Pragmatična dijagnostika malih disajnih puteva

Small airways have an inner diameter of 2 mm or less. They are characterized by lack of cartilage in their wall, sudden increase in total cross-section area, and by an abrupt switch from turbulent to laminar air flow, all of which cause minimal airflow resistance in healthy persons. Conversely, in patients with obstructive lung diseases, small airways are the primary site of airflow limitation. Small airways tests are numerous and they vary considerably in their diagnostic significance, complexity and availability. Currently, none of the existing tests represents the diagnostic “gold standard”, and none offer precise cut-off values to distinguish between small airway disease, healthy persons, and individuals with concomitant pathophysiological disorder. Negative results of these tests have significant negative predictive values, i.e. ruling out small airways as the cause of the clinical issue, while positive results of these tests should always be crosschecked to confirm the presence of small airways disorder by other methods. Results of small airways diagnostic tests do not mean much as isolated findings unless they are combined with other diagnostic methods (history, clinical findings, imaging, etc.) to elucidate any specific clinical case. On the other hand, if results are strongly suggestive of the presence of a small airways disease, that can have significant clinical implications, such as application of fine particle aerosols. The suggested diagnostic algorithm is based primarily on tests availability. It should not be implemented uncritically, but rather adapted to the healthcare system at hand.Mali disajni putevi se definišu kao disajni putevi promera 2 mm ili manjeg. Odlikuju se odsustvom hrskavice u svom zidu, naglim povećanjem ukupnog poprečnog preseka i prelaskom turbulentnog toka vazduha u laminarni, tako da je kod zdravih ljudi u njima minimalan otpor protoku vazduha. Za razliku od toga, u opstruktivnim bolestima pluća mali disajni putevi predstavljaju glavno mesto ograničenja protoka vazduha. Testovi koji se koriste u dijagnostici promena u malim disajnim putevima su brojni i oni značajno variraju u svojoj dijagnostičkoj vrednosti, složenosti i dostupnosti. Trenutno ne postoji test koji predstavlja zlatni standard u dijagnostici bolesti malih disajnih puteva, niti test sa jasnim graničnim vrednostima pomoću kojih bi se mogle razlikovati osobe sa poremećajem funkcije malih disajnih puteva i „zdrave“ osobe, odnosno osobe s pridruženim patofiziološkim poremećajima. Negativni rezultati ovih testova mogu sa velikom sigurnošću ukazati na to da mali disajni putevi ne igraju ulogu u datom kliničkom problemu, dok bi pozitivne rezultate pojedinačnih testova trebalo uvek proveriti različitim metodama da bi se potvrdilo prisustvo poremećaja u malim disajnim putevima. Rezultati dijagnostičkih testova za male disajne puteve sami po sebi ne znače mnogo ako se ne kombinuju s drugim metodama i ne uklope u dati klinički problem (anamnestički podaci, klinička slika, vizualizacioni metodi i drugo). S druge strane, ako rezultati ovih testova definitivno ukažu na problem u malim disajnim putevima, to može imati značajne kliničke implikacije, na primer, primenu aerosola sa finim česticama u lečenju. Predloženi algoritam kao osnovni kriterijum uzima dostupnost dijagnostičkih testova. Ovaj algoritam ne treba smatrati definitivnim rešenjem, već ga uvek treba prilagoditi postojećem zdravstvenom sistemu

Transcription Factor Activation during Signal-induced Apoptosis of Immature CD4+CD8+ Thymocytes: A Protective Role of c-Fos

Many signals that cause apoptotic cell death operate by inducing transcription and translation of other (presumably death effector) mediators, and it is well established that stimulus-induced apoptosis can often be blocked by inhibiting transcription and translation. Transcriptional regulation of apoptosis, however, is incompletely understood. To gain insight into nuclear events associated with signal-induced apoptosis during T cell development, we studied signal-induced apoptosis of ex vivo isolated immature CD8+4+ double-positive (DP) thymocytes. Stimuli utilizing the T cell receptor (TCR) signaling pathway or its parts (an αCD3/TCR monoclonal antibody, a Ca2+ ionophore, or a protein kinase C-activating phorbol ester) or a stimulus that antagonizes TCR signaling and apoptosis in T cell hybridoma (forskolin, a cyclic AMP-signaling activator) resulted in massive apoptosis of DP thymocytes. At the same time, these stimuli induced qualitatively similar but quantitatively unique patterns of inducible transcription factors (TFs) NF-κB/RelA-p50, AP-1 (Fos-Jun), and NUR-77. We focused our attention on the role of AP-1 (Fos-Jun) complex, which was strongly induced by all of the above stimuli and thus was a candidate for a proapoptotic TF. However, we found that AP-1/c-Fos induction was vital in prolonging DP thymocyte life, as judged by increased spontaneous and induced death of DP cells in Fos−/− mice. In direct support of this hypothesis, experiments with antisense oligonucleotides demonstrated that c-Fos plays an essential role in protecting normal DP thymocytes from Ca2+- and cAMP-induced apoptosis but not from TCR-mediated death. Together, these results demonstrate a physiological role for c-Fos in maintaining longevity of DP thymocytes

