Vol 83, No 6 (2011)


Hyperuricemia as a component of cardiorenal syndrome

Mukhin N.A., Fomin V.V., Lebedeva M.V., Mukhin N.A., Fomin V.V., Lebedeva M.V.


The role of hyperuricemia as a cardiovascular and renal risk factor and approaches to its correction are discussed.
Terapevticheskii arkhiv. 2011;83(6):5-13
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The level of endothelin-1 and reactivity of skin microvessels in patients with early stages of chronic kidney disease

Smirnov A.V., Petrishchev N.N., Panina I.Y., Mnuskina M.M., Achkasova V.V., Rumyantsev A.S., Menshutina M.A., Smirnov A.V., Petrischev N.N., Panina I.Y., Mnuskina M.M., Achkasova V.V., Rumyantsev A.S., Menshutina M.A.


Aim. To evaluate endothelin-1 (ET-1) levels and to characterize reflex vasomotor reactions of skin vessels in distant exposure to cold in patients with chronic kidney disease (CKD) of stage I and II. Material and methods. Glomerular filtration rate (GFR) was calculated by MDRD formula for 40 healthy subjects (mean age 39.2±2.0 years) and 147 CKD patients (mean age 41.4±1.8 years). All the patients were also exposed to the cold test (a modified variant). Results. Patients with CKD stage I demonstrated a 35.1% fall in blood flow rate (Qas) in response to cold stimulus, patients of stage II - a 42.2% fall, healthy patients - a 19.3%. CKD patients of stage I and II retained a Qas fall for 3 min after exposure to cold, while healthy subjects resumed skin blood circulation immediately after exposure to cold. Blood plasma ET-1 concentration in healthy subjects was 0.239±0.055 fmol/ml, in stage I CKD patients - 0.334±0.066 fmol/l, in stage II CKD patients - 0.422±0.041 fmol/l. Relationships were found between ET-1 level and GFR (Rs = 0.242; p < 0.05), 24 h proteinuria (Rs = 0.375; p < 0.003) and Qas% in the cold test (Rs = -0.389; p < 0.003) as well as time of recovery of the background Qas (Rs = -0.311; p < 0.003). Conclusion. Dysfunction of autonomic nervous system at early stages of CKD may arise by means of activation of ET-1 synthesis in response to enhancement of sympathetic impacts.
Terapevticheskii arkhiv. 2011;83(6):13-18
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Estimation of podocyte dysfunction by nephrinuria severity in proteinuric forms of chronic glomerulonephritis

Chebotareva N.V., Bobkova I.N., Kozlovskaya L.V., Tsopanova Z.G., Chebotareva N.V., Bobkova I.N., Kozlovskaya L.V., Tsopanova Z.G.


Aim. To evaluate severity of nephrinuria (NU) as a marker of podocyte dysfunction (PD) in patients with proteinuric forms of chronic glomerulonephritis (CGN) and to specify efficacy of this test for assessment of activity and prognosis of CGN. Material and methods. We examined 74 CGN patients: 18 with inactive nephritis (group 1), 18 - with subnephrotic proteinuria (group 2), 38 - with nephrotic syndrome - NS (group 3). The control group consisted of 10 healthy subjects. Urinary excretion of nephrin was studied with indirect enzyme immunoassay. A response to immunosuppressive treatment (IST) was studied in 23 NS patients depending on a baseline NU level. Results. An NU level was higher in patients with proteinuric forms of CGN (groups 2 and 3) than in inactive disease and in healthy subjects, in NS patients significantly higher than in less severe proteinuria. NU was significantly higher in arterial hypertension, in persistent NS. Remission of NS was achieved within 6 months of treatment in 9 of 11 (82%) patients with a baseline NU level < 17 ng/ml. Eight from 12 (67%) patients with high NU did not respond to IST conducted for 9 months to 2 years. ROC-curve construction showed that NU assessment in NS patients has high informative value in assessment of prognosis and efficacy of treatment in 6 months to come. Conclusion. The NU test in CGN patients is an informative diagnostic test allowing prognosis of a response to IST and assessment of PD severity.
Terapevticheskii arkhiv. 2011;83(6):18-23
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Determination of urinary markers of proteolysis/fibrinolysis and fibroangiogenesis in the kidney in hypertensive patients

Nanchikeeva M.L., Kozlovskaya L.V., Rameev V.V., Fomin V.V., Bulanov N.M., Nanchikeeva M.L., Kozlovskaya L.V., Rameev V.V., Fomin V.V., Bulanov N.M.


