The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis.

We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. The median concentrations of MAC, C5a, C3a and factor B were higher in active AAV patients (P < 0·001). Achievement of remission was associated with reductions in C3a (P = 0·005), C5a (P = 0·035) and factor B levels (P = 0·045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered into the meta-analysis. Plasma MAC, C5a and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

[Vasculotoxicity of Chemotherapy: Assessment оf Endothelial Dysfunction Biomarkers' Levels in Gastric Cancer Patients].

Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р<0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р<0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р>0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= -0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.

[Relevant aspects of identification and interpretation of the glycated hemoglobin research findings.]

The article contains the literature review on laboratory criteria of detection and monitoring of the progression of the disease in patients with the diagnosis of diabetes mellitus. It also covers the issues of methodical approaches to the identification of glycated hemoglobin (HbA1c). The findings of author's researches of glycated hemoglobin in 149 patients have been given within the framework of comparison of two methodical approaches and comparison of the results with the subsequent classification of the received data. A random laboratory finding of qualitative hemoglobinopathy has been demonstrated, and the results recognized as unqualifiable and the approach to classification of such values have been discussed.Comparison of the results of glycated hemoglobin identification performed by different methods. 149 patients underwent a one-stage identification of glycated hemoglobin from plasma stabilized with K2-EDTA on Bio-Rad D10 and Sebia Capillarys Flex Piercing 2. Comparative study of the results of glycated hemoglobin identification has shown a difference in absolute values. However, a statistically reliable (p < 0.05) correlation between the values of glycated hemoglobin, expressed as a percentage obtained by different methods, has been revealed. In this case, the choice of a method for identifying glycated hemoglobin is not a matter of principal but it is important to adhere to the same method in treatment and long-term monitoring.

[Hepcidin and its relationship with inflammation in old and older patients with anemia of chronic disease associated with CHF].

BACKGROUND: Reported levels of hepcidin, the major regulator of systemic iron homeostasis in CHF patients, are controversial. Relationship of hepcidin with inflammation markers, which are typically increased in CHF, is understudied; this issue is practically unstudied in old and older CHF patients. AIM: To study the role of hepcidin in development of anemia of chronic disease (ACD) and the association of hepcidin with inflammation in old and older CHF patients. MATERIALS AND METHODS: Ninety old and older patients with IHD were evaluated. 35 of these patients had CHF and ACD and 35 patients had CHF without ACD. The control group (CG) consisted of 20 IHD patients without CHF and ACD. Serum concentration of hepcidin was measured using ELISA by the competitive binding principle. RESULTS: Patients with severe, congestive FC IV CHF prevailed among CHF patients with ACD, and their CHF was characterized with longer duration, more frequent hospitalizations, and lower compliance with the treatment. Significantly higher mean levels of hepcidin, C-reactive protein (CRP), erythrocyte sedimentation rate, and insignificantly higher levels of ferritin were observed in CHF patients with than without ACD. The high hepcidin, indexes of inflammation tests, and a significant positive correlation of hepcidin with hemoglobin levels suggested inflammation as a cause for the increased hepcidin, which induced anemia in old and older CHF patients with ACD.

[The results of application of the rapid quantitative assay for fatty acid-binding protein at the onset of acute coronary syndrome].

Fatty acid-binding protein (FABP) appearing in blood within a few hours of acute coronary syndrome (ACS) is a marker of myocardial necrosis. We estimated the diagnostic value of rapid immunochromatographic test for FABP in patients with ACS and compared it with other cardiomarkers: troponin 1 (Tn1), myoglobin and creatin phosphokinase-MB (CPK-MB). The study included 100 patients aged 61.3 +/- 12.9 yr hospitalized with ACS within 2 hr after beginning of anginous pain. FABP was detected by CardioFABP test, Tn1, myoglobin and CPK-MB by quantitative assays. Blood samples were taken 2, 6, and 24 hr after the onset of anginous pain. Acute myocardial infarction was diagnosed in 79 patients, unstable angina in 9, FC 3-4 angina of effort in 4, vasospastic angina in 1, non-coronary pathology in 7. Sensitivity of FABP, Tn1, myoglobin and CPK-MB 2 hr after onset of pain was 84.8; 34.2, 65.8; 22.8% respectively: it was 98.7: 92.4; 96.2; 82.3% in 6 hr and 56; 100; n/d; 86.7% in 24 hr. Specificity of FABP was 100% in all time intervals. It is concluded that FABP level determined by rapid qualitative assay within 2-6 hr after onset of ACS is a more sensitive cardiomarker than Tn1, myoglobin and CPK-MB for diagnostics of ACS.

