Browsing by Author "Jaunalksne, Inta"
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Item Activation of coagulation and fibrinolysis in acute respiratory distress syndrome : a prospective pilot study(Vide Leaf, 2020-09-24) Ozoliņa, Agnese; Šarkele, Marina; Sabeļņikovs, Oļegs; Šķesters, Andrejs; Jaunalksne, Inta; Serova, Jeļena; Bjertnaes, Lars J.; Vanags, Indulis; Adeniji, Shola Elijah; Rīga Stradiņš University; Bioķīmijas zinātniskā laboratorijaIntroduction: Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS. Materials and Methods: We performed an ethically approved prospective observational pilot study. Inclusion criteria: patients with PaO2/FiO2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 hours, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria: age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA and PAI-1 at inclusion (T0) and on third (T3) and seventh day (T7) of the ICU stay with nonparametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic (ROC) curve analysis. Statistical significance: p < 0.05. Results: Of 24 patients at risk, six developed mild ARDS and four of each moderate or severe ARDS, respectively, 3 ± 2 (Mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher at T7 in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO2/FiO2 and PEEP and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78, p = 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77, p = 0.02. t-PA did not change significantly during the observation time. Conclusions: This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after seven days in ICU.Item Activation of coagulation and fibrinolysis in acute respiratory distress syndrome : A prospective pilot study(2016) Ozolina, Agnese; Sarkele, Marina; Sabelnikovs, Olegs; Skesters, Andrejs; Jaunalksne, Inta; Serova, Jelena; Ievins, Talis; Bjertnaes, Lars J.; Vanags, Indulis; Rīga Stradiņš University; Bioķīmijas zinātniskā laboratorijaIntroduction: Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS. Materials and methods: We performed an ethically approved prospective observational pilot study. Inclusion criteria were patients with PaO 2 /FiO 2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 h, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria were age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA, and PAI-1 at inclusion (tissue) and on third (T 3 ) and seventh day (T 7 ) of the ICU stay with non-parametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic curve analysis. Statistical significance: p < 0.05. Results: Of 24 patients at risk, 6 developed mild ARDS and 4 of each moderate or severe ARDS, respectively, 3 ± 2 (mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher at T7 in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO 2 /FiO 2 , and positive end-expiratory pressure and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78, p = 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77, p = 0.02. t-PA did not change significantly during the observation time. Conclusion: This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after 7 days in ICU.Item Ageing and production of the cytokines in Chernobyl clean-up workers from Latvia(2009) Kurjane, Nataļja; Bruvere, Ruta; Gabruševa, Natalija; Hagina, Elvira; Zvagule, Tija; Jaunalksne, Inta; Feldmane, Guna; Volrate, Arija; Voskresenska, NatalijaChronic low-grade inflammation with subsequent impairment of immune system function promotes the development of age-related diseases, such as cancers, degenerative and infection diseases. It is not yet clear, if exposure to ionising radiation accelerates the aging process. The aim of the present work was to estimate the production of several cytokines by peripheral blood cells of Latvia's Chernobyl clean-up workers depending on age. ELISA was employed to determine the plasma level of sIL-1β and sIL-6 as well as level of IL-4 and TNF-α spontaneous and 24h and 96h after in vitro stimulation of peripheral blood mononuclear cell cultures by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) mitogens were determined in 40 Chernobyl clean-up workers 17 years after their work in Chernobyl and in 42 blood-donors without a history of occupational radiation exposure. The ability of peripheral blood leukocytes (PBL) to produce interferons (IFNs) was determined in 73 Chernobyl clean-up workers 15 years after the work in Chernobyl and in age-matched 63 blood-donors. IFNs were tested in whole blood cultures by standard virus cytopathic inhibition micromethod after their in vitro induction by Newcastle disease virus, phytohemagglutinin or double-stranded RNA. Individuals were divided into three age groups: age < 40, age 40-49 and age > 50. The ability of PBL to produce IFN was significantly decreased in all Chernobyl clean-up worker age groups in comparison with blood-donors (control groups). The incidence of good ability to produce IFN gradually decreased with age in the control group, but increased with age in aged-matched Chernobyl clean-up workers groups. The production TNF-α and IL-4 by peripheral blood mononuclear cells as well as sIL-1β level