Aim. To determine clinical significance of urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in essential hypertension (EH). Material and methods. Examination of the kidneys was made in 71 patients with EH degree 1-3. Renal function was assessed by 24-h albuminuria, calculated glomerular filtration rate (GFR) by Cockroft-Golt. Early signs of renal damage were microalbuminuria - MAU (diurnal albuminuria 30-300 mg/day), reduction of GFR ( < 90 ml/min/1.73 m2). EH patients with hypercreatininemia and GFR under 60 ml/min/1.73m2 corresponding to stage III of chronic kidney disease were not included in the study. An additional nephropathy marker was an elevated index of resistance of interlobular renal arteries (RI > 0.65) as shown by dopplerometry. ELISA examined urinary biomarkers of intercellular and cell-matrix interactions in the kidney in EH patients and healthy controls (n = 12). Results. MAU was detected in 54 (76%) of 71 EH patients, elevated RI > 0.65 - in 37 (52%) patients. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis were higher in EH patients then in the controls. Urinary excretion of PAI-1, TGF-beta1, VEGF and collagen of type IV in EH patients with MAU was significantly higher than in patients with normoalbuminuria. A strong direct correlation between MAU and the rest above urinary biomarkers was found as well as between urinary excretion of collagen IV and RI. An inverse negative relationship was seen between RI and GFR. Conclusion. Renal impairment in EH patients is a progressive disorder. Each stage of this process has its own clinicodiagnostic markers. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in the kidney are informative for monitoring of early HNP.
Terapevticheskii arkhiv. 2011;83(6):23-27
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Association of gene TP53 polymorphic marker Pro72Arg with clinical characteristics of chronic glomerulonephritis

Kamyshova E.S., Shvetsov M.Y., Shestakov A.E., Kutyrina I.M., Nosikov V.V., Kamyshova E.S., Shvetsov M.Y., Shestakov A.E., Kutyrina I.M., Nosikov V.V.


Aim. To study association of geneTP53 polymorphic marker Pro72Arg coding synthesis of p53 protein with onset, course and progress of chronic glomerulonephritis (CGN). Material and methods. We examined 126 patients (63 males and 63 females, mean age 38.8±13.2 years) with CGN duration 13.0±9.1 years. When analyzing genetic predisposition to CGN, we compared incidence rate of alleles/genotypes of polymorphic marker Pro72Arg of gene TP53 in CGN patients and 69 controls free of renal disease. CGN clinical features were assessed retrospectively including analysis of nephritis onset, clinical and morphological variants. The course of CGN was analysed by changes in severity of hypertension, persistence of proteinuria > 3 g/day during 6 months and longer, conduction of immunosuppressive therapy and response to it. In analysis of progression rate, doubling of blood creatinine was considered as an end point. We used polymerase chain reaction with analysis of restriction fragment length for identification of alleles of Pro72Arg polymorphic marker of TP53 gene. Results. Distribution of the genotypes of the above polymorphic marker in CGN patients and in controls did not significantly differ. Depending on Pro allele carriage, CGN patients were divided into two groups: Arg/Arg group (59 carriers of genotype Arg/Arg) and Pro group (63 patients with genotype Arg/ Pro and 4 with genotype Pro/Pro). Carriage of Pro allele of gene TP53 was associated with high CGN activity at onset, presence of arteriolosclerosis and IgA deposits in kidney biopsy. Patients with genotype Arg/Arg more frequently developed nephritic syndrome without renal dysfunction syndrome. Conclusion. We have discovered association of geneTP53 polymorphic marker Pro72Arg with clinical manifestations of CGN. Carriers of Pro allele more often have signs of active glomerular inflammation and vascular impairment with renal dysfunction while carriers of Arg/Arg genotype more frequently demonstrate isolated nephritic syndrome.
Terapevticheskii arkhiv. 2011;83(6):27-32
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Cyclopheron administration in chronic pyelonephritis: changes in interferon status

Kudryashova I.P., Ospel'nikova T.P., Ershov F.I., Kudryashova I.P., Ospelnikova T.P., Ershov F.I.


