[Issues of Adipokine Regulation in Idiopathic Pulmonary Arterial Hypertension and Systemic Osteopenia].

PURPOSE: to determine the role of adipokines and vascular remodeling in formation of osteoporosis in idiopathic pulmonary arterial hypertension (IPAH). MATERIALS AND METHODS: Functional and hemodynamic parameters, bone mineral density (BMD) T-score in lumbar spine (LS) and femoral neck (FN), blood serum levels of leptin, adiponectin, visfatin and endothelin-1 were measured in 27 patients with severe IPAH and 30 healthy volunteers. RESULTS: Half of IPAH patients had osteoporosis. Serum levels of leptin, adiponectin, visfatin and endothelin-1 in IPAH group were higher than in healthy volunteers. BMD T-score was directly related to results of 6­minute walk test and inversely related to pulmonary vascular resistance (PVR). Circulating adiponectin and visfatin concentrations correlated with PVR; endothelin-1 concentration was directly related to pulmonary arterial systolic pressure, cardiac index and PVR. Relations between BMD T-score and circulating adiponectin, visfatin, and endothelin-1 were inverse. Positive correlations existed between serum adiponectin, visfatin and endothelin-1 levels. CONCLUSION: Results of our study confirm the important role of adipokine and endotheline dysregulation in development of hemodynamic disorders in severe IPAH and evidence for their possible involvement in formation of osteopenic syndrome.

ROLE OF Wip1-p53 AXIS IN RESPONSE OF MURINE CELLS TO TREATMENT WITH SODIUM BUTYRATE AND MEK/ERK SIGNALLING PATHWAY INHIBITOR.

The use of histone deacetylase inhibitors and inhibitors of MEK/ERK-pathway is proposed as a novel potential approach in cancer treatment. Here we studied the effects of histone deacetylase inhibitor, sodium butyrate, and MEK/ERK-pathway inhibitor, PD0325901, on cells with modifications in genes involved in anti-cancer therapy response, Wip1 phosphatase and p53. We have investigated the effect of these agents on cell cycle of wild-type cells, Wip1 knockout cells and cells with double deletion of Wip1 and p53. Our results showed that more severe changes in S and G2/M phases were observed in response to sodium butyrate in Wip1-defecient cells than in wild-type cells. Meanwhile, PD0325901 treatment led to G1 arrest. At the same time, a «sodium butyrate type¼ response dominated the response to combined treatment with both drugs in Wip1-deficient cells, while the response of Wip1­/­/p53­/­ cells to combined treatment was similar to the single use of PD0325901. Wip1­/­ and Wip1­/­/p53­/­ cells were more sensitive to the use of PD0325901 than wild-type cells. Obtained results suggest that Wip1 deficiency sensitizes cells to sodium butyrate and to MEK/ERK inhibitors independently from Wip1 main target protein ­ p53. Data acquired give insights into role of Wip1 in cellular responses to treatment with HDAC and MEK/ERK inhibitors.

[Role of vascular remodeling markers in the development of osteoporosis in idiopathic pulmonary arterial hypertension]. / Rol' markerov remodelirovaniya sosudov v formirovanii osteoporoza pri idiopaticheskoi legochnoi arterial'noi gipertonii.

AIM: To define the role of circulating biomarkers for the metabolism of collagen and intercellular substance and vascular remodeling in the development of osteoporosis (OP) in idiopathic pulmonary arterial hypertension (IPAH). MATERIAL AND METHODS: Functional hemodynamic parameters, bone mineral density (BMD) in the lumbar spine and femoral neck and the serum levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-9/TIMP-1 complex, C-terminal telopeptide of collagen type 1 (CITP), and endothelin-1 (ET-1) were determined in 27 high-risk IPAH patients and 30 healthy volunteers. RESULTS: OP in IPAH was detected in 50% of the examinees. The serum levels of CITP, MMP-9, TIMP-1, and ET-1 proved to be higher in the high-risk IPAH patients than in the healthy volunteers. There was a direct correlation between BMD and six-minute walk test and an inverse correlation with total pulmonary vascular resistance (TPVR). Serum TMIP-1 levels correlated with cardiac index and TPVR; ET-1 concentrations were directly related to pulmonary artery systolic pressure, cardiac index, and TPVR. Inverse relationships were found between BMD and circulating CITP, MMP-9, TMIP-1, MMP-9/TMIP-1, and ET-1. At the same time, there was only a tendency towards a positive correlation between serum CITP and ET-1 concentrations. CONCLUSION: The results of the investigation confirm that endothelin system dysregulation plays a leading role in the development of persistent hemodynamic disorders in high-risk IPAH and suggest that it is involved in the development of osteopenic syndrome. Enhanced ET-1 secretion initiates bone loss possibly via activation of connective tissue matrix destruction.