in plasma showed no significant differences between all the examined age groups. The sIL-6 level was gradually increased with age in Chernobyl clean-up workers. Our results showed that the concentration of pro-inflammation cytokine sIL-6 in peripheral blood plasma, as well as the ability of PBL to produce IFNs, in Chernobyl clean-up workers from Latvia is age dependent.Item Cellular immunity in human herpes viruses 6 and 7 infected gastrointestinal cancer patients(2009) Jaunalksne, Inta; Doniņa, Simona; Čapenko, Svetlana; Čistjakovs, Maksims; Murovska, Modra; Institute of Microbiology and VirologyCD4+ T lymphocytes appear to be the preferential target for replication of HHV-6 (human herpes virus) as well as HHV-7 viruses in vivo. In addition, CD8+ T cells, monocytes/macrophages, natural killer cells, epithelial, endothelial, neural cells and fibroblasts may be infected. By definition, however, even a tumour designated by pathologists to be early stage may be late stage when considered by the immune system. Certainly, even early stage tumours have evaded immune control, suggesting that they have acquired many immunosuppressive characteristics. The aim of the study was to clarify the influence of beta-herpes viruses on cellular immune response. In 95 gastrointestinal cancer patients we determined the immunocompetent cell level CD3, CD4, CD8, CD19, CD38, CD95, CD25 using laser flow cytofluorimeter and B- herpes viruses HHV-6, HHV-7 presence using a nested polymerase chain reaction method. Our data showed no statistically significant difference in immunocompetent cell level between negative, latent and active HHV-6, HHV-7 infection. Patients with immunocompromised immune status (lymphopenia) had a tendency to decreased CD4+, CD19+ absolute count. It may be suggested that virus-mediated immune response inhibition seems to be similar to cancer mediated, but differences in immune response among the same group of individuals had no influence on the average number of the immunocompetent cells in the group. Therefore, to characterise host-virus-tumour interactions, individual interpretation of each case is needed.Item Clinical Impact and Relevance of Antiganglioside Antibodies Test Results(2015-09-01) Ķēniņa, Viktorija; Gālzere, Ieva; Ziemele, Dace; Jaunalksne, Inta; Department of Neurology and NeurosurgeryAutoantibodies most commonly found in association with neuropathies are those against the ganglioside family antigens-GM1, GQ1b, asialo-GM1, GM2, GD1a, and GD1b. The major diagnostic role is set for two of antibodies-anti-GM1 and anti-GQ1b. This retrospective study was designed to evaluate the status of antiganglioside antibodies in patients with possible autoimmune neuropathy. The study included 85 patients tested for antiganglioside antibodies during their hospitalization. Clinical information such as demographic data and antecedent illness was collected for all patients, and paraclinical studies including results from cerebrospinal fluid and neuroelectrophysiological examination were analyzed. In our study, a total of 27 patients (32%) were found positive for at least one antiganglioside antibody. The most commonly found antibodies were against asialoGM1 (n=13) and GM1 (n=10) gangliosides. Eight patients were diagnosed with a disease where antiganglioside antibodies are used as a diagnostic marker: five patients-Guillain-Barré syndrome (GBS), 1 patient-Miller-Fisher syndrome (MFS), two patients-multifocal motor neuropathy (MMN). Three out of five patients diagnosed with GBS and one of two patients diagnosed with MMN were seronegative. The acute course of disease, positive antiganglioside antibodies and cytoalbuminologic dissociation in cerebrospinal fluid-induced patients is preference for a specific immune therapy. The results of our study support the previously described immunological association between antiganglioside antibodies and GBS, MFS, and MMN.Item Combination treatment with nivolumab and Rigvir of a progressive stage IIC skin melanoma patient(2019-06) Brokāne, Linda; Jaunalksne, Inta; Tilgase, Andra; Olmane, Evija; Petroška, Donatas; Rasa, Agnija; Alberts, PēterisA 35-year-old male patient was diagnosed with stage IIC skin melanoma that rapidly progressed after surgery. Treatment was continued with radiotherapy, which did not stop further spread of disease and the patient was put on a combination of nivolumab and Rigvir. Subsequently, the progression has slowed.Item Effects of Different Epidural Analgesic Compositions on Postoperative Pain Relief and Systemic Response to Surgery(2008-01) Golubovska, Iveta; Studers, Peteris; Jaunalksne, Inta; Vanags, Indulis; Department of Anaesthesiology, Intensive Care and Clinical simulationsDespite many achievements during the last decade, postoperative pain remains the dominant complaint after major surgery and has great potential to be influenced by the anaesthesiologist. Reports suggest that short-term effective anaesthesia and analgesia can have long-lasting beneficial effects on recovery from surgery. The aim of our study is to compare the effect of epidural analgesia, using different