The first outbreak of brucellosis in the region of Šabac

Background/Aim. In Serbia brucellosis is a primary disease of the animals in the southern parts of the country. The aim of this study was to describe the first outbreak of human and animal brucellosis in the region of Šabac, Serbia. Methods. An epidemiological investigation was conducted to identify a source of outbreak and the ways of transmission of brucellosis infection in human population. A descriptive and analytical epidemiological methods (cohort study) were used. Additional data included monthly reports of the infectious diseases from the Institutes of Public Health and data from the Veterinary Specialistic Institute in Šabac. The serological tests for human brucellosis cases were performed in the Laboratory of the Military Medical Academy; laboratory confirmation of animal brucellosis cases was obtained from the reference laboratory of the Faculty of Veterinary Medicine, Belgrade. Results. Twelve cases of brucellosis were recorded from February 9 to September 1, 2004. Total attack rate was 8.1% (7.5% of males, 14.2% of females). Relative risk (RR) of milk consumption was 8.9 (95% confidence interval: 1.63-13.38), and RR for direct contact with animals was 14 (95% confidence interval: 3.5-55.6). The prevalence of seropositive animals in 33 villages of the Mačva region accounted for 0.8%. Regarding animal species, sheep were predominant - 264 (95.7%). Out of a total number of seropositive animals, ELISA results were positive in 228 (88.7%) of them. Conclusion. As contact epidemics generally last longer, it is probable that the implemented measures of outbreak control did reduce the length of their duration

Sex Steroids Induce Apoptosis of CD8⁺CD4⁺ Double-Positive Thymocytes via TNF-α

T cell production by the thymus, thymic size, cellularity and output all decrease drastically after puberty. Among the candidates that may mediate this decrease are the sex steroids: Hypersecretion or pharmacological administration of these hormones has long been known to induce thymic hypocellularity, and their depletion yields thymic hypercellularity. Here we show that a typical sex steroid, testosterone, specifically targets CD8⁺CD4⁺ double-positive (DP) thymocytes for apoptosis via TNF-α Anti-TNF-α monoclonal antibodies abrogated testosterone-induced DP apoptosis, and TNF-a⁻^/⁻DP thymocytes were largely resistant to testosterone-mediated apoptosis in vivo. Testosterone accomplishes this effect by up-regulating TNF-α production and by simultaneously sensitizing DP thymocytes to TNF-α. Thus, TNF-α is the critical mediator of sex steroid-induced apoptosis in thymocytes, and its manipulation should provide a point of intervention to modulate T cell production in sex hormone disorders

Quality and autochthonous microbiota of dry-cured sheep ham from western Balkans

Dry-cured sheep ham is a traditional product of Western Balkans. It is prepared by dry curing specially treated whole sheep carcasses which are smoked for a short time and spontaneously fermented in air under uncontrolled conditions. Lactic acid bacteria (LAB) play a key role in defining the quality and organoleptic characteristics of dry-cured sheep ham. The aim of this research was to investigate the chemical parameters of drycured sheep ham quality as well as the isolation and preliminary categorization of LAB. To this end, samples of dry-cured sheep ham were obtained from nine sheep of average age of about five years, from three households from the geographical area Sjenica (Western Serbia). Physicochemical analysis has determined the content of water, protein, fat, mineral matter, water activity and pH values in the product. Phenotypic characterization of LAB isolated from dry-cured sheep ham was based on the general morphology of the cell, physiological tests and sugar fermentation patterns of LAB isolates. 124 isolates of LAB were preliminary identified as Lactobacillus curvatus , Lactobacillus sakei and Enterococcus faecium . Chemical analysis confirmed a harmonious relationship between the quality parameters of dry-cured sheep ham.Author's versio

Registri bolesnika s hroničnim opstruktivnim bolestima pluća – zašto su važni?

