While these manifestations are likely related to the underlying disease, there is a concern that autoimmune cytopenias may be aggravated by purine analogs. The underlying biology responsible for these autoimmune complications represents another area of needed research. The long-standing

question related to a possible increase in second malignancies also implicates an abnormal immune status in these patients, either as an intrinsic problem emanating from the leukemia or as a consequence of its treatment [53]. In a large population-based study, Hisada reported an increased incidence of Hodgkin Lymphoma, non-Hodgkin Lymphoma, and thyroid cancer [54]. Remarkably, several PI3K inhibitor patients in our experience have been observed to have both hairy cell leukemia and malignant melanoma. Considering the role of BRAF p.V600E mutations in many of these malignancies, a careful epidemiological investigation of the frequency of melanoma and thyroid cancer should be conducted in patients with this rare form of leukemia [55]. Optimal management of patients with this rare form of leukemia begins with establishing the correct diagnosis and evaluating the predictive biomarkers for risk stratification. The tremendous progress that has been made in improving the initial

responses of patients with the classic form of this disease has resulted in dramatic improvements in long-term disease Alectinib in vitro control and survival, but the ultimate progression free survival curves show no plateau, indicating that the disease is not cured by current therapies [9], [10], [11], [12] and [13]. However, prolonged durable remissions enable patients to lead highly functional lives. Long-term follow-up studies now show that patients live for periods

approximating the normal life-span. Therefore, younger patients with hairy cell leukemia have a higher chance of achieving a complete remission, but an equally high chance of experiencing several relapses throughout the course of their lifetime [8]. A recent publication examined the outcomes of patients under the age of forty with this disease and showed that they had a very long life but had multiple relapses requiring therapy [49]. Definition of prognostic subsets and the recognition that the variant form of hairy cell leukemia is a distinct clinical entity have improved the therapeutic plans for BCKDHB patients who are newly diagnosed [13], [17], [18], [19], [20], [23] and [24]. Clinical experience has long taught us that even among the classic form of the disease there are several subsets of patients with distinct prognostic profiles, and this experience has been borne out by recent molecular discoveries. Patients harboring the biomarkers predictive of less optimal response may have overlapping immunophenotypic markers, variable BRAF mutational profiles, abnormalities of TP53 genes, or stereotypical immunoglobulin gene rearrangements (e.g., IVH4-34) resulting in different clinical outcomes.

Fungos como do gênero aspergillus são encontrados nas placas, provavelmente vindos do óleo mineral contaminado usado para sobreposição das gotas do meio de cultura. São fungos ambientais contaminantes do ar os gêneros aspergillus e penicillium. 14 Em medicina reprodutiva existe risco significativo de contaminação cruzada durante a criopreservação de gametas ou embriões. Em estudo de revisão, conclui‐se que há um risco negligenciado de contaminação cruzada em condições de FIV.15 Encontrou‐se relação

entre infertilidade e vírus da hepatite C em um grupo de casais inférteis, com prevalência de 3,2% para as mulheres e 3,6% para os homens,16 que pode ser transmitida de uma mulher para outra pela contaminação transvaginal por equipamentos ou dos pais para o concepto. Recomendou‐se que pacientes inférteis fossem rastreados antes de submetidos EX 527 order a técnicas de reprodução assistida. Kastrop et al. (2007)14 AZD0530 descrevem incidência de 0,67% de contaminação nos LRH europeus. A amostra envolveu

mais de 13.000 casos.14 Um estudo de prevalência no Brasil encontrou 4,8% de contaminação nas placas por bactérias e fungos, considerando a contaminação como fator de contribuição do fracasso em reprodução assistida.17 Com a prevalência de contaminação conhecida e com os gêneros identificados, poder‐se analisar a interferência desta sobre o sucesso da reprodução assistida, pois o tipo de contaminação parece variar os resultados. Autores também divergem em seus resultados. CYTH4 Candida albicans aumentou a fragmentação do DNA e apoptose, danos que podem ter causado fracasso após a fertilização. 19 Outros autores relatam que nascimentos após a transferência de embriões inseridos em meios contaminados com leveduras ocorrem dentro das taxas normais de freqüência para reprodução assistida,

