scholarly journals Human metabolism and kinetics of the UV absorber 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) after oral administration

2021 ◽  
Author(s):  
Heike Denghel ◽  
Julia Hiller ◽  
Edgar Leibold ◽  
Thomas Göen
Keyword(s):  
Blood Levels ◽  
Systemic Availability ◽  
Renal Elimination ◽  
Human Metabolism ◽  
Elimination Kinetics ◽  
Blood Concentrations ◽  
Uv Absorber ◽  
Alkyl Side Chains ◽  
Dispersive Liquid Liquid Microextraction ◽  
Almost All

Abstract2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328; CAS: 25973-55-1) is an ultraviolet light (UV) absorber which belongs to the class of hydroxy phenol benzotriazoles. Therefore, UV 328 is added to plastics and other polymers due to its photostability to prevent discoloration and prolong product stability which may result in an exposure of consumers. However, information about the toxic effects on humans and the human metabolism are still lacking. In the present study, human metabolism pathways of UV 328 and its elimination kinetics were explored. For that purpose, three healthy volunteers were orally exposed to a single dose of 0.3 mg UV 328/kg bodyweight. UV 328 and its metabolites were investigated in blood and urine samples collected until 48 and 72 h after exposure, respectively. Thereby, previously published analytical procedures were applied for the sample analysis using dispersive liquid–liquid microextraction and subsequent measurement via gas chromatography coupled to tandem mass spectrometry with advanced electron ionization. UV 328 was found to be oxidized at its alkyl side chains leading to the formation of hydroxy and/or oxo function with maximum blood concentrations at 8–10 h after exposure for UV 328-6/3-OH, UV 328-4/3-OH and UV 328-4/3-CO. In contrast, a plateau for UV 328-4/3-CO-6/3-OH levels was reached around 10 h post-dosage. The highest blood levels were found for native UV 328 at 8 h after ingestion. Furthermore, biphasic elimination kinetics in blood were revealed for almost all detected metabolites. UV 328 and its metabolites did not occur in blood as conjugates. The renal elimination kinetics were very similar with the kinetics in blood. However, the prominence of the metabolites in urine was somewhat different compared to blood. In contrast, mostly conjugated metabolites occurred for renal elimination. In urine, UV 328-4/3-CO-6/3-OH was found to be the most dominant urinary biomarker followed by UV 328-6/3-OH and UV 328-4/3-OH. In total, approximately 0.1% of the orally administered dose was recovered in urine within 72 h. Although high levels of UV 328 in blood proved good resorption and high systemic availability of the substance in the human body, the urine results revealed a rather low quantitative metabolism and urinary excretion rate. Consequently, biliary excretion as part of the enterohepatic cycle and elimination via feces are assumed to be the preferred pathways instead of renal elimination.

scholarly journals Confirmed Plasmodium vivax Resistance to Chloroquine in Central Vietnam

2015 ◽  
Vol 59 (12) ◽  
pp. 7411-7419 ◽  
Author(s):  
Pham Vinh Thanh ◽  
Nguyen Van Hong ◽  
Nguyen Van Van ◽  
Melva Louisa ◽  
Kevin Baird ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Cumulative Risk ◽  
Artemisinin Resistance ◽  
Blood Levels ◽  
Radical Cure ◽  
Blood Concentrations ◽  
Content Type ◽  
Central Vietnam ◽  
Almost All ◽  
First Time

