Amount Of High-density Lipoprotein Research Articles

#1190 Expression of metabolic disorders in patients with hypertension and chronic kidney disease

Abstract Background and Aims To study the frequency of metabolic disorders in patients with hypertension depending on the stage of chronic kidney disease (CKD). Method The study analyzed 594 case histories of patients with AH of I-III degree (ESC/ESH 2018). CKD stages were determined according to eGFR (EPI-2021), according to the modern KDIGO 2013 classification. All patients were tested for uric acid, glucose, creatinine, and blood lipids using a Daytona autoanalyzer from RANDOX (UK). The study was conducted against the background of antihypertensive therapy (AHT). Statistical analysis was carried out using the SPSS 24.0 software package. Results Among the examined patients, intact renal function of CKD C1 (eGFR>90 ml/min/1.73 m2) was observed in 19.5% (n = 116); CKD C2 (eGFR 60-89 ml/min/1.73 m2) – in 50.5% (n = 300); CKD C3A (eGFR 45-59 ml/min/1.73 m2) – in 20.4% (n = 121); CKD C3B (eGFR 30-44 ml/min/1.73 m2) – in 6.4% (n = 38); CKD C4 (eGFR 29-15 ml/min/1.73 m2) - in 3.2% (n = 19) p < 0.0001. The terminal stage of CKD was not revealed. The mean creatinine in the groups was 66.20 ± 11.74 vs 83.44 ± 11.30 vs 105.84 ± 17.36 vs 139.78 ± 24.40 vs 212.00 ± 19.73 µmol/l, respectively (p < 0.00001) . Mean eGFR 97.99 ± 6.98 vs 75.44 ± 7.15 vs 53.46 ± 4.30 vs 37.82 ± 3.63 vs 23.11 ± 5.63 ml/min/1.73 m2, respectively, (p < 0.00001). The groups did not differ significantly in body mass index (BMI), but patients with high stage of CKD have pronounced abdominal obesity. BMI was 30.71 ± 4.4 vs 32.25 ± 5.8 vs 31.45 ± 4 vs 31.6 ± 5.6 vs 30.36 ± 10.2 kg/m2, respectively, p = 0.11. Waist measurement (WT): 98.68 ± 10 vs 104.36 ± 13.6 vs 103.62 ± 10.7 vs 104.51 ± 12.4 vs 106.94 ± 27.3 cm, respectively (p = 0.001) . It should be noted that the high stages of CKD are characterized by significantly pronounced asymptomatic hyperuremia. At the same time, the level of uric acid was 5.07 ± 1.4 vs 6.1 ± 4.7 vs 6.6 ± 1.7 vs 7.87 ± 1.7 vs 7.52 ± 1.01 µmol/l, respectively (p < 0.00001). When analyzing lipid spectrum data, total blood cholesterol (TC) and triglycerides (TG) in the blood did not differ significantly among the studied groups. However, it was found that increasing of CKD leads to significantly rising of low-density lipoproteins: 107.04 ± 42.57 vs 103.53 ± 38.04 vs 112.44 ± 44.27 vs 120.64 ± 39.27 vs 133.94 ± 29.83 mmol/l, respectively, р = 0.03, while the amount of high density lipoproteins significantly decrease: 42.64 ± 13.79 vs 41.86 ± 11.03 vs 41.51 ± 10.64 vs 39.62 ± 11.08 vs 36.72 ± 7.72 mmol/l, respectively, p = 0.0001. Conclusion In patients with hypertension and CKD, metabolic disorders are more pronounced, which increases the risk of developing complications of arterial hypertension.

