Granzyme B in peripheral blood mononuclear cells as a measure of cell-mediated immune response in paraneoplastic neurological syndromes and malignancy.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) may coexist with ovarian or lung cancers. Some tumors coexisting with PNS are smaller and have a better prognosis than tumors without PNS. PNS may constitute an opportunity to observe a natural immune antitumor response. We aimed to investigate a cytotoxic immune response by measuring granzyme B (GrB) in peripheral blood mononuclear cells (PBMC) in patients affected with ovarian or lung malignancy, with and without accompanying PNS. METHODS: We enrolled patients with: nonmalignant lesions (n = 21), ovarian cancer (n = 19), lung cancer (n = 57), and PNS (n = 30). PBMC were isolated by density gradient centrifugation with Ficoll-Paque. We evaluated the expression of GrB in PBMC lysates by ELISA and normalized to protein content as measured by the Lowry method. RESULTS: GrB levels in PBMC in the group with malignant tumors-median 1650 pg/mg protein (interquartile range 663-3260 pg/mg) and in patients with PNS-median 1890 pg/mg protein (range 1290-2640 pg/mg) was lower than in control group with nonmalignant lesions-median 5240 pg/mg protein (range 2160-7440 pg/mg), p = 0.0003 and p = 0.0038, respectively. The differences in GrB levels in PBMC between these groups were independent of epidemiological factors-age, sex, body mass index (BMI), and the number of immune cells, as confirmed by multiple regression analysis. Within the group of patients with malignancy and PNS, GrB levels in PBMC were elevated if onconeural antibodies were detected (2610; 2390-3700 pg/mg protein) as compared to patients without antibodies (1680; 970-1880 pg/mg protein, p = 0.035). GrB in PBMC was higher if the malignancy was diagnosed at the low (3060; 2120-5220 pg/mg protein) as compared to the high stage (1330; 348-2140, p = 0.00048). In patients with lung cancer, the expression of GrB in PBMC was lower (1430; 635-2660 pg/mg protein) than in the group with ovarian cancer (2580; 1730-3730, p = 0.02). CONCLUSION: The cytotoxic response measured in peripheral blood by GrB in PBMC is impaired both in the course of malignancy and PNS. Levels of GrB in PBMC were higher if onconeural antibodies were detected. Tracking reactive immune responses, such as GrB in PBMC may have diagnostic and monitoring value in malignancy and PNS.

Cardiovascular Function in Obstructive Sleep Apnea Patients with Controlled Hypertension.

This study investigated hemodynamic characteristics of obstructive sleep apnea (OSA) accompanied by hypertensive disease in obese men, in whom blood pressure was pharmacologically controlled within the normal range, not exceeding 140/90 mmHg. There were 21 severe OSA patients (mean age 54.1 ± 9.3 years, apnea-hypopnea index of 47.1 ± 18.8 episodes per hour) included in the study, in whom OSA was diagnosed with polysomnography. The control group consisted of healthy normotensive age-matched subjects. Hemodynamic profile was recorded nonivasively with impedance cardiography. Brachial blood pressure and radial artery tonometry were performed to capture and reconstruct peripheral radial and central aortic pressure waveforms in both groups of subjects. Compared to healthy men, OSA patients had a significantly higher body mass index (BMI); the mean increase in BMI amounted to 6.4 ± 1.2 kg/m2. The patients also presented significant differences in the hemodynamic profile. The difference consisted of a faster heart rate, higher peripheral pulse pressure, and reduced blood flow acceleration and velocity indices, describing myocardial contractility. Notably, the significance of hemodynamic differences in OSA patients disappeared in the analysis adjusted for the outstanding increase in BMI. In conclusion, the findings strongly suggest that obesity rather than the hypertensive disease per se is a source of hemodynamic consequences in OSA patients.

Systemic Sclerosis and Serum Content of Transforming Growth Factor.