ABSTRACTPlasmodium vivaxresistance to chloroquine (CQ) is currently reported in almost all countries whereP. vivaxis endemic. In Vietnam, despite a first report onP. vivaxresistance to chloroquine published in the early 2000s,P. vivaxwas still considered sensitive to CQ. Between May 2009 and December 2011, a 2-year cohort study was conducted in central Vietnam to assess the recommended radical cure regimen based on a 10-day course of primaquine (0.5 mg/kg/day) together with 3 days of CQ (25 mg/kg). Here we report the results of the first 28-day follow-up estimating the cumulative risk ofP. vivaxrecurrences together with the corresponding CQ blood concentrations, among other endpoints. Out of 260 recruitedP. vivaxpatients, 240 completed treatment and were followed up to day 28 according to the WHO guidelines. Eight patients (3.45%) had a recurrentP. vivaxinfection, at day 14 (n= 2), day 21 (n= 1), and day 28 (n= 5). Chloroquine blood concentrations, available for 3/8 recurrent infections (days 14, 21, and 28), were above the MIC (>100 ng/ml whole blood) in all of these cases. Fever and parasitemia (both sexual and asexual stages) were cleared by day 3. Anemia was common at day 0 (35.8%), especially in children under 10 years (50%), and hemoglobin (Hb) recovery at day 28 was substantial among anemic patients (median change from day 0 to 28, +1.7 g/dl; interquartile range [IQR], +0.7 to +3.2). This report, based on CQ blood levels measured at the time of recurrences, confirms for the first timeP. vivaxCQ resistance in central Vietnam and calls for further studies using standardized protocols for accurately monitoring the extent and evolution ofP. vivaxresistance to chloroquine in Vietnam. These results, together with the mounting evidence of artemisinin resistance in central Vietnam, further highlight the increasing threat of antimalarial drug resistance to malaria elimination in Vietnam.

scholarly journals Blood Micronutrient and Thyroid Hormone Concentrations in the Oldest-Old

2000 ◽  
Vol 85 (6) ◽  
pp. 2260-2265 ◽  
Author(s):  
Giovanni Ravaglia ◽  
Paola Forti ◽  
Fabiola Maioli ◽  
Barbara Nesi ◽  
Loredana Pratelli ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Oldest Old ◽  
Serum Zinc ◽  
Blood Levels ◽  
Elderly Age ◽  
Blood Concentrations ◽  
Significant Difference ◽  
Plasma Retinol ◽  
Age Range

Several micronutrients are involved in thyroid hormone metabolism, but it is unclear whether their marginal deficits may contribute to the alterations in thyroid function observed in extreme aging. The relationships among blood concentrations of thyroid hormones and selenium, zinc, retinol, and α-tocopherol were studied in 44 healthy Northern Italian oldest-old subjects (age range, 90–107 yr), selected by the criteria of the SENIEUR protocol. Control groups included 44 healthy adult (age range, 20–65 yr) and 44 SENIEUR elderly (age range, 65–89 yr) subjects. Oldest-old subjects had higher TSH (P < 0.01) and lower free T3 (FT3)/freeT4 (FT4) ratio, zinc, and selenium serum values (P < 0.001) than adult and elderly control subjects. No significant difference was found for plasma retinol and α-tocopherol values. The associations between micronutrients and thyroid hormones were evaluated by multivariate analysis. In oldest-old subjects, plasma retinol was negatively associated with FT4 (P = 0.019) and TSH serum levels (P = 0.040), whereas serum zinc was positively associated with serum FT3 (P = 0.010) and FT3/FT4 ratio (P = 0.011). In younger subjects, no significant association was found among thyroid variables and micronutrients. In conclusion, blood levels of specific micronutrients are associated with serum iodothyronine levels in extreme aging.

Studies on the carbohydrate metabolism of sheep. XVI. Partition of ketone bodies in blood, tissues, and urine

1962 ◽  
Vol 13 (2) ◽  
pp. 307 ◽  
Author(s):  
RL Reid
Keyword(s):  
Renal Clearance ◽  
Blood Level ◽  
Ketone Bodies ◽  
Urine Flow ◽  
Blood Levels ◽  
Renal Tubules ◽  
Hydroxybutyric Acid ◽  
Acetoacetic Acid ◽  
Tissue Concentrations ◽  
Blood Concentrations

Acetone comprised 0–40% (average 18%) of the acetoacetic acid plus acetone fraction in sheep blood, in which the level of this fraction was 0.6–5.2 mg % (as acetone). Acetoacetic acid was largely converted to acetone during storage of blood at –20°C, with intermittent thawing for analysis. Concentrations of acetoacetic acid in red cells were similar to those in plasma, but those of ß-hydroxybutyric acid were considerably lower. In contrast to acetoacetic acid, ß-hydroxybutyric acid was virtually absent from foetal blood and from brain tissue. Concentrations of both ketone fractions in liver and muscle tissue were about one-half the blood concentrations. The renal clearance of acetoacetic acid plus acetone in hyperketonaemic pregnant ewes was independent of blood level up to 20 mg % and was little affected by rate of urine flow. Clearance values were in the range of 4–9 ml per min, which indicates that most of the acetoacetic acid filtered at the glomeruli is absorbed by the renal tubules. Renal clearance of ß-hydroxybutyric acid was dependent on blood level and was more affected by rate of urine flow than that of acetoacetic acid. Very little ß-hydroxybutyric acid appeared in the urine when blood levels were below 15 mg %. Clearance increased as blood concentration rose above this level, and reached maximum values, mostly of 3–5 ml per min, at blood levels exceeding 30 mg %.

