scholarly journals Actualización en terapia biológica para psoriasis y artritis psoriática (parte I): moléculas pequeñas, inhibidores de JAK y agentes biológicos (inhibidores IL-17)

2020 ◽  
Vol 2 (2) ◽  
pp. 113-125
Author(s):  
Rodrigo Flores ◽  
Raúl de la Fuente ◽  
Francisca Bozán ◽  
Karen Vergara ◽  
Fernando Valenzuela

Psoriasis is a chronic, inflammatory skin disease associated with cardiovascular comorbidities, metabolic syndrome, neoplasms, psychiatric impairment, and arthritis, among others, which affect patients’ quality of life, as well as their life expectancy. Even though it is a multifactorial process of unknown causes, its relationship to class 1 HLA alleles and their polymorphisms has been described. Its physiopathology involves a dysregulation of the systemic inflammatory response —mediated by T Helper lymphocytes, dermal cells, cytokines, and interleukins—, as well as their interactions with keratinocytes and synovial cells. This triggers differentiation of lymphocytes towards a Th 17 phenotype, which activates inflammatory processes mediated mainly by interleukin 17 (IL-17), with the subsequent proliferation of keratinocytes and inflammatory and angiogenic mediators, resulting in the typical cutaneous and osteoarticular clinical features. Biological agents are recombinant proteins produced in different cell lines aimed at interrupting inflammatory pathways in psoriasis and psoriatic arthritis, specifically, immune or genetic mediators involved in the progression of these diseases, ultimately targeting the IL-23 / IL-17 axis. This review aims to discuss the most recent literature regarding the use of small molecules, JAK inhibitors, and biological agents (IL-17 inhibitors) in the treatment of psoriasis and psoriatic arthritis, mainly referring to their efficacy and safety. Using these molecules means a fundamental change in the approach to patients with psoriasis and psoriatic arthritis. As a specific mediator-targeted therapy, it enhances effectiveness, and at the same time, reduces the associated adverse effects. Therefore, it is essential to know how they work from a physiopathological point of view, as well as assessing their effectiveness in humans through randomized clinical trials. Current knowledge allows us to conclude that despite biological agents being the best treatment option in psoriasis as well as in psoriatic arthritis, comparative studies —among drugs of the same group and groups— are still required. Besides, their high price is another problem to solve before they can be massively used in these patients.

2020 ◽  
Vol 16 ◽  
Author(s):  
Daniel Dejcman ◽  
Valentin Sebastian Schäfer ◽  
Dirk Skowasch ◽  
Carmen Pizarro ◽  
Andreas Krause ◽  
...  

: Interstitial lung disease (ILD) is the most common form of pulmonary impairment in patients with rheumatoid arthritis (RA). However, patients with RA or other arthritic diseases such as psoriatic arthritis (PsA) or peripheral spondyloarthritis (pSpA) may develop several other pulmonary diseases such as chronic obstructive lung disease (COPD) with a higher risk than patients without arthritis. The article at hand aims at summarizing the current knowledge on the prevalence of pulmonary diseases in the above-mentioned forms of arthritis, the challenges for prevalence studies and detecting pulmonary diseases in patients with arthritis as well as possible treatment options. Dyspnea, cough or other pulmonary symptoms or findings in arthritis patients should prompt gradual diagnostic procedures considering pulmonary manifestations as a major cluster of differential diagnosis. Considering its poor prognosis and morbidity burden, RA-ILD needs to be ruled out. Treatment of manifestations often lacks solid evidencebased guidelines and referrals to specialized centers are often necessary.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1382
Author(s):  
Mina Martini ◽  
Iolanda Altomonte ◽  
Domenico Tricò ◽  
Riccardo Lapenta ◽  
Federica Salari

The increase of knowledge on the composition of donkey milk has revealed marked similarities to human milk, which led to a growing number of investigations focused on testing the potential effects of donkey milk in vitro and in vivo. This paper examines the scientific evidence regarding the beneficial effects of donkey milk on human health. Most clinical studies report a tolerability of donkey milk in 82.6–98.5% of infants with cow milk protein allergies. The average protein content of donkey milk is about 18 g/L. Caseins, which are main allergenic components of milk, are less represented compared to cow milk (56% of the total protein in donkey vs. 80% in cow milk). Donkey milk is well accepted by children due to its high concentration of lactose (about 60 g/L). Immunomodulatory properties have been reported in one study in humans and in several animal models. Donkey milk also seems to modulate the intestinal microbiota, enhance antioxidant defense mechanisms and detoxifying enzymes activities, reduce hyperglycemia and normalize dyslipidemia. Donkey milk has lower calorie and fat content compared with other milks used in human nutrition (fat ranges from 0.20% to 1.7%) and a more favourable fatty acid profile, being low in saturated fatty acids (3.02 g/L) and high in alpha-linolenic acid (about 7.25 g/100 g of fat). Until now, the beneficial properties of donkey milk have been mostly related to whey proteins, among which β-lactoglobulin is the most represented (6.06 g/L), followed by α-lactalbumin (about 2 g/L) and lysozyme (1.07 g/L). So far, the health functionality of donkey milk has been tested almost exclusively on animal models. Furthermore, in vitro studies have described inhibitory action against bacteria, viruses, and fungi. From the literature review emerges the need for new randomized clinical trials on humans to provide stronger evidence of the potential beneficial health effects of donkey milk, which could lead to new applications as an adjuvant in the treatment of cardiometabolic diseases, malnutrition, and aging.