[The assessment of the state of the immune system in the patients presenting with bronchial asthma and concomitant diseases of the nasal cavity and paranasal sinuses].

The objective of the present investigation was to study the influence of diseases of the nasal cavity (NC) and paranasal sinuses (PNS) concomitant with bronchial asthma (BA) on the development of peculiar features of the patients' immune status. Phenotypic characteristics of the main lymphocyte subpopulations from peripheral blood of 101 patients were obtained by means of flow cytometry with the use of fluorescein isocyanate- or phycoerythrin-labeled monoclonal antibodies. Special emphasis was laid on the elucidation of characteristics of humoral and cell-mediated immunity in the patients presenting with BA and concomitant NC and PNS diseases and their comparison with the respective parameters in the patients with isolated lesions in the upper respiratory tract (allergic rhinitis and polypous rhinosinusitis) and lower respiratory tract (bronchial asthma). It was shown that the patients with concurrent lesions of the upper and lower respiratory tracts experience marked intensification of the immune reactions in the form of the elevated number of activated B-lymphocytes (CD23+), serum IgE level, and peripheral eosinophil count.

[The role of interleukins in the pathogenesis of atherosclerosis].

There is now doubt today that inflammation plays one of the key roles in the development of atherosclerosis. Numerous data demonstrate a connection between acute cardiovascular complications and laboratory signs of inflammation. There is a connection between signs of inflammation and an unfavorable prognosis in cardiovascular patients. Proinflammatory cytokines are divided into several groups: interleukins, interferons, tumor necrosis factors, colony stimulating factors, and hemopoietic cytokines. All these groups of cytokines are involved in the immune inflammation process in atherosclerosis.

[Development of renal affection in obese patients].

AIM: To characterize mechanisms, early markers and clinical signs of renal damage in obesity. MATERIAL AND METHODS: The trial covered 29 males aged under 50 years (mean age 37.7+/-9.3 years) with abdominal obesity having neither carbohydrate metabolism disturbances nor chronic renal disease. All the patients were examined for microalbuminuria (MAU), serum level of leptin. Radionuclide scintigraphy of the kidneys with an acute captopril test, tests for serum concentrations of endothelin-1, homocistein, uric acid, ultrasound dopplerography of the brachial artery for assessment of endothelium-related vasodilation (ERVD) were made in 24 patients. In 9 patients MAU and ERVD were estimated after 3 months of valsartan treatment (80 mg/day). RESULTS: MAU was detected in 62% patients, its rate increasing with elevation of serum leptin and endothelin concentration. Under normal values of creatininemia and GFR, obese patients showed deletion of renal functional reserve (RFR). Patients with low RFR had maximal uricemia and homocysteinemia, serum endothelin-1. Such patients demonstrated also abnormal ERVD. 3-month valsartan intake led to elevation of ERVD and disappearance of MAU. CONCLUSION: Excessive leptin registered in obese patients provoked dysfunction of the endothelium of the intrarenal vessels manifesting with MAU, growth of endothelin-1 serum concentration and disorder of ERVD. This leads to unfavourable changes in filtrating function of the kidneys as seen from gradual deletion of RFR in the absence of hypercreatininemia. Elimination of MAU and ERVD disorders in obesity can be achieved by administration of angiotensin II receptor blockers.

[Endothelial dysfunction and renal lesion in obesity].