scholarly journals A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does Not Affect Translocation of Its Receptor

2019 ◽  
Vol 172 (2) ◽  
pp. 359-367 ◽  
Author(s):  
Maeve Shannon ◽  
Yuling Xie ◽  
Steven Verhaegen ◽  
Jodie Wilson ◽  
Hanne F Berntsen ◽  
...  
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Complex Mixture ◽  
Blood Levels ◽  
Environmental Toxicants ◽  
Blood Concentrations ◽  
Total Mixture ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of type 2 diabetes and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations, was used to expose a glucagon-like peptide 1 (GLP-1) secreting enteroendocrine cell line (pGIP/neo: STC-1) in vitro for 3 and 24 h. Significant increases of GLP-1 occurred when cells were exposed to the Total mixture at ×500 blood levels. Six sub-mixtures representing chlorinated (Cl), brominated (Br), and perfluorinated chemicals (PFAA), and their combinations (Cl + Br, Cl + PFAA, Br + PFAA) were also tested at ×500. Secretion levels seen for these remained lower than the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at ×1 blood levels. Cytotoxicity was present for ×100 and ×500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic nor antagonist effects on receptor internalization were seen for any of the mixtures. We conclude individual classes of POPs, alone or in combination, can affect GLP-1 secretion and may contribute as a molecular mechanism linking environmental toxicants and diabetes.

Serum Levels of Melatonin in Cancer Patients and their Relation to Body Sizes

1988 ◽  
Vol 3 (3) ◽  
pp. 193-196 ◽  
Author(s):  
S. Barni ◽  
P. Lissoni ◽  
S. Crispino ◽  
F. Rovelli ◽  
G. Esposti ◽  
...  
Keyword(s):  
Body Weight ◽  
Body Size ◽  
Cancer Patients ◽  
Serum Levels ◽  
Blood Levels ◽  
Melatonin Secretion ◽  
Normal Range ◽  
Blood Concentrations ◽  
Patients With Cancer ◽  
Body Sizes

Melatonin secretion is often enhanced in patients with cancer. In the light of a reported correlation between melatonin levels and body size, we investigated blood levels of this pineal hormone in a group of 72 patients affected by cancer, 30 of whom had body weight within the normal range, 30 were obese and the last 12 cases had body weight below the normal range, in order to establish whether in fact melatonin blood concentrations were related to body size. Melatonin levels were high in 19/72 patients (26%). The mean levels of the pineal hormone were similar in patients with normal, low and high body weight. Finally, there was no significant correlation between melatonin values and body weight, height or surface. Melatonin secretion thus does not appear to be influenced by body size in cancer patients.

scholarly journals Supplemented Creatine Induces Changes in Human Metabolism of Thiocompounds and One- and Two-Carbon Units

2010 ◽  
pp. 431-442
Author(s):  
T Navrátil ◽  
E Kohlíková ◽  
M Petr ◽  
D Pelclová ◽  
M Heyrovský ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
Metabolic Pathways ◽  
Blood Levels ◽  
Redox Processes ◽  
Human Metabolism ◽  
Metabolic Disturbances ◽  
Creatinine Excretion ◽  
Thiodiglycolic Acid ◽  
The Last Man

The administration of creatine (5 g/day for one month) to 11 young active sportsmen affected their urinary excretion of creatine, creatinine, and thiodiglycolic acid (TDGA) as well as blood levels of homocysteine, vitamin B12 and folates. The probands were divided into four groups, according to the amount of creatine found in urine, and of folates and vitamin B12 determined in blood. The changes of folates and vitamin B12 were mutually reciprocal. Each group utilized CR as donor of one- and two-carbon (1C and 2C) units by means of homocysteine (HoCySH), folates, and vitamin B12, in different metabolic pathways. In 10 men the creatine administration was accompanied by an increase of HoCySH level in blood, while in the last man, with accidentally discovered hyperhomocysteinemia, the HoCySH level dropped by 50 %. Differences between initial and terminal TDGA levels indicate that creatine affects equilibria of redox processes. Creatinine excretion into urine changed in the dependence on the extent of metabolic disturbances.

