scholarly journals Pathogenetic justification of the use of simvastatin in the complex therapy of vitiligo

2021 ◽  
Vol 24 (3) ◽  
pp. 227-242
Author(s):  
Alina Yu. Davletshina ◽  
Konstantin M. Lomonosov
Keyword(s):  
High Performance ◽  
Cholesterol Biosynthesis ◽  
Statistical Processing ◽  
Clinical Results ◽  
Minimal Risk ◽  
Combined Method ◽  
Active Forms Of Oxygen ◽  
Effect Of Therapy ◽  
Coa Reductase ◽  
Methods Of Treatment

BACKGROUND: Vitiligo is a chronic acquired disease with a genetic predisposition to pigmentation disorder caused by the destruction of skin melanocytes, leading to hypopigmentation. The effectiveness of currently available methods of treatment of vitiligo, on average, is about 40%. Therefore, it is necessary to search for new effective and safe methods of vitiligo therapy, characterized by minimal risk of side effects, and financial costs of the patient. Simvastatin inhibits cholesterol biosynthesis by inhibiting HMC-CoA reductase. In addition to lowering cholesterol, statins have pleiotropic effects, namely, they inhibit various inflammatory mediators and cytokines, activate the antioxidant system, and reduce the level of active forms of oxygen in melanocytes. AIMS: To develop a pathogenetic therapeutic complex using simvastatin for patients with vitiligo. MATERIALS AND METODS: To participate in the study, 81 patients with vitiligo were examined. Each patient was determined by the form and stage of the disease. The effectiveness of therapy in the groups was evaluated by assessing the area of repigmentation. The first group received treatment ― simvastatin in combination with UVB therapy 311 nm, the second group-UVB therapy 311 nm. Studies of cytokines were carried out using enzyme immunoassay. Study of the oxidative status using high-performance liquid chromatography-mass spectrometry. Statistical processing of the research materials was carried out using the SPSS Statistics software package. RESAULTS: The combined method of therapy with the inclusion of simvastatin showed the following clinical results: 6 (12%) had a pronounced positive effect; improvement ― in 34 (69%) patients. Dynamics of the immune profile: decrease in IL-6 from 101 to 8.10.6; TNF- from 18.82.1 to 12.91.1; increase in IL-10 from 3.20.4 to 7.30.3. Dynamics of the oxidative profile: malondialdehyde 1.70.12 to 1.480.11, 8-oxo-DG 0.300.03 to 0.230.02, SOD 1703 to 2077, glutathione 69736 to 94232. CONCLUSION: The combined method of vitiligo therapy with the inclusion of simvastatin is effective and safe, leading to stabilization of the process, clinical improvement and a pronounced effect of therapy in 82% of patients. It also has an immune-correcting effect and normalizes the indicators of the oxidative profile.

Comparison of Two Evaluating Methods for Establishing the Marginal Fit on Four Heat - Pressed Resin Inlays

2018 ◽  
Vol 69 (4) ◽  
pp. 890-893
Author(s):  
Sorana Baciu ◽  
Cristian Berece ◽  
Adrian Florea ◽  
Andrada Voina Tonea ◽  
Ondine Lucaciu ◽  
...  
Keyword(s):  
High Performance ◽  
Clinical Results ◽  
Marginal Fit ◽  
High Performance Polymer ◽  
Investigation Methods ◽  
Evaluating Methods

In this study were compared two investigation methods, a bi- and tri-dimensional techniques by examining the marginal fit pressed in (BioHPP) Inlays. The study pruved that the BioHPP is a high performance polymer which provides very good clinical results.

scholarly journals Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase by 15 alpha-fluorolanost-7-en-3 beta-ol. A mechanism-based inhibitor of cholesterol biosynthesis.

1993 ◽  
Vol 268 (30) ◽  
pp. 22591-22599
Author(s):  
J.M. Trzaskos ◽  
R.L. Magolda ◽  
M.F. Favata ◽  
R.T. Fischer ◽  
P.R. Johnson ◽  
...  
Keyword(s):  
Cholesterol Biosynthesis ◽  
Coa Reductase

scholarly journals The absolute rate of cholesterol biosynthesis in monocyte-macrophages from normal and familial hypercholesterolaemic subjects

1984 ◽  
Vol 219 (2) ◽  
pp. 461-470 ◽  
Author(s):  
D D Patel ◽  
C R Pullinger ◽  
B L Knight
Keyword(s):  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Specific Radioactivity ◽  
Density Lipoprotein ◽  
Cellular Protein ◽  
True Rate ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
In Cells