Systemic sclerosis is a connective tissue disease characterized by tissue fibrosis leading to interstitial lung disease. Transforming growth factor-ß (TGF-ß) has been of interest as a potential diagnostic marker and also as a drug target in systemic sclerosis. The aim of this study was to assess the serum content of TGF-ß1 in patients with systemic sclerosis and to assess its potential role in tissue fibrosis. The study included 30 patients, 5 men and 25 women, of the mean age of 46.9 ± 12.8 years, diagnosed with systemic sclerosis. The control group consisted of 19 women of the mean age of 28.4 ± 7.8 years, diagnosed with primary Raynaud's disease. TGF-ß1 serum levels were measured, chest imaging examinations were performed, and fibrotic tissue changes were assessed using the modified Rodnan Skin Score. We found that the mean serum TGF-ß1 content in patients with systemic sclerosis was 598.7 ± 242.6 pg/mL, whereas it was 568.4 ± 322.2 pg/mL in the control group (p = 0.378). We also failed to substantiate any significant relationship between TGF-ß1 serum levels and the severity of pulmonary and skin fibrosis in systemic sclerosis. In conclusion, systemic sclerosis does not seem a disease that would be accompanied by a specific enhancement of serum TGF-ß1. Thus, this cytokine is rather unlikely to play an essential role in the development and course of the disease, nor can it be considered diagnostic or prognostic marker.

Molecules of Damage-Associated Patterns in Bronchoalveolar Lavage Fluid and Serum in Chronic Obstructive Pulmonary Disease.

Chronic exposure to detrimental environmental factors may induce immunogenic cell death of structural airway cells in chronic obstructive pulmonary disease (COPD). Damage-associated molecular patterns (DAMPs) is a family of heterogeneous molecules released from injured or dead cells, which activate innate and adaptive immune responses on binding to the pattern recognition receptors on cells. This study seeks to define the content of DAMPs in the bronchoalveolar lavage fluid (BALF) and serum of COPD patients, and the possible association of these molecules with clinical disease features. Thirty COPD in advanced disease stages were enrolled into the study. Pulmonary function tests, arterial blood gas content, 6-minute walk test, and BODE index were assessed. The content of DAMPs was estimated using the commercial sandwich-ELISA kits. We found differential alterations in the content of various DAMP molecules. In the main, BALF DAMPs positively associated with age, forced expiratory volume in one second (FEV1), and residual volume (RV); and inversely with PaO2, residual volume/total lung capacity (RV/TLC) ratio, and the disease severity staging. In serum, DAMPS positively associated with the intensity of smoking and inversely with age, PaO2, and TLC. In conclusion, DAMPs are present in both BALF and serum of COPD patients, which points to enhanced both local in the lung environment as well as systemic pro-inflammatory vein in this disease. These molecules appear involved with the lung damage and clinical variables featuring COPD. However, since the involvement of various DAMPs in COPD is variable, the exact role they play is by far unsettled and is open to further exploration.

Airway Obstruction in Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is a condition of breathing pathology occurring during sleep, characterized by repeated episodes of upper airway obstruction. The aim of the study was to determine the occurrence of airway obstruction in smoking males with OSA in whom lung function tests had not been performed before. One hundred and four current smokers selected from 1241 patients were enrolled for the research. The subjects included in the study smoked minimum 20 cigarettes a day for at least 10 years. The diagnosis of OSA was confirmed by polysomnography (PSG) in the Sleep Laboratory and subjects were assigned to one of three groups, depending on the severity of OSA. The control group consisted of 30 age-matched male smokers in whom OSA was not confirmed in PSG. Patients from the study and control group scored ≥ 11points in the Epworth Sleepiness Scale. Spirometry, impulse oscillometry, and body plethysmography were used to assess pulmonary function. Airflow limitation in subjects of the control group and OSA patients was confirmed. There were no significant differences in the incidence of bronchial obstruction between the control and study groups, and among the patients of various OSA severity. We conclude that the severity of OSA in smokers does not associate with the presence of airway obstruction. However, the increased peripheral respiratory resistance found in oscillometry did relate to a longer smoking time in OSA patients.

COPD Course and Comorbidities: Are There Gender Differences?