concluindo que a contaminação pelo fungo não é razão para cancelar a transferência de embriões. 11 A primeira consequência observada, quando contaminados com patógenos, está na redução da formação de embriões viáveis para transferência. Os embriões podem não sobreviver nas primeiras clivagens, apresentar teratogenia, ou simplesmente não conseguirem implantar no útero. Também podem ocorrer síndromes que comprometam a saúde fetal, trazendo a possibilidade de aumento de natimortos, prematuridade, ou nascimento de conceptos pequenos para a idade gestacional, descritos em estudos com bovinos onde a fertilização assistida é amplamente utilizada.18 Em outra vertente, existe o risco de infectar o organismo materno, com consequências temporárias ou definitivas. Os procedimentos de controle de qualidade devem ser sempre atualizados para minimizar esses riscos, já que a contaminação pode ser vertical (dos progenitores para o embrião), ou lateral (de uma mulher para outra).

, 1998). Lactobacillus

paracasei subsp. paracasei NTU 101 was isolated from human feces, and it is resistant to gastric juice and bile salt in the natural environment ( Lin et al., 2004). It also has probiotic characteristics that are effective in reducing cholesterol in blood and in the liver ( Chiu et al., 2006). L. paracasei subsp. paracasei NTU 101 can upregulate the antigen-presenting ability of dendritic cells and expression of natural killer group 2 D molecules capable of triggering natural killer cell-mediated cytotoxicity in BALB/c mice ( Tsai et al., 2008). Hydrolysates of L. paracasei subsp. paracasei NTU 101 can induce proliferation of macrophages and splenocytes and a release of the cytokines IL-10 and IL-12 that modulate the innate and adaptive immunity Selleck Navitoclax and an inflammatory response ( Chiang et al., 2012a). Soy skim milk fermented by L. paracasei subsp. paracasei NTU 101 (NTU 101F milk), with or without

a Momordica charantia supplement, is effective at preventing and retarding hyperlipidemia-induced oxidative stress and atherosclerosis in hyperlipidemic hamsters ( Tsai et al., 2009). This type of milk is also useful for prevention of acute gastric ulcers induced by pylorus ligation and acidified ethanol (via prostaglandin E2), and it significantly enhances superoxide dismutase (SOD) activity ( Liu et al., 2009). Moreover, NTU 101F milk can attenuate bone loss in ovariectomized (OVX) mice ( Chiang and Pan, 2011) and aging-induced bone loss in BALB/c mice and can Suplatast tosilate lower the risk of osteoporosis ( Chiang et al., 2012b). In addition, NTU 101F milk can upregulate and Selleck PARP inhibitor downregulate lipolysis and

heparin-releasable lipoprotein lipase, respectively, in 3T3-L1 cells and can reduce obesity in Wistar rats fed a high-fat diet ( Lee et al., 2013). Taken together, the above data show that intake of cultured probiotic L. paracasei subsp. paracasei NTU 101 is likely to have various beneficial effects on the health of humans and animals. Hence, the safety of L. paracasei subsp. paracasei NTU 101 must be evaluated. Accordingly, the aim of this study was to assess the possible genotoxicity and mutagenicity of Vigiis 101 powder made from L. paracasei subsp. paracasei NTU 101. In addition, we performed a 28-day oral toxicity assay in Wistar rats. Sodium azide, benzo[α]pyrene, mitomycin C, 2-aminofluorene, 2-amino-anthracene, 4-nitro-o-phenylenediamine, 9-aminoacridine, acridine orange, and cyclophosphamide monohydrate were purchased from Sigma (St. Louis, MO, USA). The main media, including McCoy’s 5A medium with 10% fetal bovine serum and penicillin-streptomycin solution, minimal glucose agar plates, master plates, soft agar, and nutrient broth, were obtained from Biological Industries (Kibbutz Beit-HaEmek, North District, Israel). The probiotic used in this study was Vigiis 101 (SunWay Biotecn Co., Ltd., Taipei, Taiwan). Vigiis 101 is a dry powder which contains 6 billion bacteria of L.

