scholarly journals On the half-life of thiocyanate in the plasma of the marine fish Amphiprion ocellaris: implications for cyanide detection

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6644 ◽  
Author(s):  
Nancy E. Breen ◽  
J. Alexander Bonanno ◽  
Sara Hunt ◽  
Julia Grossman ◽  
Jordan Brown ◽  
...  
Keyword(s):  
Marine Fish ◽  
Half Life ◽  
Anthropogenic Activities ◽  
Life Forms ◽  
Fish Food ◽  
Robust Test ◽  
Coral Reef Ecosystems ◽  
C30 Column ◽  
Dose Dependent ◽  
Toxicokinetic Data

The illegal practice of using cyanide (CN) as a stunning agent to collect fish for both the marine aquarium and live fish food trades has been used throughout the Indo-Pacific for over 50 years. CN fishing is destructive to all life forms within the coral reef ecosystems where it is used and is certainly one of many anthropogenic activities that have led to 95% of the reefs in the Indo-Pacific being labeled at risk for degradation and loss. A field-deployable test for detecting fish caught using CN would assist in combating the use of this destructive practice, however, no reliable and robust test exists. Further, there is little toxicokinetic data available on marine fish to support the development of such a test, yet such data is critical to establishing the concentration range and time scale over which such a test would be viable. This study presents the first direct measurement of the half-life of the metabolite thiocyanate (SCN) after pulsed exposure to CN in a marine fish. SCN was measured in the plasma of Amphiprion ocellaris after exposure to 50 ppm CN for three exposure times (20, 45, and 60 s) using HPLC-UV and a C30 column pre-treated with polyethylene glycol. Plasma SCN levels observed are dose-dependent, reflecting a longer time for conversion of CN to SCN as the dose of CN increases. SCN plasma levels reached a maximum concentration (1.2–2.3 ppm) 12–20 h after exposure to CN. The half-life for the elimination of SCN was 1.01 ± 0.26 days for 45 s exposure and 0.44 ± 0.15 days for 20 s exposure. Fish were also directly exposed to SCN (100 ppm for 11 days) and the observed half-life for SCN elimination was 0.35 ± 0.07 days. Plasma SCN levels did not return to control levels, even after 41 days when exposed to CN but did return to control levels after 48 days when exposed to SCN. The similar half-lives observed for CN and SCN exposure suggests that SCN exposure can be used as a proxy for measuring the rate of SCN elimination following CN exposure. In order for plasma SCN to be used as a marker for CN exposure, these results must be extended to other species and endogenous levels of SCN in wild caught fish must be established.

scholarly journals Mechanisms underlying the antifibrotic properties of noninhibitory PAI-1 (PAI-1R) in experimental nephritis

2009 ◽  
Vol 297 (4) ◽  
pp. F1045-F1054 ◽  
Author(s):  
Yufeng Huang ◽  
Wayne A. Border ◽  
Daniel A. Lawrence ◽  
Nancy A. Noble
Keyword(s):  
Half Life ◽  
Stable Form ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Therapeutic Action ◽  
Protease Inhibition ◽  
Ecm Degradation ◽  
Dose Dependent ◽  
Pai 1

Administration of a mutant, noninhibitory PAI-1 (PAI-1R), reduces disease in experimental glomerulonephritis. Here we investigated the importance of vitronectin (Vn) binding, PAI-1 stability and protease binding in this therapeutic effect using a panel of PAI-1 mutants differing in half-life, protease binding, and Vn binding. PAI-1R binds Vn normally but does not inhibit proteases. PAI-1AK has a complete defect in Vn binding but retains full inhibitory activity, with a short half-life similar to wild-type (wt)-PAI-1. Mutant 14-lb is identical to wt-PAI-1 but with a longer half-life. PAI-1K has defective Vn binding, inhibits proteases normally, and has a long half-life. In vitro wt-PAI-1 dramatically inhibited degradation of mesangial cell ECM while the AK mutant had much less effect. Mutants 14-1b and PAI-1K, like wt-PAI-1, inhibited matrix degradation but PAI-1R failed to reverse this inhibition although PAI-1R reversed the wt-PAI-1-induced inhibition of ECM degradation in a plasmin-, time-, and dose-dependent manner. Thus the ability of PAI-1 to inhibit ECM degradation is dependent both on its antiproteinase activity and on maintaining an active conformation achieved either by Vn binding or mutation to a stable form. Administration of these PAI-1 mutants to nephritic rats confirmed the in vitro data; only PAI-1R showed therapeutic effects. PAI-1K did not bind to nephritic kidney, indicating that Vn binding is essential to the therapeutic action of PAI-1R. The ability of PAI-1R to remain bound to Vn even in a high-protease environment is very likely the key to its therapeutic efficacy. Furthermore, because both PAI-1R and 14-1b bound to the nephritic kidney in the same pattern and differ only in their ability to bind proteases, lack of protease inhibition is also keyed to PAI-1R's therapeutic action.

