Preparation of the donor to the removal of organs — the most common clinical problems

Przeszczepienie narządu to najskuteczniejsza metoda leczenia, gdy dochodzi do jego niewydolności. W procesie transplantacji ważne jest przygotowanie dawcy tak, aby możliwe było pobranie wielonarządowe. Na przeszkodzie temu stoi wiele procesów patofizjologicznych rozwijających się po śmierci mózgu. W części przypadków mają one bezpośredni związek z powstającą „burzą cytokinową”, a część problemów wynika z samego pobytu dawcy na oddziale intensywnej terapii — zwiększa się ryzyko rozwoju zakażeń szpitalnych. W pracy zaprezentowano najczęstsze problemy stojące na przeszkodzie pobrania jak największej liczby narządów w celu ocalenia życia innym pacjentom.An organ transplantation is the most effective method of treatment when the organ is becoming insuficient. In the process of the transplant arrangements it’s important to prepare donor for multiorgan donation. Many pathophysiological processes after the brain death making it imposible. In some cases those disorders are caused by cytokines and in the others higher risk of nosocomial infection during the treatment in ICU. In this article were presented the most common problems of multiorgan donation, which make donation impossible or less effective

Expression of selected angiogenesis-related small microRNAs in patients with abnormally increased secretion of glucocorticoids

Introduction: Higher cortisol levels are associated with cardiovascular morbidity and mortality in the elderly, partially resulting from biologic effects of glucocorticoids (GCs) on endothelial cells observed in an experimental setting. These features are replicated in patients with endogenous GC excess (Cushing’s syndrome) or with exogenous hypercortisolism due to excessive pharmacological application of GCs. Both groups present also an increased cardiovascular disease event rate. GCs may also adversely influence recovery after myocardial infarction. Recently it was proposed that microRNAs (miRNAs) — small noncoding RNAs functioning as antisense regulators of gene expression by targeting mRNA — may have a central role in regulating endothelial function through multiple mechanisms. Thus, the purpose of this study was to evaluate the effects of chronic GC excess on the expression of selected endothelium-controlling miRNAs expressed in nucleated cells circulating in peripheral blood (PBNCs) of patients with endogenous hypercortisolism either due to corticotrophin‐independent or corticotrophin‐dependent Cushing’s syndrome (CS). Material and methods: Peripheral blood nuclear cells were collected from 35 healthy subjects and 31 patients with endogenous hypercortisolism as a source of miRNAs. A self-validated individual quantitative RT-PCR study was then performed to evaluate the expression levels of selected miRNAs in PBNCs. Additionally, endothelin-1 (ET-1) expression in peripheral blood was assessed with respect to endothelial dysfunction using Western blotting. Results: The ET-1 expression levels in CS were higher than in controls, confirming endothelial dysfunction in the CS group. Furthermore, miRNA analysis revealed a significantly decreased intracellular expression of selected endothelium-related miRNAs in patients with endogenous hypercortisolism, including miRNA-17-5p, miRNA-126-3p, and miRNA-126-5p, compared to controls. In contrast, two other angiogenic miRNAs, miRNA-150-5p and miRNA-223-3p, were significantly upregulated compared to controls. Conclusions: Cardiovascular events related to hypercortisolism remain a challenging problem in medical practice. This study has demonstrated that the chronic excess of GCs in endogenous CS might induce significant dysregulation of selected miRNAs involved in the control of endothelium biology. However, the lack of knowledge about specific miRNA expression postpones the full understanding of the biological roles of such miRNAs in hypercortisolism. Moreover, dysregulated miRNAs seem to be promising targets for further research, especially to search for potential therapies for several GC-induced cardiovascular complications

