Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q3SYG4 (C18)
 23,707 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycolipid galactosyldiacylglycerol (GDG), containing C16:0 and C18:1 fatty acids, was isolated from the sea alga Petalonia bingbamiae as a potent inhibitor of the activities of mammalian DNA polymerase alpha (pol. alpha). GDG, however, had no effect on pol. alpha from a fish or a higher plant. The inhibition of pol. alpha by GDG was dose-dependent with an IC50 value of 54 microM. The compound did not influence the activities of other replicative DNA polymerases such as mammalian pol. delta, or repair-related enzymes such as mammalian pol. beta. GDG also did not influence the activities of prokaryotic DNA polymerases such as the Klenow fragment of DNA polymerase I, T4 DNA polymerase, Taq DNA polymerase, DNA polymerases from the higher plant, cauliflower, or DNA metabolic enzymes such as calf thymus terminal deoxynucleotidyl transferase, human immunodeficiency virus type 1 reverse transcriptase and deoxyribonuclease 1. Kinetic analysis of the compound showed that pol. alpha was non-competitively inhibited with respect to both the DNA template and the nucleotide substrate. In this study, we demonstrated the structure-function relationship in the selective inhibition of pol. alpha by the glycolipid group.
 ...
PMID:Galactosyldiacylglycerol, a mammalian DNA polymerase alpha-specific inhibitor from a sea alga, Petalonia bingbamiae. 1155 81

In hospitals, human milk is subjected to heat treatment to reduce risk of transmission of infectious agents such as human immunodeficiency virus (HIV), hepatitis B, cytomegalovirus, and bacterial contamination, especially during feeding of banked milk to preterm infants. Fat losses due to heat treatment have been extensively studied in cow milk but have received little attention in human milk. We studied the effect of human milk pasteurization and sterilization on total fat content available to the infant as well as on fatty acid composition. Milk samples from 12 mothers (days 5-35 of lactation) were divided into three equal parts: one remained fresh, one was pasteurized (62.5 degrees C for 30min), and one was sterilized (120 degrees C for 30min). Fat content was determined gravimetrically, and the contribution of 30 fatty acids was determined by gas chromatography. For investigation of loss of available fat in sterilized milk, milk was collected from two additional mothers and analyzed with a modified extraction method. Total fat content was the same in fresh, pasteurized, and sterilized milk. The available fat content was 3.1+/-0.4g/dL (mean +/- SE) in fresh human milk, 3.1+/-0.4g/dL in pasteurized human milk, and 2.7+/-0.3g/dL (P < 0.001 vs. fresh) in sterilized human milk because of formation of a surface skin and fat adherence to the vial wall after sterilization. The fatty acid composition of 10 saturated, 10 monounsaturated, and 10 polyunsaturated fatty acids of both the n6 and n3 series was not affected by pasteurization. In sterilized milk there was a slight decrease of linoleic acid (C18:2n6; -0.7% vs. fresh; P = 0.006) and arachidonic acid (C20:4n6; -2.5%; P = 0.045). Pasteurization and sterilization do not affect total fat content of human milk, but sterilization may reduce available fat content by >10%. Fatty acid composition of human milk is not changed by pasteurization, but is slightly changed by sterilization.
 ...
PMID:Fat content and fatty acid composition of fresh, pasteurized, or sterilized human milk. 1178 20

Anastasia Black (Russian sweet pepper) of Capsicum annuum L. var. angulosum Mill. (Solanaceae) was successively extracted with hexane, acetone, methanol and 70% methanol, and the extracts were further separated into a total of twenty-three fractions by silica gel or octadecylsilane (ODS; C18) column chromatography. These extracts and fractions were investigated for their cytotoxicity, anti-human immunodeficiency virus (HIV), anti-Helicobacter pylori (H. pylori), urease inhibition and multidrug resistance (MDR) reversal activity. Some fractions of hexane and acetone extracts showed higher cytotoxic activity against three human oral tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG) than against three normal human oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), suggesting a tumor-specific cytotoxic activity. No fractions displayed anti-HIV activity, but some hydrophobic fractions showed higher anti-H. pylori activity, urease inhibition activity and MDR reversal activity. The higher MDR activity of these fractions against MDR gene-transfected L5178 mouse lymphoma T cells may possibly be due to their higher content of carotene or polyphenol. These data suggest that Anastasia Black should be further investigated as a potent supplement for cancer chemotherapy.
 ...
PMID:Bioactivities of anastasia black (Russian sweet pepper). 1615 35