2a). However, skippers were making a considerably higher number of sets on free schools (Fig. 2b) but with a much lower success rate than sets on floating objects (46% versus 89% success rate respectively

during the period 1984–1990; data from [4]). The advantages of fishing on floating objects were obvious to skippers and fishing companies, yet opportunities to fish using this setting method were limited by the number of floating objects in the ocean. In order to continue the growth of the fishery it was necessary to generate more fishing selleck inhibitor opportunities and skippers realised that, whilst they could not influence the number of free-swimming schools, they could feasibly provide a greater number of floating objects for schools to associate with. Thus, the intensive use of purpose-built FADs began in the early 1990s and catches on floating objects increased steadily through the 1990s and 2000s. The increasing use of FADs improved catch rates and greatly

enhanced the productivity of the fishery, allowing boat owners to build the capacity of their fleets in an attempt to exploit more of the resource. Throughout the 1990s and early 2000s French and Spanish fishing companies invested in larger purse NU7441 seine vessels, which offered numerous commercial advantages including the ability to make extended fishing trips with larger fish-wells [32]. The development of the fleet included the construction of several ‘super-seiners’ (>2000 gross tonnage; GT) and even ‘super super-seiners’ (>3500 GT) and the increasing trend in capacity

matched the proliferating use of FADs (Fig. 3). However, because larger vessels are more sensitive to increasing operating SB-3CT costs (e.g. fuel price; [2]) it was necessary for fishing companies to adopt increasingly competitive fishing strategies to achieve high annual catch thresholds (e.g. circa 15–20,000 t; A. Fonteneau, personal communication). Consequently, the purse seine fishery has become increasing reliant on the use of FADs to achieve the very large catches needed to remain profitable [32] and [33]. Against the background trend in fishing capacity two episodes in particular show that other factors have an important effect on the relative use of FADs in the Indian Ocean. In the early 2000s the long-term increasing trend in the number of floating object sets flattened out and there was a clear spike in the number of sets made on free schools (Fig. 2b). This switch in the predominant fishing practice is thought to be explained by the comparatively high abundance of free-swimming tuna schools during 2003–2005, linked to increased availability of prey species as a result of higher-than-average primary productivity in the western Indian Ocean and greater vulnerability of schools to purse seine gear due to a shoaling of the thermocline [30]. During this period fishing companies moved vessels into the Indian Ocean from the Atlantic to capitalise on this boom (J.J.

Later, the system was started, turning on the radial blower to supply air Stem Cell Compound Library to the system, and also, turning on the electrical heating until the set point temperature was reached. The behavior of the bed was found through the pressure drop for each increase of air velocity. Maximum pressure drop and the minimum spouting velocity (point where the bed collapse occurred)

were found. The fluid dynamics was carried out in all temperatures used (90, 100 and 110 °C). In each geometry, chitosan was dried in three inlet air temperatures (90, 100 and 110 °C), and air velocity used in the experiments was 100% over minimum spouting velocity, as recommended by Mathur and Epstein (1974) for pastes drying. When a steady velocity regime was established, the feeding system was set in motion and the chitosan paste with solid content of 4 g 100 g−1 (wet basis) was fed (0.18 kg paste kg inert−1 h−1) into the cell, through atomization with peristaltic pump and air compressed at pressure of 105 Pa gauge. Spouted bed chitosan drying occurred by fluid-particle contact, and also by friction