Microflora of atherosclerotic plaques and blood of patients with atherosclerosis

Background. Over the past decades, the role of the microbial factor in the development of atherosclerosis has been discussed. To date, data on the composition of the microflora of atherosclerotic plaques have been accumulated, but in these studies the blood microflora in atherosclerosis was not studied.
 Aim. To determine the contamination frequency of biopsy samples of atherosclerotic plaques and peripheral blood with cultured microorganisms in patients with atherosclerosis of the brachiocephalic arteries.
 Material and methods. A cross-sectional study in 35 patients with atherosclerosis of the carotid arteries; the average age of the patients was 58.2±8.3 years, was performed. Blood and atherosclerotic plaque samples from 23 men (mean age 58.6±10.3 years) and 12 women (mean age 57.3±14.3 years) were examined. Anaerobic flasks for blood cultivation were incubated at 35 °C for up to 6 months, from which they were regularly inoculated onto solid nutrient media to obtain culture growth. Cultures of tissues of atherosclerotic plaques of the carotid arteries in test tubes with thioglycollate medium were thermostated until visible growth of the culture was obtained; observation was carried out for up to 2 months. Identification of crops was carried out using commercial kits. For statistical analysis of the results obtained, the equality of the average values in two samples was checked using the Student’s statistical reliability test. Correlation analysis of the tightness of the connection was carried out using the Spearman rank correlation method.
 Results. The frequency of detection of microorganisms in samples of atherosclerotic plaques was 48.6% (17/35), including Cutibacterium acnes — in 31.4% (11/35), the genus Staphylococcus — in 22.9% (8/35), associations of these microorganisms — in 5.7% (2/35) of samples. C. acnes was cultured in the blood of 11.4% (4/35) of patients. In 5.7% (2/35) of patients, cultures of C. acnes bacteria were isolated from both atherosclerotic plaque biopsies and blood. Bacterial cultures exhibited slow growth on nutrient media. Correlation analysis of the closeness of the connection according to the Chaddock scale demonstrated the presence of a high and very high closeness of connection between the amount of high-density lipoproteins and the daily growth of C. acnes in atherosclerotic plaques (p=0.812) and blood (rxy=–0.969), the content of leukocytes showed a very high closeness of connection with days of growth of C. acnes in the blood (rxy=–0.957); Student's t-test revealed a statistically significant relationship with the fact of detection of C. acnes cultures in atherosclerotic plaques (p=0.013).
 Conclusion. Bacterial cultures isolated from blood samples and atherosclerotic plaques of patients with atherosclerosis had slow growth on nutrient media, and the period of their growth or the fact of detection correlated with the number of leukocytes and the level of high-density lipoproteins in the blood of patients.

Cholesterol efflux mechanism revealed by structural analysis of human ABCA1 conformational states.

ATP-binding cassette transporter A1 (ABCA1) utilizes energy derived from ATP hydrolysis to export cholesterol and phospholipids from macrophages. ABCA1 plays a central role in the biosynthesis of high-density lipoprotein (HDL), which mediates reverse cholesterol transport and prevents detrimental lipid deposition. Mutations in ABCA1 cause Tangier disease characterized by a remarkable reduction in the amount of HDL in blood. Here we present cryo-electron microscopy structures of human ABCA1 in ATP-bound and nucleotide-free states. Structural comparison reveals that ATP molecules pull the nucleotide-binding domains together, inducing movements of transmembrane helices 1, 2, 7 and 8 through a series of salt-bridge interactions. Subsequently, extracellular domains (ECDs) undergo a rotation and introduce conformational changes in the ECD-transmembrane interface. In addition, while we observe a sterol-like molecule in ECDs, no such density was observed in the structure of an HDL-deficiency mutant ABCA1Y482C, demonstrating the physiological importance of ECDs and a putative interaction mode between ABCA1 and its lipid acceptors. Thus, these structures, along with cholesterol efflux assays, advance the understanding ABCA1-mediated reverse cholesterol transport.

