Nocturnal Blood Pressure Variability in Patients with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea (OSA) is a common respiratory disorder associated with hypertension and cardiovascular complications. Blood pressure variability may be a sign of risk of cardiovascular events. The aim of this study was to investigate the hypothesis that severe OSA syndrome is associated with increased blood pressure variability. Based on respiratory polygraphy, 58 patients were categorized into two groups: severe OSA with apnea/hypopnea index (AHI) greater than 29 episodes per hour (mean 52.2 ± 19.0/h) and mild-to-moderate OSA with AHI between 5 and 30 episodes per hour (mean 20.2 ± 7.8/h). A 24-h noninvasive blood pressure monitoring was performed. The standard deviation of mean blood pressure was used as the indicator of blood pressure variability. In patients with severe, compared with mild-to-moderate OSA, a higher mean nocturnal systolic blood pressure (133.2 ± 17.4 mmHg vs. 117.7 ± 31.2 mmHg, p < 0.05) and diastolic blood pressure (80.9 ± 13.1 mmHg vs. 73.8 ± 9.2, p < 0.01), nocturnal systolic blood pressure variability (12.1 ± 6.0 vs. 7.6 ± 4.3, p < 0.01) and diastolic blood pressure variability (10.5 ± 6.1 vs. 7.3 ± 4.0 p < 0.05), nocturnal mean blood pressure variability (9.1 ± 4.9 mmHg vs. 6.8 ± 3.5 mmHg) were detected. The findings of the study point to increased nocturnal systolic and diastolic arterial blood pressure and blood pressure variability as risk factors of cardiovascular complications in patients with severe OSA.

Sclerostin in Obstructive Sleep Apnea.

Sclerostin, a glycoprotein involved in vascular calcification, could play a role in cardiovascular disorders. Obstructive sleep apnea (OSA) is frequently associated with cardiovascular comorbidities. Thus, in this study we set out to assess the level of sclerostin in patients with OSA. Sclerostin was evaluated in the serum by ELISA method in 106 patients (43 women) with OSA of the mean age of 55 ± 10 years, BMI of 33.1 ± 7.9 kg/m(2), and apnea/hypopnea index (AHI) of 29.7 ± 18.9. There were 76 (72 %) patients with cardiovascular comorbidities in the OSA group. The results were compared with those in 49 healthy control subjects. We found that the level of sclerostin was higher in the female OSA patients than that in female controls (80.1 ± 36.5 pg/ml vs. 61.4 ± 24.1 pg/ml; p < 0.05) and it correlated with AHI (rs = 0.32, p < 0.01) and desaturation index (rs = 0.34, p < 0.01). Further, in OSA women with cardiovascular comorbidities, sclerostin was higher than in women without such comorbidities (87.0 ± 37.4 pg/ml vs. 57.3 ± 22.1 pg/ml; p < 0.05). In men, there were no differences in the serum sclerostin level between the OSA and control subjects, nor was there any relationship with cardiovascular diseases. In conclusion, increased serum sclerostin coincides with the severity of OSA and its cardiovascular sequelae in female patients.

Comparative Expression of Apoptotic Markers in Lung Adenocarcinoma and Squamous Cell Carcinoma.

Lung cancer is still an oncology challenge. A 5-year survival reaches less than 20 % of patients. Apoptosis disturbances are a key step in cancer development. The evaluation of apoptosis markers has a great potential in lung cancer. The goal of our study was a comparative evaluation of apoptosis regulators: p53, Bcl-2, Bax, COX-2, and survivin in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). We also evaluated the relationship between apoptosis markers and clinicopathological parameters. Fifty six patients with non-small cell lung cancer (NSCLC) were included into the study (20 women and 36 men). AC was diagnosed in 30 and SCC in 26 cases. The evaluation of markers was performed using an immunohistochemical method on paraffin embedded tissue specimens. We used monoclonal antibodies for p53, bcl-2, and COX2-proteins (clone DO7, bcl-2/100/D5, and 4H12, respectively), Bax (B-9 clone) and survivin (clone 12C4). The results of immunostaining were viewed by light microscopy. We revealed significantly more frequent expression of Bax and survivin in lung AC than SCC (p < 0.01 and p < 0.019). Bcl-2 immunoreactivity was seen more often in AC without lymph node metastases than with metastases (p = 0.046). There was no correlation between the apoptosis markers and gender or the presence of vessel emboli. A greater variability in markers expression was seen in lung AC than SCC. There were significant differences in the Bax and survivin expression in the two major pathological types of NSCLC. We did not revealed any correlation between the markers and TNM characteristics, accept for Bcl-2 presence along with the lymph node involvement in the AC group.

