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EN
The aim of the study was comparison of inflammatory response intensity through estimation of CRP, IL-6 and WBC concentration in blood serum in patients before and after inguinal hernia operations with Stoppa and TEP method.Material and methods. The study involoved 117 patients operated on inguinal hernia between 2006-2008. The patients were divided into two groups. In the first group (group I - 56) Stopp'a method was used, in the second (group II - 61) TEP method. The patients selection was coincidental. All examined patients were men between 25-75 years old (mean age 54.3). Moreover, the operation's time, state of postoperative wound, the average hospitalization time and intensity of pain were estimated. The observations were directed over two weeks after operation.Results. The inflammatory response estimated with CRP, IL-6 concentration in blood serum was considerably higher in patients operated with Stoppa method. There wasn't observed a relevant difference in increase of white blood cells' concentration in both groups. Moreover, the patients operated on with TEP method experienced lower pain. In group, operated on with Stoppa method, 3 cases of wound healing complications were observed. The operation's time was considerably shorter in the first group. The hospitalization time, was considerably shorter in patients operated on with videoscopic method.Conclusions. The operation of inguinal hernia with TEP technique in comparison with Stopp'a method is connected with considerably lower inflammatory response of organism, what directly involve with postoperative pain abridgment and reduction of hospitalization time. Moreover it may have influence on frequency of postoperative complications related with wound healing.
EN
The aim of the study was to estimate the efficacy of surgically stabilizing long bone fractures within 48 hours in patients with severe multiple injuries following life-saving procedures and compensating for circulatory-respiratory parameters.Material and methods. The study comprised 364 patients with multiple injuries scoring 7 or more LSO points, who were admitted and treated university department during 1992-2000. Upon admission patients were documented on the basis of computer case histories of diseases and the standard calculation sheets. The assumption was that all long bone fractures in patients with multiple trauma would be stabilized within 48 hours. Parameters for operating were set so that the duration time of the operative procedure could not exceed 2 hours, and the amount of blood transfused could not exceed 2 units.Results. From among 364 patients with multiple traumas scoring 7 or more LSO points, 192 patients sustained long bone fractures that required surgical attention. One-third of the patients were female, the average age of the patients was nearly 45 years, and the average injure severity was 10.28 LSO points. 146 patients underwent 226 orthopaedic operations, out of which 127 were carried out in the first 24 hours, and 23 in the next 24 hours of the hospital stay. The mortality was 13.5%.Conclusions. Stabilization of the long bone fractures within the first 48 hours in patients with multiple traumas, after compensating circulatory parameters, is a life-saving treatment.
3
Content available remote Multicenter Study of Optimal Management Strategy in Severe Multiple Trauma
88%
EN
The aim of the study. The development of a triage system to implement proper treatment based on severity of injury.Material and methods. The study is based on material from three Polish Universities' trauma departments: Cracow, Lublin, and Gdańsk. Using trauma scales, 300 of the most severely injured multiple trauma (MT) patients from 2000-2004 have been chosen for this study. Medical documentation was carefully analysed, particularly the time and extent of the surgical procedures performed as well as their potential to influence later results.Results. There are three groups of patients:1 - critically injured, with an ISS>50, LSO>15, RTS 3 pts, two body cavity involvement, multiple long bone and/or pelvis fractures. Only damage control was allowed and the definitive treatment necessary was within 48 hours.2 - severely injured, with an unstable ISS 35-50, LSO 10-15, RTS 4-10 pts, one body cavity involvement, multiple long bone and/or pelvis fractures. Life-saving operations were possible with orthopaedic management (within 48 hours) provided using the "2+2 rule" (less than 2 hours of operation and no more than 2 units of blood transfused).3 - moderately injured, with a stable ISS<35, LSO<10, RTS>10 pts, one body cavity involvement, a long bone or pelvis fracture. Classic surgical and orthopaedic management occurred within 48 hours.Conclusions. The history and course of post-traumatic syndrome from metabolic, immune and endocrine viewpoints requires a special strategy for repairing life -threatening trauma injures at the right time, in proper sequence, and with limited surgical activity in more severe cases.
EN
The interaction of adrenergic agonists and/or antagonists with the adrenergic receptors expressed on immunologically active cells including macrophages plays an important role in regulation of inflammatory responses. Our study investigated the effects of carvedilol, a unique vasodilating b-adrenergic antagonist, and endogenous adrenergic agonists (adrenalin, noradrenalin, and dopamine) and/or antagonists (prazosin, atenolol) on lipopolysaccharide-stimulated nitric oxide (NO) production from murine macrophage cell line RAW 264.7. The production of NO was determined as the concentration of nitrites in cell supernatants (Griess reaction) and inducible nitric oxide synthase (iNOS) protein expression (Western blot analysis). Scavenging properties against NO were measured electrochemically. Carvedilol in a concentration range of 1, 5, 10 and 25 µM inhibited iNOS protein expression and decreased the nitrite concentration in cell supernatants. Adrenalin, noradrenalin or dopamine also inhibited the iNOS protein expression and the nitrite accumulation. Prazosine and atenolol prevented the effect of both carvedilol and adrenergic agonists on nitrite accumulation and iNOS expression in lipopolysaccharide-stimulated cells. These results, together with the absence of scavenging properties of carvedilol against NO, imply that both carvedilol and adrenergic agonists suppress the lipopolysaccharide-evoked NO production by macrophages through the activation and modulation of signaling pathways connected with adrenergic receptors.