Remifentanil for labour pain relief

Labour is thought to be one of the most intense and painful experiences in a woman’s life. Numerous studies using a Visual Analogue Scale invariably demonstrate that 20% of women in labour describe the pain as “unbearable” and 60% describe the pain as “very intense”. Since the mid-1980s, continuous epidural analgesia during labour has been considered the gold standard of labour anaesthesia and is currently the most frequently used. There are situations in which this type of analgesia could not be used. An alternative pain management is administration of parenteral opioids, the most frequently used of which is pethidine. Its use is associated with adverse effects and unsatisfactory analgesia. Since the second half of the 20th century, a new generation of opioids, such as fentanyl or remifentanil, has been used. Despite their much better pharmacokinetic and pharmacodynamic parameters, obstetricians, midwives and neonatologists are most aware of pethidine, probably because it has been used for the longest period of time, despite its disadvantages and the risk that its use entails. The drug that is nearest to ideal is remifentanil. The countries in which it is widely used as an alternative type of labour anaesthesia have developed practice standards or guidelines practice. Guidelines and alternatives to pethidine protocols for effective labour analgesia in Poland might be merited.Labour is thought to be one of the most intense and painful experiences in a woman’s life. Numerous studies using a Visual Analogue Scale invariably demonstrate that 20% of women in labour describe the pain as “unbearable” and 60% describe the pain as “very intense”. Since the mid-1980s, continuous epidural analgesia during labour has been considered the gold standard of labour anaesthesia and is currently the most frequently used. There are situations in which this type of analgesia could not be used. An alternative pain management is administration of parenteral opioids, the most frequently used of which is pethidine. Its use is associated with adverse effects and unsatisfactory analgesia. Since the second half of the 20th century, a new generation of opioids, such as fentanyl or remifentanil, has been used. Despite their much better pharmacokinetic and pharmacodynamic parameters, obstetricians, midwives and neonatologists are most aware of pethidine, probably because it has been used for the longest period of time, despite its disadvantages and the risk that its use entails. The drug that is nearest to ideal is remifentanil. The countries in which it is widely used as an alternative type of labour anaesthesia have developed practice standards or guidelines practice. Guidelines and alternatives to pethidine protocols for effective labour analgesia in Poland might be merited

IL-18 Gene rs187238 and rs1946518 Polymorphisms and Expression in Gingival Tissue in Patients with Periodontitis

Periodontitis is a chronic disease with disturbed balance between the immune and inflammatory response of the host to bacteria. Many studies have shown that proinflammatory cytokines play a significant role in the pathogenesis of periodontal disease. In this study, we examined the association between the IL-18 gene rs187238 and rs1946518 polymorphisms and periodontitis in non-smoking and smoking patients. This study enrolled 200 patients with periodontitis (130 non-smokers and 70 smokers) and 156 control subjects (124 non-smokers and 32 smokers). There were no statistically significant differences in the distribution of the rs187238 and rs1946518 IL-18 genotypes and alleles between patients with periodontitis and control subjects, between smoking patients with periodontitis and smoking control subjects, and between non-smoking patients with periodontitis and non-smoking control subjects. There were no statistically significant differences in clinical parameters in relation to the IL18 rs187238 genotypes. In patients with the IL18 rs1946518 GG genotype, we observed increased values of bleeding on probing (BoP) and periodontal probing depth (PPD), compared to subjects with the TT genotype. In patients with periodontitis, we observed statistically significant decreased expression of the IL-18 gene in comparison with healthy subjects (0.231 ± 0.163 vs. 0.663 ± 0.197, p = 0.0008). In addition, the IL-18 gene expression in gingival tissue in patients with periodontitis correlated positively with the number of remaining teeth. The results of our study suggest that the IL-18 rs187238 and rs1946518 polymorphisms are not significant risk indicators of periodontitis in our population. However, in patients with the IL18 rs1946518 GG genotype, we observed increased values of BoP and PPD, compared to subjects with the TT genotype. In addition, in gingival tissue of patients with periodontitis, we have detected decreased expression of IL-18. The gingival expression of IL-18 in patients with periodontitis correlated positively with number of remaining teeth. The above results suggest that IL-18, in addition to its pro-inflammatory effects in periodontal disease, may also exhibit protective properties

Differential Secretion of Angiopoietic Factors and Expression of MicroRNA in Umbilical Cord Blood from Healthy Appropriate-For-Gestational-Age Preterm and Term Newborns—in Search of Biomarkers of Angiogenesis-Related Processes in Preterm Birth