between inert particles caused by the BIBW2992 solubility dmso high rate of circulation of the inert in the spouted bed interior. Dried chitosan in powder form was transported pneumatically by the drying air stream and collected in a cyclone. The dry and wet bulb temperatures of air drying were measured. The drying spouted bed experiments were carried out in 3 h, later the dried product was analyzed. Dryer performance was evaluated through determination of the accumulated mass in the bed and product recovery. Accumulated mass and product recovery were estimated by mass balance in the drier using Eqs. (1) and (2): equation(1) AC=(mFB−mIB)(1−UFB)mI×100 equation(2) R=mc(1−UF)mI×100where, AC is the mass accumulated in the bed (g 100 g−1), R is product recovery (g 100 g−1),

mFB and mIB are total bed mass in the end and in the begin of operation, respectively, UFB is final moisture content of the powder accumulated in the bed (g 100 g−1), UF is final moisture Forskolin concentration content of powder (g 100 g−1), mI and mC are total solid mass introduced into the drier and collected in the cyclone, respectively. Chitosan paste was characterized according to centesimal chemical composition (A.O.A.C., 1995), molecular weight and deacetylation degree. Chitosan powder was characterized according to molecular weight, deacetylation degree, color and particle size. In the best drying condition, TG and DTG curves, FT-IR analysis and SEM were carried out to verify the powder quality. Chitosan molecular weight was determined by viscosimetric method (Cannon-Fenske capillary viscosimeter, model Schott Gerate, GMBH-D65719, Germany). Reduced viscosity was determined by Huggins equation, and converted into molecular weight through Mark-Houwink-Sakurada equation (Eq. (3)), using K = 1.81 × 10−3 mL g−1 and α = 0.93 ( Weska et al., 2007).

Sechs Monate nach Ende der MeHg-Exposition wurde im Gehirn der Affen eine höhere Hg2+-Konzentration beobachtet, während das organische Quecksilber

aus dem Gehirn verschwunden war. Die ermittelte Halbwertszeit des organischen Quecksilbers im Gehirn dieser erwachsenen Affen betrug 37 Tage. Dieser Zeitraum war konsistent über verschiedene Gehirnregionen hinweg und vergleichbar mit der Halbwertszeit von MeHg im Gehirn von Affenbabys, AG 14699 die von Burbacher et al. bestimmt worden war [114]. Die ermittelte Halbwertszeit von Hg2+ im Gehirn derselben erwachsenen Affen variierte erheblich zwischen verschiedenen Bereichen im Gehirn: Sie betrug zwischen 227 und 540 Tagen. Die Hg2+-Konzentration unterschied sich ebenfalls deutlich zwischen den einzelnen Gehirnregionen. Sechs Monate nach dem Ende der Exposition gegenüber MeHg war sie in einigen Bereichen gleich geblieben (Thalamus), während sie in anderen (Hypophyse) auf das Doppelte angestiegen war [112]. Stereologische und autometallogeraphische Untersuchungen ergaben Hinweise darauf, dass Hg2+ im Gehirn der Affen persistierte und mit einer signifikanten Erhöhung der Anzahl der Mikroglia sowie einem Rückgang der Anzahl der Astrozyten verbunden war. Es ist bemerkenswert, dass diese Effekte 6 Monate nach dem Ende einer chronischen

Exposition gegenüber MeHg beobachtet www.selleckchem.com/products/ink128.html wurden [110], [111] and [115] und dass sie bei den erwachsenen Tieren mit Hg2+-Gehalten im Gehirn