Correlations between osteoprotegerin serum levels and body composition parameters in patients with sleep apnea syndrome and the possible influence on cardiovascular risk.

INTRODUCTION: Osteoprotegerin (OPG) is a member of the tumor necrosis factor family and a key regulator in bone turnover; it plays a role in the development of many cardiovascular diseases and may be treated as a marker of vascular damage. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition. The aim of the study was to evaluate correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk. MATERIAL AND METHODS: A total of 125 patients with newly diagnosed OSA were enrolled in the study (including 34 females). The mean age was 54.48±8.81 years, mean AHI 33.16±20.44/h and mean BMI 33.76±7.18. A control group comprised 59 healthy subjects with mean age of 51.27±12.97 years and mean BMI 29.47±5.42. All subjects underwent a nocturnal respiratory polygraphy and body composition measurements were taken with bioelectrical impedance analysis. OPG serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: In OSA patients OPG correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while there was a positive correlation between osteoprotegerin and fat mass percentage (FM%). We demonstrated higher OPG serum levels in OSA patients with cardiovascular diseases than in those without comorbidities (4.01 vs 3.46pmol/l, p<0.05). CONCLUSION: Our findings, combined with previous observations in other diseases, suggest that elevated OPG serum levels together with selected body composition parameters may be helpful in identifying OSA patients with increased cardiovascular risk.

Serum antibodies to retinal antigens in lung cancer and sarcoidosis.

OBJECTIVE: Autoantibodies to various neuronal proteins frequently accompany lung cancer and their appearance may precede cancer symptoms. In this study we examined which retinal antigens (RAs) are recognized by sera of patients with lung cancer and whether the occurrence of serum antibodies to particular RAs is characteristic for cancer in comparison with a noncancer lung disease. METHODS: Sera of 72 patients with non-small-cell lung cancer (NSCLC), 29 with small-cell lung cancer (SCLC), 27 with sarcoidosis (S), and sera of 32 healthy donors were examined in immunoblotting using retinal extracts and purified RAs as antigens. RESULTS: 69.0% of SCLC, 45.8% of NSCLC, and 44.4% of S sera displayed anti-RAs reactivity. Significantly less (p < 0.05; chi(2) test) percent of healthy control sera reacted with RAs. Lung cancer sera recognized mainly 46-, 56-, and 36-kD and to a smaller extent also 96-, 72-, 43-, and 26-kD proteins. Most of them were recognized with about 2-fold lower frequencies by S and control sera. Only lung cancer sera contained very high-titer antibodies to 46- and 26-kD RAs, identified as alpha-enolase and recoverin, respectively. CONCLUSION: Antibodies to RAs occur more frequently and in higher titers in lung cancer (especially SCLC) than in sarcoidosis or control sera. Although antibodies to retinal alpha-enolase, recoverin and other RAs are present mainly or exclusively in lung cancer sera, none of them seems to be a specific marker of a particular disease.

Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas.

The overexpression of three growth factor receptors: epidermal growth factor receptor (EGFR), ERB B2 and ERB B3 was evaluated immunohistochemically in 77 malignant and 15 benign colorectal neoplasms considering clinicopathological variables (histological structure, grade of differentiation, tumor localization, clinical stage of the disease). The relationship between the coexpression of EGFR-related proteins in individual patients was also evaluated. EGFR expression was revealed in comparable percentages of colorectal adenoma and in adenocarcinoma cases (80% and 70%) while ERB B2 expression was detectable more frequently in adenoma than in adenocarcinoma cases (87% and 54%). The presence of ERB B3 was observed in a higher percentage of adenocarcinoma than adenoma cases (65% and 40%). There was no correlation between the expression of studied tyrosine kinase receptors and histological grade or Dukes' clinical stage and localization (proximal or distal) of colorectal adenocarcinoma. The incidence of EGFR and ERB B2 expression was higher in tubulovillous (100% for both receptors) than in tubular adenomas (63% and 75%), while the ERB B3 receptor was revealed more frequently in tubular than in tubulovillous neoplasms (50% and 28%). These differences appeared to be statistically nonsignificant. The concomitant expression of two growth factor receptors was observed in a higher percentage of colorectal adenomas than adenocarcinomas, and the coexistence of three growth factors was revealed in comparable percentages in malignant and benign colorectal tumors. Our results support the promotional rather than direct transformational role for the EGFR supergene family in colorectal tumorigenesis. The frequently observed coexpression of more than one EGFR-related protein in colorectal neoplasms indicates the possible cooperation of these receptors in mitogenic signaling transduction, facilitating the development and maintenance of the malignant phenotype.

Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis.

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.