Effect of a tropical plant (Hunteria umbellata) in the management of Streptozotocin induced Diabetes Mellitus and other physiological and biochemical functions in Wistar

The antidiabetic effect of Hunteria umbellata extracts (aqueous and methanol) on hematological, lipid profile and biochemical parameters in streptozotocin-induced diabetes in female wistar rats was studied. The phytochemical screening of the seed extracts was determined using standard chemical methods. Twenty five (25) wistar rats weighing between 117g and 170g were shared into five (5) groups of five animals per group for the physiological studies. All treatment groups were administered 500 mg/kg per body weight of H. umbellata extracts. Group 1: normal control, group 2: negative or diabetic control, group 3: metformin + streptozotocin (STZ), group 4: aqueous extract of H. umbellata + STZ and group 5: methanol extract of H. umbellata + STZ. Diabetes was induced with 55mg/kg body weight streptozotocin (STZ). Quantitative phytochemical screening of aqueous and methanol seed extracts of H. umbellata reviewed the presence of secondary metabolites such as, saponins, phytate, oxalate, anthraquinones, Cyanogenic glycoside; where phenols and alkaloids recorded highest concentrations in both extracts. The hypoglycaemic studies of methanol extract revealed significant (p<0.005) reduction on the fasting blood glucose levels of experimental animals for group 5 compared to moderate reduction in group 3. Group 4 recorded increase in the blood glucose levels of wistar rats. The haematological parameters were not significant (p>0.05) for all treatment groups. Group 5 recorded significance (p<0.05) amount of high density lipoproteins (HDL), total cholesterol (CHOL), triglyceride (TRIG) and low density lipoproteins (LDL) while CHOL was significant (p<0.05) for group 3. The biochemical parameters were within safe limit. The methanol extract of H. umbellata possesses the potentials for the managements of blood glucose levels compared to conventional drug (metformin).

Inducible phospholipid transfer protein deficiency ameliorates atherosclerosis

Background and aimsAtherosclerosis progression and regression studies are related to its prevention and treatment. Although we have gained extensive knowledge on germline phospholipid transfer protein (PLTP) deficiency, the effect of inducible PLTP deficiency in atherosclerosis remains unexplored. MethodsWe generated inducible PLTP (iPLTP)-knockout (KO) mice and measured their plasma lipid levels after feeding a normal chow or a Western-type diet. Adenovirus associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9) was used to induce hypercholesterolemia in the mice. Collars were placed around the common carotid arteries, and atherosclerosis progression and regression in the carotid arteries and aortic roots were evaluated. ResultsOn a normal chow diet, iPLTP-KO mice exhibited decreased cholesterol, phospholipid, apoA-I, and apoB levels compared with control mice. Furthermore, the overall amount of high-density lipoprotein (HDL) particles was reduced in these mice, but this effect was more profound for larger HDL particles. On a Western-type diet, iPLTP-KO mice again exhibited reduced levels of all tested lipids, even though the basal lipid levels were increased. Additionally, these mice displayed significantly reduced atherosclerotic plaque sizes with increased plaque stability. Importantly, inducible PLTP deficiency significantly ameliorated atherosclerosis by reducing the size of established plaques and the number of macrophages in the plaques without causing lipid accumulation in the liver. ConclusionsInduced PLTP deficiency in adult mice reduces plasma total cholesterol and triglycerides, prevents atherosclerosis progression, and promotes atherosclerosis regression. Thus, PLTP inhibition is a promising therapeutic approach for atherosclerosis.

High density lipoprotein promotes nascent apolipoprotein A-V secretion from mRNA transfected cells

Despite its exceptionally low circulating concentration, apolipoprotein (apo) A-V is a potent modulator of plasma triacylglycerol levels. The secretion efficiency of nascent apoA-V was investigated in cultured cells transfected with mRNA. Following transfection of HepG2 cells with wild type apoA-V mRNA, apoA-V protein was detectable in cell lysates by 6 h. At 24 h post transfection, evidence of apoA-V secretion into media was obtained, although most apoA-V was recovered in the cell lysate fraction. By contrast, apoA-I was efficiently secreted into the culture medium. A positive correlation between culture medium fetal bovine serum content and the percentage of apoA-V recovered in conditioned media was observed. When transfected cells were cultured in serum-free media supplemented with increasing amounts of high density lipoprotein, a positive correlation with apoA-V secretion was observed. The data indicate that, following signal sequence cleavage, the bulk of nascent apoA-V remains cell associated. Transit of nascent apoA-V out of cultured cells is enhanced by the availability of extracellular lipid particle acceptors.