Objectives: Premature birth, defined as less than 37 weeks gestation, affects approximately 12% of all live births around the world. Advances in neonatal care have resulted in the increased survival of infants born prematurely. Although prematurity is a known risk factor for different cardiovascular diseases, little is known about the pathophysiology of vasculature during premature gestation and angiopoietic factors network during premature birth. Aims: The objective of this study was to determine whether the profile of several pro-angiogenic and anti-angiogenic factors in umbilical cord blood (UCB) is different in healthy appropriate-for-gestational-age preterm newborns and normal term babies. The second aim of this study was to investigate the microRNA (miRNAs) expression profile in UCB from preterm labor and to detect miRNAs potentially taking part in control of angogenesis-related processes (Angio-MiRs). Methods: Using an immunobead Luminex assay, we simultaneously measured the concentration of Angiogenin, Angiopoietin-1, FGF-acidic, FGF-basic, PDGF-aa, PlGF, VEGF, VEGF-D, Endostatin, Thrombospondin-2, NGF, BDNF, GDNF, and NT-4 in UCB samples collected from the preterm (n = 27) and term (n = 52) delivery. In addition, the global microRNA expression in peripheral blood mononuclear cells (PBMCs) circulating in such UCB samples was examined in this study using microarray MiRNA technique. Results: The concentrations of five from eight measured pro-angiogenic factors (VEGF, Angiopoietin-1, PDGF-AA, FGF-a, and FGF-b) were significantly lower in UCB from preterm newborns. On the contrary, two angiostatic factors (Endostatin and Thrombospondin-2) were significantly up-regulated in preterm UCB. Among analyzed neurotrophins in preterm newborns, the elevated UCB concentration was found only in the case of GDNF, whereas BDNF was significantly reduced. Moreover, two angiopoietic factors, VEGF-D and PlGF, and two neurotrophins, NT4 and NGF, did not differ in concentration in preterm and term babies. We also discovered that among the significantly down-regulated miRNAs, there were several classical Angio-MiRs (inter alia MiR-125, MiR-126, MiR-145, MiR-150, or MiR155), which are involved in angiogenesis regulation in newborn after preterm delivery. Conclusions: This is the first report of simultaneous measurements of several angiopoietic factors in UCB collected from infants during preterm and term labor. Here, we observed that several pro-angiogenic factors were at lower concentration in UCB collected from preterm newborns than term babies. In contrast, the two measured angiostatic factors, Endostatin and Thrombospondin-2, were significantly higher in UCB from preterm babies. This can suggest that distinct pathophysiological contributions from differentially expressed various angiopoietic factors may determine the clinical outcomes after preterm birth. Especially, our angiogenesis-related molecules analysis indicates that preterm birth of healthy, appropriate-for-gestational-age newborns is an “anti-angiogenic state” that may provide an increased risk for improper development and function of cardiovascular system in the adulthood. This work also contributes to a better understanding of the role of miRNAs potentially involved in angiogenesis control in preterm newborns

Plasma Levels of Interleukins 36α, 36β, and 37 in Patients with Psoriasis and Their Correlation with Disease Activity Parameters

Psoriasis is a chronic, proliferative, inflammatory skin disease characterised by skin lesions and systemic symptoms. Numerous cytokines are produced in psoriasis as a result of inflammation. The aim of this study was to examine the plasma concentrations of IL-36α, IL-36β, and IL-37 in psoriasis and their correlations with disease activity parameters. This study recruited 84 individuals, 53 with plaque-type psoriasis and 31 healthy controls. The plaque type of psoriasis is the most common type and is typically characterized by circular-to-oval red plaques distributed over body surfaces of the extremities and scalp. In patients with psoriasis, we observed statistically significantly decreased plasma concentrations of IL-36β and IL-37. The concentrations of IL-36α were increased in comparison with control group. The plasma concentrations of IL-36α and IL-36β were statistically significantly correlated with all tested parameters of disease activity: the Psoriasis Activity Severity Index, Dermatology Life Quality Index, and Body Surface Area Index. There were no statistically significant correlations between plasma levels of IL-37 and the tested parameters of disease activity. These results indicate a role of IL36α, IL-36β, and IL-37 in the pathogenesis of psoriasis