verbunden waren, die etwa fünfmal höher lagen als diejenigen, die von Burbacher et al. [114] bei den mit Ethylquecksilber behandelten Affenbabys Carnitine palmitoyltransferase II beobachtet worden waren. Bei einigen Studien zeigten MeHg und Ethylquecksilber in Experimenten an Gewebekulturen gleiche Toxizität, während sich Hg2+ in neuronalen Zellmodellsystemen sowohl von Vertebraten als auch von Invertebraten als weniger toxisch erwies. In PC12-Phäochromozytomzellen beispielsweise ist MeHg, gemessen am Überleben der Zellen, 6- bis 40-mal toxischer als Hg2+[116] and [117]. Während Hg2+ und MeHg in einer Insektenzelllinie nahezu äquivalente Zytotoxizität zeigten, inhibierte MeHg in diesen Zellen die Proliferation etwa 20-mal stärker als Hg2+[118]. Darüber hinaus verzögerte MeHg 10-mal stärker als Hg2+ das Wachstum von Nervenfasern bei Spinalganglien-Explantaten von Hühnern [119]. Insgesamt sprechen diese Untersuchungen in einer Reihe von Modellen, die von Invertebraten- bis hin zu Säugersystemen reichen, gegen die Auffassung, dass Hg2+ sowohl bei Exposition gegenüber MeHg wie auch gegenüber Ethylquecksilber die eigentliche Ursache der Schäden ist. Diese Untersuchungen sollten jedoch mit Vorsicht interpretiert werden, da sie alle unter den artifiziellen Bedingungen von Gewebekulturen durchgeführt wurden.

Biased results are generally caused by (1) too coarse a resolution of the model domain in which small-scale details are excluded or smoothed, (2) biased parameterization and boundary inputs, which can lead to significant differences between the model results even

if they are based on the same equations; such effects can be greatly amplified during a long-term run, (3) scant knowledge of interactions between different scale processes, and (4) the deterministic results of process-based models, in which the stochastic dimension inherent to the natural systems we are working with is ignored (de Vriend 2001). Climate change is assumed to be linear, and short-term learn more fluctuations are excluded from our current modelling work. The authors Anti-infection Compound Library cell assay admit that there is large uncertainty of climate change in the future and it is not possible to specify accurate climate input conditions for future predictions. Thus, our results are projection results based on certain particular climate scenarios rather than accurate future predictions. The aim of this study is to identify the key coastal areas most vulnerable to climate change impacts, such as accelerated sea level rise and increased storm frequency, and reveal the nonlinear

effects on the coastal morphological evolution caused by these climate factors. Although uncertainty of climate change exists, the hypothesis of linear climate change

seems to be acceptable for the simulation of the Darss-Zingst peninsula from 1696 to 2300. This is probably due to two main reasons: (1) the research area has a relatively stable coastline boundary, which does not allow for much change caused by stochastic climate fluctuations; (2) studies of the North Atlantic Oscillation Lck (NAO), which turns out to be an important factor influencing the climate of the Baltic Sea in winter (Klavins et al. 2009), indicate that although variability has existed on an annual scale during the last two centuries (HELCOM 2006), the 30-year averaged NAO index series of the last three centuries fluctuates slightly from the value of zero (Trouet et al. 2009). This supports the feasibility of periodic climate inputs generated on the basis of the 50-year wind data analysis for the historical hindcast or future projection on a centennial scale in the model. However, this hypothesis may be violated when the model is applied to a longer time span (millennial scale), as the model boundary is more variable and the non-linear effects caused by the linear parameterization of climate conditions can accumulate and may ultimately dominate the results. The estimation and quantification of these uncertainties for the simulation of millennial-scale coastal evolution (either hindcast or prediction) remain a challenge for our model work.

Purified κ and λ FLC calibrator materials were separately incubated with biotinamidohexanoyl-6-aminohexanoic acid, N-hydroxysuccinimide ester in dimethyl sulfoxide overnight (all Sigma