Validation and Application of a Novel Cholesterol Efflux Assay Using Immobilized Liposomes as a Substitute for Cultured Cells

Estimation of the function as well as the amount of high-density lipoprotein (HDL) is required to predict the risk of cardiovascular disease development. Cholesterol efflux capacity (CEC) is the key metric for determining the antiatherosclerotic function of HDL. However, the assay methods currently used to calculate CEC are not ideal for clinical use as they require the culture of cells. In the present study, we developed a novel CEC assay using immobilized liposome-bound gel beads (ILGs), containing fluorescently labeled cholesterol, as a substitute for cultured cells. When apolipoprotein B-100 depleted serum, obtained by polyethylene glycol precipitation, was used as the cholesterol acceptors, the basic properties of this method, such as the available range of HDL-cholesterol, efflux temperature and time, and normalization parameters, indicate that this method is sufficient to estimate CEC. Furthermore, the CEC values obtained with this ILG method were also correlated with those obtained with a conventional method using THP-1 macrophages derived foam cells and 3H-cholesterol as a tracer (r = 0.932). Overall, this novel cholesterol efflux assay method is a realistic and effective alternative to current methods in the field while also being easier to use in clinical laboratories as neither cell culture, radioisotope nor ultracentrifugation is required.

Validation and application of a novel cholesterol efflux assay using immobilized liposomes as a substitute for cultured cells.

Estimation of the function as well as the amount of high-density lipoprotein (HDL) is required to predict the risk of cardiovascular disease development. Cholesterol efflux capacity (CEC) is the key metric for determining the antiatherosclerotic function of HDL. However, the assay methods currently used to calculate CEC are not ideal for clinical use as they require the culture of cells. In the present study, we developed a novel CEC assay using immobilized liposome-bound gel beads (ILGs), containing fluorescently labeled cholesterol, as a substitute for cultured cells. When apolipoprotein B-100 depleted serum, obtained by polyethylene glycol precipitation, was used as the cholesterol acceptors, the basic properties of this method, such as the available range of HDL-cholesterol, efflux temperature and time, and normalization parameters, indicate that this method is sufficient to estimate CEC. Furthermore, the CEC values obtained with this ILG method were also correlated with those obtained with a conventional method using THP-1 macrophages derived foam cells and 3H-cholesterol as a tracer (r = 0.932). Overall, this novel cholesterol efflux assay method is a realistic and effective alternative to current methods in the field while also being easier to use in clinical laboratories as neither cell culture, radioisotope nor ultracentrifugation is required.

Use of multivitamin, acidifier and Azolla in the diet of broiler chickens.

