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Substantial Concentrations (substantial + concentration)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Stereoselective halofantrine and desbutylhalofantrine disposition in the rat: cardiac and plasma concentrations and plasma protein binding

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2002
Dion R. Brocks
Abstract Halofantrine (HF) is a chiral antimalarial drug known to cause cardiac arrhythmias in susceptible patients. In this study, the cardiac uptake and plasma protein binding of HF and desbutylhalofantrine (DHF) enantiomers were examined in the rat. Rats were given 2 mg/kg of either HF HCl or DHF HCl intravenously, then sacrificed at various times after dosing. Specimens were assayed using stereospecific methods. Uptake of HF and DHF enantiomers into heart was rapid. Substantial concentrations of both HF and DHF enantiomers were observed in rat heart, with stereoselectivity being noted for both in plasma and heart. Stereoselectivity was more pronounced for HF (AUC (+):(,) ratio= 1.58) than DHF (AUC (+):(,) ratio =1.16) in heart tissue. Heart:plasma AUC ratios of 6.8,8.0, and 9.3,21, were observed for HF and DHF enantiomers, respectively, indicating that DHF has greater cardiac uptake than HF itself. Plasma protein binding was extensive for both HF and DHF (>99.95%), and was stereoselective for DHF, with a 38% higher unbound fraction for (,)-DHF than antipode. In contrast, binding of HF enantiomers was nonstereoselective. The lower degree of stereoselectivity for DHF in heart tissues was attributable to its greater stereoselectivity in plasma protein binding. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Investigation of the Absorption of Hypericin into the Skin of Hairless Mice

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2000
APPOLINARY R. KAMUHABWA
The skin absorption of hypericin was evaluated in hairless mice to develop an optimised hypericin topical formulation that could be used in the clinical study of psoriasis. Hypericin (0.01,1.0%) in Beeler basis, polyethylene glycol ointment, carbopol gel, cetomacrogol cream, petrolatum or emulsifying ointment, with and without skin-absorption enhancers (isopropylidene glycerol and diethylene glycol monoethyl ether), was tested in-vivo on hairless mice skin. Using a skin-stripping technique and the intrinsic fluorescence of hypericin under standardised UV365 irradiation, it was demonstrated that the absorption of hypericin very much depended on the vehicle used. The concentrations of hypericin in the skin were then estimated by HPLC analysis. For this purpose, two vehicles were employed, with which hypericin penetrated the skin of hairless mice well (emulsifying ointment with isopropylidene glycerol) or very poorly (polyethylene glycol ointment). In the case of emulsifying ointment with isopropylidene glycerol (0.05% hypericin), a substantial concentration of hypericin (8.6±3.2 ,g g,1) (mean ± s.d., n = 5) was found in the skin. With polyethylene glycol ointment, however, only a limited hypericin skin concentration (0.38 ± 0.34 ,g g,1, n = 5) was achieved. These results show that emulsifying ointment with polyethylene glycol holds promise as an effective topical vehicle for the treatment of skin diseases, such as psoriasis, with hypericin. [source]

Sponge halogenated natural products found at parts-per-million levels in marine mammals

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2002
Walter Vetter
Abstract Several unknown, abundant brominated compounds (BCs) were recently detected in the blubber of dolphins and other marine mammals from Queensland (northeast Australia). The BCs were interpreted as potential natural products due to the lack of anthropogenic sources for these compounds. This study investigated whether some of the BCs accumulated by diverse marine mammal species are identical with natural BCs previously isolated from sponges (Dysidea sp.) living in the same habitat. Isolates from sponges and mollusks (Asteronotus cespitosus) were compared with the signals detected in the mammals' tissue. Mass spectra and gas chromatography retention times on four different capillary columns of the isolates from sponges and mammals were identical in all respects. This proves that the chemical name of the compound previously labeled BC-2 is 4,6-dibromo-2-(2,,4,-dibromo)phenoxyanisole and that the chemical name of BC-11 is 3,5-dibromo-2-(3,,5,-dibromo,2,-methoxy)phenoxyanisole. Using a quantitative reference solution of BC-2, we established that the concentrations of the brominated metabolites found in the marine mammals are frequently >1 mg/kg. The highest concentration (3.8 mg/kg), found in a sample of pygmy sperm whale (Kogia breviceps), indicates that BC-2 is a bioaccumulative, natural organohalogen compound. This is supported by the concentrations of the BCs in our samples being equal to the highest concentrations of anthropogenic BCs in any environmental sample. The quantitative determination of BC-2 in blubber of marine mammals from Africa and the Antarctic suggests that BC-2 is widespread. These results are direct proof that marine biota can produce persistent organic chemicals that accumulate to substantial concentrations in higher trophic organisms. [source]

Employee share ownership and investment concentration: which employee shareholders fail to diversify?

HUMAN RESOURCE MANAGEMENT JOURNAL, Issue 2 2010
Andrew Pendleton
Using data from a survey of employees in three UK companies, the article examines concentration of savings in employer shares. It is found that a substantial minority of employees hold most of their savings in employer shares despite the risks. The article examines the distribution and determinants of portfolio concentration. It is found that portfolio concentration is more likely to be found among men, those on higher incomes, and those who are in early middle-age. Regression analysis indicates that organisational commitment and the duration of participation in the share ownership plan also affects the probability of having a concentrated portfolio. There is no clear evidence that those with substantial concentrations of employer shares take active steps to monitor their investments more closely than those with smaller shareholdings. [source]