The true rate of cholesterogenesis in cultured monocyte-macrophages was determined from the incorporation of [2-14C]acetate into cholesterol, using the desmosterol (cholesta-5,24-dien-3 beta-ol) that accumulated in the presence of the drug triparanol to estimate the specific radioactivity of the newly formed sterols. It was shown that this procedure could be successfully adapted for use with cultured monocytes despite the accumulation of other unidentified biosynthetic intermediates. In cells maintained in 20% (v/v) whole serum approx. 25% of the sterol carbon was derived from exogenous acetate. Cholesterol synthesis was as high in normal cells as in cells from homozygous familial hypercholesterolaemic (FH) subjects and accounted for 50% of the increase in cellular cholesterol. The addition of extra low-density lipoprotein (LDL) reduced cholesterol synthesis, apparently through a decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). When incubated in lipoprotein-deficient serum some cells did not survive, but those that remained showed a normal increase in protein content; the amount of cellular protein and cholesterol in each well did not increase and cholesterol synthesis was reduced by over 80%. HMG-CoA reductase activity fell less dramatically and the proportion of sterol carbon derived from exogenous acetate increased, suggesting that the low rate of cholesterogenesis with lipoprotein-deficient serum was due to a shortage of substrate. The results indicate that under normal conditions monocyte-macrophages obtain cholesterol from endogenous synthesis rather than through receptor-mediated uptake of LDL, and that synthesis together with non-saturable uptake of LDL provides the majority of the cholesterol required to support growth.

Treatment of mammalian cells with the endoplasmic reticulum-proliferator compactin strongly induces recombinant and endogenous xenobiotic metabolizing enzymes and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro

1999 ◽  
Vol 112 (4) ◽  
pp. 515-523
Author(s):  
L. McLaughlin ◽  
B. Burchell ◽  
M. Pritchard ◽  
C.R. Wolf ◽  
T. Friedberg
Keyword(s):  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Transcriptional Activation ◽  
Mammalian Cells ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Metabolizing Enzymes ◽  
P450 Reductase ◽  
Coa Reductase

Some xenobiotics induce membrane-bound drug metabolizing enzymes (Xme) and a profound proliferation of the endoplasmic reticulum (ER) in vivo. However these effects are much weaker in vitro, possibly due to absence of certain transcription factors. We tested the possibility that ER proliferation can affect the level of ER-resident enzymes even in the absence of transcriptional activation. For this purpose we analysed the effects of compactin, which has been shown to induce ER proliferation in vitro, on recombinant Xme, which were expressed from a constitutive viral promoter. High levels of recombinant UDP-glucuronosyltransferase UGT1A6 were achieved by amplification of the UGT1A6 cDNA using the dihydrofolate reductase cDNA as selectable marker in DHFR- CHO cells. Treatment of the resulting cell lines with lipoprotein-deficient serum in the absence and presence of compactin for 5 days resulted in a 1.3- and 2.3-fold, respectively, increase of the UGT enzyme activity towards 4-methylumbelliferone, paralleled by an induction of immunoreactive UGT1A6 protein. Similarly, treatment with this 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor increased the endogenous P450 reductase activity 2.6-fold, concomitant with an increase of immunodetectable protein. As expected compactin induced the level of 3-hydroxy-3-methylglutaryl-CoA reductase. Increased levels of this protein have been associated with a proliferation of the ER. Compactin treatment of a separate cell line that expressed recombinant human P450 reductase increased this enzyme activity fivefold. Pulse-chase experiments revealed that the induction of the recombinant Xme by compactin was most likely due to decreased protein degradation. Our results show that enzyme systems unrelated to those involved in cholesterol biosynthesis are affected by compounds known to affect membrane biogenesis. Since this effect extends to heterologously expressed enzymes, it also provides an efficient means by which to increase the levels of recombinant ER proteins.

ASSOCIATION BETWEEN SINGLE POLYMORPHISM IN THE LOCUS RS17216473 OF THE GENE THAT ENCODES 5-LIPOXYGENASEACTIVATING PROTEIN AND RISK OF MYOCARDIAL INFARCTION

2020 ◽  
Vol 73 (11) ◽  
pp. 2431-2437
Author(s):  
Oleksii Ur. Pavlenko ◽  
Iryna G. Strokina ◽  
Tetiana I. Drevytska ◽  
Liudmyla M. Sokurenko ◽  
Viktor E. Dosenko
Keyword(s):  
Myocardial Infarction ◽  
Statistical Processing ◽  
Minor Allele ◽  
Control Group ◽  
Minimal Risk ◽  
Moderate Risk ◽  
Myocardium Infarction ◽  
A Minor ◽  
First Time ◽  
Genotype A

