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Effect of cyclosporine on host defence.

To discover whether cyclosporine administered daily in therapeutic equivalent doses for 3 consecutive weeks suppressed host defence, the authors measured the delayed-type hypersensitivity (DTH) skin response to keyhole-limpet hemocyanin (KLH) in rats. Twenty, male, Sprague-Dawley rats were sensitized to KLH and reactivity was confirmed 14 days later. Following sensitization, cyclosporine (20 mg/kg orally) was administered daily for 21 days to 10 rats. The other 10 (control group) received equivalent volumes of diluent (polysorbate 80 and ethanol). There was no difference in the DTH response between the cyclosporine and control groups for 5 weeks following treatment. Larger doses of cyclosporine (100 mg/kg) given intraperitoneally 30 minutes before and 6 hours after skin testing, suppressed the DTH response (7.2 mm to 2.4 mm) but resulted in a high mortality (eight of nine rats) at 48 hours. Delayed-type hypersensitivity was also suppressed in the control group but to a lesser extent and with no deaths (6.4 to 3.9 mm, p less than 0.05). Cyclosporine, in therapeutic equivalent doses, does not suppress the nonspecific immune component of host defence as reflected by the DTH skin response in previously sensitized animals. This may partially explain the lower frequency of septic morbidity and mortality in cyclosporine-treated transplant patients, compared with those receiving conventional therapy.

Animals↗

Experimental infection of lactating goats with Leptospira interrogans serovars pomona and hardjo.

Pathogenesis of Leptospira interrogans serovars pomona and hardjo was evaluated in 14 lactating goats. Although mild clinical signs of leptospiral infection characterized by pyrexia and reduction in milk yield appeared in some animals, a consistent clinical pattern was not observed in the inoculated animals. The pomona serovar was isolated from the kidney of 1 of the 4 goats inoculated with serovar pomona. The hardjo serovar (strain UI 750) was isolated in the rabbit serum-supplemented bovine albumin polysorbate-80 liquid medium only from the mammary gland of 1 of 4 goats at 13 days after inoculation with serovar hardjo. The positive culture was detected after an 8-month incubation period.

Animals↗

Growth of hebdomadis group of leptospires in solid medium.

Leptospira hardjo, szwajizak, and sejroe produced colonial growth in bovine albumin polysorbate 80 (BAP80) solid medium which had been supplemented either with sodium pyruvate (100 micrograms/ml) or with 5% rabbit serum. Leptospira hardjo produced two morphologic types of colonies in both supplemented media. Growth did not occur with any of the three serovars in the unsupplemented BAP80 medium. These results indicate that addition of either rabbit serum or sodium pyruvate would aid in promoting growth of some fastidious leptospires.

Culture Media↗

Effect of formulation on dissolution and bioavailability of phenytoin tablets.

Bioavailability of different phenytoin tablets was calculated from saliva phenytoin levels in healthy human volunteers in a single dose study. Tablets containing different excipients and either phenytoin free acid or sodium phenytoin were chose on the basis of an in vitro dissolution rate study of different tablets. Tablets containing phenytoin precipitated with polysorbate 80 showed faster in vitro dissolution and also higher bioavailability than tablets prepared with phenytoin free acid with different excipients. In vivo studies showed that proper formulation of a tablet containing the free acid form of phenytoin can give rise to the same bioavailability than that of sodium phenytoin. In vitro dissolution of the formulation reflected in vivo bioavailability.

Adult↗

[The comparative efficacy of treating patients with chronic bronchitis and late pregnancy toxicosis by using different enterosorbents].

Enterosorbents Polysorb MP and Polyfepan were tried in patients with chronic bronchitis in the stage of aggravation and with late gestosis. The trends in clinical and laboratory indices, in external respiration, cellular and humoral immunity, in the content of middle-weight molecules in relevant patients undergoing enterosorption with the above sorbents against the controls were more favourable. This supports validity of enterosorption in patients with chronic bronchitis and late gestosis.

Bronchitis↗

[Development of a selective differential medium for the isolation of Corynebacterium urealyticum (group D-2)].