Author(s):  
Alessandro Tufano ◽  
Riccardo Accorsi ◽  
Andrea Gallo ◽  
Riccardo Manzini

"Contract catering industry is concerned with the production of ready-to-eat meals for schools, hospitals and private companies. The structure of this market is highly competitive, and customers are rarely willing to pay a high price for this catering service. A single production sites may be demanded up to 10.000 meals per day and these operations can hardly be managed via rule of thumbs without any quantitative decision support tool. This situation is common at several stages of a food supply chain and the methodologies presented in this paper are addressed to any food batch production system with similar complexity and trade-offs. This paper proposes an original KPI dashboard, designed to control costs, time and quality efficiency and helping managers to identify criticalities. Special emphasis is given on food safety control which is the management’s main concern and must be carefully monitored in each stage of the production. To calculate the value of KPIs a Montecarlo simulation approach is used to deal with production complexity and uncertainty. A case study showcases the potential of simulation in this complex industrial field. The case study illustrates an application of the methodology on an Italian company suffering local recipe contamination. The company aims at defining the best standard for production, identifying cycles being sustainable from an economic and environmental point of view."


2013 ◽  
Vol 40 (8) ◽  
pp. 1434-1437 ◽  
Author(s):  
April W. Armstrong ◽  
Joel M. Gelfand ◽  
Wolf-Henning Boehncke ◽  
Ehrin J. Armstrong

At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Stockholm, Sweden, several GRAPPA members led a panel discussion on cardiovascular (CV) comorbidities of psoriasis and psoriatic arthritis (PsA). The panelists discussed the role of insulin resistance in the pathophysiology of psoriasis, the possible effect of tumor necrosis factor inhibitors on CV comorbidities, and the effect of 12/23 monoclonal antibodies on CV outcomes. The panelists also addressed how lessons from CV comorbidity research could be applied to other areas of comorbidity research in psoriasis and PsA and identified future research directions in this area.


2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.


Toxics ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 222
Author(s):  
Aneta Markova ◽  
Michaela Hympanova ◽  
Marek Matula ◽  
Lukas Prchal ◽  
Radek Sleha ◽  
...  

Benzoxonium chloride belongs to the group of quaternary ammonium salts, which have been widely used for decades as disinfectants because of their high efficacy, low toxicity, and thermal stability. In this study, we have prepared the C10-C18 set of benzoxonium-like salts to evaluate the effect of their chemical and biological decontamination capabilities. In particular, biocidal activity against a panel of bacterial strains including Staphylococcus aureus in biofilm form was screened. In addition, the most promising compounds were successfully tested against Francisella tularensis as a representative of potential biological warfare agents. From a point of view of chemical warfare protection, the efficiency of BOC-like compounds to degrade the organophosphate simulant fenitrothion was examined. Notwithstanding that no single compound with universal effectiveness was identified, a mixture of only two compounds from this group would be able to satisfactorily cover the proposed decontamination spectrum. In addition, the compounds were evaluated for their cytotoxicity as a basic safety parameter for potential use in practice. In summary, the dual effect on chemical and biological agents of benzoxonium-like salts offer attractive potential as active components of decontamination mixtures in the case of a terrorist threat or chemical or biological accidents.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4942
Author(s):  
Maria Grazia Ronga ◽  
Marco Cavallone ◽  
Annalisa Patriarca ◽  
Amelia Maia Leite ◽  
Pierre Loap ◽  
...  

The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.


2021 ◽  
pp. jrheum.210349
Author(s):  
George E. Fragoulis ◽  
Elena Nikiphorou ◽  
Iain B. McInnes ◽  
Stefan Siebert

Psoriatic arthritis (PsA) affects about 0.8% of the general population. Together with psoriasis is termed psoriatic disease. Comorbidities play an important role in the clinical expression and treatment of psoriatic disease. Ageing adds another level of complexity, partly because age directly accrues increasing risk of comorbidities, but also due to its complex interactions with several factors such as depression and social determinants. Ageing seems to have a "paradoxical association" with cardiovascular comorbidities for which the relative risk is more pronounced in younger patients with psoriatic disease and also to affect treatment decisions and response in patients with psoriatic disease. Finally, there is convincing evidence that there are clinical, genetic and histopathological differences between young- and late- onset PsA and psoriasis. Herein, we review the effect of age in patients with psoriatic disease, with a focus on PsA, highlighting the need to consider this feature in routine clinical practice as well as in the research domain.


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