The prevalence of chronic obstructive pulmonary disease (COPD) has increased more rapidly in women than in men during the past two decades. Clinical presentation, comorbidities and prognosis may differ between genders and may influence management decisions. The influence of gender on COPD expression has not been clearly explained to date. Thus, the aim of this study was to evaluate significant differences between women and men suffering from COPD, regarding clinical presentation, pulmonary function test results, comorbidities, and prognosis. We prospectively recruited 470 patients with stable COPD with a history of smoking (152 women, 318 men, mean age 65.5 ± 8.8 vs. 66.6 ± 9.4 years, respectively). Comorbidities and exacerbations were recorded. Spirometry, body plethysmography, carbon monoxide diffusing capacity and 6-min walk tests were performed. The BODE prognostic score was also calculated. We found that women smoked less in comparison to men (30.4 vs. 41.9 pack-years, p < 0.05), showed more exacerbations (2.5 vs. 1.7, p = 0.01), higher forced expiratory volume in 1 s (FEV1%predicted), and increased residual volume/total lung capacity (RV/%TLC), but they had the same intensity of dyspnea. Women showed fewer comorbidities, on average, per patient (5.4 vs. 6.4, p = 0.002), but had a higher prevalence of at least seven comorbidities per patient (48.7% of women vs. 33.0% of men, p < 0.05). Women also had a significantly worse prognosis (4.6 vs. 3.1 BODE score, p < 0.05) that correlated with the number of comorbidities (r = 0.33, p < 0.01). In conclusion, this study strongly supports the existence of different gender phenotypes in COPD, especially regarding exacerbations, comorbidities, and prognosis. The gender difference may indicate a need for a targeted assessment and management of COPD in women and men.

Autoimmune response in lung cancer patients with neurological paraneoplastic syndromes.

AIM OF THE STUDY: The aim of this study was to evaluate granzyme B, perforin and FasL expression in peripheral blood mononuclear cells (PBMCs) in lung cancer patients and in paraneoplastic neurological syndromes (PNS). CLINICAL RATIONALE FOR THE STUDY: Cellular immune response is activated as part of anti-tumour reaction of the malignancy-bearing host. Paraneoplastic neurological syndromes (PNS) are defined as indirect effects of cancer on the nervous system and are considered immune-mediated. Such stimulation of the immune system may limit the aggressiveness of cancer and the development of metastasis, and thereby improve survival. Granzyme B and perforin pathway, and Fas ligand (FasL) - Fas receptor interaction play an important role in cytotoxic response. MATERIALS AND METHODS: Fifty-two patients were included in the study: 28 subjects with PNS and 24 subjects with lung cancer. PNS cases were diagnosed according to the Graus criteria. The presence of onconeural antibodies (anti-Hu/anti-Ri/anti-Yo/anti-Ma/Ta/anti-CV2/anti-amphiphysin/anti-myelin/anti-neuroendothelium/anti-MAG/anti-GAD) was detected with indirect immunofluorescence and confirmed with Line Blotting. The expression of granzyme B, perforin and FasL was detected in PBMCs with ELISA. RESULTS: PPBMC-FasL expression was increased in lung cancer compared to other patient groups. The granzyme to FasL ratio was significantly higher in lung cancer patients with peripheral than with central PNS involvement. In a multiple regression model, sex was an independent factor influencing PBMC expression of granzyme and perforin. CONCLUSIONS: FasL expression in PBMCs is up-regulated in lung cancer patients. The interplay between granzyme B and FasL may be involved in the development of PNS at the level of the peripheral and the central nervous systems in different manners. Gender is associated with PBMC expression of granzyme B and perforin in lung cancer patients. CLINICAL IMPLICATIONS: The novel findings that we report broaden the current knowledge on PNS pathomechanism, with aspects that have not been previously explored. Our findings provide a rationale for further exploration of the granzyme B/FasL pathway with regards to its potential diagnostic value. However, our study is preliminary and needs further research, especially in the context of the prognostic value of the proposed markers.

Congruence Between Pulmonary Function and Computed Tomography Imaging Assessment of Cystic Fibrosis Severity.

In cystic fibrosis, pulmonary function tests (PFTs) and computed tomography are used to assess lung function and structure, respectively. Although both techniques of assessment are congruent there are lingering doubts about which PFTs variables show the best congruence with computed tomography scoring. In this study we addressed the issue by reinvestigating the association between PFTs variables and the score of changes seen in computed tomography scans in patients with cystic fibrosis with and without pulmonary exacerbation. This retrospective study comprised 40 patients in whom PFTs and computed tomography were performed no longer than 3 weeks apart. Images (inspiratory: 0.625 mm slice thickness, 0.625 mm interval; expiratory: 1.250 mm slice thickness, 10 mm interval) were evaluated with the Bhalla scoring system. The most frequent structural abnormality found in scans were bronchiectases and peribronchial thickening. The strongest relationship was found between the Bhalla sore and forced expiratory volume in 1 s (FEV1). The Bhalla sore also was related to forced vital capacity (FVC), FEV1/FVC ratio, residual volume (RV), and RV/total lung capacity (TLC) ratio. We conclude that lung structural data obtained from the computed tomography examination are highly congruent to lung function data. Thus, computed tomography imaging may supersede functional assessment in cases of poor compliance with spirometry procedures in the lederly or children. Computed tomography also seems more sensitive than PFTs in the assessment of cystic fibrosis progression. Moreover, in early phases of cystic fibrosis, computed tomography, due to its excellent resolution, may be irreplaceable in monitoring pulmonary damage.