ObjectiveThe experiments were carried out to measure the effect of multivitamin, acidifier and Azolla on growth performance, profitability and lipid profiles of blood of broiler chickens to produce safe and cost effective broilers.MethodsIn experiment 1, 240 day-old Cobb-500 broiler chicks were fed diets; D1 (control), D2 (D1 with 1 mL multivitamin/liter water), D3 (D1 with 1 mL acidifier/liter water), D4 (D1 with 1 mL multivitamin and 2 mL acidifier/liter water) having 3 replications in each, and 20 chicks/replication. In experiment 2, 150 day-old Cobb-500 broiler chicks were fed diets; T1 (control), T2 (5% Azolla in the diet), T3 (7% Azolla in the diet) and T4 (T1 with 1 mL multivitamin and 1 mL acidifier/liter water) having 3 replications in each, and 20 chicks/replication in control, and 10 chicks/replication in the remaining dietary treatment groups for 35 days.ResultsIn experiment 1, the highest live weight was observed in D4 (p<0.05), however, feed intake was statistically similar between diets (p>0.05). The lowest feed conversion ratio (FCR) (p<0.001) and mortality (p<0.05) were observed in D2 followed by D4, D1, and D3, respectively. There were no significant differences between diets for feed cost and net profit (p>0.05). However, evidently but not significantly, the highest net profit was obtained in D2 followed by D4, D1, and D3, respectively. In experiment 2, the highest live weight (p<0.05) and feed intake (p<0.001) were observed in T4. Mortality (p<0.01), FCR (p<0.01), feed cost (p<0.05) and net profit (p<0.05) were significantly different among diets. Considering net profit, T2 was the best performing dietary group followed by T3, T1, and T4, respectively. The lowest lipid profiles were observed in D3 followed by D1, D4, and D2, respectively (p<0.05). In experiment 2, the lowest total cholesterol, TG, and the highest amount of high density lipoprotein were observed in T2, followed by T3, T1, and T4, respectively (p<0.05). Evidently but not significantly, low density lipoprotein was the highest in T2 followed by T3, T4, and T1, respectively (p>0.05).ConclusionIn conclusion, Azolla and acidifier reduced lipid profiles of broiler chickens. Considering net profit and lipid profiles, 5% Azolla may be the suitable dietary group for producing safe and profitable broilers. However, more studies are needed to confirm this study prior to suggesting using Azolla in the poultry industry.

Effects ofRhizoctonia solaniAgglutinins on Intermediary Metabolism ofPieris brassicae(Lepidoptera: Pieridae)

Effects of two purified agglutinins from Rhizoctonia solani Kuhen (Rhizoctonia solani agglutinin) were determined on larval intermediary metabolism of Pieris brassicae L. Two concentrations of Rhizoctonia solani agglutinin (RSA; 1 and 2 mg ml−1) significantly decreased activities of both alanine and aspartate aminotransferases, but no significant activity was observed on γ-glutamyl transferase. However, activity of aldolase decreased in the treated larvae by both concentrations of RSAs, but lactate dehydrogenase showed the highest activity when the larvae fed on 2 mg ml−1 of RSAs. Activities of acid- and alkaline phosphatases significantly decreased followed by feeding on the diets containing RSAs. Similar results were observed in the amounts of high-density lipoprotein and low-density lipoprotein. The amounts of protein and triacylglycerol significantly decreased in the treated larvae, while glycogen significantly increased in the larvae fed on RSAs-containing diets. Gene expression analyses of glycerol-3-phosphate in the control and treated larvae revealed significant expression in the larvae fed on RSAI in comparison with other treatments. These results demonstrated intervening effects of RSAs on intermediary metabolism of P. brassicae larvae, further confirming their entomotoxic effects.

Homogeneous static magnetic field of different orientation induces biological changes in subacutely exposed mice

It has been shown that static magnetic field (SMF) of moderate intensity produces considerable impact on biological systems. SMF can be homogeneous or inhomogeneous. In many studies, inhomogeneous SMF was employed. Aware that inhomogeneous SMF could result in experimental variability, we investigated the influence of a vertical homogeneous SMF of different orientation. Male Swiss-Webster 9- to 10-week-old mice were subacutely exposed to upward- and downward-oriented SMF of 128mT generated by a cyclotron for 1h/day during a 5-day period. We found that SMF affected various organs and that these effects were, to some degree, dependent on SMF orientation. Both upward- and downward-oriented SMF caused a reduction in the amount of total white blood cells (WBC) and lymphocytes in serum, a decrease of granulocytes in the spleen, kidney inflammation, and an increase in the amount of high-density lipoprotein (HDL). In addition, upward-oriented SMF caused brain edema and increased spleen cellularity. In contrast, downward-oriented SMF induced liver inflammation and a decrease in the amount of serum granulocytes. These effects might represent a specific redistribution of pro-inflammatory cells in blood and among various organs. It appears that homogeneous SMF of 128mT affected specific organs in the body, rather than simultaneously and equally influencing the entire body system.