scholarly journals Dose dependent changes in propranolol half life when used as an adjunct to neuroleptic treatment

1982 ◽  
Vol 78 (1) ◽  
pp. 96-96
Author(s):  
D. H. Staniforth ◽  
N. J. Yorkston ◽  
S. A. Zaki
Keyword(s):  
Half Life ◽  
Neuroleptic Treatment ◽  
Dose Dependent

Follicle-stimulating hormone stimulates inhibin in the serum of male monkeys (Macaca mulatta)

1990 ◽  
Vol 122 (1) ◽  
pp. 96-100 ◽  
Author(s):  
Ulrich Fingscheidt ◽  
Gerhard F. Weinbauer ◽  
Shafiq A. Khan ◽  
Eberhard Nieschlag
Keyword(s):  
Macaca Mulatta ◽  
Half Life ◽  
Rhesus Monkeys ◽  
Follicle Stimulating Hormone ◽  
Serum Levels ◽  
Lag Time ◽  
Dependent Manner ◽  
Control Serum ◽  
Dose Dependent ◽  
Stimulating Hormone

Abstract. Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.

scholarly journals Ecologicala Spectsin Relation to Digenean Trematodeparasites in Fresh Water Fish Channa Striatus (BLOCH)

2021 ◽  
Vol 7 (09) ◽  
pp. 119-129
Author(s):  
Singh Prashant and Mishra D. B
Keyword(s):  
Research Work ◽  
Life Forms ◽  
Water Sources ◽  
Considerable Change ◽  
Fresh Water Fish ◽  
Human Beings ◽  
Infection Level ◽  
Fish Food ◽  
Food Borne ◽  
Different Water Sources

Fishes are found adequately in the different water sources of Jaunpur India. Five rivers (Gomti, Sai,Varuna,Pili and Basuhi) ,Gujar tal and different pond are available here as a aquatic habitat. In research work author consider only two sites of river Gomti and two different ponds in district Jaunpur, U.P. They are external as well as internal .In this studyauthor focused on digenetic trematodes parasites. Digenean trematodes are completing their life cycle in two hosts so both are susceptible to the infection. There are considerable change occur in the environment wih the passage of time. We also know that environmental factors affect the life forms of any place. So it is important to study the different ecological terms in relation to the host and their infectious agents. From ancient time humans beings use large amount of fish food for survival because they are easily available from different water sources. When human beings eat unadequate cooked fish then suffered with food borne tremadiases.So it is important to know the infection level in the fishes.

Diversity of macrophytes in the Amazon deforestation arc: information on their distribution, life-forms and habits

Rodriguésia ◽  
2021 ◽  
Vol 72 ◽  
Author(s):  
Ana Luísa Biondi Fares ◽  
Raimundo Luiz Morais de Sousa ◽  
Ely Simone Cajueiro Gurgel ◽  
André dos Santos Bragança Gil ◽  
Carlos Alberto Santos da Silva ◽  
...  
Keyword(s):  
Aquatic Ecosystems ◽  
Aquatic Macrophytes ◽  
Anthropogenic Activities ◽  
Life Forms ◽  
Biological Processes ◽  
Macrophyte Species ◽  
Form Part ◽  
Arc Of Deforestation ◽  
Northern Brazil ◽  
Suitable Habitats

