Biomedical subjects
Publications and source records attributed to M G Tvorogova.
Solid-phase ELISA revealed increased content of macrophage-granulocyte colony-stimulating factor and basic fibroblast growth factor in the serum of hyperlipoproteinemic patients.
AIM: To assess efficacy of combination therapy with fluvastatin and fenofibrate in ischemic heart disease (IHD) patients with combined hyperlipidemia and type 2 diabetes. MATERIAL: Patients with IHD and combined hyperlipidemia with (n=56)) or without type 2 diabetes (n=30). METHODS: After 8-week diet period the patients were randomized to 4 weeks monotherapy with either fluvastatin (40 mg/day) or micronized fenofibrate (200 mg/day). In patients whose low-density lipoprotein cholesterol (LDL CH) remained > 2,6 mmol/1 and triglycerides (TG) > 2.3 mmol/1 combination of fluvastatin 40 mg/day and fenofibrate 200 mg/day was used for the next 12 weeks. RESULTS: Target levels of LDL CH and TG were achieved in 75 and 88%, respectively, of diabetics, and in 73 and 88%, respectively, of non-diabetics. CONCLUSION: The use of combination of fluvastatin and fenofibrate was more effective then monotherapy for correction of lipid abnormalities in combined hyperlipidemia both in diabetics and non-diabetics with IHD.
The number of dual bonds (DB) was determined by the ozonization method in the lipid fraction of blood serm (BS) in healthy subjects and in patients with hyperlipidemia (HLP). Single-direction changes were detected in the DB quantity and in the lipid level in case of HLP; besides, a highly reliable positive correlation was established between the DB concentration and the basic BS lipid classes. The results suggest that an increasing DB quantity in HLP is preconditioned by a growing lipid contents and show their tense relation with components of the lipid transport system (LTS). The determination of the DB concentration, as of an index of the total unsaturation of the BS lipid fraction, provides for obtaining extra data useful in describing the LTS in different-type impairments of lipid metabolism.
Fifty-five patients (mean age 42.3) with clinical signs of metabolic syndrome were investigated. The peroral glucose-tolerance and insulin-modified intravenous glucose-tolerance tests were used in the diagnosis of insulin-resistance. According to the SI index, a lower tissue sensitivity to insulin was detected in 48 (87%) of patients; it is noteworthy, that a low SI index was registered in some of them, when indirect signs of insulin-resistance, like hyperglycemia, hyperinsulinemia, were absent.
Ten lipid fractions were detected in patients with psoriasis by the method of unidimensional chromatography in a thin layer of silica gel with two solvent systems designed for separating a lipid extract of high-density lipoproteins (HDLP). Four phospholipids fractions were identified as follows: three main ones, i.e. phosphatidylcholine, lisophosphatidylcholine and sphyngomielin, and one minor fraction, i.e. phosphatidylethanolamine. The HDLP lipid comprises free cholesterol and its esters. Three glyceride fractions were detected: mono-, di- and triglicerides and free fatty acids. The ratio of the individual phospholipid fractions, on the one hand, and of free to ester-bound cholesterol was found in HDLP by computer-aided densitometry of chromatograms and coincided with the routinely obtained data. The described method designed to evaluate the HDLP lipid composition can be handy in investigations of HDLP in patients with psoriasis.
Serum albumin binding capacity (ABC) was studied using K-35 hydrophobic fluorescent probe in order evaluate the passive transfer and absorption of saturated fatty acids (s-FA) by the cells. ABC decreases on day 3 of myocardial infarction and remains low till discharge and is paralleled by hyperTG. We believe that ABC decrease reflects activation of passive transfer and absorption of s-FA by the cells during simultaneous blocking (presumably by acute phase proteins) of active apoE/B-100 receptor endocytosis of s-FA in the form of TG as VLDL remnants. Decrease of ABC reflects a later than erythrocyte sedimentation rate and acute phase proteins normalization of metabolic consequences of inflammation. ABC helps indirectly evaluate the blocking of active (receptor) absorption of s-FA in the form of TG and activation of passive absorption of s-FA from associations with albumin by the cells.
