Assessment of NLRP3 inflammasome activation in patients with chronic obstructive pulmonary disease before and after lung transplantation.

The interplay between purinergic receptors as well as pattern recognition receptors like Toll-like receptors (TLRs) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) might have a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to determine and compare the concentrations of the damage-associated molecular patterns (DAMPs) heat shock protein 70 (Hsp70) and adenosine triphosphate (ATP), and gene expression of their respective receptors as well as NLRP3 inflammasome-related molecules in the peripheral blood of patients with end-stage COPD before and 1 year after lung transplantation (LT). Lung function was assessed by spirometry and diffusion capacity for carbon monoxide (DLCO). Quantitative polymerase chain reaction (qPCR) was applied for detection of TLR2, TLR4, P2X7R, P2Y2R, IL1B, CASP1, and NLRP3 expression. High-sensitivity ELISA kits were used for extracellular (e) Hsp70 and IL-1ß, and luminescence assay for eATP measurements. Concentrations of eHsp70 and eATP as well as IL-1ß were significantly increased in the plasma of end-stage COPD patients and significantly decreased after LT. In addition, TLR4, P2Y2R, IL1B, CASP1, and NLRP3 expression was up-regulated in COPD patients before LT, while it was significantly suppressed after LT. In conclusion, it could be assumed that NLRP3 inflammasome is activated in the peripheral blood of end-stage COPD patients and that eHsp70 and eATP could be responsible for its activation through triggering their receptors. On the other hand, previously enhanced pro-inflammatory reactions seem to be suppressed to the healthy population levels in lung recipients without allograft rejection.

Pseudoaneurysm as an Etiological Cause of Hemoptysis in Extensive Tuberculosis.

Hemoptysis is a life-threatening emergency and a possible first sign of pulmonary tuberculosis. Minor hemoptysis, as a possible clinical aspect of adult tuberculosis, usually has limited course and in most cases, is resolved with antitubercular therapy. However, massive hemoptysis is a life-threatening condition associated with a mortality rate of >50% in the absence of well-timed and proper handling. Hence, prompt diagnosis and early interventions are essential. In this study, we present a rare case of pseudoaneurysm causing massive hemoptysis in a patient with pulmonary tuberculosis.

Activation of NLRP3 inflammasome in stable chronic obstructive pulmonary disease.

Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays an important role in chronic obstructive pulmonary disease (COPD) pathogenesis and might be involved in ongoing chronic inflammation. This study aimed to determine interleukin-1beta (IL-1ß) plasma concentration as well as IL1B, NLRP3 and caspase-1 (CASP1) gene expression in the Croatian COPD patients. 109 patients with stable COPD and age- and sex-matched 95 controls were included in the study. Plasma IL-1ß concentration was measured by Luminex technology, and gene expression analysis was performed using TaqMan assays. It was shown that COPD patients had increased concentration of IL-1ß and enhanced gene expression of IL1B, NLRP3 and CASP1 compared to controls. There was no difference in IL-1ß or IL1B, NLRP3 and CASP1 in patients with COPD regarding airflow obstruction severity and smoking history. Finally, the diagnostic potential of the determined parameters was evaluated, and it was found that IL-1ß correctly classified 89% of cases in the combination with common inflammatory biomarkers, white blood cell count and fibrinogen, showing a potential in COPD prediction. In conclusion, up-regulation of IL1B, NLRP3, CASP1 and increased IL-1ß concentration suggest the activation of NLRP3 inflammasome in the systemic compartment of patients with stable COPD.

Influence of disease severity, smoking status and therapy regimes on leukocyte subsets and their ratios in stable chronic obstructive pulmonary disease.

