scholarly journals Differential metabolism of choline supplements in adult volunteers

2021 ◽  
Author(s):  
Katrin A. Böckmann ◽  
Axel R. Franz ◽  
Michaela Minarski ◽  
Anna Shunova ◽  
Christian A. Maiwald ◽  
...  
Keyword(s):  
Choline Chloride ◽  
Plasma Concentrations ◽  
Clinical Importance ◽  
Water Soluble ◽  
Bacterial Degradation ◽  
Adult Men ◽  
Adult Volunteers ◽  
Kinetics Of ◽  
Supplement Intake ◽  
Egg Pc

Abstract Background Adequate intake of choline is essential for growth and homeostasis, but its supply does often not meet requirements. Choline deficiency decreases phosphatidylcholine (PC) and betaine synthesis, resulting in organ pathology, especially of liver, lung, and brain. This is of particular clinical importance in preterm infants and cystic fibrosis patients. We compared four different choline supplements for their impact on plasma concentration and kinetics of choline, betaine as a methyl donor and trimethylamine oxide (TMAO) as a marker of bacterial degradation prior to absorption. Methods Prospective randomized cross-over study (1/2020–4/2020) in six healthy adult men. Participants received a single dose of 550 mg/d choline equivalent in the form of choline chloride, choline bitartrate, α-glycerophosphocholine (GPC), and egg-PC in randomized sequence at least 1 week apart. Blood was taken from t = − 0.1–6 h after supplement intake. Choline, betaine, TMAO, and total PC concentrations were analyzed by tandem mass spectrometry. Results are shown as medians and interquartile range. Results There was no difference in the AUC of choline plasma concentrations after intake of the different supplements. Individual plasma kinetics of choline and betaine differed and concentrations peaked latest for PC (at ≈3 h). All supplements similarly increased plasma betaine. All water-soluble supplements rapidly increased TMAO, whereas egg-PC did not. Conclusion All supplements tested rapidly increased choline and betaine levels to a similar extent, with egg-PC showing the latest peak. Assuming that TMAO may have undesirable effects, egg-PC might be best suited for choline supplementation in adults. Study registration This study was registered at “Deutsches Register Klinischer Studien” (DRKS) (German Register for Clinical Studies), 17.01.2020, DRKS00020454.

scholarly journals Oral absorption and drug interaction kinetics of moxifloxacin in an animal model of weightlessness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Liang ◽  
Jing Ma ◽  
Bo Wei
Keyword(s):  
Oral Dose ◽  
Oral Absorption ◽  
Jugular Vein ◽  
Plasma Concentrations ◽  
Pharmacokinetic Data ◽  
Simulated Weightlessness ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Interaction Kinetics ◽  
Kinetics Of

AbstractTo investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.

scholarly journals Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2237
Author(s):  
Leonid Kaluzhskiy ◽  
Pavel Ershov ◽  
Evgeniy Yablokov ◽  
Tatsiana Shkel ◽  
Irina Grabovec ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Clinical Importance ◽  
Optical Biosensor ◽  
Water Soluble ◽  
Soluble Form ◽  
Redox Partner ◽  
Access Channel ◽  
Kd Values ◽  
Key Steps

Widespread pathologies such as atherosclerosis, metabolic syndrome and cancer are associated with dysregulation of sterol biosynthesis and metabolism. Cholesterol modulates the signaling pathways of neoplastic transformation and tumor progression. Lanosterol 14-alpha demethylase (cytochrome P450(51), CYP51A1) catalyzes one of the key steps in cholesterol biosynthesis. The fairly low somatic mutation frequency of CYP51A1, its druggability, as well as the possibility of interfering with cholesterol metabolism in cancer cells collectively suggest the clinical importance of CYP51A1. Here, we show that the natural flavonoid, luteolin 7,3′-disulfate, inhibits CYP51A1 activity. We also screened baicalein and luteolin, known to have antitumor activities and low toxicity, for their ability to interact with CYP51A1. The Kd values were estimated using both a surface plasmon resonance optical biosensor and spectral titration assays. Unexpectedly, in the enzymatic activity assays, only the water-soluble form of luteolin—luteolin 7,3′-disulfate—showed the ability to potently inhibit CYP51A1. Based on molecular docking, luteolin 7,3′-disulfate binding suggests blocking of the substrate access channel. However, an alternative site on the proximal surface where the redox partner binds cannot be excluded. Overall, flavonoids have the potential to inhibit the activity of human CYP51A1 and should be further explored for their cholesterol-lowering and anti-cancer activity.