AIM: To evaluate the efficiency of 6-month therapy with xenical (gastrointestinal lipase inhibitor) in combination with diet in patients with stable angina pectoris associated with obesity and hyperlipemia. MATERIAL AND METHODS: An open comparative randomized study of the efficiency of xenical in combination with diet was carried out in patients with stable angina pectoris concomitant with obesity and hyperlipemia. Thirty coronary patients aged 45-65 years with stable angina of effort (functional class I-II) with body weight index 28.1-45.6 kg/m2 (mean 33.5 kg/m2) were examined. All patients presented with dyslipemia (low density lipoprotein (LDL) cholesterol more than 4.14 mmol/liter, triglycerides (TG) more than 2.2 mmol/liter). Controls (n = 15) were treated with diets alone for 6 months. In the main group diets were supplemented by xenical in a dose of 360 mg/day. RESULTS: Body weight index decreased in both groups (by 9.9% in the main group and by 4.2% in the control). Body weight stabilization during 6 months of treatment and the fact that it was slow and gradual were essential. In patients treated with xenical total cholesterol level decreased by 10.9% and of LDL cholesterol by 12.2% after 6 months (p < 0.05). Changes in the levels of high density lipoprotein cholesterol and TG were insignificant. The drug did not affect the incidence of angina attacks and improved exercise tolerance after 6-month therapy. Blood biochemistry (transaminases, alkaline phosphatase, glucose, and creatinine) changed negligibly. No side effects were observed; all patients received a complete 6-month course. CONCLUSION: The results confirm that xenical (orlistat) can be used for long therapy of patients with stable angina of effort concomitant with obesity and hyperlipemia.
There are limited data concerning influence of hormone replacement therapy (HRT) on lipid profile in women with type 2 diabetes. Aim of the study was to compare changes of blood lipids during HRT in postmenopausal women with and without type 2 diabetes. Seventy seven women included in the study were assigned to 1 of 4 groups, basing on being diabetic or nondiabetic, and further subdivided into users of estrogen alone (ERT), and of estrogen plus progestin (EPRT). Effect of 6-month ERT (oral estradiol valerate 2 mg/day) and EPRT (oral estradiol valerate 2 mg/day sequentially combined with cyproterone acetate 1 mg/day) on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and lipoprotein (a) [Lp(a)] was separately assessed. EPRT and ERT caused decrease in LDL-C by 15% and 12%, and increase in HDL-C by 12% and 13%, respectively, in patients with diabetes (p<0.05 in all cases). LDL-C decreased by 11% and 15%, respectively, in women without diabetes (p<0.05 in all cases). Lp(a) was also reduced 25% with EPRT (p<0.01) and ERT (p<0.05). HDL-C increased 10% (p<0.05) with ERT but remained unchanged with EPRT. In conclusion, changes in all lipid parameters except Lp(a) caused by ERT and EPRT were comparable in postmenopausal women with and without type 2 diabetes.
AIM: To study the influence of treatment with HMG-CoA reductase inhibitor atorvastatin on endothelial function in patients with familial hypercholesterolemia type IIa. MATERIALS AND METHODS: Sixteen patients (5m/11w, 51-/+3 years) with familial hypercholesterolemia were studied before and after 3 months of therapy with atorvastatin 20 mg/day. EDRF release test (D.Celermajer, 1992) was used to assess flow-mediated endothelium-dependent vasodilatation (FMD) of the brachial artery in response to reactive hyperemia. Plasma nitrite/nitrate (NOx) levels were measured as an indirect index of nitric oxide (NO) production in vivo using HPLC. RESULTS: Atorvastatin treatment resulted in a 32% reduction in total serum cholesterol (CH), 41% reduction in low density lipoprotein (LDL) CH, 16% reduction in triglycerides and a 21% increase in high density lipoprotein CH. Flow mediated dilatation (FMD) was impaired at baseline (5.8-/+0.9%) and significantly improved up to 9.5-/+0.9% after 3 month atorvastatin therapy (p<0.002). Change in FMD inversely correlated with baseline FMD (r = -0.58, p<0.05). There was no significant correlation between FMD and neither total serum CH nor LDL CH levels at baseline. During atorvastatin therapy significant reduction of plasma NOx levels occurred from 53.4-/+5.1 mcmol/l at baseline (range 42.6-86.2 mcmol/l) to 35.5-/+5.1 mcmol/l (18.4-46.0 mcmol/l) after treatment (p<0.02, n=7). CONCLUSION: In patients with familial hypercholesterolemia atorvastatin produced beneficial effect on endothelial function (increase in flow-mediated dilatation, decrease in NOx).
