63 research outputs found

    Influence of aging on phenotypic and functional characteristics of dendritic cells from different rat strains

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    Dendritske ćelije (DĆ) su profesionalne antigen-prezentujuće ćelije koje čine sponu između urođenog i stečenog imuniteta i imaju važnu ulogu u imunskom odgovoru. Pored toga, DĆ imaju ulogu u uspostavljanju i održavanju imunoloÅ”ke tolerancije, kao i u patogenezi autoimunskih bolesti. Istraživanja na polju biologije starenja ćelija imunskog sistem su pokazala da tokom starenja komponente i urođenog i stečenog imuniteta podležu promenama. Podaci vezani za uticaj starenja na DĆ nisu konzistentni i uglavnom se odnose na ćelije humanog porekla, ćelije primata i miÅ”eva, dok nema podataka o uticaju starenja na DĆ pacova. Cilj ove doktorske disertacije je bio da se ispita uticaj starenja na fenotipske i funkcijske karakteristike konvencionalnih DĆ (kDĆ) pacova, kao i mogući značaj sojnih razlika za nastanak starenjem uslovljenih promena ovih ćelija. Takođe, cilj je bio i da se utvrdi da li starenjem uslovljene promene kDĆ pacova koreliraju sa promenom osetljivosti pacova na indukciju organ-specifičnih autoimunskih bolesti. Ispitivane su sveže izolovane kDĆ i stimulisane in vitro lipopolisaharidom (LPS). Konvencionalne DĆ su izolovane iz slezina pacova uzrasta 3 meseca (mladi odrasli pacovi) i 26 meseci (stari pacovi) Albino Oxford (AO) i Dark Agouti (DA) soja, koji pokazuju različit stepen osetljivosti na indukciju organ-specifične autoimunske bolesti posredovane Th1/Th17 limfocitima, kao Å”to je eksperimentalni autoimunski encefalomijelitis (EAE). Starenje dovodi do veće zastupljenosti ćelija CD4- fenotipa u populaciji sveže izolovanih kDĆ starih AO pacova za razliku od mladih životinja, kod kojih je brojnija CD4+ subpopulacija, a ne utiče na zastupljenost ovih subpopulacija kod DA pacova, tako da je kod njih u oba uzrasta dominantna CD4- subpopulacija. Osim toga, sveže izolovane kDĆ starih AO pacova pokazuju nezreliji, a starih DA pacova zreliji fenotip, u odnosu na kDĆ mladih pacova odgovarajućeg soja, a Å”to je procenjeno na osnovu nivoa ispoljenosti aktivacionih molekula (CD80, CD86 i CD40). U skladu sa fenotipom, endocitozni kapacitet kDĆ starih AO pacova je bio veći, dok je kod kDĆ starih DA pacova bio manji. Starenje dovodi do promena u ekspresiji iRNK za proinflamatorne i imunoregulatorne citokine kod pacova oba soja, s tim Å”to su te promene suprotne kada je u pitanju iRNK za IL-6 i IL-1Ī² (starenje smanjuje ekspresiju iRNK za IL-6, a povećava ekspresiju iRNK za IL-1Ī² kod AO), različite (iRNK za IL-10 raste kod DA, a ne menja se kod AO pacova) ili slične (ekspresija TNF-a se povećava kod oba soja pacova, a iRNK za TGF-Ī² se značajno ne menja)...Dendritic cells (DCs) are the professional antigen-presenting cells that form an interface between innate and adaptive immunity and play an important role in the immune response. They are also central in the establishment and maintenance of immune tolerance, as well as in the pathogenesis of autoimmune diseases. Aging is associated with the progressive immune system changes, which involve all types of immune cells. The data on age-associated DC alterations origin mainly from studies in mice and human, and are largely inconsistent, while there are no data on the influence of aging on rat DCs. The aim of this thesis was to elucidate the influence of aging on the phenotypic and functional characteristics of conventional DCs (cDCs), and the possible significance of strain differences in the development of age-related changes. In addition, this thesis was aimed to investigate a putative correlation between age-related changes in cDC biology and rat susceptibility to induction of organ-specific autoimmune diseases. Freshly isolated cDCs and cDCs stimulated in vitro with lipopolysaccharide (LPS) were investigated. The cells were isolated from the spleens of 3- (young adult) and 26 monthold (aged) rats of Albino Oxford (AO) and Dark Agouti (DA) strain, which are relatively resistant (AO) and susceptible (DA) to the induction of Th1/Th17-mediated organ-specific autoimmune disease, as it is experimental autoimmune encephalomyelitis (EAE). In AO rats aging increased relative proportion of cells exhibiting CD4- phenotype within population of freshly isolated cDCs, while in young animals CD4+ cells represented the predominant subpopulation within cDCs. In DA rats aging did not affect cDC subset composition, so predominance of CD4- subset within cDCs in rats of both ages was found. Aging affected surface phenotype and endocytic capacity of freshly isolated cDCs in a strain-specific manner. Namely, the lower surface density of activation markers (CD80, CD86 and CD40) on cDCs from aged AO rats and their higher endocytic capacity suggested that they were less mature that cDCs from young rats. To the contrary, increased surface expression of activation markers on cDCs and decreased endocytic capacity of these cells in aged DA rats suggested that they were more mature that corresponding cells from young rats..