The algorithm for the combined treatment of pyoinflammatory ENT diseases in the patients with diabetes mellitus

The objective of the present study was to determine the leading clinical and pathogenetic factors determining the clinical course of the pyoinflammatory ENT diseases in the patients with diabetes mellitus (DM) and to develop the algorithm for the rational therapy of these conditions. A total of 145 patients presenting with pyoinflammatory ENT diseases and concomitant diabetes mellitus were available for the examination that included the microbiological and biochemical studies, determination of the total lipid spectrum, glycated hemoglobin (HbA1c) level, and glycemic profile. Also, the body mass index of the patients was estimated along with the type and severity of obesity. Moreover, the character of antibacterial and hypoglycemic therapy was evaluated. The mathematical analysis of the data obtained revealed the clinical and biochemical parameters determining the clinical picture of the pyoinflammatory ENT diseases in the patients with diabetes mellitus. These were localization of the pyogenic process in the larynx, abdominal obesity, fasting hyperglycemia in excess of 8.3 mmol/l, and dyslipidemia accompanied by the reduction in the amount of high density lipoproteins to below 40 mg/100 ml and the increase of low density lipoproteins to above 155 mg/100 ml. The results of the study were used to develop the differentialalgorithm for the combined treatment of pyoinflammatory ENT diseases in the patients with diabetes mellitus based on the proposed original scale for the prediction of pyogenic complications.

Effects of Citrullus colocynthis agglutinin on intermediary metabolism of Ectomyelois ceratoniae Zeller (Lepidoptera: Pyralidae)

In the current study, we examined the effects of Citrullus colocynthis agglutinin (CCA) on the intermediary metabolism of Ectomyelois ceratoniae larvae as a means of determining effectiveness of the lectin in pest control. Larvae were fed on control diets and diets containing CCA (2%) for 24 and 48h. The activities of digestive α-amylase and general proteases significantly decreased in the larvae fed on the CCA diet, but no statistically significant changes were found in the case of TAG-lipase. Meanwhile, the activities of all specific proteases, except aminopeptidase, changed in the treated larvae for all time intervals. The activity of alanine aminotransferase significantly decreased in the treated larvae but the activities of aspartate aminotransferase and γ-glutamyl transferase increased 24h post-feeding on the CCA diet. The activity of aldolase decreased 48h post-feeding but lactate dehydrogenase (LDH) showed inverse results at the same time interval. The activities of acid phosphatase (ACP) and alkaline phosphatase (ALP) decreased 48h post-feeding for ACP and at both time intervals for ALP. The amount of high-density lipoprotein (HDL) showed no statistical differences between control and CCA-fed larvae, but the amount of low-density lipoprotein (LDL) significantly increased in the CCA-fed larvae at both time intervals. The amount of protein increased in the larvae fed on the CCA diet, but the amounts of glycogen and triacylglycerol significantly decreased at both time intervals. Results of the current study clearly reveal that ingestion of CCA significantly influences the activities of digestive enzymes and disrupts the intermediary metabolism of E. ceratoniae larvae. Further studies on genetic engineering of CCA to provide resistant varieties might open a new avenue for safe and efficient control of the pest.

Ajuga iva aqueous extract improves reverse cholesterol transport in streptozotocin-induced diabetic rat

The aim of this study was to determine the effects of Ajuga iva aqueous extract on lecithin : cholesterol acyltransferase (LCAT) activity and amount and composition of high-density lipoprotein (HDL)(2) and (HDL)(3), in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar rats by intraperitoneal injection of STZ (60 mg/kg body weight). Diabetic rats (n = 12) were divided into two groups. The diabetic control group (D) received a 20% casein diet and the diabetic treated group received the same diet supplemented with A. iva aqueous extract (0.5 g/100 g diet) (DAi), for 4 weeks. Total cholesterol and HDL(3) -C were respectively decreased by 32% and 55% in the DAi group compared with the D group, whereas HDL(2)-C was increased by 30%. The amounts of HDL(2) and HDL(3), which were the sum of apolipoproteins, unesterified cholesterol (UC), cholesteryl esters (CEs), triacylglycerols (TGs) and phospholipids (PLs), showed no significant difference. A. iva treatment increased LCAT by 33% and its cofactor-activator, apolipoprotein A-I, by 58%. HDL(3)-PL (enzyme substrate) and HDL(3)-UC (acyl group acceptor) were respectively decreased by 70% and 57%, whereas HDL(2)-CE (product of LCAT reaction) was enhanced by 30%. In STZ-induced diabetic rats, A. iva improves reverse cholesterol transport by enhancing LCAT activity, leading to anti-atherogenic effects.