Aim. To detect correlations between changes in interferon (INF) system and a course of chronic pyelonephritis (CP), to ascertain a corrective effect of cyclopheron in combined treatment with antibacterial drugs. Material and methods. We examined 30 CP patients in different periods of the disease: group 1 had latent CP without laboratory evidence for exacerbation, group 2 had CP exacerbation treated with antibiotics, group 3 had exacerbation given basic treatment and cyclopheron by a standard scheme. All the patients were examined for interferon status, patients of groups 2 and 3 were examined once more after therapy. Results. Patients of all the groups showed diminished ability of blood leukocytes to produce IFN, especially IFN-gamma. Cyclopheron addition to antibacterial therapy significantly stimulated production of IFN alpha and gamma by blood cells compared to basic therapy. Examination of 5 patients after 1-year follow-up detected preserved ability of blood cells to produce IFN and reduce the number of exacerbations after combined treatment with cyclopheron. Conclusion. Administration of cyclopheron in combination with standard antibacterial treatment results in persistent correction of IFN status.
Terapevticheskii arkhiv. 2011;83(6):33-35
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Comparative characteristics of hemostasis system in patients with end-stage renal disease admitted for urgent and elective hemodialysis

Kotlyarova G.V., Kozlovskaya N.L., Lashutin S.V., Komyagin Y.V., Shakhnova E.A., Dobrosmyslov I.A., Shilov E.M., Nesterova S.G., Kotlyarova G.V., Kozlovskaya N.L., Lashutin S.V., Komyagin Y.V., Shakhnova E.A., Dobrosmyslov I.A., Shilov E.M., Nesterova S.G.


Aim. To evaluate parameters of hemostasis system in patients with end-stage renal disease (ESRD) with consideration of elective or urgent start of dialysis treatment. Material and methods. A total of 47 patients with ESRD entered the study. They were divided into two groups depending on urgent (group 1) or elective (group 2) start of hemodialysis. Group 1 consisted of 31 patients (13 female, 18 male) aged 18-86 years, group 2 - of 16 patients (9 female, 7 male) aged 36-79 years. The patients were comparable by ESRD causes. Clinical and laboratory findings were compared: activated partial thromboplastin time, prothrombin time, levels of fibrinogen, soluble complexes fibrin-monomers (SCFM). Results. Azotemia, hyperkalemia and anemia were close to similar. Group 1 patients had more severe alterations of nutrition status and fat metabolism, marked hyperhydration and hypervolemia, arterial hypertension, more frequent neurological and infectious complications, symptoms of enteritis. Thrombotic complications developed in 51.5%, thromboses of the vascular access in 45% in group 1 vs group 2 which demonstrated only one type of thrombotic complications - thromboses of primary arteriovenous fistula (in 1 patient, 6.25%). Hemorrhagic complications were absent in group 2, in group 1 these developed 5 times less frequently than thromboses. Platelet count was significantly less (p = 0.001) in group 1 than in group 2. Hyperfibrinogenemia occurred in about 65% patients of group 1 and in 46% in group 2. SCFM levels were elevated in both groups, but in group 1 these levels were by 50% higher than in group 2 (p = 0.005). This evidences for stronger activation of intravascular coagulation in patients on urgent hemodialysis. Conclusion. ESRD patients admitted for urgent hemodialysis had more severe uremic syndrome with stronger activation of blood coagulation than patients admitted for elective hemodialysis. Frequency of thrombosis in patients admitted for urgent hemodialysis was 8.3 times higher than in patients admitted for elective hemodialysis.
Terapevticheskii arkhiv. 2011;83(6):36-41
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Left ventricular hypertrophy in end-stage renal disease and its possible regression as a result of correction of anemia and arterial hypertension

Dzgoeva F.U., Gatagonova T.M., Kadzaeva Z.K., Khamitsaeva O.V., Kochisova Z.K., Dzutseva A.T., Bazaeva B.G., Dzgoeva F.U., Gatagonova T.M., Kadzaeva Z.K., Khamitsaeva O.V., Kochisova Z.K., Dzutseva A.T., Bazaeva B.G.