Introduction: Blood cells are involved in systemic inflammation in chronic obstructive pulmonary disease (COPD). We aimed to assess differences in leukocyte subsets and their ratios between COPD patients and healthy individuals as well as their association with disease severity, smoking status and therapy in COPD. Material and methods: One hundred and nine patients in the stable phase of COPD and 95 controls participated in the study. After blood sampling, white blood cells (WBC), neutrophils (NEUTRO), monocytes (MO), lymphocytes (LY) and basophils (BA) were determined on a Sysmex XN-1000 analyser, and ratios were calculated afterwards. Results: White blood cells, NEUTRO, MO and BA were higher in COPD patients than in controls. Also, COPD patients had increased neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), monocyte to lymphocyte ratio (MLR), basophil to lymphocyte ratio (BLR), basophil to monocyte ratio (BMR) and monocyte/granulocyte to lymphocyte ratio (M/GLR). Smoking has an impact on leukocyte counts, with BA, BLR and BMR being higher in COPD smokers vs. ex-smokers. Patients with very severe COPD were distinguished from moderate COPD by NLR, dNLR and M/GLR. In addition, those parameters were associated with lung function and dyspnoea, and NLR and dNLR also with multicomponent COPD indices BODCAT and DOSE. Great potential of dNLR, NLR and M/GLR in identifying COPD patients was observed regarding their odds ratios (OR) of 5.07, 2.86, 2.60, respectively (p < 0.001). Common COPD therapy did not affect any of the parameters investigated. Conclusions: Leukocyte subsets and their ratios could be implemented in COPD assessment, especially in evaluating disease severity and prediction.

Lipid profile and atherogenic indices in patients with stable chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Limited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy. METHODS AND RESULTS: The study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated. HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742-0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases. CONCLUSION: Lipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.

Depression and circadian typology.

BACKGROUND: The relationship between circadian disruptions and depressive disorders is a topic of great interest in contemporary psychiatry. Circadian rhythms include all physiological processes displaying a period around 24 hours. Sleep/wake cycles, body temperature, hormone secretion and other functions are subjected to person's individual circadian rhythm. Circadian typology includes three chronotypes: morning, neither and evening. The aim of this study was to examine the chronobiological aspects of depression. METHODS: This cross-sectional study aimed to determine circadian rhythmic expression in 60 patients suffering from depression. The patients were in remission and were treated as outpatients at the Department of Psychiatry of the University Hospital Center Zagreb. The data were compared to a control group consisting of 40 medical workers employed at the University Hospital Centre Zagreb. A self-report measure of circadian typology was utilized - the Morningness-Eveningness Questionnaire. RESULTS: According to our findings, among depressed patients 35% were morning, 58.3% neither and 6.7% evening types. In the control group 46% were morning, 48% neither and 6.0% evening types. Depressed patients reported stronger morning fatigue. Further, they tended to go to sleep earlier and felt more tired earlier in the evening, and they were less prone to choosing morning periods for completing complex cognitive tasks. CONCLUSION: This study supports the association between depression and some alterations in circadian rhythms of behavior and sleep. Depression may be considered as the consequence or trigger of circadian disturbances. However, both depression and circadian rhythm disturbances may have a common aetiology: a decreased cellular resilience associated with lower resistance to stressful events.

Dependence of cerebrospinal fluid pressure and volume on the changes in serum osmolarity in cats.

OBJECTIVES: To study the effect of blood osmolarity on cerebrospinal fluid (CSF) volume and CSF pressure in cats. METHODS: Three types of methods were used on anesthetized cats. The first, ventriculo-cisternal perfusion (12.96 µL/min) before and after i.v. application of 20% mannitol; the second, measuring the outflow of CSF by cisternal free drainage; and the third, measuring CSF pressure in the ventricles of an intact CSF system, with the second and third method being performed before and after the i.p. application of a hypo-osmolar substance (distilled water). RESULTS: In the first group, the application of 20% mannitol led to a significantly reduced (p < 0.005) outflow volume (from 12.60 ± 0.29 to 0.94 ± 0.09 µL/min). In the second group, the outflow CSF volume significantly increased (p < 0.001) after the application of distilled water (from 18.8 ± 0.3 to 28.2 ± 0.7 µL/min). In the third group, after the application of distilled water, the CSF pressure also significantly increased (p < 0.05; from 8.3 ± 0.8 to 16.1 ± 0.14 cm H(2)O). CONCLUSION: We conclude that changes in serum osmolarity change the CSF volume because of the osmotic gradient between the blood and all of the CSF compartments, and also that the change in CSF pressure is closely associated with changes in CSF volume.