Wojciech Dąbrowski

Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells

Abstract Background. Kynurenic acid (KYNA), a tryptophan metabolite, was found in human saliva, gastric juice, bile, pancreatic juice and mucus of rat small intestine. Methods. KYNA content in mucus aspirated from human caecum or colon ascendens and KYNA production in colon epithelial and cancer cells were determined using HPLC. Moreover, biological properties of KYNA and kynurenine aminotransferases (KATs) expression in colon epithelial and colon cancer cells were studied. Results. Considerably higher KYNA concentration was detected in samples from patients diagnosed with colon carcinoma (269.40 ± 107.00 pmol/ml, N = 4), Adenoma tubulovillosum (200.50 ± 36.72, N = 10) or Adenoma tubulare (243.50 ± 38.09, N = 9) than in control group (82.22 ± 7.61 pmol/ml, N = 30). Moreover, colon epithelium CCD 841 CoTr cells actively synthesized KYNA in a concentration- and time-dependent manner. This process was decreased by aminooxyacetic acid and L-glutamate in opposite to 4-aminopyridine treatment. Interestingly, KYNA production in colon cancer cells (HT-29 1.39 ± 0.27, LS-180 1.18 ± 0.15 and Caco-2 4.21 ± 0.30 pmol/1 × 105 cells/2 h) was considerably higher in comparison to normal colon epithelial cells (0.70 ± 0.07 pmol/1 × 105 cells/2 h). However, KATs I and II were expressed at similar level in both colon epithelium and cancer cells. Furthermore, KYNA exerted an antiproliferative effect at higher micro- and milimolar concentrations against colon cancer cells with the IC50 of 0.9, 0.2 and 1.2 mM for HT-29, LS-180 and Caco-2 cells, respectively. Conclusion. Summarizing, this is the first report presenting KYNA synthesis and KAT expression in colon derived normal and cancer cells.

Intra-Abdominal Pressure Correlates with Extracellular Water Content

Background Secondary increase in intra-abdominal pressure (IAP) may result from extra-abdominal pathology, such as massive fluid resuscitation, capillary leak or sepsis. All these conditions increase the extravascular water content. The aim of this study was to analyze the relationship between IAP and body water volume. Material and Methods Adult patients treated for sepsis or septic shock with acute kidney injury (AKI) and patients undergoing elective pharyngolaryngeal or orthopedic surgery were enrolled. IAP was measured in the urinary bladder. Total body water (TBW), extracellular water content (ECW) and volume excess (VE) were measured by whole body bioimpedance. Among critically ill patients, all parameters were analyzed over three consecutive days, and parameters were evaluated perioperatively in surgical patients. Results One hundred twenty patients were studied. Taken together, the correlations between IAP and VE, TBW, and ECW were measured at 408 time points. In all participants, IAP strongly correlated with ECW and VE. In critically ill patients, IAP correlated with ECW and VE. In surgical patients, IAP correlated with ECW and TBW. IAP strongly correlated with ECW and VE in the mixed population. IAP also correlated with VE in critically ill patients. ROC curve analysis showed that ECW and VE might be discriminative parameters of risk for increased IAP. Conclusion IAP strongly correlates with ECW.

Acute left main coronary artery occlusion following inadvertent delivery of radiofrequency energy during ventricular tachycardia ablation successfully treated by rescue angioplasty with stenting: A two-year follow-up

Radiofrequency catheter ablation (RFCA) is a treatment mode in patients with recurrent, symptomatic, ventricular arrhythmias. A rare but potentially life-threatening complication of RFCA includes injury to the coronary arteries, which leads to acute occlusion and myocardial infarction. In the few reported cases, the most frequently affected vessel has been the left main coronary artery. We present the case of a 28 year-old female. During the RFCA procedure, an acute occlusion of the left main coronary artery occurred, which was treated successfully with emergency angioplasty.

Carotid surgery affects plasma kynurenic acid concentration: a pilot study.