Aim. To ascertain mechanisms of development of left ventricular hypertrophy (LVH) and possible cardioprotective action of anemia correction in patients with end-stage renal disease. Material and methods. A total of 98 patients (53 females and 45 males aged 49.4±14 years) on hemodialysis participated in the study. The patients were examined clinically with estimation of the levels of parathormone, calcium, phosphorus, erythrocytic indices, serum ferritin, blood transferrin. Echocardiography with dopplerography on Aloka-4000 unit were made. Left ventricular geometry was assessed by J. Gottdiener classification. Therapeutic policy aimed at correction of anemia, arterial hypertension, phosphorus-calcium metabolism. Results. The patients were treated and followed up for 18 months. The examination was done before treatment, 12 and 18 months later. After the trial the patients were divided into 4 groups depending on the results obtained on LVH development. Blood pressure, hemoglobin, echocardiographic parameters changed according to the patient's group. After 18 months of observation and treatment with erythropoietin and iron preparations, ACE inhibitors, angiotensin II receptor blockers, beta-adrenoblockers, drugs regulating phosphorus-calcium metabolism some cases were seen of reduction of systolic blood pressure, achievement of target hemoglobin level, regression of LVH. Conclusion. Combined treatment of hemodialysis patients including antianemic, antihypertensive drugs promoted improvement of LVH or its regression in some cases.
Terapevticheskii arkhiv. 2011;83(6):42-46
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The role of leptin, adiponectin and insulin-resistance markers in development of early stages of chronic kidney disease and atherosclerosis of carotid arteries in obese patients

Saginova E.A., Gallyamov M.G., Severova M.M., Surkova O.A., Fomin V.V., Ermakov N.V., Rodina A.V., Mukhin N.A., Saginova E.A., Gallyamov M.G., Severova M.M., Surkova O.A., Fomin V.V., Ermakov N.V., Rodina A.V., Mukhin N.A.


Aim. To characterize clinicopathogenetically factors influencing development of early chronic kidney disease (CKD) and impairment of other target organs in obese patients. Material and methods. The examination of 86 obese patients (64 males and 22 females, mean age 44±11 years) included standard clinical tests, test for albuminuria, calculation of glomerular filtration rate (GFR) by MDRD formula, ultrasound investigation of the carotid arteries to detect atherosclerotic lesion of the carotid arteries, assessment of insulin resistance -IR (plasma concentration of insulin before meal and blood C-peptide, HOMA-index), test for plasma adipokinins (leptin, adiponectin). Results. Significant direct correlations were found between blood plasma leptin concentration, body mass index (BMI), plasma concentration of insulin and C-peptide, HOMA index, adiponectinemia and albuminuria. CKD patients have significantly higher than patients free of CKD levels of IR markers, waist circumference, BMI, leptinemia (38.2±28.8 and 21.6±19.8 ng/ml, respectively; p < 0.01). Obstructive sleep apnea syndrome was associated with higher IR and albuminuria, significantly lower estimated GFR (81±2 and 95±2 ml/min/1.73 m2, respectively; p < 0.05). Ultrasound evidence for atherosclerotic lesions of the carotid arteries was associated with a significant increase in blood plasma concentration of C-peptide, reduction of adiponectinemia (14.9±10.8 and 32.5±22.5 mcg/ml; p < 0.01), a rise in proportion fasting insulinemia/adiponectinemia (1.6±1.2 and 0.6±0.8, respectively; p < 0.05) and reduction of estimated GFR (86±19 and 102±25 ml/min/1.73 m2, respectively; p = 0.001). Conclusion. In obesity, CKD at early stages develops in parallel with atherosclerotic lesion of the carotid arteries, which correlates with progression of leptinemia, IR and attenuation of organ-protecting properties of adiponectin.
Terapevticheskii arkhiv. 2011;83(6):47-53
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Efficacy of levosimendan vs dopamine in patients with resistant cardiac failure

Dzhaiani N.A., Kositsyna I.V., Gnidkina N.A., Tereshchenko S.N., Dzhaiani N.A., Kositsyna I.V., Gnidkina N.A., Tereschenko S.N.