[Therapy and Rehabilitation of Patients with Pulmonary Tuberculosis and Different Treatment Adherence].

The pulmonary tuberculosis process as dependent on the disease form and the therapy efficacy with the use of Cycloferon in the treatment scheme were investigated. The study had two stages. At the first stage the data concerning 358 patients with primary pulmonary tuberculosis and infiltration (93 patients) or degradation (89 patients) and 176 patients with pulmonary fibrocavernous tuberculosis were analysed. At the second stage the efficacy of the treatment schemes applied to the patients with pulmonary fibrocavernous tuberculosis was compared. The etiotropic therapy intensive phase was applied to all the patients. Moreover, 56 patients (group 1) under the therapy and rehabilitatinon were treated with Cycloferon in a dose of 0.25 administered intramuscularly twice a week (not less than 16 injections for the course), 60 patients (group 2) were treated with Omega 3, 30 patients (group 3) were given the standard complex (vitamins and tonics), 30 patients (group 4) were under the etiotropic therapy alone. The following additional factors promoting progression and aggravation of the tuberculosis process were confirmed: degradation at the time of the disease diagnosis, high resistance of the pathogen to antituberculosis drugs, low adherence to the treatment, social desadaptation and especially psychofunctional state of the patients. The use of Cycloferon in the schemes of the intensive phase treatment of the primary fibrocavernous tuberculosis resulted in reduction of the intoxication signs, bacteria isolation, positive dynamics of the cavity healing, lower lung infiltration and consequently high frequency of the treatment positive outcomes (94.1 ± 3.33%).

Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy.

Inactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criterion of the screen was increased sensitivity of p53-negative tumor cells to cisplatin (CDDP) in a Wip1-dependent manner. We have found that a treatment with a low dose (75 nM) of MK-1775, a recently described specific chemical inhibitor of Wee1, decreases CDDP-induced H2AX phosphorylation in p53-negative cells and enhances the Wip1-sensitization of p53-negative tumors. We were able to reduce CDDP effective concentration by 40% with a combination of Wip1 overexpression and Wee1 kinase inhibition. We have observed that Wee1 inhibition potentiates Wip1-dependent tumor sensitization effect by reducing levels of Hipk2 kinase, a negative regulator of Wip1 pathway. In addition, during CDDP treatment, the combination of Wee1 inhibition and Wip1 overexpression has a mild but significant protective effect in normal cells and tissues. Our results indicate that inhibition of the negative regulators of Wip1 pathway, Wee1 and Hipk2, in p53-negative tumors could potentiate efficiency of chemotherapeutic agents without concomitant increase of cytotoxicity in normal tissues. The development and clinical use of Wee1 and Hipk1 kinase chemical inhibitors might be a promising strategy to improve anti-cancer therapy.

CHLOROQUINE DOES NOT CANCEL E1A+cHa-Ras TRANSFORMANTS' DEATH INDUCED BY mTOR KINASE INHIBITOR pp242.

We have studied the dependence of cell viability on cell autophagy in control and senescent E1A+cHa-Ras transformed rat embryo fibroblasts. pp242, a TORC1/C2 kinase inhibitor, was used as a trigger of cell autophagy. Cell senescence was induced in the cells by sodium butyrate. pp242 inhibitor occurred to dramatically reduce the functional activity of mitochondria in intact cells causing their death by mitophagy and apoptosis. The presence of chloroquine that blocks lysosome and autophagosome fusion does not cancel pp242 effects. Senescent cells were more resistant to pp242 than control ones. However, their viability was significantly reduced in the presence of chloroquine and pp242. Thus, our results allow us to consider that the usage of chloroquine and pp242 combination is an effective way of cell death induction in intact and senescent Ras-transformants.

CHLOROQUINE DOES NOT CANCEL E1A+cHa-Ras TRANSFORMANTS' DEATH INDUCED BY mTOR KINASE INHIBITOR pp242. .