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Hypocholesterolemia and hypotriglyceridemia during the first days of myocardial infarction (MI) is a result of enhanced absorption of saturated fatty acids in the form of triglycerides within very low density lipoproteins (VLDL) through apoE/B-100 receptors. This is followed by inhibition of this endocytosis, accumulation of saturated fatty acids VLDL in the blood, and hypertriglyceridemia. Permanent level of double bonds in MI (ozone titration) results not from MI but from blocking of cell absorption of polyenic fatty acids in the form of cholesterol polyesters in low-density lipoproteins (LDL) through apoB-100 receptors, which is characteristic of atherosclerosis. High molar ratio of double bonds/cholesterol in comparison with the double bonds/glycerol ratio indicates that the majority of polyenic fatty acids in the blood lipoproteins present as cholesterol polyesters. Lipoprotein transfer and cell absorption of saturated fatty acids alone are selectively impaired in MI. Selective impairment of cell absorption of saturated or polyenic fatty acids alone or a combination of both is observed in some diseases. Ozone titration of serum lipid double bonds reflects impaired absorption of essential polyenic fatty acids by cells.
In this article the method of definition of double binders in lipids of blood serum in patients with different diseases basically atherosclerosis and ischemic heart disease, with use titration by ozone is given. The received data testify to an opportunity of use of this method in the diagnostic purposes.
AIM: To elucidate efficacy, safety and tolerance of lipobay (cerivastatin), a new HMG-CoA-reductase inhibitor (0.2 mg/day) in patients with primary hyperlipidemia (PHL). MATERIALS AND METHODS: The trial enrolled 15 men aged 21-64 years with PHL of type 2a and 2b. After 1 and 3 months of treatment all the patients underwent a general clinical examination with measurements of blood lipids (total cholesterol, triglycerides, high density lipoprotein cholesterol--HDL-C), apolipoproteins (apo A-1 and apo B). RESULTS: After 3 months of treatment total cholesterol, LDL-C and apolipoprotein B decreased by 24.94 +/- 2.87%, 28.94 +/- 3.08%, 19.32 +/- 2.43% (p = 0.0001), respectively, while LDL-C levels were < 3.4 mmol/l in 4 patients. Triglycerides dropped by 17.84 +/- 6.41%, while HDL-C rose by 5.01 +/- 4.47%, but the changes were not significant. Lipobay in doses 0.2 mg/day was well tolerated. One patient stopped taking the drug because of severe abdominal pain. CONCLUSION: Lipobay is a novel, effective and well-tolerated drug for treatment of patients with primary hyperlipidemia of type 2a and 2b.
AIM: To reveal the metabolic parameters of lipoproteins (L), which determine the benefits of hypolipidemic effects of simvastatin (S) and fluvastatin (F); to trace changes in the activity of lecithin-cholesterol acyltransferase (LCA) and cholesterol (C) ester transfer (CET) from high density lipoproteins to very low density lipoproteins (VLDL) and low density lipoproteins (LDL) and the levels of apoE in the blood and in some L classes during therapy with the above drugs. MATERIALS AND METHODS: Thirty six patients took S, 10 mg/day, and 25 received F, 20 mg/day, for 3 months. The levels of lipids were measured by enzyme assays, apoprotein (apo) was determined by immunoturbidimetry and immunodiffusion. RESULTS: The hypocholesterolemic and hypotriglyceridemic effect of S (19.6 and 25.5, respectively) and F (19.0 and 30.5%) were similar. With S, the reduction in the blood levels of C and LDL C positively correlated with the baseline apoE levels. With F, it did with C and LDL C before treatment. Lower blood apoE was found with S and F and lower HDL apoE/(VLDL + LDL) ratio was detected only with F. F treatment significantly lowered the activity of CET and LCA; before and after S treatment, they did not differ significantly. CONCLUSION: Analyzing the relationship between the benefits of the hypolipidemic effect and the baseline parameters of L metabolism indicates that the changes in serum C, LDL C and HDL C are due to the composition of HDL particles and the distribution of apoE among different L classes in the patient to a greater degree.