COPD is most probably not just a single disease, but a syndrome made up of numerous individual overlapping diseases. The concept of phenotyping COPD patients would not be feasible without major population-based studies and patient registries. The aim of setting up a COPD registry has been defined as the need to establish the disease prevalence, phenotype incidence, clinical features, co-morbidities, treatment specificities, together with monitoring of the disease’s natural course and its outcome on a large sample of patients. In Serbia, an online registry of COPD patients has been operational since 2016, and the recent insight (before the manuscript’s submission) shows over 4,200 entries. Analysis of the population of patients entered shows that an average patient is male (63%), smoker or ex-smoker (90.48%), over 60 years of age (82.01%). Pulmonary function analysis shows that the majority of enrolled patients (82%) have moderate to severe obstruction, with an average FEV1 of 52.82% of the predicted value, while 45% of patients have FEV1 value below 50% of the predicted value. The Charlson Comorbidity Index shows that half of the patients (49.97%) have one comorbidity. Most common comorbidities are arterial hypertension, diabetes mellitus, liver disease, congestive heart failure, and coronary ischemic disease. Comorbidities such as osteoporosis, depression, and anxiety have been reported very rarely. The phenotype analysis showed equal shares of two predominant groups: non-exacerbators (51.12%), and exacerbators (48.88%) within which there are groups of patients with pulmonary emphysema (34.35%) and patients with chronic bronchitis (14.53%). The data indicate that strategy for COPD treatment in our environment is changing towards adoption of modern recommendations and guidelines for treatment of this disease. The data enable a comprehensive insight into the disease and drawing up of feasible treatment strategies that give us hope for success.HOBP verovatno nije samo jedna bolest već sindrom sačinjen od brojnih, pojedinačnih bolesti koje se preklapaju. Koncept fenotipizacije pacijenata sa HOBP-om ne bi bio moguć bez velikih, populacionih studija i registara pacijenata. Cilj kreiranja registara pacijenata sa HOBP-om je definisan potrebom da se na velikom uzorku utvrdi prevalenca bolesti, učestalost fenotipova, kliničke karakteristike, komorbiditeti, specifičnosti terapije, uz praćenje prirodnog toka bolesti do njenog ishoda. U Srbiji od 2016. godine postoji elektronski (onlajn) registar pacijenata sa hroničnom opstruktivnom bolešću pluća, koji je u momentu pisanja ovog teksta brojao više od 4200 unosa. Analiza populacije pacijenta unetih u registar HOBP-a ukazuje na to da je prosečan pacijent muškarac (63% pacijenata), pušač ili bivši pušač (ukupno 90,48% pacijenata), stariji od 60 godina (82,01% pacijenata). Analiza plućne funkcije pokazuje da većina pacijenata (82%) ima umerenu i srednje tešku opstrukciju, sa prosečnom vrednošću FEV1 od 52,82% predviđene vrednosti, dok 45% pacijenata ima vrednost FEV1 nižu od 50% predviđene vrednosti. Čarlsonov indeks komorbiditeta je pokazao da polovina pacijenata (49,97%) ima jedan komorbiditet. Najučestaliji komorbiditeti su: arterijska hipertenzija, dijabetes melitus, bolesti jetre, kongestivna srčana slabost i koronarna ishemijska bolest. Komorbiditeti poput osteoporoze, depresije i anksioznosti su vrlo retko prijavljivani. U pogledu fenotipova zapaža se da je učestalost dve dominirajuće grupe bolesnika izjednačena: grupa neegzacerbatora (51,12%), zatim egzacerbatora (48,88%), u okviru kojih se nalaze grupe pacijenata sa emfizemom pluća sa 34,35% zastupljenosti i pacijenata sa hroničnim bronhitisom sa 14,53% zastupljenosti. Podaci ukazuju na to da se strategija lečenja HOBP-a u našoj sredini ipak menja, uz usvajanje savremenih preporuka i smernica za lečenje ove bolesti. Ovakvi podaci nam omogućavaju da sagledamo bolest iz svih uglova i kreiramo realno izvodljive strategije lečenja koje daju nadu za postizanje uspeha

Tobacco control in Serbia – what control?

Aim and Objective Tobacco smoking is the world-wide health problem, with about billion smokers worldwide, over 6 million deaths caused by smoking only in 2016 and estimated 100 million deaths caused by smoking since end of WW II. In Serbia, smoking is also widespread poor habit. Over 34% of adult population actively smokes and more than half of overall population is exposed to tobacco smoke. Methods Estimated cigarette consumption of cigarettes in Serbia is 2924 per year, which places it on second place in Europe. About 58/100 smokers per year die from cardiovascular event and 17/100 from malignancy. Public awareness about health problems caused by smoking is very high, with 87% of active smokers agree that smoking is cause of serious health. But, majority of them is still reluctant to accept smoking banning from public places, such as public sport places, pools and even children playgrounds. Findings Tobacco control in Serbia is regulated by Law on population protection from tobacco smoke. National office for tobacco prevention, which works in the Institute for Public Health of Serbia is responsible to lead and coordinate smoking cessation and prevention activities in Serbia. Several Departments for smoking cessation exist in major health institutions in Serbia, and occasionally major public campaigns are launched national wide. Unfortunately, the Law is not strictly enforced, or not enforced at all, and itself has several concessions to restaurant and bar owners. Inefficient implementation of the Law together with general poor attitude of population in upholding the regulations and lowest prices of cigarettes in Europe are cause of above mentioned data. Conclusion Stricter implementation of regulation, sharp increase in taxes on tobacco products and persistent activities on rising public awareness of health problems caused by smoking are some of the measures that could, at least, reduce the consumption of tobacco products in Serbia

Biochemical and Kinetic Characterization of the Glucocorticoid-Induced Apoptosis of Immature CD4+CD8+ Thymocytes.