Scytovirin (SVN) is a novel anti-human immunodeficiency virus (HIV) protein isolated from aqueous extracts of the cultured cyanobacterium Scytonema varium. The protein consists of a single 95-amino acid chain with significant internal sequence duplication and 10 cysteines forming five intrachain disulfide bonds. A synthetic gene that encodes scytovirin was constructed, and expressed in Escherichia coli, with thioredoxin (TRX) fused to its N-terminus (TRX-SVN). Most of the expressed protein was in soluble form, which was purified by a polyhistidine tag affinity purification step. SVN was then cleaved from TRX with enterokinase and separated from the TRX partner by C18 reversed-phase HPLC. This production method has proven superior to earlier synthetic attempts and recombinant procedures using a standard expression system. The current system resulted in yields of 5-10mg/L of purified SVN for structural studies and for preclinical development of SVN as a topical microbicide for HIV prophylaxis.
 ...
PMID:Overexpression and purification of scytovirin, a potent, novel anti-HIV protein from the cultured cyanobacterium Scytonema varium. 1628 3

Posaconazole is a new antifungal drug used in prophylaxis and therapy of fungal infections in patients with immunodeficiency. In the clinical development, posaconazole exhibits variable oral bioavailability. Hence drug monitoring is recommended. For this purpose, a rapid and a convenient high-performance liquid chromatography (HPLC) method has been developed. To 200 mul serum, 50 mul internal standard (itraconazole) was added. After precipitation of the proteins with acetonitrile, the clear supernatant was evaporated in a centrifugal evaporator, and the residue was dissolved in the HPLC elution. Separation was done on a chromatography performed by injecting a 50 mul aliquot of the resuspended sample onto a Multohyp C18 BDS column (250 x 4 mm). Column temperature was maintained at 50 degrees C. The flow rate was 1 ml min(-1). Retention time of posaconazole was about 9 min and those of itraconazole was 17 min. The limit of quantification was 50 mug l(-1) and the limit of detection about 10 mug l(-1). Until now the concentration of posaconazole was measured in 14 patients (64 samples). After a daily dosage of 600-800 mg posaconazole the serum concentrations varied between 100 and 3000 mug l(-1) (582 +/- 579 mug l(-1)). Oral bioavailability was especially low in patients with cytostatic therapy and/or bone marrow transplantation. Further studies are needed to establish the therapeutic range of the posaconazole concentrations.
 ...
PMID:HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases. 1696 77

Lamivudine (3TC) and zidovudine (AZT) are systemic antiviral substances extensively used in human immunodeficiency virus (HIV) infected patients. Nowadays, 3TC, AZT, and several other pharmacologically potent pharmaceuticals are manufactured in the same production area. To assure quality of drug products and patient safety, properly validated cleaning methodology is necessary. A carefully designed cleaning validation and its evaluation can ensure that residues of 3TC and AZT will not carry over and cross contaminate the subsequent product. The aim of this study was to validate a simple analytical method for verification of residual 3TC and AZT in equipment used in the production area and to confirm the efficiency of the cleaning procedure. The liquid chromatography method was validated using a Nova-Pak C18 column (3.9 x 150 mm, 4 microm particle size) and methanol-water (20 + 80, v/v) as the mobile phase at a flow rate of 1.0 mL/min. Ultraviolet detection was made at 266 nm. The calibration curve was linear over a concentration range of 2.0-22.0 microg/mL with a correlation coefficient of 0.9998. The detection and quantitation limits were 0.36 and 1.21 microg/mL, respectively. The intra-day and interday precision expressed as relative standard deviation were below 2.0%. The mean recovery of the method was 99.19%. The mean extraction recovery from manufacturing equipment was 83.5%.
 ...
PMID:Quantitative determination and sampling of lamivudine and zidovudine residues for cleaning validation in a production area. 1758 Jun 24

BMS-378806 is a human immunodeficiency virus (HIV) entry inhibitor that is being developed for the oral treatment of HIV infection. Human plasma and urine LC/MS/ MS methods have been developed and validated for the quantitation of BMS-378806. For human plasma method, methyl t-butyl ether was used to extract BMS-378806 from plasma in a 96-well format, and the organic layers were dried down and then reconstituted for the injection, while a dilute-and-shoot approach was used for human urine method in a 96-well format. Chromatographic separation was achieved isocratically on a Phenomenex C18 (2) Luna column (2 x 50 mm2, 5 microm). The mobile phase contained 60:40 v/v of 0.1% formic acid in water and ACN. Detection was by positive ion electrospray MS/MS. The standard curves ranged from 1.25 to 1000 ng/mL for the plasma assay and from 10 to 5000 ng/mL for the urine assay. The curves were fitted to a 1/x2 weighted quadratic regression model for both methods. The validation results demonstrated that both methods had satisfactory precision and accuracy across the calibration ranges. The methods were applied to the analysis of human plasma and urine samples from a single ascending dose clinical study to assess the pharmacokinetics of the drug. The pharmacokinetic analysis results indicated the absorption and disposition of the drug was rapid. The systemic exposure of BMS-378806 was generally dose proportional among the doses from 100 to 1200 mg, but not dose proportional to 1600 mg. There were modest increases in the systemic exposure when the drug was given with food or given as a solution formulation. Renal excretion was not a substantial elimination pathway of the drug. BMS378806 was safe and well tolerated over a dose range of 100-1600 mg administered as a single oral dose.
 ...
PMID:Quantitative determination of BMS-378806 in human plasma and urine by high-performance liquid chromatography/tandem mass spectrometry. 1762 67

