The role of measuring exhaled breath biomarkers in sarcoidosis: A systematic review

Introduction: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment. Objectives: We undertook a systematic review and meta-analysis, to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non-breath based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment. Methods: Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis. Results: 353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I2 of 93.4% (p<0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment. Conclusions: The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role

Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer

Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant

Quinolone antibiotics

The quinolone antibiotics arose in the early 1960s, with the first examples possessing a narrow-spectrum of activity with unfavorable pharmacokinetic properties. Over time, the development of new quinolone antibiotics has led to improved analogues with an expanded spectrum and high efficacy. Nowadays, quinolones are widely used for treating a variety of infections. Quinolones are broad-spectrum antibiotics that are active against both Gram-positive and Gram-negative bacteria, including mycobacteria, and anaerobes. They exert their actions by inhibiting bacterial nucleic acid synthesis through disrupting the enzymes topoisomerase IV and DNA gyrase, and by causing breakage of bacterial chromosomes. However, bacteria have acquired resistance to quinolones, similar to other antibacterial agents, due to the overuse of these drugs. Mechanisms contributing to quinolone resistance are mediated by chromosomal mutations and/or plasmid gene uptake that alter the topoisomerase targets, modify the quinolone, and/or reduce drug accumulation by either decreased uptake or increased efflux. This review discusses the development of this class of antibiotics in terms of potency, pharmacokinetics and toxicity, along with the resistance mechanisms which reduce the quinolones' activity against pathogens. Potential strategies for future generations of quinolone antibiotics with enhanced activity against resistant strains are suggested

Celiac disease – return to the years seventies. Eleven-month-old girl with celiac disease crisis – case report

Celiac disease is an autoimmune disorder, which occurs not only in children’s population but also among adults. Its frequency permanently rise. The reason of celiac disease in an autoimmune process, which is began by contact of gluten from diet with mucous membrane in bowel. Clinical feature of celiac disease is very different, therefore it should interest physicians of various speciality. Often the symptoms are not from alimentary canal, which suggest to make the screening test on a larger scale. In diagnostics the genetic test HLA-DQ2/-DQ8 are more popular. The new guidelines made in 2012 suggest to begin the diagnostics with the genetic test in some cases. The main treatment of celiac disease is a gluten-free diet, which is based on elimination wheat, rye, barley and oat. The occurrence of gluten in great number of groceries, makes the diet extremely challenge for parents and patients. Only diet respected for whole life makes the chance of good function and grow. The paper presents the case report of 11-month-old girl at the time of diagnosis of celiac disease, with serious diarrhoea, peripheral oedema, dehydration, and severe electrolytes disturbances, which is a rare clinical manifestation nowadays. Such situation was common in the years seventies XX century, because gluten introduction into diet of the newborn was too early.Celiakia jest chorobą autoimmunologiczną, spotykaną nie tylko w populacji dziecięcej, lecz także wśród osób dorosłych. Częstość jej występowania wykazuje stale trend wzrostowy. U podłoża celiakii leżą procesy autoimmunologiczne, zapoczątkowane przez kontakt glutenu zawartego w diecie z błoną śluzową jelit. Obraz kliniczny tej choroby cechuje ogromne zróżnicowanie, dlatego też powinna pozostawać w kręgu zainteresowań lekarzy różnych specjalności. Niejednokrotnie jej objawy dotyczą różnych układów poza przewodem pokarmowym, co powinno skłaniać do wykonywania badań przesiewowych w kierunku celiakii u coraz szerszej grupy pacjentów. Wśród badań diagnostycznych coraz większą popularnością cieszą się badania genetyczne w kierunku HLA-DQ2/-DQ8. Najnowsze kryteria diagnostyczne opracowane w 2012 roku w niektórych okolicznościach zalecają wręcz rozpoczęcie procesu diagnostycznego od wykonania badań genetycznych. Podstawą leczenia choroby trzewnej jest dieta bezglutenowa, która opiera się na eliminacji pokarmów z udziałem pszenicy, żyta, jęczmienia i owsa. Obecność glutenu w licznych produktach spożywczych jest ogromnym wyzwaniem dla rodziców i pacjentów. Tylko dieta stosowana przez całe życie umożliwia chorym dobre funkcjonowanie i rozwój. W niniejszej pracy omówiono przypadek 11-miesięcznej dziewczynki ze świeżo rozpoznaną chorobą trzewną, przebiegającą z ciężką biegunką, obrzękami obwodowymi, odwodnieniem i poważnymi zaburzeniami elektrolitowymi, stanowiący rzadką w dzisiejszych czasach manifestację kliniczną celiakii. Taki przebieg choroby stosunkowo często spotykano w latach 70. XX wieku, co było związane ze zbyt wczesnym wprowadzeniem glutenu do diety niemowląt

Increased Expression of CCL4/MIP-1β IN CD8 +

Sarcoidosis is a granulomatous disease with an increased accumulation of T cells in lungs as a result of on-site proliferation and chemotaxis induced by chemokines. It has already been demonstrated that CCL3-5 levels were increased in BAL fluid of sarcoidosis patients. To analyze the expression of CCL3-5 chemokines by T-cell subtypes (CD4+, CD8+, Th1, Th2, Tc1 or Tc2) in the lungs of sarcoidosis patients, fifteen untreated sarcoidosis patients and eighteen control subjects were enrolled in this study. CD4+and CD8+cells were isolated from BAL fluid by positive magnetic selection. The expression of CCL3-5 and other cytokines in CD4+and CD8+cells were measured by flow cytometry. The percentage of CD4+or CD8+cells expressing CCL4 were significantly higher in sarcoidosis patients (22.3% and 58.1%) compared to those seen in healthy subjects (11.1% and 16.5%, P = 0.04 and P = 0.02, respectively). In addition, the expression of CCL3, CCL4 and CCL5 was significantly elevated in CD8+cells (8.9%, 58.1% and 2.1%) compared to CD4+cells (2.1%, 22.3% and 0.7%; P = 0.04, P = 0.009 and P = 0.04, respectively), whereas CCL4 was expressed by significantly more Tc1 than Th1 cells in sarcoidosis patients (P = 0.006). Our study shows the possible role of CD8+cells and CD4+cells in recruiting T cells to the site of inflammation in sarcoidosis through the release of CCL4, either alone or together with Th1/Tc1-associated cytokines