compositions, including glucocorticoids (methylprednisolone), and habitual composition of bupivacaine-morphine, in regard to analgesic and anti-inflammatory properties. A total of 129 patients participated in the study in four different treatment groups: patients from Group I received glucocorticoid methylprednisolone succinate and long-acting opioid morphine hydrochloride, Group II received local anaesthetic bupivacaine hydrochloride and morphine hydrochloride, Group III received methylprednisolone succinate and short-acting opioid fentanyl, and Group IV received glucocorticoid methylprednisolone succinate. We obtained good analgesic profiles in all groups. However, significantly better results were achieved using the combination of methylprednisolone and morphine. Epidural methylprednisolone in dose 80 mg/24 h is more effective, compared to the conventional local anaesthetics-opioid composition, when administered as a part of multimodal preventive postoperative analgesia after major joint replacement surgery. Epidural methylprednisolone has a reliable anti-inflammatory and immunomodulatory potential. It attenuates profiles of acute inflammatory response markers as Interleukin-6 and C-reactive protein and stress hormone cortisol. The novelty of this study was application of epidural glucocorticoids for acute postoperative pain relief as part of daily perioperative care. By developing studies on anti-inflammatory and immunomodulatory properties of glucocorticoids, we expect to improve patient rehabilitation in the postoperative period.Item PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass(2012-10-30) Ozolina, Agnese; Strīķe, Eva; Jaunalksne, Inta; Krumina, Angelika; Bjertnaes, Lars J.; Vanags, Indulis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Department of InfectologyBackground: Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor - 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding.Methods: Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS.Results: Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = - 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively.Conclusions: Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.Item Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery(2015-09-04) Ozolina, Agnese; Strike, Eva; Nikitina-Zake, Liene; Jaunalksne, Inta; Krumina, Angelika; Lacis, Romans; Bjertnaes, Lars J.; Vanags, Indulis; Rīga Stradiņš University; Department of InfectologyBackground: Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. Methods: We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. Results: The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. Conclusions: Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.Item Relation of endothelial dysfunction and adipokines levels to insulin resistance in metabolic syndrome patients(2009) Tretjakovs, Peteris; Jurka, Antra; Bormane, Inga; Miķelsone, Indra; Reihmane, Dace; Balode, Liga; Jaunalksne, Inta; Mackevičs, Vitolds; Stuķena, Inga; Bahs, Guntis; Lejnieks, Aivars; Aivars, Juris; Pirags, Valdis; Rīga Stradiņš UniversityObese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P < 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P < 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P < 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P < 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P < 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P < 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.Item The role of oxidative stress markers in developing of acute respiratory distress syndrome(2014-12-01) Sarkele, Marina; Ozoliņa, Agnese; Sabeļņikovs, Oļegs; Šķesters, Andrejs; Silova, Alise; Jaunalksne, Inta; Strīķe, Eva; Krūmiņa, Angelika; Vanags, Indulis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Bioķīmijas zinātniskā laboratorija; Department of InfectologyAcute respiratory distress syndrome (ARDS) is common and multi factorial, clinically described as an inflammatory lung disorder that is associated with major morbidity and high mortality in intensive care patients. Recently, investigators have revised the AECC criteria from 1994. To diagnose ARDS and discover its severity we presently use Berlin definition criteria. An important role in developing of ARDS may be through a disbalance between reactive oxygen species (ROS), which have both oxidant and antioxidant compartments. The pathogenesis of ARDS is very complex, and unfortunately, the dynamic development of ARDS in an individual patient is difficult to recognise. ROS can initiate cellular tissue damage by modifying lipids, proteins and DNA, which can seriously compromise cell life ability or induce a large number of cellular responses through generation of secondary reactive species, leading, at last, to cell death by necrosis or apoptosis. Studies have shown that many patients with organ malfunction at admission to the intensive care units (ICU) show decreased antioxidative properties, worsening the harmful effects of lipid peroxidation. That is the reason why predicting development of ARDS has great value for intensive care specialists.