scholarly journals Mixing state and compositional effects on CCN activity and droplet growth kinetics of size-resolved CCN in an urban environment

2012 ◽  
Vol 12 (21) ◽  
pp. 10239-10255 ◽  
Author(s):  
L. T. Padró ◽  
R. H. Moore ◽  
X. Zhang ◽  
N. Rastogi ◽  
R. J. Weber ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Water Soluble ◽  
Anthropogenic Sources ◽  
Droplet Growth ◽  
Mixing State ◽  
Aerosol Composition ◽  
Activation Kinetics ◽  
Aerosol Mixing State ◽  
Kinetics Of ◽  
Ccn Activity

Abstract. Aerosol composition and mixing state near anthropogenic sources can be highly variable and can challenge predictions of cloud condensation nuclei (CCN). The impacts of chemical composition on CCN activation kinetics is also an important, but largely unknown, aspect of cloud droplet formation. Towards this, we present in-situ size-resolved CCN measurements carried out during the 2008 summertime August Mini Intensive Gas and Aerosol Study (AMIGAS) campaign in Atlanta, GA. Aerosol chemical composition was measured by two particle-into-liquid samplers measuring water-soluble inorganic ions and total water-soluble organic carbon. Size-resolved CCN data were collected using the Scanning Mobility CCN Analysis (SMCA) method and were used to obtain characteristic aerosol hygroscopicity distributions, whose breadth reflects the aerosol compositional variability and mixing state. Knowledge of aerosol mixing state is important for accurate predictions of CCN concentrations and that the influence of an externally-mixed, CCN-active aerosol fraction varies with size from 31% for particle diameters less than 40 nm to 93% for accumulation mode aerosol during the day. Assuming size-dependent aerosol mixing state and size-invariant chemical composition decreases the average CCN concentration overprediction (for all but one mixing state and chemical composition scenario considered) from over 190–240% to less than 20%. CCN activity is parameterized using a single hygroscopicity parameter, κ, which averages to 0.16 ± 0.07 for 80 nm particles and exhibits considerable variability (from 0.03 to 0.48) throughout the study period. Particles in the 60–100 nm range exhibited similar hygroscopicity, with a κ range for 60 nm between 0.06–0.076 (mean of 0.18 ± 0.09). Smaller particles (40 nm) had on average greater κ, with a range of 0.20–0.92 (mean of 0.3 ± 0.12). Analysis of the droplet activation kinetics of the aerosol sampled suggests that most of the CCN activate as rapidly as calibration aerosol, suggesting that aerosol composition exhibits a minor (if any) impact on CCN activation kinetics.

Advancements in the Use of Platinum Complexes as Anticancer Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajiv Sharma ◽  
Vikram Jeet Singh ◽  
Pooja A Chawla
Keyword(s):  
Anticancer Agents ◽  
Biomedical Applications ◽  
Clinical Importance ◽  
Platinum Complexes ◽  
Water Soluble ◽  
Platinum Compounds ◽  
Anticancer Compounds ◽  
Cellular Resistance ◽  
Anti Cancer ◽  
Target Effects