Abstract The Amazon possesses the largest fluvial system on the planet, harboring a diverse biota. Still, many species remain undescribed, because of the Amazon’s immense scale and complexity, and because many habitats are now increasingly under pressure from anthropogenic activities. Macrophytes are important to physical and biological processes in aquatic ecosystems but remain poorly studied in Northern Brazil. The objective of this study was to provide a checklist of macrophyte species that occur in municipalities that form part of the Arc of Deforestation, Pará state, Brazil, bringing information on their habits and life-forms. We sampled 36 sites at three types of aquatic ecosystems (streams, ponds and lakes). In total, we recorded 50 species, 38 genera and 24 families. Most species were amphibious or emergent. Degraded streams have environmental characteristics similar to lentic habitats, which could provide more suitable habitats for macrophytes that otherwise would not occur in lotic habitats, thus explaining the higher diversity in these ecosystems. Macrophyte diversity in this region follows similar patterns to other Brazilian regions. This study contributes to the assessment of aquatic macrophytes in the Amazon, especially in more degraded regions, such as the Amazon deforestation arc.

Pharmacokinetics and Tolerability of a New Low Molecular Mass Heparin (RO-11) in Healthy Volunteers – A Dose-Finding Study within the Therapeutical Range

1997 ◽  
Vol 77 (01) ◽  
pp. 133-136 ◽  
Author(s):  
Liliana Falkon ◽  
Miriam M Bayés ◽  
Guillem Frontera ◽  
Mercè Garí ◽  
Manel Barbanoj ◽  
...  
Keyword(s):  
Phase I ◽  
Molecular Mass ◽  
Half Life ◽  
Dose Finding ◽  
Dose Effect ◽  
Efficacy And Safety ◽  
First Order ◽  
Finding Study ◽  
Dose Finding Study ◽  
Dose Dependent

SummaryThis paper reports on the results of a Phase I, dose-finding study with a new low molecular mass heparin (LMMH) called RO-11. The study focused on pharmacokinetics, dose-effect relationship and on tolerability of three single subcutaneous (SC) doses within the therapeutical range. After the injection of 7,500, 9,000 and 12,500 anti-FXa IU, the anti-FXa effect peaked between 3-6 h and showed a dose-dependent response. The absorption and elimination were first-order processes and the long half-life (>5 h) kept constant after increasing doses. The compound was tolerated very well and no clinically relevant prolongation of APTT, prothrombin and thrombin clotting tests was observed. At the dose of 7,500 IU, which corresponded to 110 anti-FXa IU/Kg, RO-11 exerted anti-FXa effect for at least 18-20 h. We recommend using this dose in a single SC injection, to evaluate the efficacy and safety of RO-11 in the initial treatment of DVT or PE.

scholarly journals In Vivo Pharmacodynamic Activity of the Glycopeptide Dalbavancin

2007 ◽  
Vol 51 (5) ◽  
pp. 1633-1642 ◽  
Author(s):  
David Andes ◽  
William A. Craig
Keyword(s):  
Half Life ◽  
Dose Range ◽  
Lung Infection ◽  
Free Drug ◽  
Infection Model ◽  
Gram Positive ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Dose Dependent