Aim. Effects of levosimendan treatment compared to dopamine treatment on a clinical course, central hemodynamics and prognosis in patients with resistant cardiac failure (RCF). Material and methods. A total of 30 RCF patients (16 females and 14 males aged 50-80 years) were divided into two groups. Patients of group 1 received inotropic drug levosimendan intravenously in the initial dose 12-24 mcg/kg for 10 min with subsequent 24-hour infusion in a dose 0.1 mcg/kg/min. Patients of group 2 received dopamine intravenously for 24 hours in a mean dose 2.2 mcg/kg/min. The patients were followed up for 6 months. Results. In group 1 cardiac failure regressed earlier than in group 2. Left ventricular performance index after infusion hour 1 increased from 2.9 to 3.3 (kg.m)/m2, in group 2 it decreased from 2.6 to 2.3 (kg.m)/m2; p = 0.028). To infusion hour 24 this index in group 1 was 3.2 (kg.m)/m2, in group 2 - 2.6 (kg.m)/m2. Cardiac index (CI) in group 1 increased from 2.3 l/min/m2 at infusion min 1 to 2.7 l/min/ m2 after 10 min of infusion and 2.9 l/min/m2 after 24 hours, i.e. there was a 26% rise (p = 0.025). In group 2 the CI rise was insignificant - from 2.4 to 2.5 l/min/m2. To the end of levosimendan injection, systemic vascular resistance fell from 1520.9 to 1174.6 dyne.s.cm-5 (p = 0.031), in group 2 no significant changes were seen. Hospital mortality in group 1 was 1 patient, in group 2 - 6 patients. Conclusion. Inotropic treatment in RCF patients with levosimendan vs dopamine produces earlier regress of cardiac failure symptoms, better improvement of myocardial contractivity, is associated with a good prognosis.
Terapevticheskii arkhiv. 2011;83(6):53-59
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Polymorphisms of genes CYP2C9 and VKORC1 in patients with venous thromboembolic complications in Moscow population: effects on stability of anticoagulant therapy and frequency of hemorrhage

Vorob'eva N.M., Panchenko E.P., Dobrovol'skiy A.B., Titaeva E.V., Khasaeva Z.B., Konovalova N.V., Postnov A.Y., Kirienko A.I., Vorobyeva N.M., Panchenko E.P., Dobrovolsky A.B., Titaeva E.V., Khasaeva Z.B., Konovalova N.V., Postnov A.Y., Kirienko A.I.


Aim. To investigate frequency of carriage of genetic polymorphisms CYP2C9 and VKORC1 in patients with venous thromboembolic complications (VTEC) in Moscow population given warfarin treatment and effects of this carriage on stability of anticoagulation and frequency of hemorrhagic complications (HC) in warfarin treatment. Material and methods. The study included 111 patients with the history of deep vein thrombosis and/ or pulmonary artery thromboembolism. All the patients received non-fractionated or low-molecular heparin for at least 5 days, then warfarin (target INR 2.0-3.0). Warfarin dose was selected empirically. Gene CYP2C9 and VKORC1 polymorphisms were studied. HC were end points. Results. Genotype CYP2C9*1/*1 (a "wild" type) was detected in 94 (84.7%) patients. Of other genotypes - heterozygotes CYP2C9*1/*2 (4.5%) and CYP2C9*1/*3 (10.8%). Genotyping by VKORC1 detected genotype GG (a wild type) in 42.3%, genotype GA - in 48.6%, genotype AA - in 9.1% patients. A mean warfarin dose, supporting an adequaite INR, was asspciated with both genotype CYP2C9 and VKORC1. Warfarin doses were highest in carriers of wile genotypes CYP2C9 and VKORC1 (6,9 and 8,8 mg/day), the lowest - in patients with genotypes CYP2C9*1/*3 and __ VKORC1 (4,5 and 4,0 mg/day). The carriers of polymorphisms CYP2C9*1/*3 and VKORC1 showed less stable anticoagulation vs carriers of allele variants CYP2C9*1/*1, CYP2C9*1/*2 and genotypes GG, GA VKORC1. An HC rate depended, as a rule, on carriage of genotypes CYP2C9*1/*3 and AA VKORC1. The highest risk of HC was associated with genotype CYP2C9*1/*3. The results of multifactorial regression analysis also indicated that carriage of genotype CYP2C9*1/*3, a female gender and the range of INR in warfarin treatment ≥ 2,66 are independent predictors of HC in VTEC patients on warfarin treatment. Conclusion. Carriage of gene CYP2C9 and VKORC1 polymorphisms affects suppoting dose of warfarin and rate of hemorrhage in patients with VTEC in Moscow population. Frequency of HC is the highest in carriers of genotypes CYP2C9*1/*3 and AA VKORC1, they need minimal supporting dose of warfarin. Carriage of genotype CYP2C9*1/*3 in line with a female gender and instability of INR is an independent predictor of HC in VTEC patients in Moscow population on warfarin treatment.
Terapevticheskii arkhiv. 2011;83(6):59-65
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Obesity and chronic kidney disease