We characterized kinetic and biochemical changes during glucocorticoid (GC)-induced apoptosis of immature CD8+CD4+ double-positive (DP) thymocytes. A GC analog dexamethasone (Dex) induced rapid apoptotic commitment and a transient up-regulation of the NF-kappaB/RelA-p50-binding activity in DP cells. This required an early activation of proteasome, as judged by the ability of a specific proteasomal inhibitor, lactacystine, to delay apoptosis and to suppress Dex-dependent NF-kappaB activation. Dex-induced apoptotic commitment was preceded by the rapid (3 h) cleavage of both a typical caspase substrate, poly(ADP-ribose) polymerase (PARP), and of nuclear transcription factors AP-1, NF-kappaB p50-p50 and NUR-77. By contrast, phorbol myristate acetate (PMA) and/or ionomycin-induced apoptosis had much slower kinetics, were preceded by an early increase of NF-kappaB/RelA-p50, AP-1 and NUR-77 activities, and were insensitive to proteasome inhibition. Both the transgenic Bcl-2 and zVAD-fmk, an inhibitor of caspases, affected all features of Dex-induced apoptosis in a similar fashion, by inhibiting cell death and PARP cleavage, and by stabilizing AP-1, NF-kappaB p50-p50 and NUR-77 levels. Furthermore, Bcl-2 prevented Dex-induced RelA-p50 activation. However, a higher gene dosage of the transgenic Bcl-2 was required for protection against Dex, compared to the PMA and/or ionomycin-induced apoptosis. These findings highlight the unique mechanistic features of GC-induced apoptosis

Performance comparison of modified poly(vinyl alcohol) based membranes in alkaline fuel cells

There are several problems which are holding back the use of fuel cells. The utilization of fuel cells depends on the start-up costs which are very high due to the use of expensive materials for their construction. In that respect, we describe a cost-effective alkaline fuel cell (AFC) that uses solid, polymer based, membrane instead of conventionaly used, highly concentrated, corrosive, liquid alkaline electrolyte. This approach to AFC is potentially the basis of a simple, low-cost system, that can solve one of the problems of the highly-efficient and environment-friendly AFC. The focus of this paper are low cost composite alkaline membranes, based on poly(vinyl alcohol) (PVA). The PVA matrix is made by solution cast method and gamma irradiation crosslinking. Three different types of membranes are obtained in this manner plain PVA membrane, PVA membrane cross-linked using gamma irradiation (gamma-PVA) and composite PVA membrane doped with Mo (PVA-Mo). These membranes are immersed in the alkaline solution and investigated as anion exchange membranes. The performance of the solid alkaline fuel cells (SAFCs) containing these PVA membranes has been studied under hydrogen and oxygen gas flow on the Pt/C catalyst. Both, gamma-PVA and PVA-Mo membranes are modified to absorb larger amounts of alkaline solution than the PVA membrane, thus greatly improving the performance of the SAFC, in terms of output power. This is clearly indicated in the polarisation curves. The electrochemical impedance spectroscopy measurements during the SAFC operation were also performed to give better insight in the effect observed. Investigation presented in this paper clearly indicates that solid alkaline PVA membranes can be used for the construction of the SAFCs. Copyright (C) 2011, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved

Energy consumption and stability of the Ni-Mo electrodes for the alkaline hydrogen production at industrial conditions

Hydrogen production via electrolysis of water from alkaline aqueous electrolytes is a well-established conventional technology. However, the cost of hydrogen produced in such a way is high. To improve this process we have investigated in situ activation with Ni-Mo electrocatalytic material for electrodes. This two d-metal combination possesses one of the highest known activities for the HER. Ni-Mo based catalyst was not applied at industrial applications yet, because under industrial conditions (high temperature and concentrated alkaline solution), permanent destruction of the Ni-Mo alloy coating occurs. The most important result of this study is that the Ni-Mo deposit obtained by in situ activation, under industrial conditions, exhibit long term stability and the electrodes retain their high catalytic performance. The process of adding Ni-Mo activating compounds in situ exhibits savings of the energy consumption that can go beyond 20% in some cases. Copyright (C) 2011, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved