Poor bioavailability of CGS 8216 in a water/tween vehicle following intraperitoneal injection.
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Carnitine palmitoyltransferase (CPT) was studied in muscle homogenates of four patients with recurrent attacks of rhabdomyolysis due to muscular CPT deficiency and in those of the clinically asymptomatic father and mother of two patients. In controls CPT II was readily solubilized by the addition of Triton X-100 and 1% Tween 20. In contrast, CPT I was inactivated by Triton X-100 but remained catalytically active and membrane bound in the presence of 1% Tween 20. Total CPT activity was normal in patients and in both parents when measured under optimal assay conditions. After addition of 1% Tween 20 the insoluble CPT activity was also normal in patients and in both parents. The soluble CPT activity, however, was almost completely lost in patients but was only partially decreased in both parents. The data indicate that in patients an enzymatically active CPT II exists which is abnormally sensitive to inhibition by Tween 20, and that CPT I activity is not compensatorily increased in patients. A partial CPT II deficiency can be identified in heterozygotes most sensitively by the separate determination of soluble and insoluble CPT activities in the presence of 1% Tween 20.
Fatty acid (FA) binding by fatty acid-binding protein (FABP) is frequently monitored with the so-called Lipidex 1000 assay, in which protein associated and non-protein bound FA are separated by selectively binding the latter to Lipidex 1000. Careful evaluation of this assay showed that the use of aqueous FA solutions resulted in a marked decrease (60 to 70%) of FA concentration due to their aspecific binding to the surface of the test-tube used. In addition, solutions of rat heart FABP in the micromolar range also showed a concentration decrease up to 80% due to protein binding to the surface of the test-tube. Introduction of detergents, Triton X-100 or Tween 20, limited the FA loss to less than 20% and totally eliminated FABP adsorption. Kinetic parameters for the binding of [1-14C]oleic acid by purified rat heart FABP, assayed in the presence of Triton X-100, were found to be similar to those assayed in the absence of detergent, when adequate corrections were made for losses of FA and FABP due to surface adsorption. Use of Tween 20 resulted in a substantial increase of the dissociation constant. The addition of 100 microM Triton X-100 to the assay medium considerably facilitates the determination of kinetic parameters of fatty acid-binding by proteins.
Tween 80 was shown to enhance significantly the cytotoxic activities of the four drugs (adriamycin, epodyl, mitomycin-c, thiotepa) most frequently administered intravesically to treat superficial bladder cancer. The colony forming ability of a human bladder cancer cell line, RT112, was measured following a 1 h exposure to each of the four drugs both alone and in combination with 0.1% and 0.3% Tween 80. Cell survival was not reduced by 0.1% Tween 80 alone. We conclude that the combination of Tween 80 with these drugs might increase the therapeutic index of intravesical chemotherapy.
The absorption of Adriamycin (ADM) into the systemic circulation after intravesical administration, using an experimental model in the rat, was closely related to the volume of the instilled solution and the concentration of the drug. The post instillation plasma concentration of ADM was increased after addition of Tween 80 to the instilled solution but the magnitude of the absorption was still discreet and, from a clinical point of view, negligible.
The absorption of chemotherapeutics after local application in the urinary bladder is important for optimum therapy. We therefore investigated the absorption of Cisplatinum (Pt) through the bladder wall in 100 female Sprague-Dawley-rats after instillation under different clinical and pharmacological conditions. Only low platinum (Pt)-concentrations of about 1 microgram/ml could be detected in the serum using unmodified Cisplatinum solutions for instillation in the rat bladder indicating a rather low absorption rate for Cisplatinum. The extent of the absorption of Cisplatinum through the instilled bladder increased with the instilled volume. The absorption rate also increased after electrocoagulation and during cystitis with a maximum concentration of about 2.64 micrograms/ml. Correspondingly the vesicoplasmatic gradient factor clearly decreased. On addition of the detergent Tween 80, the serum Pt-concentration increased rapidly during the initial 30 min. Under these conditions Cisplatinum penetrated the bladder wall, about three times more effectively than in the absence of Tween while entering the systemic circulation only at about twice the normal rate without Tween 80. On addition of the polar organic solvent dimethylsulfoxide (DMSO) serum Pt-concentration increased continuously during the following 2 to 3 h reaching maximum values of about 13.3 micrograms/ml. The greatest accumulation of Pt in the bladder tissue (about 1,600 micrograms Pt/g tissue) was also observed under these conditions. A comparison of the Pt-concentration in serum with that in the bladder wall showed the most favourable relation of high tissue penetration and low serum concentration using Tween 80.
The absorption of Adriamycin (ADM) into the systemic circulation and into different organs including the urinary bladder was investigated in the rat after intravesical instillation of ADM with or without a surface active detergent, Tween 80. The postinstillation plasma concentration of ADM increased significantly with increasing dose of the drug. Even though the leakage of ADM into the systemic circulation and into extravesical organs in general was slight a significant increase was observed after addition of Tween 80. The uptake of ADM into the urinary bladder wall was also significantly enhanced by Tween 80 thus the role of this agent in conjunction with intravesical chemotherapy should be further investigated.
The growth kinetics and the macromolecular content of the yeast and ethanol-induced hyphal forms of Aureobasidium pullulans were studied. During the morphological transition from yeasts to hyphae, both the protein and RNA content decreased significantly, the mycelial form containing only 76% of the amount of protein in the yeasts, and 38% of the RNA. The DNA was the only component tested whose level increased during the transition. Among several compounds inhibiting macromolecular synthesis, only hydroxyurea showed a remarkable effect on the morphology of A. pullulans, inducing the mycelial morphology. The macromolecular composition of hydroxyurea-treated cultures changed with time in a way similar to that of the ethanol-Tween 80-ammonia medium, and to that of carbon-starved cultures, without ethanol or glucose.