Background: The platinum (II) complexes as anticancer agents have been well explored for the development of novel analogs. Yet, none of them achieved clinical importance in oncology. At present, anticancer compounds containing platinum (II) complexes have been employed in the treatment of colorectal, lung, and genitourinary tumors. Among the platinum-based anticancer drugs, Cisplatin (cis-diamine dichloroplatinum (II), cis-[Pt(NH3)2Cl2]) is one of the most potent components of cancer chemotherapy. The nephrotoxicity, neurotoxicity and ototoxicity, and platinum compounds associated resistant cancer are some major disadvantages. Objective: With the rapidly growing interest in platinum (II) complexes in tumor chemotherapy, researchers have synthesized many new platinum analogs as anticancer agents that show better cytotoxicity, and less off-target effects with less cellular resistance. This follows the introduction of oxaliplatin, water-soluble carboplatin, multinuclear platinum and newly synthesized complexes, etc. Method: This review emphasizes recent advancements in drug design and development, the mechanism of platinum (II) complexes, their stereochemistry, current updates, and biomedical applications of platinum-based anticancer agents. Conclusion: In the last few decades, the popularity of platinum complexes as potent anti-cancer agents has risen as scientists have synthesized many new platinum complexes that exhibit better cytotoxicity coupled with less off-target effects.

Solution Kinetics of a Water-Soluble Hydrocortisone Prodrug: Hydrocortisone-21-lysinate

1985 ◽  
Vol 74 (1) ◽  
pp. 87-89 ◽  
Author(s):  
Kevin Johnson ◽  
Gordon L. Amidon ◽  
Stefano Pogany
Keyword(s):  
Water Soluble ◽  
Kinetics Of ◽  
Solution Kinetics

scholarly journals Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations

2000 ◽  
Vol 44 (5) ◽  
pp. 1337-1341 ◽  
Author(s):  
John E. Conte ◽  
Jeffrey A. Golden ◽  
Mari McQuitty ◽  
Juliana Kipps ◽  
Emil T. Lin ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Antimycobacterial Activity ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Epithelial Lining ◽  
Alveolar Cells ◽  
Epithelial Lining Fluid ◽  
Healthy Men ◽  
And Gender ◽  
Adult Volunteers

ABSTRACT Ethionamide, 250 mg every 12 h for a total of nine doses, was administered to 40 adult volunteers (10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women). Blood was obtained for drug assay prior to administration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Ethionamide was measured in epithelial lining fluid (ELF) and alveolar cells (AC) using a new mass spectrometric method. The presence of AIDS or gender was without significant effect on the concentrations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean ± standard deviation [SD]) were 0.97 ± 0.65 and 0.65 ± 0.35 μg/ml at 2 and 4 h after the last dose, respectively, and both values were significantly greater than the concentration of ethionamide in AC (0.38 ± 0.47 μg/ml) (P < 0.05). The concentration of ethionamide was significantly greater in ELF (5.63 ± 3.8 μg/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible strains of Mycobacterium tuberculosis. For all 40 subjects, the ELF/plasma concentration ratios (mean ± SD) at 2 and 4 h were 8.7 ± 11.7 and 9.7 ± 5.6, respectively. We conclude that the absorption of orally administered ethionamide, as measured in this study, was not affected by gender or the presence of AIDS. Ethionamide concentrations were significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial activity resides in this compartment.

scholarly journals Automated System for Kinetic Analysis of Particle Size Distributions for Pharmaceutically Relevant Systems

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
John-Bruce D. Green ◽  
Phillip W. Carter ◽  
Yingqing Zhang ◽  
Dipa Patel ◽  
Priyanka Kotha ◽  
...  
Keyword(s):  
Particle Size ◽  
Clinical Importance ◽  
Automated System ◽  
Size Distributions ◽  
Mixing Conditions ◽  
Particle Size Distributions ◽  
Complex Formulation ◽  
Wide Range ◽  
Key Variables ◽  
Kinetics Of

Detailing the kinetics of particle formation for pharmaceutically relevant solutions is challenging, especially when considering the combination of formulations, containers, and timescales of clinical importance. This paper describes a method for using commercial software Automate with a stream-selector valve capable of sampling container solutions from within an environmental chamber. The tool was built to monitor changes in particle size distributions via instrumental particle counters but can be adapted to other solution-based sensors. The tool and methodology were demonstrated to be highly effective for measuring dynamic changes in emulsion globule distributions as a function of storage and mixing conditions important for parenteral nutrition. Higher levels of agitation induced the fastest growth of large globules (≥5 μm) while the gentler conditions actually showed a decrease in the number of these large globules. The same methodology recorded calcium phosphate precipitation kinetics as a function of [Ca2+] and pH. This automated system is readily adaptable to a wide range of pharmaceutically relevant systems where the particle size is expected to vary with time. This instrumentation can dramatically reduce the time and resources needed to probe complex formulation issues while providing new insights for monitoring the kinetics as a function of key variables.