Time to consider an Asian guideline for management of dyslipidemia?

Time to consider an Asian guideline for management of dyslipidemia?

Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid

BackgroundHigh-dose administration of a steroid hormone has been associated with a major risk of osteonecrosis. In this study we investigated the effects of a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke-prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks). MethodsA total of 71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40) and a steroid hormone group (S group, n = 31) given 5mg (about 20 mg/kg) of methylprednisolone acetate during the 17th week of age. We compared the groups’ laboratory data, histological appearance, incidence of osteonecrosis, and expression of oxidative stress on immunohistochemical analysis using the monoclonal antibodies anti-4HNE and anti-8OHdG. ResultsThe S group showed an increase in total cholesterol, with the amounts of high-density lipoprotein, low-density lipoprotein, and triglycerides all significantly higher than in the C group. Histological examination showed that the frequency of necrosis of the femoral head was significantly higher in the S group (95.2%) than in the C group (51.2%). Most of the histological features of the osteonecrosis demonstrated typical features of a similar sort in the two groups. However, the S group showed bone marrow spaces in the femoral head that were occupied by an increased number of adipocytes and that were swollen, partially degenerative, and necrotic. On immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody were stronger in the S group than in the C group. ConclusionsThis study confirmed, to a remarkable degree, the suspicion that the administration of steroid hormone increases the number of adipocytes in marrow. Fat degeneration and necrosis, considered early signs of osteonecrosis, were also observed. It has been hypothesized that osteonecrosis is produced by the ischemic change accompanying compartment pressure load in marrow, where fat degeneration, necrosis, and endothelial cell injury might occur together with oxidative stress.

THE ROLE OF ADRENAL CORTEX FUNCTIONAL ACTIVITY IN REGULATION OF BLOOD LIPOPROTEINS CHOLESTEROL CONTENT IN RATS AT BACTERIAL ENDOTOXINEMIA

It was established experimentally on rats that bacterial endotoxinemia of various origins, caused by pyrogenal injection and by CLP-peritonitis, was accompanied by disturbance of temperature homeostasis, activation of adrenal cortex and atherogenic changes in cholesterol content of blood lipoproteins: decrease of the amount of high density lipoprotein (HDL) cholesterol and increase of low and very low density lipoprotein (LDL and VLDL) cholesterol blood levels. Injection of exogenous glucocorticoid prednizolone during pyrogenal action prevents the decrease of the amount of HDL cholesterol but strengthens the increase of LDL and VLDL cholesterol blood levels. Activation of adrenal cortex at bacterial endotoxinemia is accompanied by inhibition of the negative feed-back mechanism in hypothalamic-pituitary-adrenal axis, what provides high activity of steroidogenesis during systemic inflammation.

Molecular Mechanism of the Blockade of Plasma Cholesteryl Ester Transfer Protein by Its Physiological Inhibitor Apolipoprotein CI