We have studied the dependence of cell viability on cell autophagy in control and senescent E1A+cHa-Ras transformed rat embryo fibroblasts. pp242, a TORC1/C2 kinase inhibitor, was used as a trigger of cell autophagy. Cell senescence was induced in the cells by sodium butyrate. pp242 inhibitor occurred to dramatically reduce the functional activity of mitochondria in intact cells causing their death by mitophagy and apoptosis. The presence of chloroquine that blocks lysosome and autophagosome fusion does not cancel pp242 effects. Senescent cells were more resistant to pp242 than control ones. However, their viability was significantly reduced in the presence of chloroquine and pp242. Thus, our results allow us to consider that the usage of chloroquine and pp242 combination is an effective way of cell death induction in intact and senescent Ras-transformants.

MEK/ERK-PATHWAY IS REQUIRED TO MAINTAIN CYTOPROTECTIVE AUTOPHAGY PROCESS IN IRRADIATED E1A+cHa-Ras TRANSFORMANTS.

Autophagy is a conservative process of misfolded protein and damaged organelle degradation that serves to support cellular viability. Autophagy is often induced in response to stress, DNA damage, retinoids, starvation and growth factor withdrawal. The aim of the present work was to study autophagic response of E1A+cHa-Ras-transformed cells to irradiation and to analyze the role of MEK/ERK pathway in regulation of autophagy induced by irradiation. MEK/ERK suppression has been found to decrease the viability of irradiated cells. Inhibition of MEK/ERK pathway leads to the changes in the autophagy induced by irradiation connected with disturbances of final stages followed by accumulation of adaptor protein p62/SQSTM1 in autophagic cavities within cytoplasm. Thus, the data obtained allow to suggest that active MEK/ERK pathway is required to support, the cytoprotective autophagy which is induced in response to irradiation of transformed E1A+cHa-ras cells.

[Role of MEK/ERK pathway in the regulation of HDACI-induced senescence of transformed rat embryo fibroblasts].

A key regulator of cellular senescence, mTORC1 complex, is the target of many signaling cascades including Ras/Raf/MEK/ERK-signaling cascade. In this paper we investigated the role of MEK/ERK-branch of this cascade in the process of cellular senescence induced by histone deacetylase inhibitor (HDACI) sodium butyrate (NaBut), in transformed rat embryo fibroblasts. Suppression of MEK/ERK activity by inhibitor PD0325901 does not prevent activation of mTORC1 complex induced by NaBut treatment. After the suppression of MEK/ERK, activity of mTORC1 increased as well as complex mTORC2. Activation of mTOR-containing complexes accompanied by the reorganization of the actin cytoskeleton with the formation of actin stress fibers and the appearance of some markers of cellular senescence. In contrast to NaBut-induced senescence accumulation of proteins was not observed, which may be due to increased activity of the degradation processes. Furthermore, the induction of senescence in conditions suppressed MEK/ERK leads to a drastic decrease in cell viability. Thus, NaBut-induced senescence upon suppressed activity of MEK/ERK-branch of MAP kinase cascade has a more pronounced tumor-suppressor effect associated with stronger activation of both mTOR-complexes, reorganization of the actin cytoskeleton and protein degradation.

[Predictors of osteopenic syndrome in idiopathic pulmonary fibrosis].

AIM: To evaluate the functional state of bone tissue in patients with idiopathic pulmonary fibrosis (IPF), waiting for lung transplantation, and to determine possible predictors of lower bone mineral density (BMD) in this pathology in the pretransplantation period. SUBJECTS AND METHODS: Forty-nine IPF patients waiting for lung transplantation were examined. The patients' mean age was 53.4 +/- 6.4 years. BMD in the lumbar spine (L(II)-L(IV)) and femoral neck (FN) was estimated using dual-energy X-ray absorptiometry. All the patients underwent external respiratory function test, pulmonary diffusing capacity (DL(CO)), gasometry, and 6-minute walk test (6'WT). RESULTS: Osteopenia was recorded in 77% of the examinees, of them 28% had osteoporosis (OP). Normal BMD in both L(II)-L(IV) and FN was found only in 13% of the patients. The T score in L(II)-L(IV) was directly related to body mass index. There was a direct correlation between BMD in L(II)-L(IV) and FN, forced vital capacity (FVC), DL(CO), and arterial blood oxygen saturation (SaO2) and an inverse correlation with arterial carbon dioxide partial pressure (pCO2). No significant correlation was found between the distance covered in 6'WT, FEV1, pO2, and BMD in both L(II)-L(IV) and FN. Six (15%) subjects had atraumatic fractures at different sites. CONCLUSION: Osteopenia is a common systemic manifestation in patients with IPF in the pre-transplantation period. BMI, FVC, exercise desaturation, and DL(CO) may be considered as predictors for the development of OP initiated by IPF.