scholarly journals Complement factor D is linked to platelet activation in human and rodent sepsis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
O. Sommerfeld ◽  
K. Dahlke ◽  
M. Sossdorf ◽  
R. A. Claus ◽  
A. Scherag ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Physiological Function ◽  
Plasma Concentrations ◽  
Cecal Ligation ◽  
Clinical Importance ◽  
Surface Expression ◽  
Antiplatelet Drugs ◽  
Complement Factor ◽  
Wild Type ◽  
Deficient Mice

Abstract Background The complement factor D (CFD) exerts a regulatory role during infection. However, its physiological function in coagulopathy and its impact on the course of an infection remains unclear. Materials Wild-type and CFD-deficient mice (n = 91) were subjected to cecal ligation and puncture to induce sepsis. At several time points, markers of coagulation and the host-immune response were determined. Furthermore, in patients (n = 79) with sepsis or SIRS, CFD levels were related to clinical characteristics, use of antiplatelet drugs and outcome. Results Septic CFD-deficient mice displayed higher TAT complexes (p = 0.02), impaired maximal clot firmness, but no relevant platelet drop and reduced GPIIb/IIIa surface expression on platelets (p = 0.03) compared to septic wild-type mice. In humans, higher CFD levels (non-survivors, 5.0 µg/ml to survivors, 3.6 µg/ml; p = 0.015) were associated with organ failure (SOFA score: r = 0.33; p = 0.003) and mortality (75% percentile, 61.1% to 25% percentile, 26.3%). CFD level was lower in patients with antiplatelet drugs (4.5–5.3 µg/ml) than in patients without. Conclusion In mice, CFD is linked to pronounced platelet activation, depicted by higher GPIIb/IIIa surface expression in wild-type mice. This might be of clinical importance since high CFD plasma concentrations were also associated with increased mortality in sepsis patients.

scholarly journals Chlorine and Chlorinated Compounds Removal from Industrial Wastewater Discharges: A Review

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Mohammad Al-Hwaiti ◽  
Hamidi Abdul Aziz ◽  
Mohd Azmier Ahmad ◽  
Reyad Al-Shawabkeh
Keyword(s):  
Industrial Wastewater ◽  
Electrochemical Techniques ◽  
Parent Compound ◽  
Water Soluble ◽  
Human Beings ◽  
Catalytic Method ◽  
Chlorinated Compounds ◽  
Water Treatment Process ◽  
Chlorine Removal ◽  
Kinetics Of

Adsorption techniques for industrial wastewater treatment rich in heavy metals and aqueous solutions of water-soluble such as Cl−, F−, HCO3−, NO3−, SO2−4, and PO3−, often include technologies for toxicity removals. The recent advancement and technical applicability in the treatment of chlorine and chlorinated compounds from industrial wastewater are reviewed in this article. Chlorine and chlorinated compounds are among the common discharged constituents from numerous industries. They can be carcinogenic or naturally toxic and can pose issues to aquatic ecosystems and human beings. Thus, elimination of chlorides and chlorinated compounds from water or wastewater is inevitable to get rid of the problem. Several techniques are being applied for the reduction of chlorine and chlorinated compounds in water. These include biodegradation, photochemical, adsorption, chemical, electrochemical, photo-electrochemical, membrane, supercritical extraction and catalytic method. Chlorine can react with various organic and inorganic micro-pollutants. However, the potential reactivity of chlorine for specific compounds is small, and only minor variations in the structure of the parent compound are anticipated in the water treatment process under typical conditions. This paper reviews different techniques and aspects related to chlorine removal, the types of chlorine species in solution and their catalyst, chlorine fate and transport into the environment, electrochemical techniques for de-chlorination of water, kinetics, mechanisms of reduction of chlorinated compounds, and kinetics of the electrochemical reaction of chlorine compounds. Keywords: Industrial waste, Kinetics, Wastewater, Water purification

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