutic drug monitoring of tumour necrosis factor inhibitor offers a rational approach to the optimization of the treatment of chronic inflammatory disease. Although prospective controlled trials yield little conclusive evidence of its benefits, there is growing acceptance of its value in clinical practice.

New probiotic strains for inflammatory bowel disease management identified by combining in vitro and in vivo approaches.

Alterations in the gut microbiota composition play a key role in the development of chronic diseases such as inflammatory bowel disease (IBD). The potential use of probiotics therefore gained attention, although outcomes were sometimes conflicting and results largely strain-dependent. The present study aimed to identify new probiotic strains that have a high potential for the management of this type of pathologies. Strains were selected from a large collection by combining different in vitro and in vivo approaches, addressing both anti-inflammatory potential and ability to improve the gut barrier function. We identified six strains with an interesting anti-inflammatory profile on peripheral blood mononuclear cells and with the ability to restore the gut barrier using a gut permeability model based on Caco-2 cells sensitized with hydrogen peroxide. The in vivo evaluation in two 2,4,6-trinitrobenzene sulfonic acid-induced murine models of colitis highlighted that some of the strains exhibited beneficial activities against acute colitis while others improved chronic colitis. Bifidobacterium bifidum PI22, the strain that exhibited the most protective capacities against acute colitis was only slightly efficacious against chronic colitis, while Bifidobacterium lactis LA804 which was less efficacious in the acute model was the most protective against chronic colitis. Lactobacillus helveticus PI5 was not anti-inflammatory in vitro but the best in strengthening the epithelial barrier and as such able to significantly dampen murine acute colitis. Interestingly, Lactobacillus salivarius LA307 protected mice significantly against both types of colitis. This work provides crucial clues for selecting the best strains for more efficacious therapeutic approaches in the management of chronic inflammatory diseases. The strategy employed allowed us to identify four strains with different characteristics and a high potential for the management of inflammatory diseases, such as IBD.

Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralizing Potency and Multifunctionality, Generated for Therapeutic Development.

The management of chronic inflammatory diseases, such as inflammatory bowel disease, psoriasis, and rheumatoid arthritis has significantly improved over the last decade with the clinical availability of anti-TNF-α biologics. Despite this undoubted treatment success, a combination of acquired resistance together with an increased risk of systemic complications, means that a significant number of patients either fail to find a suitable targeted therapy or frustratingly discover that an approach that did work is no longer efficacious. Here, we report the isolation and characterization of a new class of super-neutralizing anti-TNF-α biologics formats, the building blocks of which were originally derived as variable new antigen receptor (VNAR) domains from an immunized nurse shark. These parental small, stable VNAR monomers recognize and neutralize tumor necrosis factor (TNF)-α, in cell-based assays, at nanomolar concentrations. However, the simple, single-chain molecular architecture of VNARs allows for easy and multiple reformatting options. Through reformatting, we achieved a 50,000-fold enhancement in in vitro efficacy with super-neutralizing fusion proteins able to block TNF-α induced cytotoxicity in the 2–5 pM range while retaining other functionality through the addition of fusion proteins known to extend serum half-life in vivo. In an in vitro intestinal epithelial barrier dysfunction efficacy model, the lead VNAR domains, restored barrier function and prevented paracellular flux with comparable efficacy to adalimumab (Humira®). In addition, all multivalent VNAR constructs restored trans-epithelial electrical resistance (TEER) to approximately 94% of the untreated control. Reformatted VNAR domains should be considered as a new class of biologic agents for the treatment of hTNF-α driven diseases; either used systemically with appropriate half-life extension or alternatively where site-specific delivery of small and stable neutralizers may provide improvements to current therapy options.

Anti-arthritic potential of marine macroalgae Turbinaria ornata in Complete Freund’s Adjuvant induced rats

T. ornata a macroalgae rich in bioactive molecules possess various biological activities. Herein, the aim of the study is to evaluate the aqueous extract and the sulphated polysaccharide isolated from T. ornata for its anti-arthritic potential in Complete Freund’s Adjuvant (CFA) induced arthritis in rats. Anti-arthritic potential of aqueous T. ornata (ATO) and T. ornata sulphated polysaccharide (TSP) was evidenced by the significant reduction in paw volume and arthritic score. Inflammatory and antioxidant markers were found to be restored in the drug treated groups which was found to be in line with dexamethasone a standard anti-inflammatory drug. The histopathological and radiological examination adds on the support to the above findings confirming the anti-arthritic potential of ATO and TSP. It is interesting to note that the sulphated polysaccharide inhibits inflammation and bone damage at very low dose itself. Hence, TSP could be considered as a better candidate in the management of chronic inflammatory diseases like rheumatoid arthritis.

Infective endocarditis following tumor necrosis factor-\u03b1 antagonist therapy for management of psoriatic erythroderma: a case report

BackgroundThe introduction of biological agents, such as infliximab, which act against tumor necrosis factor-α was a major advance for the treatment of an increasing number of chronic diseases. Tumor necrosis factor-α antagonists represent a major therapeutic advance for the management of chronic inflammatory diseases, such as psoriasis. Previous studies have reported that the use of tumor necrosis factor-α antagonists increased the risk of opportunistic infections and reactivation of latent bacterial infections. Cardiac involvement, such as infective endocarditis, is very rare in the literature.Case presentationA 77-year-old Asian man with a 10-year history of psoriatic erythroderma was referred due to high fever and general malaise. He was treated with Predonine (prednisolone) and infliximab. After treatment, cardiac echography showed mitral valve vegetation and brain magnetic resonance imaging indicated multiple fresh infarctions. He died from large brain infarction in October 2013. An autopsy showed fresh thrombosis in his left middle cerebral artery, mitral valve vegetations, and septic micro-embolisms in multiple organs.ConclusionsLethal bacterial endocarditis was revealed after administration of tumor necrosis factor-α inhibitor, infliximab, for the treatment of psoriatic erythroderma. An autopsy showed vegetation in his mitral valve and brain infarction with fresh purulent embolism in his left middle cerebral artery and septic micro-embolisms.