PL
Rodzina czynników transkrypcyjnych NF-κ B pełni ważną rolę w regulacji odpowiedzi immunologicznej oraz profliferacji i przeżyciu komórek, w związku z czym niepoprawna aktywacja NF-κ prowadzi do poważnych problemów zdrowotnych. Jednak skomplikowany sposób aktywacji i regulacji NF-κ nie jest jeszcze w pełni zbadany. W tej pracy proponujemy i analizujemy dwie wersje modelu matematycznego uwzględniającego dodatnie sprzężenie zwrotne między NF-κB i cytokinami oraz ujemne sprzężenie zwrotne między NF-κB i jego inhibitorami. Ten model matematyczny obrazuje przejściową aktywację NF-κB, i jest jednocześnie na tyle prosty, aby pozwolić na otrzymanie analitycznych warunków na stabilność stanów stacjonarnych. Oczekujemy, że lepsze zrozumienie systemu regulacji NF-κB zwiększy efektywność terapii opartych na inhibicji tego czynnika transkrypcyjnego. Ponadto, zmodyfikowany model jest na tyle ogólny, że jego analiza może się okazać przydatna w modelowaniu innych procesów biologicznych.
EN
The family of transcription factors NF-κB plays a crucial role in immune response regulation, cell proliferation and cell survival; therefore, deregulated NF-κB activation results in severe health problems. However, its elaborate regulatory network is not yet fully understood. In this paper, we propose and analyze modifications of a mathematical model of the regulatory network that considers the positive feedback between NF-κB and cytokines and the negative feedback between NF-κBand its inhibitors. This mathematical framework captures the transient dynamics of NF-κB while remaining simple enough to obtain a stability condition of the equilibria. We anticipate that a deeper understanding of the NF-κB framework will increase the effectiveness of therapeutic strategies based on NF-κB inhibition.
9
Content available remote The effect of fiberoptic bronchoscopy on exhaled nitric oxide
75%
EN
Nitric oxide has been extensively studied as a noninvasive marker of airway inflammation. Assuming that bronchoscopy can produce not only systemic but also local inflammatory response, we hypothesized that bronchofiberoscopy can be responsible for an increase in nitric oxide synthesis with resulting increase in fractional concentration of exhaled nitric oxide (FENO). Fifty five subjects (F/M-23/32; mean age 53.9 ±17.3 yr) undergoing diagnostic bronchoscopy participated in the study. The indications for bronchoscopy were as follows: interstitial lung diseases (n=13; 23.6%), lung cancer (n=11; 20.0%), hemoptysis (n=10; 18.2%), differential diagnosis of asthma/dyspnea (n=9; 16.4%), pulmonary infections (n=7; 12.7%), and others (n=5; 9.1%). During bronchoscopy bronchial washing (n=18), bronchoalveolar lavage (BAL) (n=26), and bronchial biopsies (n=24) were performed. FENO was analyzed on-line with chemiluminescence analyzer (NIOX, Aerocrine, Sweden) according to the ATS guidelines, before and at 1, 2, 3 and 24 h after bronchoscopy. The mean FENO before bronchoscopy was 21.0 ±3.31(SE) ppb, it decreased to 14.8 ±2.10 ppb 1 h after bronchoscopy, reached a nadir at 2 h (14.4 ±2.28 ppb; P<0.05), and was not different from baseline 24 h after bronchoscopy (22.8 ±2.90 ppb). There were no differences in the FENO profile in BAL patients compared with those in whom only the bronchial washing was performed. We conclude that bronchoscopy leads to a decrease in FENO. The underlying mechanisms are at present unclear.
EN
 The bronchial epithelium is a very important factor during the inflammatory response, it produces many key regulators involved in the pathophysiology of asthma and COPD. Local influx of eosinophils, basophils, Th2 lymphocytes and macrophages is the source of many cytotoxic proteins, cytokines and other mediators of inflammation. These cells are attracted by eotaxins (eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26). Inhibitors of phosphodiesterase 4 (PDE4) are new anti-inflammatory drugs which cause cAMP accumulation in the cell and inhibit numerous stages of allergic inflammation. The aim of our study was to evaluate the influence of PDE4 inhibitors: rolipram and RO-20-1724 on the expression of eotaxins in human primary bronchial epithelial cells. Cells were preincubated with PDE4 inhibitors for 1 hour and then stimulated with IL-4 or IL-13 alone or in combination with TNF-α. After 48 hours, eotaxin protein level was measured by ELISA and mRNA level by real time PCR. These cells produce CCL24 and CCL26. PDE4 inhibitors increased CCL24 and CCL26 mRNA level irrespectively of the used stimulators. Rolipram and RO-20-1724 had no effect on eotaxin protein production in our experimental conditions. Thus PDE4 inhibitors have no effect on eotaxin protein expression in human primary bronchial epithelial cells. In vitro experiments should be performed using a primary cell model rather than immortalized lines.
EN
In the majority of potential applications gene therapy will require an effective transfer of a transgene in vivo resulting in high-level and long-term transgene expression, all in the absence of significant toxicity or inflammatory responses. The most efficient vehicles for delivery of foreign genes to the target tissues are modified adenoviruses. Adenoviral vectors of the first generation, despite the high infection efficacy, have an essential drawback: they induce strong immune response, which leads to short term expression of the transgene, and limits their usefulness in clinical trials. In contrast, helper-dependent adenoviral vectors (HdAd) lacking all viral coding sequences display only minimal immunogenicity and negligible side-effects, allowing for long-term transgene expression. Thus, HdAd vehicles have become the carrier of choice for adenoviral vector-mediated experimental gene therapy, effectively used in animal models for delivery of transgenes into the liver, skeletal muscle, myocardium or brain. Strong and long-lasting expression of therapeutic genes has allowed for successful treatment of dyslipidemias, muscular dystrophy, obesity, hemophilia, and diabetes. Additionally, the large cloning capacity of HdAd, up to 37 kb, facilitates the use of physiologically regulated, endogenous promoters, instead of artificial viral promoter sequences. This enables also generation of the single vectors expressing multiple genes, which can be potentially useful for treatment of polygenic diseases. In this review we characterize the basic features of HdAd vectors and describe some of their experimental and potential clinical applications.
17
Content available remote Functional analysis of eicosanoids from white blood cells in sepsis and SIRS
63%
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tom 57
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nr 12
25-33
EN
Sepsis and SIRS are affections with major alterations in inflammatory activity. The impact of prostaglandins (PG) and leukotrienes (LT) produced from white blood cells (WBC) in this context is not completely understood. Thirty nine patients with sepsis or SIRS were investigated in comparison to 10 healthy controls. WBC were collected and separately exposed to arachidonic acid (AA) or to nothing else. After centrifugation, the generated PGE2 and LTCDE4 with or without stimulation were measured in the supernatant. LT-levels were significantly higher during sepsis/SIRS than in controls whereas PG-levels of patients were decreased to those of controls in basic condition. The relation between the level with and without stimulation showed a significant higher ratio in PG in contrast to LTs. The survivor’s ratio in LT levels was significantly higher than that of non-survivors, which did not differ from controls. Generation of LT from WBC is enhanced during sepsis/SIRS, but LT generation after stimulation only in survivors but not in non-survivors. This inability of WBC to generate LT during sepsis in non-survivors could be predictive regarding the outcome of sepsis/SIRS and may be part of the “immunoparalysis” seen during sepsis in association with bad outcome.
EN
The family of transcription factors NF-κB plays a crucial role in immune response regulation, cell proliferation and cell survival; therefore, deregulated NF-κB activation results in severe health problems. However, its elaborate regulatory network is not yet fully understood. In this paper, we propose and analyze modifications of a mathematical model of the regulatory network that considers the positive feedback between NF-κB and cytokines and the negative feedback between NF-κB and its inhibitors. This mathematical framework captures the transient dynamics of NF-κB while remaining simple enough to obtain a stability condition of the equilibria. We anticipate that a deeper understanding of the NF-κB framework will increase the effectiveness of therapeutic strategies based on NF-κB inhibition. Moreover, the modified model is generic enough to prove useful in modelling different biological processes.
PL
Rodzina czynników transkrypcyjnych NF-κB pełni ważną rolę w regulacji odpowiedzi immunologicznej oraz profliferacji i przeżyciu komórek, w związku z czym niepoprawna aktywacja NF-κB prowadzi do poważnych problemów zdrowotnych. Jednak skomplikowany sposób aktywacji i regulacji NF-κB nie jest jeszcze w pełni zbadany. W tej pracy proponujemy i analizujemy dwie wersje modelu matematycznego uwzględniającego dodatnie sprzężenie zwrotne między NF-κB i cytokinami oraz ujemne sprzężenie zwrotne między NF-κB i jego inhibitorami. Ten model matematyczny obrazuje przejściową aktywację NF-κB, i jest jednocześnie na tyle prosty, aby pozwolić na otrzymanie analitycznych warunków na stabilność stanów stacjonarnych. Oczekujemy, że lepsze zrozumienie systemu regulacji NF-κB zwiększy efektywność terapii opartych na inhibicji tego czynnika transkrypcyjnego. Ponadto, zmodyfikowany model jest na tyle ogólny, że jego analiza może się okazać przydatna w modelowaniu innych procesów biologicznych.
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