[Gaseous disorders and their role in the development of hepatopulmonary syndrome in liver cirrhosis associated with COPD].

OBJECTIVE: To evaluate the indicators of arterial blood gasometry and levels of nitric oxide (NO) in exhaled breath of patients with liver cirrhosis (LC) in combination with COPD, and determine frequency of occurrence of hepatopulmonary syndrome (HPS). The comparison group consisted of 20 patients with COPD, control - 15 volunteers. Gas measurement was estimated by ABL 725 radiometer (Denmark). MATERIAL AND METHODS: We examined 57 patients with liver cirrhosis. The patients were divided into 2 groups: 1st--Patients with liver cirrhosis (n = 48), 2nd group--the CPU and COPD (n = 9). Comparison group consisted of 20 patients with COPD, control - 15 volunteers. The gasometry was evaluated by ABL 725 radiometer (Denmark). NO levels in exhaled air was estimated using the NIOX MINO (Sweden). Contrast electrocardiography was performed on ATL HDI 5000 (Bothell, WA, USA). RESULTS: We found that the PaO2 was lower in the 2nd group compared with the control and with the 1st group (81.4 +/- 5.2; 95.5 +/- 5.3 and 94.5 +/- 5.1 mm Hg; p < 0.05), but the lowest PaO2 was in the group with COPD (68.4 mm Hg). AaDO2 was higher in the group with COPD (37.7 mm Hg). In the 2nd group this indicator was higher as compared with the control and with the 1st group (26.8 +/- 5.4; 8.2 +/- 4.5 and 14.9 +/- 5.2 mm Hg; p < 0.05). A strong negative correlation in the 1st and the 2nd groups between AaDO2 and PaO2 (r = -0.67 and r = -0.93; p < 0.05) was obtained. Content of NO in exhaled air was higher in the 1st and 2nd groups compared with control (18.7 +/- 4.1; 18,9 +/- 4.5 and 11.0 +/- 3.3 ppb; p < 0.05). Intrapulmonary shunts were detected in 3 patients in the 1st and 2nd groups. CONCLUSION: The relationship between measures of blood gas composition showed the leading role of hypoxemia in increasing the risk of formation of HPS in the LC, especially when combined with COPD.

[Experience with simvastatin therapy for the achievement of osteoprotective effects in women with hyperlipidemia].

The aim of the work was to study the influence of statins on the functional and metabolic state of bone tissue during correction of type IIA and IIB hyperlipidemia in women with osteopenia. 53 of the 83 patients aged 45-50 years were treated with statins (20 mg/d) and low-fat diet. Bone mineral density (BMD) was measured in the lumbar spine region (LII-LIV) and femoral neck by DEXA. Simultaneously the lipid profile and serum bone metabolism markers (osteocalcin, beta-CrossLaps CL) were detected. Simvastatin therapy led to normalization of osteocalcin level (p<0.01) within 6 months. In the control group, it remained unaltered and tended to decrease after 12 months (p>0.05). The level of bone resorption marker (CL) dropped within 3 months after the onset of therapy (p<0.050) and continued to decrease by the 12th month (p<0.05). It was significantly lower than in controls (p<0.05) both after 6 and 12 months. BMD in the femoral neck and LII-LIV increased by 2.2 and 2.6% respectively after 12 months of simvastatin therapy and by 1.4 and 1.7% after consumption of low-fat diet. It is concluded that simvaststin therapy (20 mg/d) during 12 months has positive effect on bone metabolism during treatment of atherogenic hyperlipidemia in patients with osteopenia.

[Role of matrix metalloproteinase-9 in the pathogenesis of osteoporosis in patients with chronic obstructive pulmonary disease].