Clinical Utility of Berlin Questionnaire in Comparison to Polysomnography in Patients with Obstructive Sleep Apnea.

The aim of this study was to assess the utility of the Berlin questionnaire (BQ) in adult patients at high risk of obstructive sleep apnea (OSA). The study consisted of 64 patients recruited for the polysomnography diagnostics of sleep respiratory disturbances. The anthropometric assessment included body weight, height, and body mass index (BMI), all related to the risk of OSA. The BQ consisted of the following three categories: 1 - snoring, 2 - daytime somnolence, and 3 - hypertension. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. Likelihood ratio was used to assess the diagnostic accuracy. We found that patients were, on average obese; the mean BMI amounted to 31.9 ± 6.0 kg/m2. Polysomnography identified OSA in 73.4% of patients (AHI >5), where the BQ categorized 87.5% of patients at high risk of OSA. Sensitivity of the BQ was 87.2%, specificity 11.8%, PPV 73.2%, and NPV 25.0%. Diagnostic accuracy assessed by the likelihood ratio had a value of 1.00. The BQ had a false discovery rate of 31.2% and misclassification rate of 32.8%. We conclude that the BQ is a sensitive tool that should be used in clinical settings in which the benefit of high sensitivity outweighs the disadvantage of low specificity.

Small Airway Obstruction in Chronic Obstructive Pulmonary Disease: Potential Parameters for Early Detection.

The impulse oscillometry (IOS) is recognized as a complementary method to spirometry in the diagnostics of obstructive pulmonary disorders. The IOS enables to measure total respiratory resistance (R5) and proximal respiratory resistance (R20), with the R5-R20 difference reflecting small airway resistance. This study seeks to evaluate the usefulness of R5-R20, maximal mid-expiratory flow (MMEF), and forced expiratory volume in 3 s/forced vital capacity ratio (FEV3/FVC), in the assessment of small airway obstruction in chronic obstructive pulmonary disease (COPD). One hundred and six COPD patients and 43 control subjects, aged over 55, were investigated. Spirometry and IOS were used to assess pulmonary function. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were evaluated. The findings demonstrate significant reductions in FEV3/FVC and MMEF, and an increase in R5-R20 difference in COPD patients; the changes that depended on the severity of airway obstruction. The sensitivity of R5-R20 in reflecting the MMEF was 84%, specificity 44.2%, PPV 72.4%, and NPV 61.3%. We conclude that the R5-R20 difference is superior to spirometry in the assessment of small bronchi obstruction. A high sensitivity of R5-R20 in reflecting the MMEF makes the IOS method particularly useful for detection of mild lung injury, while a high specificity of the spirometric FEV3/FVC ratio makes it useful to exclude obstruction of small airways. Both methods are thus complimentary.

Body Composition, Anthropometric Indices and Hydration Status of Obstructive Sleep Apnea Patients: Can Cachexia Coexist with Obesity?

The aim of this study was to elucidate body composition, anthropometric indices, and hydration status in obstructive sleep apnea (OSA) patients, taking into account different disease stages, gender, and the possibility of the presence of cachexia. There were 98 OSA patients and 23 control subjects enrolled into the study. All study participants underwent polysomnography examination. Body mass index (BMI), fat mass index (FMI), fat free mass, muscle mass, body cell mass, total body water, and extracellular and intracellular water were evaluated. The neck, abdominal, and waist circumference was measured. We found that overweight and obesity were present in 96% of patients. Cachexia was present in one OSA individual with comorbidities. Apnea-hypopnea index correlated with the neck and waist circumference, and with BMI in OSA patients. All muscle indices and water contents above outlined were significantly higher in severe OSA compared with control subjects. BMI, FMI, neck circumference, and extracellular water were greater in a subset of severe OSA compared with a moderate OSA stage. The female OSA patients had a higher FMI than that present in males at a comparable BMI. We conclude that the most body composition indices differed significantly between severe OSA patients and control subjects. A higher FMI in females at a comparable BMI could be due to a discordance between BMI and FMI. Cachexia occurs rarely in OSA and seems to coexist with comorbidities.