Background An increase in plasma kynurenic acid (KYNA) concentration has been observed following surgery, inflammation, and cerebral pathologies. The aim of the present study was to analyze the changes in plasma KYNA concentration in patients undergoing carotid surgery (CS). Material/Methods Adult patients undergoing elective carotid endarterectomy (CEA) or carotid angioplasty with stent placement (CAS) were studied. Plasma KYNA concentrations were analyzed before surgery and at 4 time points after CS. The amount of inflammation was measured as neutrophil-lymphocyte ratio (NLR). Results Forty patients (10 female and 30 male) aged 55–86 years of age were evaluated in this study. In patients with unstable carotid plaque, the plasma KYNA concentration was higher than in patients with stable carotid plaque. Moreover, the NLR was significantly higher in patients with unstable carotid plaque undergoing CEA than in patients undergoing CAS. Plasma KYNA concentration increased after surgery in patients undergoing CEA and CAS. There was a strong correlation between plasma KYNA concentration and NLR in patients with postoperative neurological disorders. Conclusions CS increases plasma KYNA concentration, and changes in plasma KYNA concentration can indicate neurologic outcomes in patients undergoing CS.

Kynurenic Acid in Plasma and Endometrium in Bitches with Pyometra

Kynurenic acid (KYNA) is produced enzymatically in humans and animals from kynurenine. Reports concerning changes of kynurenine metabolism during inflammation are available in the literature. Pyometra is a pathological condition characterized by the accumulation of pus in the uterine lumen and bacterial infection. The objective of the study was to compare the serum and endometrial KYNA concentrations in healthy bitches and those with pyometra. KYNA was determined by means of high-performance liquid chromatography with fluorometric detection. The serum content of KYNA in bitches with pyometra was significantly higher than in healthy bitches. The KYNA content in the endometrium of bitches with pyometra was higher, yet the difference was not statistically significant. Our result indicates that determination of KYNA might be a marker of pyometra in bitches.

[Kynurenic acid--a new tool in the treatment of hiperhomocysteinemia and its consequences?].

Atherosclerosis together with its cardiovascular consequences is the most common and significant cause of death, particularly in highly developed countries. The process of atherogenesis begins as soon as in childhood and depends on classical risk factors. Atherosclerosis also results from a chronic inflammatory-immune process which takes place in the vascular walls. Furthermore, it has been known for a number of years that the development of atherosclerotic lesions is closely connected with the concentration of homocysteine in serum. Homocysteine is a sulfur amino acid originating from methionine. An increased concentration of homocysteine in blood harmfully influences blood vessels, leading to a higher risk of ischemic heart disease and stroke. Since tackling classical atherosclerosis risk factors is not efficient enough when it comes to protecting the cardiovascular system from diseases, new substances possessing anti-atherogenic properties, especially endogenous ones, are sought. Recently, researchers have paid attention to a connection between homocysteine and an endogenous tryptophan derivative, kynurenic acid. Recently, it was revealed that kynurenic acid counteracts the harmful effects of homocysteine on endothelium cells in vitro. The hypothesis assuming homocysteine-kynurenate interplay suggests the existence of a new mechanism of atherogenesis and gives us an opportunity to use this knowledge in both prevention and treatment of cardiovascular diseases.

Syndecan-4 Is an Independent Predictor of All-Cause as Well as Cardiovascular Mortality in Hemodialysis Patients

Background Left ventricular hypertrophy is associated withincreased mortality in hemodialysis (HD) patients.Syndecan-4 plays a role in many processes that are involved in the heart fibrosis and hypertrophy.We designed this study to prospectively determine whether syndecan-4 was predictive of mortality in a group of HD patients. Methods In total, 191 HD patients were included. Clinical, biochemical and echocardiographic parameters were recorded. HD patients were followed-up for 23.18 ± 4.02 months. Results Syndecan-4 levels correlated strongly with geometrical echocardiographic parameters and ejection fraction. Relations with pressure-related parameters were weak and only marginally significant. Using the receiver operating characteristics the optimal cut-off points in predicting all-cause as well as cardiovascular (CV) mortality were evaluated and patients were divided into low and high syndecan-4 groups. A Kaplan–Meier analysis showed that the cumulative incidences of all-cause as well as CV mortality were higher in high serum syndecan-4 group compared with those with low serum syndecan-4 (p<0.001 in both cases).A multivariate Cox proportional hazards regression analysis revealed syndecan-4 concentration to be an independent and significant predictor of all-cause (hazard ratio, 2.99; confidence interval, 2.34 to 3.113; p<0.001)as well as CV mortality (hazard ratio, 2.81;confidence interval, 2.28to3.02; p<0.001). Conclusions Serum syndecan-4 concentration reflects predominantly geometrical echocardiographic parameters. In HD patients serum syndecan-4 concentration is independently associated with all-cause as well as CV mortality.