AIM: To determine a relationship between matrix metalloproteinase-9 (MMP-9) activity and its tissue inhibitors TIMP-1 and 2, tumor necrosis factor-alpha (TNF-alpha), bone mineral density (BMD), and bone exchange in chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Seventy-six patients with COPD and 20 healthy volunteers were examined using dual-energy X-ray absorptiometry n the lumbar spine (L(II)-L(IV)) and femoral neck (FN). The serum levels of MMP-9, TIMP-1 and TIMP-2, TNF-alpha, and beta-Crosslaps (betaCL) were measured. RESULTS: There was a higher MMP-9 level in COPD than that in the controls ((383.8 +/- 54.2 and 137.6 +/- 31.4 pg/ml, respectively; p < 0.01). The levels of TIMP-1 and TIMP-2 were not different from those in the control group. An inverse correlation was found between forced expiratory volume in one second (FEV1) and MMP-9 concentration (r = -0.59; p = 0.002) and a positive correlation with smoking index (r = 0.47; p = 0.04). There was an inverse correlation between MMP-9 concentration and BMD in both L(II)-L(IV) and FN (r = -0.67; p < 0.001 and r = -0.61; p < 0.01, respectively) and a direct correlation with betaCL (r = 0.53; p = 0.04). An inverse correlation was established between TNF-alpha and T index in both L(II)-L(IV) (r = -0.54; p < 0.01) and FN (r = -0.48; p < 0.01). At the same time, the level of TNF-alpha directly correlated with the bone resorption marker betaCL (r = 0.53; p = 0.002) and MMP-9 (r = 0.57; p = 0.003). CONCLUSION: Elevated MMP-9 levels may play an important role in type I collagen degradation, giving rise to enhanced bone resorption in COPD.

[Association between adipokines and the development of osteopenic syndrome in end-stage lung disease].

AIM: To study of an association between adipokines, nutritional status, and bone mineral density (BMD) in end-stage lung disease (ESLD). SUBJECTS AND METHODS: Forty-seven patients aged 26 to 62 years with ESLD were examined. BMD in the lumbar spine (L(II)-L(IV)) and left femoral neck (FN) was estimated using dual-energy X-ray absorptiometry (DXA). The serum levels of adipokines (leptin, adiponectin resistin, tumor necrosis factor-alpha (TNF-alpha), and its receptors sTNFR I, II) were determined. A control group consisted of 45 healthy volunteers matched for age and gender. RESULTS: Osteopenic syndrome (T-score < -1 SD) was recorded in 43 (91%) of the 47 examined patients with ESLD. In lung diseases, the concentrations of adiponectin, resistin, TNF-alpha, and its receptors were higher and the level of leptin was lower than in the control group. There was a positive correlation between the content of leptin (r = 0.64, p = 0.0002; r = 0.52, p = 0.009) and a negative correlation between adiponectin (r = -0.54, p = 0.009; r = -0.47, p = 0.003), TNF-alpha (r = -0.43, p = 0.03; r = -0.41, p = 0.04), and BMD in FN and FN L(II)-L(IV). Correlation analysis showed a positive correlation between the level of resistin (r = 0.57; p = 0.004), sTNFR I (r = 0.42; p = 0.03), sTNFR II (r = 0.44; p = 0.04), and BMD in L(II)-L(IV) only. The serum leptin level was positively correlated with body mass index (BMI) (r = 0.82; p < 0.0001) and total fat mass (TFM) (r = 0.84; p < 0.0001). On the contrary, the level of adiponectin was inversely correlated with BMI (r = -0.68; p < 0.001), serum resistin concentration (r = -0.57; p = 0.004), sTNFR I (r = -0.58; p = 0.007), and sTNFR II (r = -0.53; p = 0.006). It was stated that there was a strong inverse correction between the levels of leptin and adiponectin (r = -0.67; p = 0.0008). CONCLUSION: The found associations between adipokines and BMD may suggest that these markers are implicated in the pathogenesis of osteopenic syndrome in ESLD.

[Involvement of MAP-kinase cascades into the regulation of sodium butyrate induced premature cell senescence].

We studied the role of p38 kinase and JNK1,2 in the activation of the complex mTORC1 and the program of senescence induced by histone deacetylase inhibitor, sodium butyrate (NaBut), in mouse embryonic fibroblasts transformed by E1A+cHa-Ras oncogenes. It was found that transformants from knockouts for the genes p38, were able to implement the program of NaBut-induced senescence, according to the data of the cell cycle arrest, inhibition of proliferation, hypertrophic changes associated with the activation of mTORC1 and SA-beta-galactosidase activity. According to the behavior of these markers, cell knockouts for the genes jnk1,2 were unable to implement NaBut-induced senescence. Induction of senescence closely correlates with the activation of the complex mTORC1, as it was shown by inhibiting mTORC1 with rapamycin. We believe that JNK 1,2 kinases are required for mTORC1 activation and acquiring the markers of premature senescence, induced by NaBut in the E1A+cHa-Ras transformants.

[Osteoprotegerin and bone mineral density in patients with chronic obstructive pulmonary disease].