Aldrich). Biotinylated light chains were then separated using NAP™ 5 Columns (Sephadex G-25 DNA grade; GE Healthcare), eluted in PBS, and the concentration of the eluate was measured by spectrophotometry. After the addition of 0.099% sodium azide, biotinylated light chains were stored at 4 °C, until required. Prior to assaying, each of the anti-κ FLC and anti-λ FLC mAbs was covalently coupled to four different 5.5 μm polystyrene Xmap® beads (Bio-Rad UK) using a two step carbodiimide reaction protocol. Specifically, the different bead regions used were #27 (BUCIS 01), OSI-906 concentration #28 (BUCIS 04), #29 (BUCIS 03), and #30 (BUCIS 09). After sonication and vortexing, beads were incubated with N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) for 30 min in activation buffer (0.1 M PBS, pH 6.2). Following two

wash procedures, the bead pellet was incubated for 3 h with the relevant mAbs (100 μL at 1 mg/mL) on a rotor, in the dark, at room temperature. Beads were then washed twice, and finally, the pellet was resuspended in blocking/storage buffer (0.1 M PBS, 0.05% Tween20, 1% BSA, 0.05% NaN3, pH 7.2). The beads see more were enumerated using a haemocytometer to ensure consistency between conjugations. Labelled beads were stored in blocking/storage buffer in the dark at 4 °C until required selleck screening library in the assay; the beads were found to be stable for at least 6 months in these conditions (data not shown). The efficiency of mAb conjugation to each beadset was determined in a one-step assay by incubating each beadset with goat anti-mouse IgG labelled with phycoerythrin (PE; Southern Biotech, USA), and subsequent measurement by Luminex®. The effectiveness of each mAb-bead complex at detecting κ and λ FLCs was tested in a two-step assay by (1) incubating beads with biotinylated purified κ and λ FLCs, and (2) incubation with streptavidin-PE (Invitrogen, UK), and subsequent

measurement by Luminex®. A minimum median fluorescent intensity (mfi) was set at > 10,000 mfi units for mAb conjugation to beads and > 5000 mfi units for detection of κ and λ FLCs, as this provided calibration curves with the most sustained linearity, and, hence, more reliable and reproducible results on patient samples. Human κ and λ FLCs were measured in a multi-plex competitive inhibition format. 40 μl of biotinylated FLC diluted 1 in 400 in FLC buffer (PBS, 12.5% 2 M Tris, 1% BSA, 0.099% NaN3, 0.05% Tween20) was added to each well in a 1.2 μm MV Multiscreen (Millipore, UK) 96-well filter plate, followed by 40 μl of each sample, calibrators or controls, and then incubated for 30 min with mAb coupled beads. Each sample was diluted 1 in 5 in assay buffer (PBS, 1% BSA, 0.

3). During this inotropic intervention no changes in coronary perfusion pressure were observed. In order to investigate the underlying mechanisms that could explain those mechanical effects on hearts from mercury-treated rats, NKA and myosin ATPase activities were measured. Myocardial myosin ATPase activity was increased (Ct: 257.7 ± 11.7 vs HgCl2: 301.5 ± 9,3 nmol Pi/min/mg, P < 0.05) while NKA activity was reduced (Ct: 59.8 ± 4.5 vs HgCl2: 35.3 ± 8.6 nmol Pi/min/mg, P < 0.05) in the mercury-treated group. Protein expressions of NCX, α1 and α2 subunits of NKA, SERCA, phospholamban and its

phosphorilated fraction were measured (Fig. 4 and Fig. 5) in order to evaluate calcium handling mechanisms. After 30-day selleck chemicals mercury treatment reduces expression of alfa-1 NKA subunit and NCX expression, but expression of alfa-2 NKA subunit did not change. Moreover, after exposure to low doses of mercury, SERCA expression and phosphorilated phospholamban were reduced while phospholamban expression was increased. These changes led to a reduction in SERCA/PLB ratio, suggesting the reduction in calcium uptake by the sarcoplasmic reticulum contributing to the calcium overload. Since no changes Crizotinib concentration in myocardial mass were found analyzing ventricular

weight we investigated myocardial morphology by analyzing putative actions of mercury treatment on cell morphometry. No changes for morphometric results were observed for perimeter, width, length and area of myocardial cells (results not shown). In addition, no changes Tryptophan synthase were observed in collagen fraction in left ventricle from the mercury-treated group as compared with controls (5.1 ± 0.8 vs 4.7 ± 0.6% of tissue area). To investigate if such changes could produce hemodynamic effects, we performed measurements of systolic, diastolic, mean arterial pressure and heart rate in anesthetized rats. No differences were observed between the two groups (Table 2). The measurement of ventricular pressures, LVSP