Genetically engineered mice demonstrated that apolipoprotein (apo) CI is a potent, physiological inhibitor of plasma cholesteryl ester transfer protein (CETP) activity. The goal of this study was to determine the molecular mechanism of the apoCI-mediated blockade of CETP activity. Kinetic analyses revealed that the inhibitory property of apoCI is independent of the amount of active CETP, but it is tightly dependent on the amount of high density lipoproteins (HDL) in the incubation mixtures. The electrostatic charge of HDL, i.e. the main carrier of apoCI in human plasma, is gradually modified with increasing amounts of apoCI, and the neutralization of apoCI lysine residues by acetylation produces a marked reduction in its inhibitory potential. The inhibitory property of full-length apoCI is shared by its C-terminal alpha-helix with significant electrostratic properties, whereas its N-terminal alpha-helix with no CETP inhibitory property has no effect on HDL electronegativity. Finally, binding experiments demonstrated that apoCI and to a lower extent its C-terminal alpha-helix are able to disrupt CETP-lipoprotein complexes in a concentration-dependent manner. It was concluded that the inhibition of CETP activity by apoCI is in direct link with its specific electrostatic properties, and the apoCI-mediated reduction in the binding properties of lipoproteins results in weaker CETP-HDL interactions and fewer cholesteryl ester transfers.

Effects of fenofibrate on high-density lipoprotein particle size in patients with hyperlipidemia: A randomized, double-blind, placebo-controlled, multicenter, crossover study

Background: Fenofibrate lowers serum total cholesterol and triglyceride levels while it elevates serum high-density lipoprotein cholesterol (HDL-C) level. Objective: The aim of this study was to investigate the effects of fenofibrate on the particle size of high-density lipoprotein (HDL). Methods: Patients with hyperlipidemia (as defined by serum triglyceride level ≥150 mg/dL in the fasting state) were enrolled in this randomized, double-blind, placebo-controlled, multicenter, crossover study. Fenofibrate 300 mg (corresponding to 200 mg of micronized fenofibrate) or placebo was administered orally once daily after dinner for 8 weeks, followed by crossover of the 2 drugs for an additional 8 weeks. Results: Fifty hyperlipidemic patients (31 men, 19 women; mean [SD] age, 54.6 [12.7] years) were enrolled. Serum total cholesterol and triglyceride levels were significantly reduced with fenofibrate treatment compared with placebo (9.4% [ P = 0.007] and 34.4% [ P < 0.001], respectively), whereas HDL-C levels were significantly elevated (by 25.8% [ P < 0.001]). Lipoprotein lipase (LPL) activity, LPL protein level, and hepatic triglyceride lipase activity increased by 10.5%, 13.4%, and 11.4%, respectively, with fenofibrate compared with placebo. HDL was classified into 3 groups by particle size: HDL 3 <88 Å; HDL 2 a ≥88 Å but <98 Å; and HDL 2 b ≥98 Å. The amount of HDL 3 increased significantly with fenofibrate compared with placebo ( P < 0.001). Fenofibrate was well tolerated during the study. Abnormal clinical laboratory values were noted in 20 of 48 patients (41.7%), but these events were mild and not clinically significant. Conclusion: Taken together, these findings indicate that fenofibrate therapy increased the HDL subfraction with the smallest diameter (HDL 3), which is largely responsible for withdrawing cholesterol from peripheral cells.

Cholesteryl Ester Transfer Protein Reaction between Plasma Lipoproteins

The rate of the non-directional transfer of cholesteryl ester and triglyceride by human cholesteryl ester transfer protein (CETP) was measured between human plasma lipoproteins by monitoring fluorescence spectrum of pyrene-labeled lipid. The transfer rates between high density lipoproteins (HDLs) and between low density lipoproteins (LDLs) were both directly proportional to the substrate lipid concentration within the physiological range of the lipoprotein concentration. Higher preference of cholesteryl ester transfer to triglyceride was demonstrated with HDL than LDL. Although the highly selective binding of CETP to HDL was observed in the electrophoretic analysis, the transfer rate was only moderately higher with HDL for cholesteryl ester and not so at all for triglyceride. In addition, the rate of cholesteryl ester transfer between LDLs was uninfluenced by the presence of a small amount of HDL that is just sufficient to absorb all the CETP in the reaction mixture. The results indicated the preferential transfer of cholesteryl ester over triglyceride by CETP in the interaction with HDL in non-directional lipid transfer reaction among lipoproteins. However, the apparent binding of CETP to HDL does not seem to play an essential role in this type of lipid transfer by CETP.