AIM: to study a relationship between the serum level of osteoprotegerin (OPG), the markers of bone metabolism, tumor necrosis factor-alpha (TNF-alpha), and bone mineral density (BMD) in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Fifty-five patients aged 44 to 58 years who had COPD were examined. BMD in the lumbar spine (L(II)-L(IV)) and left femoral neck (FN) was estimated by dual-energy X-ray absorptiometry (DXA) on Lunar Prodigy Densitometer (USA). The serum levels of OPG, BCrossLaps (BCL), and TNF-alpha were measured. A control group comprised 25 healthy non-smoking gender- and age-matched volunteers. RESULTS: Osteopenic syndrome (T-test < -1SD) was recorded in 43 (78%) of the 55 examined patients with COPD. In 29 (52%) of them, T-test was lower in two zones towards osteoporosis in 14 (25%) towards osteopenia. In patients with COPD, TNF-alpha concentrations were significantly higher than that in the control group. At the same time, TNF-alpha levels correlated positively with the bone resorption marker BCL (r = 0.52; p = 0.042) and negatively with OPG (r = 0.56; p = 0.003). A direct correlation was established between serum OPG concentrations and BMD in both L(II)-L(IV) and FN (r = 0.56; p < 0.01 and r = 0.47; p < 0.05, respectively) CONCLUSION: The patients with COPD were found to have lower BMD, elevated TNF-alpha concentrations, an increased bone resorption marker, and lower serum OPG levels. The associations between the levels of OPG, TNF-alpha, and BMD suggest that these markers are implicated in the pathogenesis of osteopenic syndrome in COPD.

[Osteoporosis in patients with end-stage lung disease].

AIM: To estimate the bone mineral density (BMD) in end-stage lung disease (ESLD) and to determine risk factors for reduced BMD and correlations between lung functional parameters and pretransplantation bone mass. MATERIALS AND METHODS: Sixty-five case histories were retrospectively analyzed in patients with ESLD who were to undergo lung transplantation. BMD in the lumbar spine (LS) and femoral neck (FN) was estimated by dual-energy X-ray absorptiometry. External respiratory function was investigated; gasometry and six-minute walk test (SMWT) were carried out. RESULTS: Osteopenic syndrome was recorded in 89% of the patients. Normal LS and FN BMD was found only in 7(11%) patients. T-scores (in both L(II)-L(IV) and FN) were directly related to the body mass index. There was a direct correlation of BMD with forced expiratory volume in one second and an inverse correction with arterial blood pCO2. There was no significant relationship between the results of SMWT and BMD in both L(II)-L(IV). CONCLUSION: Osteoporosis is a common severe systemic manifestation in patients with ESLD.

[Intracardiac hemodynamics in patients with isolated chronic obstructive pulmonary disease and coronary heart disease].

Analysis of intracardiac hemodynamics is presented in patients with isolated stage II, III and IV chronic obstructive pulmonary disease (COPD) in the period of exacerbation and in those having COPD with concomitant coronary heart disease (stable angina of functional class II). Retrospective evaluation included 100 medical histories. Color Doppler echoCG was performed and parameters of systolic and diastolic function of both ventricles measured. Results of correlation analysis of systolic and diastolic function of left and right ventricles are presented along with the data on blood pressure in the right chambers of the heart.

[Hepatopulmonary syndrome characteristics in hepatic cirrhosis associated with COPD].

AIM: To evaluate specific features of hepatopulmonary syndrome (HPS) in patients with cirrhosis and cirrhosis associated with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: We made a retrospective analysis of case histories of 75 patients with hepatic cirrhosis (HC) of different etiology. The patients were divided into two groups: 23 patients with HC and COPD (group 1); 52 patients with HC without COPD (group 2). The patients were examined with spirography, gasometry. Single-breath carbon monoxide diffusion capacity (Dlco), TCO and TCO/VA were estimated. Transthoracic contrast-enhanced echocardiography was conducted for detection of intrapulmonary bypass in AaDO2 > 15 mm Hg. RESULTS: COPD stage I and II were diagnosed in 14 of 23 and 9 of 23 patients of group 1, respectively. TCO and TCO/VA had a trend to lowering in group 1 (p > 0.05). PaO2 was lower (p < 0.05) while AaDO2 was higher (p < 0.05) in group 1. Four patients of group I had intrapulmonary bypasses: of the first degree (2 patients with hypoxemia) and of the first and second degree (2 patients with normoxemia). In group 2 three patients had intrapulmonary bypasses: of the fourth degree in 1 patient with hypoxemia and of the first and second degree in 2 patients with normoxemia. CONCLUSION: HC patients with COPD had more severe hypoxemia. Mild and moderate HPS were registered in both groups. In COPD the risk of HPS is 3 times higher.