AIM: Study of the incidence of hyperlipidemias and coronary atherosclerosis risk factors. MATERIALS AND METHODS: A clinical and biochemical study of 35 children (25 men and 10 women aged 6 to 27 years) from 30 families of probands with primary hyperlipoproteinemias (HLP) was carried out. Use of modified risk factors (RF) in the examined group permitted the detection of hypodynamia in 25 subjects, obesity in 4, alcohol abuse and tobacco smoking in 1, and disorders of lipid metabolism in 31 (88%) cases. RESULTS: Hypercholesterolemia was detected in 26 examinees, combined HLP in 1, hypoalphacholesterolemia in 3, and type V hyperlipoproteinemia in 1 case. The level of lipoprotein (a) was increased and positively correlated with xanthomatosis and the age of examinees. The level of basal immunoreactive insulin was within the normal range of values. Analysis of the relationship of this parameter and other coronary atherosclerosis RF revealed a correlation of the level of immunoreactive insulin and content of blood low-density lipoprotein cholesterol. In only 2 of the 30 examined families of probands with primary HLP there were no disorders of lipid metabolism and other modified RF. CONCLUSION: Children, adolescents, and young people from families with primary HLP represent a risk group; they are to be regularly examined in order to prevent coronary disease and atherosclerosis and to detect and treat it in time.
AIM: To specify characteristics of lipoproteins (LPs) metabolism in patients with diverse forms of hereditary hyperlipoproteinemia (HLP) and determine biochemical tests for their differential diagnosis. MATERIALS AND METHODS: According to the criteria of polygenic hypercholesterolemia (PHCE), family combined hyperlipidemia (FCHL), family hypertriglyceridemia (FHTG) and family hypercholesterolemia (FHCE), 157 patients were selected aged 7 to 70 years of 192 examinees (76 patients with primary HLP and 116 their close relatives). Lipids were measured by enzyme methods, apoproteins (apo)--by immunoturbidimetry and immune diffusion. RESULTS: Compared to healthy subjects, PHCE patients were characterized by higher apoB level and proportion cholesterol (CS)/apoB in very low and low density lipoproteins (VLDL and LDL). In unchanged level of high density lipoprotein (HDL) CS and proportion HDLP CS/apoA1 there were reduced quantities of free HDLP CS, HDLP2 CS and apoA1. In FHCE and FCHL there were also low levels of HDL CS in elevated ones of apoE in (VLDL + LDL). However, in FCHL, contrary to FHCE, the proportion SC (VLDP + LDL)/apoB was as in control group. FHTG patients differed from healthy subjects by diminished HDL parameters: lower HDL CS due to free CS and its esters, apoA1 and proportion HDL Cs/apoA. There were no differences with controls by content of apoB and proportion CS (VLDL + LDL)/apoB, apoE levels in different class lipoproteins. CONCLUSION: Biochemical parameters are proposed which can differentiate various forms of hereditary hyperlipoproteinemia.
Unidimensional chromatography in a thin layer of silica gel with two solvent systems for separation of the lipid extract of high density lipoproteins (HDLP) detected 10 lipid fractions in subjects with normal lipidemia. Four phospholipid fractions were identified: three main (phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin) and one minor, phosphatidylethanolamine. HDLP lipids include free cholesterol and its esters; three glyceride fractions are detected: mono- di, and triglycerides, and free fatty acids. The ratio of individual phospholipid fractions and of free to ester-bound cholesterol in HDLP determined by computer-aided densitometry of chromatograms coincides with the data obtained routinely. Such a method for assessing the HDLP lipid composition is useful in studies of HDLP in patients with disorders of HDLP metabolism and for assessing the changes in HDLP composition during hypolipidemic therapy.