BACKGROUND: We have developed a new selective culture medium for the isolation of C. urealyticum, with the aim of improving and making easier the isolation and identification of this microorganism. MATERIAL AND METHODS: The medium is based on components similar to other media, usually used for diagnosis of urinary tract infections, also containing glucose, urea, phenol red, polysorbate 80 (Tween 80), polymixin B, amphotericin B, nalidixic acid and lyncomycin. The medium was tested in 65 clinical isolates and three type strains, and in 533 clinical samples of urine. RESULTS: All 65 clinical strains and 3 reference strains of C. urealyticum tested grew faster on this medium than on blood agar. E. coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., M. morganii, Proteus spp., S. aureus, Enterococcus spp. and Corynebacterium spp. did not grow in the selective agar. S. epidermidis and Streptococcus spp. grew in less than 10% of cases, P. aeruginosa in 29.2% and Serratia spp. in 41.7%. The colonies were always easily differentiated from C. urealyticum. In the studies performed on 553 clinical samples from patients with urinary tract infections, six infections by C. urealyticum were detected. The growth of all strains being faster on this medium than on blood-agar. CONCLUSIONS: This new selective medium may be a valuable tool for diagnosis of UTIs caused by C. urealyticum in patients with retard risk factors.

Bacteria↗

Hydrocarbons and chlorinated hydrocarbons in the air in the greater Split area.

The content of hydrocarbons and chlorinated hydrocarbons was examined in samples of air from the greater Split area. Organic pollutants were accumulated from the air by adsorption on Polysorb-10 and desorption with hot water vapour. Gaseous and liquid phases were analysed by gas chromatography. Hydrocarbon concentrations were within permissible limits and their effects on human health were negligible. There were marked differences between pollutant concentrations in air samples taken from the industrial zone, crossroads in the city centre and "clean" zones.

Air Pollutants↗

[The evaluation of the mutagenic activity of gaseous particles in the atmospheric air by using a microbiological test].

Total mutagen activity of a gas component in chemical pollutions of the atmospheric air in a number of industrially developed towns of Ukraine has been studied and assessed in a microbiological test on Salmonella typhimurium. The towns were chosen proceeding from the specificity of industry: metallurgical industry (Mariupol, Zaporozhye, Donetsk, Krivoi Rog, Makeevka); chemical industry (Cherkassy, Chernigov; Kremenchug, Severodonetsk, Lisichansk, Gorlovka, Rovno, Sumy) and conditionally control ones (Simferopol, Sevastopol, Nikolaev, Poltava, Zhitomir). The air samples, 100 m3, have been taken in each town weekly during a month by special absorbers of Polysorb-2 type. The extraction of chemical matters from absorbers was carried out by traditional methods. Chemical matters were dissolved in dimethyl sulphoxide and tested for its ability to induce the gene mutations. The studies have shown that the atmospheric air samples from the group of "metallurgical" towns prove the mutagen activity, classified as the "middle" one (the number of revertant colonies in the experiment exceeded the control 10.3 to 22.2 times). The mutagenicity of "chemical" towns was on the level of "middle" and "weak", that of conditionally control ones was on the level of "weak" only.

Air Pollutants↗

The effect of indoxole on the corneal immunologic response.

To study the effect of locally administered indoxole (with polysorbate 80) on the inflammatory and immunologic responses, we made unilateral intracorneal injections of rabbit eyes with bovine gamma globulin (BGG). The indoxole was injected subconjunctivally one day before, and 1, 2, 3, and 5 days after the BGG injection. The homolateral lymph nodes, uveal tracts, and corneas of rabbits killed on postinjection days 6 and 12 were tested for antibody-forming cells (AFC) by a modification of the Jerne plaque technique. On day 6 the indoxole-treated eyes were more inflamed and had a greater number of AFC in the tested tissues than the control eyes, but in neither of these respects was there any essential difference between the treated and control eyes on day 12. The possible mechanisms by which indoxole achieved its effect were explored.

Animals↗

Identification of antioxidants for prevention of peroxide-mediated oxidation of recombinant human ciliary neurotrophic factor and recombinant human nerve growth factor.

Peroxides present in non-ionic surfactants used to stabilize certain recombinant protein formulations (e.g. polysorbate 80) can result in the oxidative degradation of proteins. In this study, the ability of various pharmaceutically acceptable antioxidants to prevent the oxidative degradation of two therapeutic proteins, recombinant human Ciliary Neurotrophic Factor (rhCNTF) and recombinant human Nerve Growth Factor (rhNGF), caused by alkyl hydroperoxides and hydrogen peroxide was studied. For rhCNTF, the rank order of effectiveness of the antioxidants tested was: thiols (cysteine, glutathione, thioglycerol) >> thioethers (methionine). Other parenterally acceptable antioxidants (ascorbic acid, propyl gallate and sodium bisulfite) destabilized the protein. The thiol antioxidants (cysteine and glutathione) were also the most effective antioxidants for rhNGF; however, in contrast to rhCNTF, ascorbic acid did not destabilize rhNGF. The rank order of effective antioxidants for rhNGF was: thiols (cysteine, glutathione) > > thioethers (methionine) > ascorbic acid.