Quality of life, depression and dietary intake in Obstructive Sleep Apnea patients.

BACKGROUND: The aim of this study was to analyze the association between depression, quality of life and dietary intake in newly diagnosed Obstructive Sleep Apnea (OSA) patients. METHODS: From 153 eligible patients suffering from sleep disturbances, 64 met inclusion and exclusion criteria. The polysomnography was used for OSA diagnosis. The quality of life (QOL) was assessed by WHOQOL-BREF questionnaire, self-reported chronotype by morningness-eveningness questionnaire and level of depression by Beck's Depression Inventory. Blood pressure and parameters of glucose and lipid metabolism were assessed by routine methods. The dietary intake was evaluated by 24-hr dietary recalls. RESULTS: Significantly negative associations were found between depression inventory and QOL. Better QOL for physical health and social relationships was observed in the "definitely morning" chronotype. The "morning type" of patients was positively related to the intake of fat, monounsaturated fatty acids and vitamin B12. Correlations between QOL and diastolic blood pressure, HDL-cholesterol, TG, fasting glucose, as well as protein and vitamin B6 intake were found. CONCLUSIONS: In conclusion, both chornotype and depression influence QOL in OSA patients where morning type is associated with better physical health and social relationships and increase in depression index deteriorate physical health, psychological and social relationship QOL domains. QOL as well as depression and chornotype are also influenced by selected cardio-metabolic factors and dietary intake.

LIPID PROFILE OF POLISH PRIMARY CARE PATIENTS AGED 35-55 YEARS LIVING IN THE DISTRICT OF PLESZEW.

In Poland, more than half of the adult population suffers from lipid disorders. Among the 18 million Polish people with hypercholesterolemia, over 10.8 million are unaware of this problem. To estimate the lipid profile of selected primary care patients in the district of Pleszew (Western Poland), general practitioners (GPs) recruited 681 patients aged 35-55 years in 2011. Fasting serum lipids were evaluated. We found statistically significant differences in all lipid parameters between all younger (35-45 years) and older (46-55 years) patients, between all female and male subjects, between women and men ages 35-45 years; in total cholesterol (TC), LDL-cholesterol (LDL-C) and triglycerides (TG) between younger and older female population; in HDL-cholesterol (HDL-C) and TG between women and men ages 46-55 years. Dyslipidemia, both, newly detected and previously treated, was detected in 591 patients (86.8%): 322 females (84.3%) and 269 males (90.0%). The highest percentage of lipid disorders was found in males aged 46-55 years (91.9%) and the lowest among women aged 35-45 years (78.0%). Age and gender differences in the prevalence of dyslipidemia proved of statistical importance. Among 155 patients on lipid-lowering therapy, only 28 subjects (18.1%) reached the target value of serum lipids. The prevalence of lipid disorders among primary care patients aged 35-55 years in the district of Pleszew was significantly high, and it was proved that dyslipidemia is statistically prominent in males and older patients. Polish healthcare professionals should make more efforts to improve the detection and treatment of lipid disorders.

Chemotherapy-induced peripheral neuropathy - diagnosis, evolution and treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activi-ties and lead to severe impairment of the patient's quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN. The purpose of this article is to review current knowledge of diagnostic techniques, prevention and management strategies in the context of CIPN.

The feasibility and efficacy of secondary neck dissections in thyroid cancer metastases.

The purpose of the study was to assess the feasibility of secondary neck dissections (ND) in different types of thyroid cancer (TC), to evaluate the influence of ND extent on morbidity and to describe biochemical and clinical outcomes. 51 patients previously operated for TC (33-well differentiated TC-WDTC, 15 medullary TC-MTC, 3 poorly differentiated TC-PDTC) presenting detectable nodal disease. Reoperations covered I-VII neck levels. Radical neck dissection was performed in 22 patients, selective neck dissection in 29 patients. 14 central compartment (CC), 10 mediastinal and 41 level IV excisions were performed. Postoperative complications occurred in 13 patients: 4 chyle leaks, 3 massive bleedings, 8 permanent vocal cord pareses, hypoparathyroidism in 22 patients (43.1%), 2 patients expired in perioperative period. In WDTC: in seven patients thyroglobulin level normalized directly after ND, in ten patients in the follow-up; six patients developed distant metastases. None of the patients with MTC achieved calcitonin level <10 pg/ml; nine patients developed distant metastases. None of the patients with PDTC achieved Tg <2 mg/ml; two patients died, the third developed distant metastases. Secondary ND in TC present a challenge by means of surgical approach and possibility of complications. In MTC and PDTC the long-term results were unsatisfactory. In WDTC, the secondary ND should be performed due to strong indications. Metastases localization in levels IV, VI, VII were connected with high complication rate, but these surgeries were crucial for satisfactory oncological outcomes.