and time derivatives also did not change. However, only LVEDP increased in the 30-day mercury-treated group. The main findings presented here show that 30-day treatment with low mercury concentration produced a negative inotropic effect in perfused hearts, although myosin ATPase activity increased. This contractility reduction was explained by alterations in calcium-handling mechanisms because of both diminished protein expression of SERCA, NKA (α1 subunit) and NCX, and increased PLB expression together with a reduced response to β-adrenergic stimulation. This treatment did not change arterial or ventricular pressures, although it produced a small but significant increase of LVEDP in anesthetized rats. Mercury is known to be an environmental risk factor for cardiovascular diseases (Houston, 2007).

In children with EP, the most important factors involve: muscle hypotonia,

malnutrition, adverse effects of used medicines, GER and hypoproteinemia. Our findings indicate that in children with PE and neuromuscular diseases, the course of lower respiratory tract infections is the most severe. In these patients there are numerous coexisting factors that significantly hinder effective treatment. In children with EP, the most important factors involve: muscle hypotonia, malnutrition, adverse effects of used medicines, GER and hypoproteinemia. Our findings not only enrich the knowledge on lower respiratory tract infections in children with chronic neurological disorders, but also have significant practical implications since they indicate the main problems in FDA-approved Drug Library in vitro the treatment of respiratory tract infections in children with nervous system dysfunction. A complex treatment Linsitinib order of recurrent lower respiratory tract infections in children with chronic diseases

of the nervous system should include: 1. Elimination of deficiencies and disturbances such as hypoproteinemia, energy deficiency or electrolyte imbalance and the concomitant treatment of other systemic dysfunctions, e.g. GER or cardiovascular conditions. Autorzy pracy nie zgłaszają konfliktu interesów “
“Pierwotne niedobory odporności (PNO) stanowią grupę bardzo rzadkich wrodzonych schorzeń spowodowanych mutacjami genetycznymi. Częstość występowania

zależy od rodzaju defektu odporności, średnio 1:10 000 żywych urodzeń z wyjątkiem CYTH4 wrodzonego niedoboru IgA [1, 2]. Celem tej publikacji jest przybliżenie zagadnienia pierwotnych niedoborów odporności wśród pediatrów i lekarzy rodzinnych oraz wskazanie, kiedy należy myśleć o PNO, jakie podstawowe badania należy wykonać, a w przypadku już rozpoznanych wrodzonych defektów, w jaki sposób leczyć i postępować z chorymi. Immunologia kliniczna jest nową dyscypliną medyczną, pierwsze opisy PNO pochodzą dopiero z lat 50. XX wieku. W ostatnich latach dokonał się ogromny postęp w diagnostyce immunologicznej i genetycznej PNO. Spowodowało to poznanie coraz większej liczby genów odpowiedzialnych za występowanie wrodzonych defektów odporności oraz lepsze zrozumienie patomechanizmów chorób. Dotychczas poznano podłoże genetyczne ponad 130 różnych rodzajów PNO. Charakterystykę molekularną PNO ułatwia rozwój nowoczesnych metod diagnostycznych opartych na analizie ekspresji protein kodowanych przez specyficzne geny pierwotnych niedoborów odporności. Jednocześnie nastąpił duży postęp w leczeniu chorych z PNO możliwy dzięki stosowaniu dożylnych i podskórnych immunoglobulin, przeszczepianiu macierzystych komórek krwiotwórczych (Heamatopoietic Stem Cell Transplantation; HSCT) i terapii genowej 1., 2., 3. and 4.. PNO mogą być spowodowane genetycznymi defektami przekazywanymi od rodziców albo nowopowstałą mutacją.