Bondar' I.A., Klimontov V.V., Simakova A.I., Bondar I.A., Klimontov V.V., Simakova A.I.


Obesity and overweight are now characterized as epidemics. It is shown that body overweight is associated with functional and structural changes in the kidneys. The results of epidemiological studies indicate that obesity can be the risk factor of chronic kidney disease (CKD) irrespective of the presence or absence of diabetes, arterial hypertension and other comorbidities. Manifestations of renal pathology in obese persons include microalbuminuria and proteinuria, hyperfiltration or impaired renal function. Glomerulomegaly and focal segmental glomerulosclerosis are the most typical structural signs of obesity-related nephropathy. More evidence is accumulated on the link between CKD in obesity and abnormalities in adypokine secretion (hyperleptinemia, lack of adiponectin), activation of rennin-angiotensin system, chronic inflammation, endothelial dysfunction, lipid accumulation, impaired renal hemodynamics and diminished nephron number related to body mass. A decrease of body weight following lifestyle modification or bariatric surgery leads to reduction in albuminuria and eliminates hyperfiltration in obese subjects. Thus, prevention and treatment of obesity may reduce CKD incidence in general population.
Terapevticheskii arkhiv. 2011;83(6):66-70
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The role of D2 vitamin metabolite paricalcitol in nephroprotective strategy in chronic disease of the kidneys

Milovanov Y.S., Kozlovskaya L.V., Milovanova L.Y., Milovanov Y.S., Kozlovskaya L.V., Milovanova L.Y.


Calcitriol is important in nephroprotective strategy in chronic disease of the kidneys (CDK). However, its long-term use often results in hypercalciemia with metastatic calcification. Compared to calcitriol, paricalcitol (zemplar) - metabolite of vitamin D2 - leads to hypercalciemia less frequently, has a more potent nephroprotective effect and more rapidly decreases blood levels of parathyroid hormone. Paricalcitol in combination with lozartan has more pronounced nephroprotective effect. Morphological analysis detected inhibition of development of glomerulosclerosis and tubulointerstitial fibrosis. A cardioprotective effect of paricalcitol manifests with reduction of mortality from cardiovascular complications both at CDK predialysis stage and in regular hemodialysis.
Terapevticheskii arkhiv. 2011;83(6):70-73
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Bronchial asthma and gastroesophageal reflux disease: view of the clinician and pathophysiologist

Lyamina S.V., Maev I.V., Yurenev G.L., Malyshev I.Y., Lyamina S.V., Maev I.V., Yurenev G.L., Malyshev I.Y.


Combination of bronchial asthma (BA) with gastroesophageal reflux disease (GRD) is now most prevalent among combined pathology of the respiratory and gastrointestinal tracts. Interaction of these diseases is stated basing on clinical picture and pathogenetic aspects of BA development in the presence of GRD and GRD in the presence of BA. Development of combined affection of gastrointestinal and respiratory tracts occurs in secondary immunodeficiency. Main lines of the paradigm of macrophage phenotypes M1/M2 and mechanisms of alternative development of the immune response Th1/Th2 in combination of GRD with BA are presented. Investigation of macrophage functional activity and Th1/ Th2 balance gives ground for development of the method of macrophage phenotype reprogramming which is a promising approach to effective treatment of combined pathology of the respiratory tract and upper gastrointestinal tract including cases resistant to pharmacological treatment.
Terapevticheskii arkhiv. 2011;83(6):73-80
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