scholarly journals Methadone, Buprenorphine, Oxycodone, Fentanyl, and Tramadol in Multiple Postmortem Matrices

2021 ◽  
Author(s):  
Stine Marie Havig ◽  
Vigdis Vindenes ◽  
Åse Marit Leere Øiestad ◽  
Sidsel Rogde ◽  
Cecilie Hasselø Thaulow
Keyword(s):  
Peripheral Blood ◽  
Vitreous Humor ◽  
Pericardial Fluid ◽  
Limited Information ◽  
Blood Concentrations ◽  
Bodily Fluids ◽  
Drug Concentrations ◽  
Quantitative Analyses ◽  
Alternative Matrices ◽  
Almost All

Abstract Peripheral blood concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid, muscle, and vitreous humor have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl, and tramadol in postmortem samples of pericardial fluid, skeletal muscle, and vitreous humor, in addition to peripheral and cardiac blood; and if drug concentrations in these alternative matrices were comparable to those in peripheral blood, and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl, and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except for in vitreous humor, were relatively similar to those in peripheral blood. Larger variations in concentrations were found for buprenorphine, oxycodone, and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but interpretation of quantitative results must be performed with caution.

Interleukin-4 Blood Concentrations in Early and Metastatic Human Solid Neoplasms

1997 ◽  
Vol 12 (2) ◽  
pp. 75-78 ◽  
Author(s):  
P. Lissoni ◽  
D. Merlini ◽  
D. Pirato ◽  
S. Meregalli
Keyword(s):  
Cancer Patients ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Control Group ◽  
Blood Levels ◽  
Neoplastic Disease ◽  
Blood Concentrations ◽  
Mean Values ◽  
Cell Functions ◽  
Th2 Cell

Blood levels of the immunosuppressive cytokines IL-6 and IL-10 are often abnormally high in patients with advanced cancer. However, since IL-6 and IL-10 may be produced by macrophages and TH2 cells, the evidence of abnormally high values of IL-6 and/or IL-10 may reflect hyperactivation either of the macrophage system or of TH2 cell functions. In contrast, IL-4 is almost completely produced by the TH2 lymphocytes. Therefore, evaluation of IL-4 levels could help to differentiate macrophage from TH2 cell hyperactivation. This study was performed to investigate IL-4 serum levels in a group of cancer patients in relation to the stage of disease and to the secretion of other cytokines. The study included 50 patients, 28 of whom showed distant organ metastases. Lung cancer and gastrointestinal cancers were the most frequent neoplasms in our patients. The control group consisted of 60 healthy subjects. IL-4 was measured by the Elisa method. No patient showed high levels of IL-4. No significant differences were seen between controls and cancer patients, nor between metastatic and non-metastatic patients. In addition, no significant differences in IL-4 mean values were found between patients with normal or high levels of IL-6 and IL-10, or between patients with normal or low IL-2 concentrations. This preliminary study seems to exclude cancer-related abnormally high secretion of IL-4. Therefore, the high levels of IL-6 and/or IL-10 often occurring in advanced neoplastic disease would mainly depend on macrophage production.

Pharmacokinetics of Intravenous Potassium Cyanide

1988 ◽  
Vol 7 (2) ◽  
pp. 183-186 ◽  
Author(s):  
J.E. Bright ◽  
T.C. Marrs
Keyword(s):  
Potassium Cyanide ◽  
Blood Levels ◽  
Second Phase ◽  
Elimination Kinetics ◽  
First Order ◽  
Blood Cyanide

The pharmacokinetics of intravenously injected potassium cyanide have been studied in Beagle bitches. In the period up to about 80 min after dosing, blood levels fell in a manner consistent with first-order elimination kinetics. Thereafter blood cyanide concentrations fell at a slower rate, indicating that a second phase of slower elimination had been entered.

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