Antioxidants↗

Isolation and identification of Staphylococcus hyicus.

A selective medium for the isolation of Staphylococcus hyicus, with potassium thiocyanate as selective substance and the polysorbate 80 reaction as elective marker, was developed. The organism could be identified during the routine examination of samples derived from pigs, using 2 relatively simple tests: the slide coagulase (clumping factor) and the deoxyribonuclease plate reaction. The S hyicus was isolated from 54% of 684 samples collected from nares, external ears, and skin covering the nose of pigs not affected by exudative epidermatitis. Isolates from these animals did not appear to differ in pathogenic potentials from those obtained from lesions.

Animals↗

Nanoparticles and microparticles for drug and vaccine delivery.

Nanoparticles are polymeric particles in the nanometer size range whereas microparticles are particles in the micrometre size range. Both types of particle are used as drug carriers into which drugs or antigens may be incorporated in the form of solid solutions or solid dispersions or onto which these materials may be absorbed or chemically bound. These particles have been shown to enhance the delivery of certain drugs across a number of natural and artificial membranes. In addition, the particles were shown to accumulate in areas of the intestine that appear to be the Peyer's patches. Possibly because of the combination of both effects these particles were able to significantly improve the bioavailability of some drugs after peroral administration in comparison with solutions. Recently nanoparticles coated with polysorbate 80 enabled the passage of small peptides and other drugs across the blood-brain barrier and the exhibition of a pharmacological effect after intravenous injection. Without the use of this type of nanoparticles the drugs did not cross this barrier and yielded no effect.

Administration, Oral↗

Etoposide phosphate: what, why, where, and how?

The podophyllotoxin derivatives etoposide and teniposide are active in the treatment of a variety of malignant conditions. Both represent chemical modifications of podophyllin, an extract of Podophyllum peltatum (May apple, mandrake, Indian apple, wild lemon, or duck's foot), a plant long used as a folk remedy and recognized in the 19th century to be effective in the treatment of cancer. While etoposide is active in the treatment of many cancers and is widely used, it has a number of limitations due to its lack of water solubility. Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is rapidly and completely converted to the parent compound after intravenous dosing. The pharmacokinetic profile of etoposide after treatment with either etoposide or etoposide phosphate is identical. Toxicity and clinical activity also are the same. Because etoposide phosphate is water soluble and can be made up to a concentration of 20 mg/mL, however, it can be given as a 5-minute bolus, in high doses in small volumes, and as a continuous infusion. Furthermore, it is not formulated with polyethylene glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and does not cause acidosis when given at high doses. The easier-to-use etoposide phosphate represents an improved formulation of etoposide.

Antineoplastic Agents↗

A phase I study of etoposide phosphate plus paclitaxel.

Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble derivative of etoposide, a semisynthetic podophyllotoxin that is important in the treatment of a variety of malignancies, including lung cancer, germ cell tumors, non-Hodgkin's lymphoma, Hodgkin's lymphoma, acute leukemia, etc. Because etoposide is poorly water soluble, it must be dissolved in a polysorbate 80-based solvent mixture, which is moderately allergenic and requires a large volume of saline for administration. Etoposide phosphate is water soluble and is rapidly converted in vivo to etoposide by endogenous phosphatases. Because it is water soluble, etoposide phosphate can be administered in volumes much smaller than those required with etoposide therapy, permitting rapid intravenous administration in the outpatient setting. We recently reported the results of a phase I study using etoposide phosphate on a bolus, daily x 5 schedule. Like others, we demonstrated that etoposide phosphate has pharmacokinetic properties virtually identical to those of etoposide. Our dose-finding study indicated that etoposide phosphate can be used in doses up to 100 mg/m2/d x 5 every 3 weeks in patients who have not had extensive prior chemotherapy, and that a dose of 75 mg/m2 would be appropriate for patients who had undergone multiple prior therapies or who had prior radiotherapy. The dose-limiting toxicity was neutropenia. Paclitaxel, a microtubule-stabilizing agent, is active against a variety of solid and hematopoietic malignancies that overlap with those against which etoposide is active. Because the mechanisms of action of these two agents differ, it is logical to suppose that the combination of the two agents might produce some additive effect when used to treat cancers that respond to both individual agents. We therefore undertook a phase I study using paclitaxel as a 3-hour infusion in combination with a 5-minute infusion of etoposide phosphate daily x 3 every 21 days. We used the 3-hour paclitaxel schedule because it has been shown to be less myelotoxic than longer infusions at the same doses. Our goal in this ongoing study is to determine the maximum tolerated doses of the two drugs in combination, to determine the toxicities of the regimen, and to assess its anticancer activity.