Antioxidative mechanism in the course of varicose veins

Objective Our objective was to evaluate the state of oxidative stress in the great saphenous varicose vein wall and blood of varicose vein patients taken from the antecubital vein. Methods The superoxide dismutase, reduced glutathione (GSH) and total antioxidant status were measured with commercially available colorimetric kits in erythrocytes, plasma and varicose vein wall of 65 patients (second degree of clinical state classification, etiology, anatomy and pathophysiology) aged 22–70 (49 women, 16 men) in comparison to normal great saphenous vein walls collected from 10 patients who underwent coronary artery bypass graft and blood collected from 20 healthy individuals. Results A statistically significant decrease (p < 0.001) in superoxide dismutase activity in erythrocytes and the increase (p < 0.05) in superoxide dismutase activity in varicose vein has been observed. There have been no significant changes in the concentration of GSH in plasma and in varicose vein. The decreased concentration of total antioxidant status in plasma (p < 0.001) and in varicose vein wall (p < 0.05) in comparison to the control has been noticed. Conclusion The varicose vein patients are affected by oxidative stress. Our results indicate impaired antioxidant defense mechanism in the blood of varicose vein patients. In contrast to the blood, an increased process of antioxidant defense in the varicose vein wall was noticed.

Leigh syndrome in individuals bearing m.9185T>C MTATP6 variant. Is hyperventilation a factor which starts its development?

Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C MTATP6 variant. Mechanism of LS development remains unknown. We report on the acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hyperventilation with low pCO2). In patient 1, the deterioration occurred in temporal relation to passive oxygen therapy. To the contrary, on the recovery, she demonstrated a relatively low respiratory drive, suggesting that a “hypoventilation” might be beneficial for m.9185T>C carriers. As long as circumstances of the development of LS have not been fully explained, we recommend to counteract hyperventilation and carefully dose oxygen in patients with m.9185T>C related LS.

Effectiveness of Haemophilus influenzae type b vaccination after splenectomy - impact on selected immunological parameters

ABSTRACT Splenectomy is a surgery indicated in case of splenic rupture after injury, when there are tumors in the spleen, or as a treatment for certain diseases, such as idiopathic thrombocytopenic purpura and spherocytosis. The aims of the study were to assess the immunological response to the Haemophilus influenzae type b (Hib) vaccine and the post-vaccination changes in lymphocyte subsets and cell activation markers in splenectomized patients and healthy volunteers. Blood samples were collected from 25 patients that had undergone splenectomy and from 15 healthy, non-splenectomized volunteers. All participants received a single dose of Hib vaccine. The concentration of specific Hib antibodies was assessed by an enzyme-linked immunosorbent assay. Selected immune cell populations were evaluated using flow cytometry. The analysis of the antibody titers against Hib showed statistically significant differences in both groups. There was a significantly higher percentage (p = 0.0012) and absolute value (p = 0.0003) of natural killer T (NKT)-like cells (CD3+/CD16+ CD56+) in the study group, compared to the control group. The levels of natural killer (NK) and NKT cells did not change relative to the cause and age of splenectomy. The quantity and percentage of regulatory T (Treg) cells were higher in the study group compared to the control group (p < 0.0001). No significant correlations were found between the time elapsed since splenectomy, the age of the patients, and the Treg levels. Our study showed that spleen resection results in an important deterioration of Treg cells and Th17 cell balance which may contribute to an incomplete immunological response.