Preeclampsia is a multifactorial pregnancy-specific disease. In some cases, severe preeclampsia and related disorders of acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, low platelets syndrome are associated with inherited defects in mitochondrial beta-oxidation of fatty acids, especially a deficiency of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD). Recently, an unexplained increase in the incidence of preeclampsia has been documented in human immunodeficiency virus (HIV)-infected pregnant women on treatment with highly active antiretroviral therapy (HAART). We performed this study to determine if antiretroviral drugs affect mitochondrial beta-oxidation fatty acids in vitro. Two normal and 1 heterozygous LCHAD-deficient cell lines were exposed to up to 5 times the therapeutic concentrations of the following antiretroviral drugs: nevirapine, didanosine, lamivudine, and a combination of nelfinavir, zidovudine, and lamivudine. One homozygous LCHAD-deficient cell line served as the positive control. After exposure of the fibroblasts to these drugs for periods ranging from 2 to 10 days, accumulations of even-chain 3-hydroxy fatty acids (3-OH-C6 to 3-OH-C18) in the culture media were measured by stable-isotope dilution gas chromatography/mass spectrometry. Compared to the respective unexposed fibroblasts, there was no significant build-up of 3-hydroxy fatty acids in the culture media of normal or heterozygous LCHAD-deficient fibroblasts exposed to antiretroviral drugs. Our results show that the commonly used antiretroviral drugs do not adversely affect fatty acid oxidation in fibroblasts. Therefore, an altered fatty acid oxidation may not be the mechanism for the reported increased risk of preeclampsia in HIV-infected pregnant women on HAART.
 ...
PMID:Highly active antiretroviral therapy does not affect mitochondrial beta-oxidation of fatty acids: an in vitro study in fibroblasts. 1824 Aug 71

Combination therapy with protease inhibitors (PIs) is used for the treatment of patients infected with the human immunodeficiency virus (HIV). To achieve optimal drug concentrations for viral suppression and avoidance of drug toxicity, therapeutic drug monitoring of PIs levels has been considered essential. In this study an analytical procedure for simultaneous monitoring the plasma concentrations of a total four protease inhibitors: indinavir, lopinavir, nelfinavir and saquinavir was presented. The plasma samples were liquid/liquid extracted and subjected to high performance liquid chromatography (HPLC) analysis. The lopinavir and saquinavir in the patient plasma samples were monitored by ultraviolet detection at 215 nm. Extraction procedure using methyl tert-butyl ether and the mobile phase consisted from acetonitrile with phosphate buffer on a Symmetry C18 column were used to monitor these two compounds. Linearity of the method was obtained in the concentration range of 0.1 - 15.0 mg/mL for all four protease inhibitors. Under steady state conditions, the plasma concentrations of protein inhibitors in 23 patients were determined and area under the plasma concentration-time curve was estimated to maintain optimal viral suppression. We developed a simple and specific method for the simultaneous determination of lopinavir and saquinavir.
 ...
PMID:Pharmacokinetic monitoring of HIV-1 protease inhibitors in the antiretroviral therapy. 1853 80

For pharmacokinetic monitoring, measurement of antiretroviral agents in plasma is the gold standard. However, human immunodeficiency virus protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) exert their action within the infected cell. Cell-associated concentrations may therefore more adequately reflect therapy outcome. Therefore, for the quantification of nine PIs (amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir and tipranavir), 1 active PI metabolite (nelfinavir M8) and 2 NNRTIs (efavirenz and nevirapine) in lysate of peripheral blood mononuclear cells (PBMCs) an assay was developed and validated, using liquid chromatography coupled with tandem mass spectrometry. Analytes were extracted from a PBMC pellet by means of a one-step extraction with 50% methanol containing the internal standards D6-indinavir, D5-saquinavir, 13C6-efavirenz and dibenzepine. Chromatographic separation was performed on a reversed phase C18 column (150mmx2.0mm, particle size 5microm) with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.25mL/min. The analytical run time was 10min. The triple quadrupole mass spectrometer was operated in the positive ion-mode and multiple reaction monitoring was used for drug quantification. The method was validated over a range of 1-500ng/mL in PBMC lysate for all analytes. The method was proven to be specific, accurate, precise and robust. The mean precision and accuracy was less than +/-12% at all concentration levels. Using the developed assay and a previously developed assay for these analytes in plasma, the relationship between plasma and intracellular pharmacokinetics and their relationship with therapy outcome can now be determined.
 ...
PMID:Quantification of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cell lysate using liquid chromatography coupled with tandem mass spectrometry. 1916 2


<< Previous 1 2 3 Next >>