The subjects of the study were 29 men (mean age 37.7+/-9.3 years) suffering from abdominal obesity without carbohydrate exchange disturbances or signs of chronic renal diseases. The results of the study show that the surplus of leptin, typical of obese patients, leads to the development of intrarenal vascular endothelial dysfunction, which is manifested by microalbuminuria, the growth of endothelin-1 serum level, and endothelium-dependent vasodilatation impairment, leading to unfavorable changes in renal filtration. Administration of angiotensin II receptor blockers results in the elimination of microalbuminuria and the recovery of endothelium-dependent vasodilatation in obese patients.

[Thyroid-stimulating hormone receptor antibodies in the differential diagnosis of toxic goiter].

The production of stimulating thyroid-stimulating hormone (TSH) receptor antibodies (TSHR-Ab) whose level measurement has come into clinical use underlies the pathogenesis of Graves'disease (GD). This paper deals with the diagnostic and differentially diagnostic value of measurement of TSHR-Ab levels using two first-generation techniques (with heterological TSH): radioreceptor assay ("CIS bio international", France) and enzyme immunoassay ("Medizym" T.R.A."). The levels of TSHT-Ab, as well as thyroid peroxidase antibodies (TH-Ab) and thyroglobulin antibodies (TG-Ab) were studied in 206 patients among whom 176 patients were diagnosed as having GD and 30 had clinical thyroid functional autonomy (FA) generally appeared as multinodal toxic goiter. A comparative analysis of these two assays did not reveal some advantages of them and their results showed a significantly positive correlation (r = 0.91; p < 0.001). The diagnostic sensitivity of the assays was about 80-88% and their specificity was 60-70%. The findings led to the conclusion that in the absence of significant endocrine ophthalmopathy (EOF), clinical and routine instrumental and laboratory studies fail to differentiate GD and throid FA to sufficient accuracy whereas the measurement of the levels of TSHR-Ab substantially makes diagnosis easier. Moreover, it has been shown that the determination of the level of TBII using the test systems containing heterological TSH may not be used for the evaluation of the course of EOF.

[Acute coronary syndrome without elevation of the ST segment: prognostic significance of determining the levels of troponin I and CPK-MBmass]. / Ostryi koronarnyi sindrom bez pod''ema segmenta ST: prognosticheskoe znachenie opredeleniia urovnia troponina I i KFK-MBmass.

AIM: To assess diagnostic and prognostic role of CPK-MBmass and troponin I(TnI) in patients with acute coronary syndrome without persistent ST segment elevation (ACS). MATERIAL AND METHODS: Standard laboratory and device tests, measurements of CPK-MBmass and TnI levels at admission, 12 and 24 hours after hospitalization were performed in 51 ACS patients (33 men, 18 women, mean age 63 +/- 8.2 years). Early and late (1 month and 6, 12 months after hospitalization, respectively) complications were studied. RESULTS: The analysis of the immediate outcomes has revealed that treatment brought about stabilization of the condition in 45 (88.2%) patients, 6 patients had myocardial infarction within a month since the disease onset, one patient died. Late MI developed in 6 patients. For 6 months 2 more patients died. One patient died in the following 6 months. Thus ACS points to adverse 1-month prognosis in 12 and 1-year prognosis in 23.5% patients. TnI levels and CPK-MBmass are sensitive and specific for an adverse outcome in 91.7 and 100%, 82 and 89.7%, respectively. A predictive value for positive outcomes was 61.1 and 75%, respectively, for negative results 96.9 and 100%, respectively. CONCLUSION: Estimation of CPK-MBmass and TnI is essential in diagnosis of non-Q-wave MI and is predictable in relation to both short- and long-term prognosis.

[Comparative analysis of serum analyte level measurements by commercial diagnostic kits from four manufacturers (Alkor-Bio, Roche, Diagnostic Products Corporation-DCP, and Bayer Corporation)]. / Sravnitel'nyi analiz opredeleniia kontsentratsii riada analitov v syvorotke krovi s ispol'zovaniem kommercheski dostupnykh naborov reagentov chetyrekh firm-proizvoditelei ("Alkor Bio", "Roche", "Diagnostic Products Corporation"-DCP i "Bayer Corporation").