ABSTRACT Dalbavancin is a lipoglycopeptide antibiotic with broad-spectrum activity against gram-positive cocci and a markedly prolonged serum elimination half-life. We used the neutropenic murine thigh and lung infection models to characterize the pharmacodynamics of dalbavancin. Single-dose pharmacokinetic studies demonstrated linear kinetics and a prolonged elimination half-life which ranged from 7.6 to 13.1 h over the dose range of 2.5 to 80 mg/kg of body weight. The level of protein binding in mouse serum was 98.4%. The time course of in vivo activity of dalbavancin over the same dose range was examined in neutropenic ICR Swiss mice infected with a strain of either Streptococcus pneumoniae or Staphylococcus aureus by using the thigh infection model. The burden of organisms for S. pneumoniae was markedly reduced over the initial 24 h of study, and organism regrowth was suppressed in a dose-dependent fashion for up to the entire 96 h of study following dalbavancin doses of 2.5 mg/kg or greater. Dalbavancin doses of 20 mg/kg or greater resulted in less killing of S. aureus but were still followed by a prolonged suppression of regrowth. Multiple-dosing-regimen studies with the same organisms were used to determined which of the pharmacodynamic indices (maximum concentration in serum [C max]/MIC, area under the concentration-versus-time curve [AUC]/MIC, or the duration of time that levels in serum exceed the MIC) best correlated with treatment efficacy. These studies used a dose range of 3.8 to 480 mg/kg/6 days fractionated into 2, 4, 6, or 12 doses over the 144-h dosing period. Nonlinear regression analysis was used to examine the data fit with each pharmacodynamic index. Dalbavancin administration by the use of large, widely spaced doses was the most efficacious for both organisms. Both the 24-h AUC/MIC and the C max/MIC parameters correlated well with the in vivo efficacy of treatment against S. pneumoniae and S. aureus (for 24-h AUC/MIC, R 2 = 78 and 77%, respectively; for C max/MIC, R 2 = 90 and 57%, respectively). The free-drug 24-h AUC/MICs required for a bacteriostatic effect were 17 ± 7 for five S. pneumoniae isolates. A similar treatment endpoint for the treatment against five strains of S. aureus required a larger dalbavancin exposure, with a mean free-drug 24-h AUC/MIC of 265 ± 143. Beta-lactam resistance did not affect the pharmacodynamic target. The dose-response curves were relatively steep for both species; thus, the pharmacodynamic target needed to achieve organism reductions of 1 or 2 log10 in the mice were not appreciably larger (1.3- to 1.6-fold). Treatment was similarly efficacious in neutropenic mice and in the lung infection model. The dose-dependent efficacy and prolonged elimination half-life of dalbavancin support the widely spaced regimens used in clinical trials. The free-drug 24-h AUC/MIC targets identified in these studies should be helpful for discerning rational susceptibility breakpoints. The current MIC90 for the target gram-positive organisms would fall within this value.

scholarly journals Compartmental Pharmacokinetics and Tissue Drug Distribution of the Pradimicin Derivative BMS 181184 in Rabbits

1998 ◽  
Vol 42 (10) ◽  
pp. 2700-2705 ◽  
Author(s):  
Andreas H. Groll ◽  
Tin Sein ◽  
Vidas Petraitis ◽  
Ruta Petraitiene ◽  
Diana Callender ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Peak Plasma ◽  
Volume Of Distribution ◽  
Multiple Dosing ◽  
Time Curve ◽  
Dose Administration ◽  
Single Dose Administration ◽  
Elimination Half ◽  
Dose Dependent

ABSTRACT The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, BMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage. After single-dose administration, the mean peak plasma BMS 181184 concentration (C max) ranged from 120 μg/ml at 10 mg/kg to 648 μg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC0–24) ranged from 726 to 2,130 μg · h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 toP < 0.001). No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC0–24 below the values obtained at 50 mg/kg (P < 0.01) and after single-dose administration of the same dosage (P < 0.05). Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of BMS 181184 from plasma and renal accumulation of the compound after multiple dosing.

scholarly journals The biliary excretion of enterokinase in rats. Studies in normal, chronic ethanol-maintained and cirrhotic rats

1981 ◽  
Vol 198 (2) ◽  
pp. 315-319 ◽  
Author(s):  
D A W Grant ◽  
P A Jones ◽  
J Hermon-Taylor
Keyword(s):  
Carbon Tetrachloride ◽  
Intravenous Administration ◽  
Half Life ◽  
Pancreatic Disease ◽  
Chronic Ethanol ◽  
Hepatic Bile ◽  
Catalytically Active ◽  
Dose Number ◽  
The Mean ◽  
Dose Dependent

The excretion of catalytically active human or pig enterokinase in hepatic bile after intravenous administration to normal rats or rats that had been maintained on 20% (v/v) ethanol for 1 year showed similar kinetics to that described for other serum-derived bile proteins. The half-life in serum was 2.5 min or less, and most of the enzyme was excreted within 45 min of administration. This was maintained when up to six successive doses were given at 90 min intervals. The mean amount excreted per dose was independent of the dose number and varied from 0.8% to 2.1% in the normal animals and 1.2% to 2.0% in the chronic ethanol-maintained animals. When three doses of enzyme were given at 30 min intervals, the total amount of active enterokinase recovered in bile was dose-dependent and was consistently higher in the rats drinking 20% (v/v) ethanol. The serum half-life of enterokinase in rats made cirrhotic by inhalation of carbon tetrachloride vapour was extended to 6 min or more. The amount of active enzyme recovered in bile was at least 50% less than in weight-matched normal rats, and excretion was not complete 2h after intravenous administration. The possible significance of these findings in liver and pancreatic disease is discussed.

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