Evaluation of outcomes after reoperative neck dissection due to thyroid cancer.

AIM OF THE STUDY: Aim of the study was to assess the results of surgical treatment of cervical recurrences in patients with thyroid cancer. MATERIAL AND METHODS: We assessed 66 reoperations of thyroid cancer recurrences in 51 patients. Reoperative surgeries covered I-VII neck levels. RESULTS AND CONCLUSIONS: The localization of cervical recurrence and the number of removed nodes did not depend on the type of thyroid cancer. Metastatic spread was predominantly observed in the central neck. Bilateral changes tended to be observed more often in younger patients (p = 0.07). Radical neck dissections were performed more often at younger age (p < 0.01). Postoperative vocal cord paresis was noted in 13 patients; in 5 permanent tracheotomy was necessary, and 2 underwent laser glottis procedures (posterior cordectomies). Two patients died in the postoperative period - 1 due to chylothorax and 1 due to severe bleeding from the common carotid artery.

Natural Killer Cells as a Further Insight into the Course of Chronic Obstructive Pulmonary Disease.

The role of natural killer (NK) cells in chronic obstructive pulmonary disease (COPD) pathogenesis has been discussed but is not yet clearly understood. This current study aimed to evaluate the associations between immunophenotypes, degrees of maturity, and the expression level of functional receptors of NK cells in the lung environment present in bronchoalveolar lavage fluid (BALF), and an attempt was made to determine their relationship in the course and progression of COPD. A total of 15 COPD patients and 14 healthy smokers were included. The clinical parameters of COPD were evaluated. In both groups, NK cells using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry were assessed in the peripheral blood. Additionally, NK cells using the same method were assessed in BALF in the COPD subgroup. The blood's NK cells differed from the estimated group's maturity and receptor expression. Functional receptors CD158b+, CD314+, and CD336+ expressed by NK cells were significantly interlinked with age, RV, TLC, 6MWT, smoking, and the number of exacerbations. These results confirm the essential role of NK cells in COPD pathogenesis. Additionally, the relationship between clinical parameters and NK cell expression may indicate its participation in the disease progression and exacerbation and allow for a better understanding of NK cell biology in COPD.

Blood antioxidant status, dysglycemia and obstructive sleep apnea.

Obstructive sleep apnea (OSA) patients present increased cardiovascular morbidity and mortality. Oxidative stress is involved in OSA and cardiovascular pathology. The aim of the study was to assess oxidative stress markers in the blood of OSA males during oral glucose tolerance test (OGTT). The study involved OSA-suspected obese males (BMI ≥ 25 kg/m(2)) aged 35-64, with no acute or chronic disorders, appointed for polysomnography to diagnose OSA (AHI ≥ 5). The results of OGTT allowed to select prediabetic (Pre) subjects and normal glucose tolerance (N), excluding newly diagnosed diabetes. Blood was collected at 0 min (fasting) and 120 min of the test. Plasma glucose, total antioxidant status (TAS), thiobarbituric acid-reacting substances (TBARS), and activity of superoxide dismutase-1 (SOD) in erythrocytes, were determined at the two time points and the difference (D) between the 120 and 0 min time points was calculated for either oxidative stress variable (D-TAS, D-SOD and D-TBARS). Fasting serum insulin and lipids also were measured fasting. There were four groups of subjects, each consisting of 22 individuals N-OSA-neg(ative), N-OSA-pos(itive), Pre-OSA-neg and Pre-OSA-pos. The N-OSA-pos and Pre-OSA-pos subjects demonstrated decreased SOD-0 compared with OSA-negative groups. In N-OSA-neg and N-OSA-pos groups, the positive differences D-SOD and D-TAS were observed, while Pre-OSA subjects presented negative differences. In conclusion, prediabetic OSA patients may consume blood antioxidant factors to counter the effects of oxidative stress, more than individuals with normal glucose tolerance.

Autoantibodies and Clinical Correlations in Polish Systemic Sclerosis Patients: A Cross-Sectional Study.