Hydrocortisone, progesterone, testosterone, triiodothyronine, thyroxine, chorionic gonadotropin, prolactin, alpha-fetoprotein, luteinizing, follicle-stimulating, and thyrotropic hormones were measured in human sera and in Lyphochek Immunoassay Plus Control reference sera (Bio-Rad Laboratories, USA) using 4 commercial kits (Alkor Bio Inc. and Roche, automated analyzer Roche Cobas Core; DPC, automated analyzer Immulite; Bayer, automated analyzer ACS:180). Coordination and correlation between these kits was observed, the coordination decreasing in the series Alkor Bio/Bayer, Alkor Bio/Roche, and Alkor Bio/DPC.

The diurnal rhythm of adrenocorticotropic hormone secretion in the assessment of the adequacy of replacement therapy in primary chronic adrenal failure.

Utilization of the daily rhythm of ACTH secretion was assessed as a measure of the adequacy of replacement therapy in primary chronic adrenal failure (PCAF: Addison's disease) with glucocorticoids (GC) by assaying plasma ACTH by radioimmunoassay every 4 h for one day in three groups of patients. Patients of group 1 had PCAF (n = 14) and received replacement therapy consisting of prednisolone (5 mg at 09:00 and 2.5 mg at 14:00) and group 2 patients received dexamethasone (0.5 mg at 23:00) in combination with prednisolone (2.5 mg at 14:00). All patients with PCAF also received 0.005-0.01 mg/day of 9alpha-fluorocortisol. The control group consisted of 14 healthy volunteers. Both types of replacement therapy resulted in high levels of variability in ACTH levels as compared with that in normal subjects. The areas under the curve (AUC) of the ACTH concentration over one day were not significantly different between groups 1 and 2 or between group 2 and controls. The AUC of ACTH in group 1 was significantly larger than that in controls. The mean ACTH concentration in group 1 at 07:00 and 11:00 was significantly greater than those in the other two groups. The daily rhythm of ACTH was generally closer to normal in patients given dexamethasone. Since our own clinical experience shows that at least two thirds of patients are initially given dexamethasone and that this had to be withdrawn because of the development of overdosage syndrome (weight gain, increased appetite, insomnia), it appears that there is a lack of concordance between the clinical data and the daily rhythm of ACTH secretion. When assessing the adequacy of replacement therapy in PCAF, it is important to note that the appearance of a normal rhythm of ACTH secretion over one day does not exclude the possibility of GC overdosage, with the effect that interpretation of the results of this type of measurement must take the clinical picture into account.

[Clinico-laboratory algorithms for assessing the functional activity of the thyroid gland]. / Kliniko-laboratornye algoritmy otsenki funktsional'noi aktivnosti shchitovidnoi zhelezy.

Three diagnostic algorithms making use of automated chemiluminescent analyzers are proposed for evaluation of the thyroid function, depending on the clinical situation. Laboratory criteria of hypothyrosis and thyrotoxicosis therapy monitoring are discussed. Main variants of disagreement between clinical data and values of thyrotropic hormone and free T4 are presented.

[Cytokines and extracellular matrix in experimental glomerulopathies]. / Tsitokiny i vnekletochnyi matriks pri éksperimental'nykh glomerulopatiiakh.

An acute stage of both immune (nephrotoxic nephritis) and non-immune (puromycin-aminonucleoside nephrosis) damage is characterized by an affected area infiltration with mononuclear leucocytes which produce cytokines that control mesangial cells proliferation and their production of the extracellular matrix components. This mononuclear infiltration is very intensive in the immune kidney damage and rather weak in the non-immune damage. Accumulation of the extracellular matrix in a chronic stage of puromycin-aminonucleoside nephrosis is very slight against the background of a weak mononuclear infiltration of the kidney glomeruli. Nephrotoxic nephritis is characterized by intensive infiltration of a glomerulus with mononuclear leukocytes and this results in high proliferation of mesangial cells and an extracellular matrix accumulation with appearance of an atypical interstitial collagen of types I and III. The absence or excessive number of mononuclear leukocytes in the affected area may result in metabolism disturbances of the extracellular matrix components with an increasing risk of glomerulosclerosis.