    Pregled aktuelnih vakcina za profilaksu bakterijskih infekcija

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    Antibacterial vaccines play a central role in modern medicine by providing an effective approach to combating infectious diseases caused by bacteria. The importance of these vaccines lies in their ability to stimulate the immune system to recognise and neutralise bacterial pathogens, or exotoxins produced by them, thereby preventing, or mitigating the severity of bacterial infections. The development and widespread use of antibacterial vaccines have contributed significantly to reducing the global burden of diseases such as pneumonia, meningitis, and sepsis. Today, the global increase in vaccine-preventable diseases is a worrying trend that is closely linked to the emergence and advocacy of anti-vaccination policies. According to the latest World Health Organisation report, vaccination coverage in Serbia has declined over the past decade, jeopardising the collective immunity and led to recent outbreaks of vaccine-preventable diseases such as whooping cough and measles. Understanding the significance of antibacterial vaccines underscores their importance in promoting individual and community immunity, which ultimately leads to a healthier population and the prevention of antibiotic resistance. This paper summarises the main characteristics of the different types of antibacterial vaccines, such as whole cell vaccines, subunit vaccines and toxoid vaccines, and provides an overview of the types of bacterial antigens contained in vaccines available for mandatory immunisation (vaccines against tuberculosis, diphtheria, tetanus, pertussis, Haemophilus influenzae and pneumoccus) or for non-mandatory immunisation (meningococcal vaccine, typhoid vaccine, cholera vaccine).Antibakterijske vakcine igraju glavnu ulogu u savremenoj medicini obezbeđujući efikasan pristup u borbi protiv zaraznih bolesti izazvanih bakterijama. Važnost ovih vakcina leži u njihovoj sposobnosti da stimuliÅ”u imunski sistem da prepozna i neutraliÅ”e bakterijske patogene, ili egzotoksine koje oni proizvode, čime sprečavaju ili ublažavaju ozbiljnost bakterijskih infekcija. Razvoj i Å”iroka upotreba antibakterijskih vakcina značajno su doprineli smanjenju globalnog tereta bolesti kao Å”to su pneumonija, meningitis i sepsa. Danas je globalni porast bolesti koje se mogu sprečiti vakcinama zabrinjavajući trend koji je usko povezan sa pojavom i zagovaranjem politike protiv vakcinacije. Prema poslednjem izveÅ”taju Svetske zdravstvene organizacije, pokrivenost vakcinacijom u Srbiji je opala tokom protekle decenije, Å”to je ugrozilo kolektivni imunitet i dovelo do nedavnih izbijanja bolesti koje se mogu sprečiti vakcinom, poput velikog kaÅ”lja i malih boginja. Razumevanje značaja antibakterijskih vakcina naglaÅ”ava njihov značaj u promovisanju imuniteta pojedinca i zajednice, Å”to na kraju dovodi do zdravije populacije i prevencije rezistencije na antibiotike. Ovaj rad sumira glavne karakteristike različitih tipova antibakterijskih vakcina, kao Å”to su celo ćelijske vakcine, podjedinične vakcine i toksoidne vakcine, i daje pregled tipova bakterijskih antigena sadržanih u vakcinama dostupnim za obaveznu imunizaciju (vakcine protiv tuberkuloze, difterije, tetanusa, pertusisa, Haemophilus influenzae i pneumoka) ili za neobaveznu imunizaciju (vakcina protiv meningokoka, tifusa i kolere)

    Bezbednost i efikasnost inhibitora interleukina u terapiji reumatoidnog artritisa, psorijaze i psorijaznog artritisa u populaciji starih osoba