Adult↗

[The enterosorption treatment of patients with acute intestinal infections and chronic colitis with diarrhea].

A total of 234 patients with acute intestinal infections (AII) and chronic colitis presenting with diarrhoea were examined. In an acute phase of AII induced by conditionally pathogenic flora, salmonellae and shigellae, as well as in exacerbation of chronic colitis, blood aggregability appears to be on the increase, with the ability of erythrocytes to deformation getting worse. In rectal mucosa hemodynamic disorders are common, manifested by decrease in pulse blood filling, rate of bloodflow predominantly in small and medium-size arteries as well as blood supply as a whole. Applying polysorb to rectal mucosa of such patients with the aid of an atomizer in speedier manner than it is usually done in conventional modes of treatment makes for regression of clinical symptoms of the illness, decreases the level of endotoxicosis, speeds up normalization of blood aggregability, red cell deformability, promoting quick restoration of rectal mucose bloodflow, the anal canal sphincter strength, with its rigidity returning to normal.

Acute Disease↗

Anaphylactic shock induced by intraarticular injection of methylprednisolone acetate.

There are numerous reports of hypersensitivity reactions to corticosteroids. However, cases of anaphylactic shock after intraarticular injection of corticosteroids are exceedingly rare. We describe a case of anaphylaxis in a 31-year-old woman after intraarticular injection of synthetic methylprednisolone acetate. Immediately after injection she developed sneezing, angioedema, tachycardia, and marked hypotension. She responded promptly to treatment with subcutaneous epinephrine. She had received uneventfully one intraarticular injection of the same compound 4 years earlier. Intradermal skin testing showed strong reactivity to methylprednisolone acetate suspension, moderate reactivity to hydrocortisone, and weak reactivity to betamethasone. Tests with dexamethasone, triamcinolone, lidocaine, latex and nonsteroid constituents of the injected suspension including polyethylene glycol, polysorbate 80, mono and dibasic sodium phosphate, and myristyl-gamma-picolinium chloride were negative. This patient had developed anaphylaxis due to methylprednisolone acetate alone. Although such events are very rare, it is advisable to keep injectable epinephrine in the offices of rheumatologists.

Adrenal Cortex Hormones↗

[Acute hepatitis following amiodarone administration].

A 61 year old man, treated with amiodarone since 1993 for resistant supraventricular arrhythmias, developed acute hepatitis after an intravenous amiodarone administration. Kidney and liver function tests were performed and pointed out abnormal results. Symptoms ascribable to hepatotoxicity were absent. These changes returned to normal levels within 20 days from withdrawal of the drug. Amiodarone hepatotoxicity can be related to prolonged therapy with a high dose. Intravenous amiodarone may cause acute hepatic disease, but it is suggested that polysorbate 80, a solvent added to the intravenous infusion, is a more likely cause of this complication.

Acute Disease↗

Breaking strength and diameter of absorbable sutures after in vivo exposure in the rat.

Although absorbable sutures are commonly used in clinical practice, the rate of decay of strength in various tissues has not been studied. The purpose of this study was to assess breaking strength (BS) and diameter of monofilament (chromic gut, polydiaxanone, Maxon, Monocryl) and multifilament (Vicryl, Dexon, Polysorb) absorbable sutures implanted in various sites and measured at specific time intervals. A 15 cm length of 4-0 suture from a single lot of each material was implanted in the pleural space, rectus abdominus muscle, subcutaneous tissue, intravascular space, peritoneal cavity, and stomach lumen in the rat. A precipitous decrease in BS was noted in all multifilament sutures after 7 days, and in chromic gut and Monocryl sutures after 1 day. Polydiaxanone and Maxon sutures maintained the highest BS over the 28-day period, 71 per cent and 59 per cent of their initial BS, respectively. Suture diameter remained essentially unchanged except for chromic gut and the multifilament sutures which exhibited increased diameter. This increase was attributed to inflammatory tissue infiltration.

Animals↗