Results of pancreatic blood shunting into the systemic blood flow in insulin-dependent diabetics.

A new surgical method of treating patients with unstable insulin-dependent diabetes (IDD) has been developed--that of surgically shunting pancreatic blood into the systemic blood flow with the purpose of creating a more optimal interaction of subcutaneously administered insulin and pancreas-secreted glucagon. The long term results of the operation depend on the patency of a splenorenal anastomosis. This has been studied by following up 137 patients over periods from half a year to three years. Anastomotic patency was determined by renal and splenic venography and celiacy arteriography, which revealed a patent anastomosis in 114 patients, and an obliterated one in 23. Patients with patent anastomoses showed a lowering of glycosylated hemoglobin (HbA1c) from 13.3 +/- 0.3% to 9.3 +/- 0.6%, p < 0.05, a decrease of the injected insulin dose from 0.97 +/- 0.04 to 0.72 +/- 0.03 U/kg, p < 0.05, disappearance or considerable abatement of pain in the lower extremities, and of hypoglycemia. Improvement of clinical status was accompanied by an increase of glucagon in the systemic blood stream from 60.8 +/- 10.1 to 91.5 +/- 9.4 pg/ml, p < 0.05, a rise of tissue oxygen pressure, pO2, from 49.2 +/- 2.4 to 58.1 +/- 1.9 mm Hg, p < 0.05. In patients with oblivious anastomoses postoperative HbA1c levels did not change from preoperative values: 12.9 +/- 0.4% and 12.8 +/- 0.7%, p < 0.05, respectively; the insulin dose remained the same--0.91 +/- 0.07 U/kg and 0.85 +/- 0.07 U/kg, p < 0.05, no rise of the systemic blood glucagon content was noted, and former complaints continued. The suggested method is not an alternative for insulin therapy, but considerably enhances its potential.

[Visceral lesions in alcoholism]. / Vistseral'nye porazheniia pri alkogolizme.

Rich clinical material has been gained on carbohydrate and lipid metabolisms, cardiovascular, hepatic, pancreatic, gastric parameters in chronic alcoholics. Functional and morphological changes correlated with duration of chronic alcoholism. No definite relationship existed between the stage of alcoholism and alterations in laboratory and instrumental findings in the course of abstinence syndrome.

[Topical diagnosis of pancreatic insulinomas]. / Topicheskaia diagnostika insulinom podzheludochnoi zhelezy.

Diagnosis of pancreatic insulinomas has been performed. Celiacography appeared to be the most efficient diagnostic method (more than 50% of sensitivity). Intraoperative ultrasound testing, that have been done in 16 patients, managed to make a topical diagnosis with a high accuracy and to evaluate relation of a tumor with portal vessels and pancreatic duct that is very important in choosing a proper surgical technique.

[Effects of a number of cytokines on the proliferation of mesangial cells and the production of extracellular matrix in anti-GBM nephritis]. / Vliianie riada tsitokinov na proliferatsiiu mezangial'nykh kletok i produktsiiu vnekletochnogo matriksa pri anti-GBM-nefrite.

The interaction of IL-1 and TNF alpha in the autolous phase of anti-GBM nephritis was studied. The influx of mononuclear leukocytes into the glomerulus and high cytokine levels induced a decrease in mesangial cell proliferation and an increase in extracellular matrix production. The methylprednisolone suppression of mononuclear leukocyte infiltration caused the autocine cytokine secretion of mesangial cells. Cyclophosphamide decreased cytokine production, but did not affect mononuclear leukocyte infiltration. The absence of mononuclear leukocytes in the site of the injury induced by imbalance between the synthesis and degradation of extracellular matrix components. The uncontrolled metabolism of the extracellular matrix may be induced glomerulosclerosis.