The microbial contamination of 44 samples of a vitamin A preparation in sucrose syrup was investigated. The contaminants were almost exclusively yeasts and moulds. Microbiological and physicochemical studies showed that sorbic acid was the preservative of choice for this formulation. The results are discussed with respect to the preservation of non-sterile pharmaceuticals.
Lipid-phosphorus and lipid-galactose content and phospholipid and fatty acid composition of Bifidobacterium bifidum subsp. pennsylvanicum were examined under a wide variety of growth conditions. Cells from 29-C cultures contained less lipid-phosphorus than did cells from 37-C cultures, but their lipid-galactose content and phospholipid composition did not differ. At both temperatures, the growth phase influenced the lipid composition similarly. Phosphate, Mg2+ and K+ concentrations in the medium did neither significantly change the cellular lipid-phosphorus content nor the phospholipid composition. Only Mg2+-deficiency markedly reduced growth and lowered the content of cellular lipid-galactose. Omission of Tween 80 from the medium did not affect growth, but lowered the content of lipid-galactose and augmented those of lipid-phosphorus and diphosphatidylglycerol in the cell. Increased osmolarity and substitution of other Tween for Tween 80 caused the same changes in lipid composition, and besides inhibited growth. Omitting Tween 80 and replacing it by other Tweens dramatically reduced the percentage of unsaturated fatty acids. C12- and C14-fatty acids made up about 50% of total fatty acids in cells from Tween 20 cultures and 12-14% in cells from Tween 40 and Tween 60 cultures. The differences in the decline of unsaturated fatty acids and in the degree of replacement of these acids by C12- and C14-fatty acids may be related to the variations in growth in cultures with various Tweens by way of changes in the physical state of the membrane lipids.
The cation content of Bifidobacterium bifidum subsp. pennsylvanicum was markedly influenced by the washing procedure of the cells, by the growth phase and the temperature, and by the composition of the culture medium. Optimal retention of cations was achieved by washing with 0.25 M MgCl2 at 20C. The intracellular Na+ concentration rose during growth in normal medium to a constant value in the stationary phase, the K+ concentration rose in the exponential phase, but fell in the stationary phase. Cells from 29-C cultures contained more Na+ and less K+ in the stationary phase than did cells from 37-C cultures, but the total cation content was the same at 29 and 37C. Intracellular Na+ and K+ concentrations were dependent on the concentrations in the medium and on its osmolarity. The intracellular Na+/K+ ratio varied from 0.04 to 2.3. The concentrations of Na+,K+ and phosphate in the medium hardly affected growth. Mg2+-deficiency of the medium markedly decreased the concentration of Mg2+ within the cell; its concentration in the cell sap was greatly affected, but the amount of sedimentable, bound Mg2+ only slightly. The content of K+ within the cell decreased in Mg2+-deficient medium, but the concentration of Na+ did not. Omission of Tween 80 as well as its substitution by Tween 20 caused a decrease of intracellular K+. Cells from Tween 40 and Tween 60 cultures additionally contained markedly less Na+.
In patients with chromosomal instability and healthy subjects, significant differences were observed in the chromosomal breakage incidence in simultaneous lymphocyte cultures set up with TC medium 199, Eagle's Minimum Essential Medium, or RPMI, or RPMI 1629. The importance of the choice of culture medium for mutagenicity testing and studies of so-called spontaneous breakage is shown. Cultures incubated with TC Medium 199 showed the highest chromosomal breakage incidence.
The genus Malassezia has been revised using morphology, ultrastructure, physiology and molecular biology. As a result the genus has been enlarged to include seven species comprising the three former taxa M. furfur, M. pachydermatis and M. sympodialis, and four new taxa M. globosa, M. obtusa, M. restricta and M. slooffiae. The descriptions of all the species include morphology of the colonies and of the cells, together with ultrastructural details. The physiological properties studied were the presence of catalase, the tolerance of 37 degrees C and the ability to utilize certain concentrations of Tween 20, 40, 60 and 80 as a source of lipid in a simple medium. Information is given for each of the taxa on mole% GC and also the rRNA sequence from the comparison previously described for the genus.
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Two vehicles for the intraperitoneal administration of delta9-tetrahydrocannabinol (delta9-THC) were compared, using aspects of social behaviour in mice and 5 doses of delta9- THC, with vehicle alone and saline control groups. 10% propane-1,2-diol-1% Tween 80-saline (vehicle B) seemed to be more effective than 1% Tween 80-saline (vehicle A) since depressant effects of --1 delta9-THC on behaviour tended to occur at lower doses with this vehicle. Few differences in behaviour could be detected among the three control groups. In general the overall number of behavioural acts decreased with increasing doses of delta9-THC, but with vehicle B low doses selectively decreased the number of 'social' (including aggressive) as distinct from 'individual' acts. Low doses of the drug in vehicle A sometimes stimulated behaviour, whereas with vehicle B such doses mostly produced depression; however, 2.5 mg/kg delta9-THC, in either vehicle, markedly increased the percentage of animals which showed both aggression and flight acts--a rare combination among controls. Our findings are consistent with other evidence that propylene glycol is an effective vehicle for the i.p. administration of delta9-THC.
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Six different cultural media (corn meal agar, rice extract agar, chlamydospore agar, PCB, Tween 80-oxgall-caffeic acid and diluted milk) were compared for chlamydospore production by 224 yeastlike fungi isolates. Candida albicans formed chlamydospores to a variable degree in all of the media, as did C. stellatoidea to a lesser extent. C. tropicalis, C. parasilopsis, C. guilliermondii and C. krusei did no produce chlamydospores in any of the media tested. Statistically, the most productive media were the milk and TOC media. Milk medium is particularly useful because of its simplicity and economy.
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