The aim: To study the association between A/A, G/A, A/A genotypes, alleles A, G of the SNP rs17216473 of the gene that encodes ALOX5AP and the risk of myocardial infarction within the Ukrainian population. Materials and methods: PCR in real time and the analysis to discriminate alleles were used. The statistical processing was carried out by χ2 criteria and by χ2 criteria with Yates correction. Results: For the first time the SNP rs17216473 of gene that encodes ALOX5AP has been established to be statistically significantly associated with the risk of myocardial infarction in Ukrainian population. The connection with genotype A/A was opposite to that with genotype G/G. That is, A/A contribution to myocardium infarction has been statistically significant whereas, G/G has been statistically significantly associated with the absence of myocardial infarction. G/A genotype has not been statistically significantly associated with myocardial infarction. It has also been established a statistically significant connection exists between the risk of myocardial infarction and the presence of allele A (minor allele) of the polymorphism. Allele G, however, has a statistically significant association with the absence of myocardial infarction. All humans-homozygotes with the minor allele A had suffered from myocardial infarction. In the control group, humans-homozygotes with the minor allele A were not found. Conclusions: Summarizing our obtained results, we assume the carriers of G/G genotype to have a minimal risk of myocardial infarction onset, the carriers of G/A genotype to have a moderate risk and the carriers of A/A to have a great risk.

Dose-Dependent Effect of Hydroxymethylglutaryl – Coenzyme A Reductase Inhibitor on Serum Cholesterol with Limited Dietary Restrictions: A Case Study

1993 ◽  
Vol 21 (2) ◽  
pp. 105-111
Author(s):  
S Okada ◽  
K Ichiki ◽  
S Tanokuchi ◽  
Z Ota
Keyword(s):  
Serum Cholesterol ◽  
Reductase Inhibitor ◽  
Coenzyme A ◽  
Cholesterol Biosynthesis ◽  
Dependent Diabetes Mellitus ◽  
Hmg Coa Reductase ◽  
Dietary Restrictions ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase ◽  
Dose Dependent

Hydroxymethylglutaryl–coenzyme A (HMG–CoA) reductase inhibitor (pravastatin sodium) can selectively inhibit cholesterol biosynthesis in the liver and may lower serum cholesterol concentrations even where there are no particular dietary restrictions. A 72-year old housewife with non-insulin-dependent diabetes mellitus complicated by hyperlipaemia type IIb, who did not follow directions for diet therapy or kinesitherapy, was administered HMG–CoA reductase inhibitor. The initial dose of 10 mg/day HMG–CoA reductase inhibitor was increased by 10 mg/day every 4 weeks to 30 mg/day, maintained at 30 mg/day for 8 weeks and then reduced gradually until discontinuation after a further 27 weeks. Test results showed the changes in low-density lipoprotein cholesterol and apoprotein B to be dose-dependent. The findings represent the first clinical evidence that hypercholesterolaemia can be adequately managed by the use of HMG–CoA reductase inhibitor, even when no specific dietary restrictions are imposed, and may contribute to improvements in the quality of daily life for many patients suffering from hyperlipaemia type IIb.

scholarly journals Regulation of hepatic cholesterol biosynthesis. Effects of a cytochrome P-450 inhibitor on the formation and metabolism of oxygenated sterol products of lanosterol

1989 ◽  
Vol 264 (2) ◽  
pp. 495-502 ◽  
Author(s):  
J Iglesias ◽  
G F Gibbons
Keyword(s):  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Mevalonic Acid ◽  
Subcellular Fractions ◽  
Hmg Coa Reductase ◽  
Hepatocyte Cultures ◽  
C 32 ◽  
Lanosterol Demethylase ◽  
Cholesterol Precursor ◽  
Coa Reductase

The involvement of oxygenated cholesterol precursors in the regulation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was studied by examining the effect of ketoconazole on the metabolism of mevalonic acid, lanosterol and the lanosterol metabolites, lanost-8-ene-3 beta,32-diol,3 beta-hydroxylanost-8-en-32-al and 4,4-dimethylcholesta-8,14-dien-3 beta-ol, in liver subcellular fractions and hepatocyte cultures. Inhibition of cholesterol synthesis from mevalonate by ketoconazole at concentrations up to 30 microM was due exclusively to a suppression of cytochrome P-450LDM (LDM = lanosterol demethylase) activity, resulting in a decreased rate of lanosterol 14 alpha-demethylation. No enzyme after the 14 alpha-demethylase step was affected. When [14C]mevalonate was the cholesterol precursor, inhibition of cytochrome P450LDM was accompanied by the accumulation of several labelled oxygenated sterols, quantitatively the most important of which was the C-32 aldehyde derivative of lanosterol. There was no accumulation of the 24,25-oxide derivative of lanosterol, nor of the C-32 alcohol. Under these conditions the activity of HMG-CoA reductase declined. The C-32 aldehyde accumulated to a far greater extent when lanost-8-ene-3 beta,32-diol rather than mevalonate was used as the cholesterol precursor in the presence of ketoconazole. With both precursors, this accumulation was reversed at higher concentrations of ketoconazole in liver subcellular fractions. A similar reversal was not observed in hepatocyte cultures.

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