We evaluated the prevalence of systemic sclerosis (SSc)-related autoantibodies and their clinical significance and compared the sensitivity of two line immunoblot assays on a prospective study group of 96 Polish SSc patients (ACR-EULAR 2013 criteria) whose sera were assessed by indirect immunofluorescence (HEp-2 and monkey liver) and line immunoblot assays: ANA Profile 3 and Systemic Sclerosis Profile by EUROIMMUN (Lübeck, Germany). Organ involvement was evaluated according to the EUSTAR Minimal Essential Data Set. The following autoantibodies' prevalence was found: Scl-70 (36%), Ro-52 (28%), CENP-B (22%), CENP-A (20%), PM-Scl-75 (20%), PM-Scl-100 (14%), fibrillarin (7%), Th/To (7%), RNA polymerase III 11 kDa (5%), RNA polymerase III 155 kDa (3%), PDGFR (3%), NOR-90 (2%), and Ku (1%). Significant associations between the autoantibodies' presence and organ involvement were found: ATA (dcSSc > lcSSc, less prevalent muscle weakness), Ro-52 (gangrene, DLCO < 60), CENP-B and A (lcSSc > dcSSc, normal CK), CENP-B (rarer digital ulcers and joint contractures), PM-Scl-100 and 75 (PM/SSc overlap, CK increase, muscle weakness, muscle atrophy), PM-Scl-100 (dcSSc unlikely), PM-Scl-75 (lung fibrosis), fibrillarin (muscle atrophy, proteinuria, conduction blocks, palpitations), Th/To (proteinuria, arthritis, muscle weakness, and rarer esophageal symptoms), RNA Polymerase III 11 kDa (arterial hypertension, renal crisis), RNA polymerase III 155 kDa (renal crisis), and PDGFR (dcSSc, tendon friction rubs). Additionally, the Systemic Sclerosis Profile was significantly more sensitive in detecting SSc-related autoantibodies than ANA Profile 3 (p = 0.002). In conclusion, individual autoantibodies associated with specific characteristics of SSc.

[Anti-heat shock protein 70 (anti - Hsp 70) antibodies in alcohol use disorder patients]. / Przeciwciala przeciw bialku wstrzasu termicznego 70 kDa (anty- Hsp 70) u osób z zespolem zaleznosci alkoholowej.

The expression of the most important chaperone protein - Hsp70 and autoimmunity directed against it is a risk factor of cardiovascular diseases, increased in subjects with alcohol use disorder (AUD). The aim of the study was to evaluate the level of anti-Hsp 70 protein antibodies (anti-Hsp 70) in sera of AUD patients during abstinence period. Material and methods. The study included 54 subjects with AUD diagnosed basing on DSM IV criteria. In the studied group clinimetric evaluation was performed, plasma lipids, basic transketolase activity in erythrocytes (TK), thiamine pyrophosphate (TPP) activation of transketolase and the level of anti-Hsp 70 antibodies were evaluated as well. Results. In AUD subjects anti-Hsp 70 level was decreased during abstinence period. During first month of abstinency it correlated negatively with total cholesterol concentration (rS=-0.8857, p=0.0188) and the percentage of TPP stimulation (rS=-0.5960, p<0.05), and during 6 months of abstinence with HDL cholesterol (rS=-0.6848, p=0.0289). After 1 year of abstinence anti-Hsp 70 correlated positively with basic TK activity (rS=0.9550, p=0.0008). Sex is an independent factor influencing anti-Hsp 70 level in AUD subjects (B=60.9469, p=0.0435). In multiple regression model including results of clinimetric evaluation and its effect on the level of anti-Hsp 70 antibodies in AUD patients during 1 month of abstinency anti-Hsp 70 correlated with TWEAK scale score (BETA=-1.4543, p=0.0144) and AUDIT score (BETA-=1.2255, p=0.0224). In 2-6 months of abstinency anti-Hsp 70 correlated with TWEAK score (BETA=1.1110, p=0.0418). After 1 year of abstinency anti-Hsp 70 correlated with AUDIT score (BETA=-1.2161, p=0.0210). Conclusion. The autoimmune reaction against Hsp 70 is decreased during abstinency in AUD patients. Its relation with plasma lipids and thiamine deficiency may lead to increased risk of cardiovascular disorders. TWEAK and AUDIT scoring seem to be most useful for clinimetric evaluation in the context of the role of anti-Hsp 70 antibodies.