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    Elderly patients with rheumatoid arthritis, psoriasis and psoriatic arthritis encompass those with elderly-onset disease, over 60 years of age, but also those with earlier disease onset who entered old age. Considering the age-related changes of the immune system, possible frailty, susceptibility to infection and concomitant comorbidity that implies multiple medicines, the treatment of these diseases in elderly patients can be challenging. Interleukin inhibitors have been shown to be an efficient and safe treatment for these diseases. However, elderly patients with these diseases were often included in the pivotal clinical trials for interleukin inhibitors in numbers insufficient to determine whether they responded differently from younger subjects. The aim of this paper was to review the findings on the efficacy and safety of interleukin inhibitor treatment in elderly patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis.The findings suggest that, for all the interleukin inhibitors reviewed herein, used in elderly patients with rheumatoid arthritis, or with psoriasis and psoriatic arthritis, the efficacy was comparable to younger patients. Furthermore, the incidence of reported adverse events was similar in these two age groups. Severe adverse events, which were related to sarilumab treatment for rheumatoid arthritis and secukinumab treatment for psoriasis, were higher in elderly patients.The reviewed findings suggest that the interleukin inhibitors approved and currently in use in clinical practice for the treatment of rheumatoid arthritis, psoriasis, and psoriatic arthritis can be considered a safe and efficient option for these diseases in elderly patients.Stariji pacijenti koji boluju od reumatoidnog artritisa, psorijaze ili psorijaznog artritisa uključuju one kod kojih je bolest imala kasni početak, nakon 60. godine starosti, ali takođe i one pacijente kod kojih je bolest počela ranije, a koji su uÅ”li u staro doba. Imajući u vidu starenjem uslovljene promene imunskog sistema, moguću slabost starijih, podložnost infekcijama, prateći komorbiditet, koji uključuje i uzimanje viÅ”e lekova, terapija ovih bolesti kod starijih pacijenata može predstavljati izazov. Inhibitori interleukina su se pokazali kao efikasna i bezbedna terapija ovih poremećaja. Međutim, stariji pacijenti sa ovim bolestima su često bili nedovoljno zastupljeni u ključnim kliničkim ispitivanjima inhibitora interleukina da bi se moglo sa sigurnoŔću utvrditi da postoji razlika u terapijskom odgovoru kod ovih pacijenata u odnosu na isti kod mlađih pacijenata. Cilj ovog rada bio je da prikaže nalaze od značaja za bezbednost i efikasnost terapije inhibitorima interleukina kod starijih pacijenata sa reumatoidnim artritisom, psorijazom ili psorijaznim artritisom. Nalazi ukazuju da je efikasnost inhibitora interleukina, prikazanih u ovom radu, uporediva kod starijih i mlađih pacijenata. Osim toga, incidencija neželjenih događaja se nije razlikovala između ove dve starosne grupe. Veća incidencija teÅ”kih neželjenih događaja kod starijih pacijenata u odnosu na mlađe bila je zabeležena u terapiji reumatoidnog artritisa sarilumabom i psorijaze secukinumabom. Terapija reumatoidnog artritisa, psorijaze i psorijaznog artritisa inhibitorima interleukina može se smatrati efikasnom i bezbednom u populaciji starih pacijenata

    Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review

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    Hashimoto autoimmune thyroiditis (AIT) is the most common cause of acquired hypothyroidism in the pediatric population. Development of AIT is mediated mainly by cellular immune response directed toward thyroid autoantigens, leading to inflammation and impaired function of thyroid gland. Both thyroid dysfunction and inflammation affect the metabolism of plasma lipoproteins. The alterations in lipid profile worsen with the advancement of hypothyroidism, ranging from discrete changes in euthyroid AIT patients, to atherogenic dyslipidemia in the overt hypothyroidism. In this review, characteristics of dyslipidemia in pediatric AIT patients, and the consequences in respect to the risk for cardiovascular disease (CVD) development are discussed. Additionally, benefit of L-thyroxine treatment on serum lipid profile in pediatric AIT patients is addressed. Finally, potential usefulness of novel lipid biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), non-cholesterol sterols, low-density lipoprotein particle size and number, and high-density lipoprotein structure and functionality in AIT patients is also covered. Further longitudinal studies are needed in order to elucidate the long-term cardiovascular outcomes of dyslipidemia in pediatric patients with Hashimoto AIT.articl

    Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression

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    Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3-month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund's adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-alpha and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+: CD4-DC ratio towards CD4- cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+: CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-alpha mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1 beta (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1 beta compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction

    Razvoj monoklonskih antitela za terapijsku primenu - od miŔjih do humanih

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    Therapeutical monoclonal antibodies (mAbs) represent one of the fastest growing area of the pharmaceutical industry. High target specificity and specific molecular structure are features that make antibodies attractive drug candidates for therapeutical use. Besides high specificity, other characteristics including immunogenicity, affinity, effector functions, half-life as well as easy of production, stability and cost must be considered when an antibody is designed as drug. In this paper the structure and function of antibody, new technologies for the generation of partly and fully human mAbs and their fragments and methods for enhancing their affinity, effector functions and pharmacokinetics will be describe.Monoklonska antitela (mAt) i njihovi derivati su najveća grupa proteina koji se koriste u terapiji i predstavljaju segment farmaceutske industrije koji se najbrže razvija. Osobine antitela koje ih čine izuzetno interesantnim za primenu u terapiji su prvenstveno njihova visoka specifičnost za ciljni molekul a zatim i njihova karakteristična građa. Pored visoke specifičnosti, i druge osobine antitela kao Å”to su imunogenost, afinitet, stabilnost, efektorske funkcije, poluživot, penetracija i distribucija u tkiva, moraju se uzeti u obzir kada se ove molekule koriste kao lekovi. Sa stanoviÅ”ta proizvodnje, Å”to lakÅ”e dobijanje, stabilnost i manja cena su najvažniji zadaci koje farmaceutska industrija treba da ostvari. U ovom radu biće opisana građa i funkcija antitela, savremene metode za dobijanje delimično i kompletno humanih mAt i njihovih derivata, kao i načini za poboljÅ”anje njihovog afiniteta, efektorske funkcije i farmakokinetike

    In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections

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    Bacterial biofilms play an important role in the pathogenesis of chronic upper respiratory tract infections. In addition to conventional antimicrobial therapy, N-acetyl-L-cysteine (NAC) and propolis are dietary supplements that are often recommended as supportive therapy for upper respiratory tract infections. However, no data on the beneficial effect of their combination against bacterial biofilms can be found in the scientific literature. Therefore, the aim of our study was to investigate the in vitro effect of N-acetyl-L-cysteine (NAC) and dry propolis extract in fixed combinations (NAC/dry propolis extract fixed combination) on biofilm formation by bacterial species isolated from patients with chronic rhinosinusitis, chronic otitis media, and chronic adenoiditis. The prospective study included 48 adults with chronic rhinosinusitis, 29 adults with chronic otitis media, and 33 children with chronic adenoiditis. Bacteria were isolated from tissue samples obtained intraoperatively and identified using the MALDI-TOF Vitek MS System. The antimicrobial activity, synergism, and antibiofilm effect of NAC/dry propolis extract fixed combination were studied in vitro. A total of 116 different strains were isolated from the tissue samples, with staphylococci being the most frequently isolated in all patients (57.8%). MICs of the NAC/dry propolis extract fixed combination ranged from 1.25/0.125 to 20/2 mg NAC/mg propolis. A synergistic effect (FICI ā‰¤ 0.5) was observed in 51.7% of strains. The majority of isolates from patients with chronic otitis media were moderate biofilm producers and in chronic adenoiditis they were weak biofilm producers, while the same number of isolates in patients with chronic rhinosinusitis were weak and moderate biofilm producers. Subinhibitory concentrations of the NAC/propolis combination ranging from 0.625ā€“0.156 mg/mL to 10ā€“2.5 mg/mL of NAC combined with 0.062ā€“0.016 mg/mL to 1ā€“0.25 mg/mL of propolis inhibited biofilm formation in all bacterial strains. Suprainhibitory concentrations ranging from 2.5ā€“10 mg/mL to 40ā€“160 mg/mL of NAC in combination with 0.25ā€“1 mg/mL to 4ā€“16 mg/mL of propolis completely eradicated the biofilm. In conclusion, the fixed combination of NAC and dry propolis extract has a synergistic effect on all stages of biofilm formation and eradication of the formed biofilm in bacteria isolated from upper respiratory tract infections

    Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis

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    The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-gamma /IL-4 production ratio was shifted towards IFN-gamma. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research

    Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration

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    Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration Jelena Mitrović1, Tanja Ilić1, Ivan Jančić2, Biljana Bufan2, Miroslav Savić3, Snežana Savić1 1 Department of Pharmaceutical Technology and Cosmetology, University of Belgrade ā€“ Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 2 Department of Microbiology and Immunology, University of Belgrade ā€“ Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 3 Department of Pharmacology, University of Belgrade ā€“ Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia Estimation of endotoxin level in parenteral formulations is a prerequisite for numerous in vitro tests in preclinical studies and for future clinical development. However, the Limulus amoebocyte lysate (LAL) test in formulations containing nanoparticles could often lead to misinterpretation of results. Therefore, we tested if endotoxins could be detected in nanocrystal dispersions by the commercial gel clot assay kit. Nanocrystals of DK-I-56-1 (7ā€‘methoxyā€‘2-(4ā€‘methoxyā€‘d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one) were prepared by wet-ball milling, lyophilized and reconstituted with water for injection prior experiment. Different dilutions of nanocrystal dispersion in LAL reagent water were prepared as well as positive and negative control. Despite difficulties to detect gel clots, they were visible in the sample at dilutions 1:75 and below. According to the protocol, the endotoxin limit was estimated to be 25.00 EU/ml, which corresponds to <12.50 EU/mg of DK-I-56-1. This value relates to the endotoxin limit for diazepam, with the similar dosing regimen as proposed for DK-I-56-1

    Normalna ljudska mikrobiota i disbioza - implikacije po zdravlje i bolest

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    The normal human microbiota, formerly called the "microbial flora," consists of bacteria, fungi, viruses, and parasites that colonise the skin and mucous membranes of the respiratory, gastrointestinal, and genitourinary tracts. The number and diversity of microorganisms varies between different body niches and is greatest in the intestinal tract. The microbiota contributes to the homeostasis of the human organism by preventing colonisation by pathogenic microorganisms, participating in digestive processes and metabolism, and regulating immune functions. Various environmental and genetic factors can lead to an imbalance in the human microbiota, called dysbiosis, which can affect human health. Dysbiosis is usually the result of decreased microbial diversity and a lower number of saprophytic microorganisms, followed by an overgrowth of opportunistic species. The most common diseases directly related to intestinal dysbiosis are antibiotic-associated diarrhoea and pseudomembranous colitis, both of which are associated with the excessive growth of harmful bacteria and Clostridioides difficile following broad-spectrum antibiotic therapy. Dysbiosis is associated with various health conditions or diseases such as acne, psoriasis, eczema, chronic obstructive pulmonary disease, inflammatory bowel disease, obesity, metabolic syndrome, type 2 diabetes, autoimmune diseases and allergies, neurological diseases such as Parkinson's disease, Alzheimer's disease, epilepsy and stroke, depression, anxiety, infertility, preterm birth, and malignancies.Normalna ljudska mikrobiota, koja se ranije nazivala ā€žmikrofloraā€œ, sastoji se od bakterija, gljivica, virusa i parazita koji kolonizuju kožu i sluzokožu respiratornog, gastrointestinalnog i genitourinarnog trakta. Broj i raznovrsnost mikroorganizama variraju između različitih telesnih niÅ”a i najveći su u crevnom traktu. Mikrobiota doprinosi homeostazi ljudskog organizma tako Å”to sprečava kolonizaciju patogenim mikroorganizmima, učestvuje u procesima varenja i metabolizma i reguliÅ”e imunoloÅ”ke funkcije. Disbioza je stanje u kome dolazi do neravnoteže sastava mikrobiote usled uticaja različitih egzogenih ili endogenih faktora, Å”to može uticati na ljudsko zdravlje. Ona je najčeŔće rezultat smanjene raznovrsnosti mikroorganizama i manjeg broja saprofitnih bakterija, Å”to je praćeno prekomernim rastom potencijalno Å”tetnih vrsta. NajčeŔće bolesti koje su direktno povezane sa crevnom disbiozom su dijareja povezana sa primenom antibiotika i pseudomembranozni kolitis, a obe nastaju kao posledica prekomernog rasta Å”tetnih bakterija i Clostridioides difficile nakon terapije antibioticima Å”irokog spektra. Disbioza je povezana sa različitim zdravstvenim stanjima ili bolestima kao Å”to su akne, psorijaza, ekcem, hronična opstruktivna bolest pluća, inflamatorna bolest creva, gojaznost, metabolički sindrom, dijabetes tipa 2, autoimunske bolesti i alergije, neuroloÅ”ke bolesti kao Å”to su Parkinsonova bolest, Alchajmerova demencija, epilepsija i moždani udar, depresija, anksioznost, neplodnost, prevremeni porođaj i maligni tumori
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