Ultrasonication-assisted preparation and characterization of emulsions and emulsion gels for topical drug delivery.

The current study describes the use of ultrasonication for the preparation of biphasic emulsions and emulsion gels for topical drug delivery. Sorbitan monostearate (SMS) was used as the surfactant for stabilizing the interface of sesame oil (apolar phase) and water (polar phase). Emulsions were formed at lower concentrations of SMS, whereas emulsion gels were formed at higher concentrations of SMS. The formulations were characterized by fluorescent microscopy, X-ray diffraction, viscosity, stress relaxation, spreadability, and differential scanning calorimetry studies. Fluorescence microscopy suggested formation of oil-in-water type of formulations. There was an increase in the viscosity, bulk resistance, and firmness of the formulations as the proportions of SMS was increased. The emulsion gels were viscoelastic in nature. Thermal studies suggested higher thermodynamic stability at higher proportions of either SMS or water. Metronidazole, a model antimicrobial drug, was incorporated within the formulations. The release of the drug from the formulations was found to be diffusion mediated. The drug-loaded formulations showed sufficient antimicrobial efficiency to be used as carriers for topical antimicrobial drug delivery.

Angiographic, hemodynamic, and histologic evaluation of portal hypertension and periportal fibrosis induced in the dog by retrograde biliary injections of sesame oil.

Periportal fibrosis and portal hypertension were induced by periodic retrograde biliary injections of sesame oil for two to three months in 12 cholecystectomized dogs equipped with Thomas cannulas. Stable portal hypertension between 18 and 24 cm of water occurred in four of 12 dogs (baseline: 10.4 +/- 0.5 cm of water); the remaining eight dogs required continuous biliary oil injections to maintain the portal pressure in that range. Portosystemic venous collaterals were first seen three weeks after the initial biliary oil injection and were extensively developed after two months. Hepatopetal portal blood flow decreased 61 +/- 5% during the first six months, with the greatest decrease of 32 +/- 4% occurring in the first month. Hepatic arterial flow did not change in the first month and then began to rise slowly to peak at nine months at 170 +/- 32% of its baseline value. The greatest increase in hepatic arterial flow was found between the sixth and ninth month when the portal flow no longer changed significantly. Hepatic fibrosis originating from the portal triads and around extravasated oil droplets appeared to progress slowly during the entire observation period. Animals with advanced hepatic fibrosis remained in satisfactory general health with liver enzymes usually remaining in the high normal to low pathologic range, allowing extensive follow-up examinations at regular intervals.

The toxicity of brominated sesame oil and brominated soybean oil in miniature swine.

Miniature swine were fed brominated sesame oil at dietary levels of 0, 5, 25, 50 or 500 mg/kg of body weight for 17 weeks and brominated soybean oil at levels of 0, 5, 50 or 500 mg/kg of body weight for 28 weeks. Growth rate and food intake were decreased only at the high dose level in the brominated sesame oil study. In both studies, signs of lethargy and ataxia occurred in pigs fed the highest dose, and were probably due to a dose-related increase in serum bromine concentrations. Marked elevations in lactic dehydrogenase (LDH), serum glutamic-oxalacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) values were seen at the highest dose level with both substances and these enzyme activities were increased at the 50 mg/kg dose level in the brominated sesame oil study. Histopathologic lesions were confined to animals given the highest dose level of either oil. Marked fatty degeneration of the hepatic plate cells and renal tubular epithelial cells were seen in both studies. In the brominated sesame oil study, neutral fat was moderately increased in the myocardium of the pigs fed 500 mg/kg. However, marked diffuse accumulation of LDH, marked diffuse fatty degeneration and focal degeneration, and/or necrosis of individual or small groups of cardiac muscle fibers were seen in the group fed brominated soybean oil at 500 mg/kg. A moderate to marked testicular atrophy was also observed in this group. A dose-related accumulation of total and hexane-soluble bromine was observed in all tissues examined in both studies; the highest concentrations occurred in adipose tissue of the pigs given the highest dose level. Kidneys, livers, hearts and thyroids of these groups also contained large amounts of bromine. In pigs given the 50 mg/kg dose level, total and hexane-soluble bromine concentrations were higher in the brominated sesame oil study than in the longer brominated soybean oil study and may be responsible for the elevations in LDH, SGPT and SGOT activities in this group.

Diverse biological activities of healthy foods.

Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))] were investigated. The pine needle, sesame and powdered coffee was also extracted successively by ethanol and hot water, and lyophilized. The pine needle and coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as compared with other 4 lipophilic healthy foods. However, propolis showed slightly lower, but significant cytotoxic and bactericidal activity with much reduced oxidation potential. ESR spectroscopy demonstrated that the cytotoxic activity of these extracts was closely related to their radical generation and O2- scavenging activities. Healthy food components may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with pine needle, sesame or powdered coffee extract significantly reduced the lethality of bacterial infection, possibly due to their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was detected in mice by oral administration of 10 g/kg of these extracts. This data suggest the medicinal efficacy of healthy foods.

Identification of cytotoxic dimers in oxidation product from sesamol, a potent antioxidant of sesame oil.

Phytophenols of edible plants have recently attracted much attention as potent antioxidants and related bioactive substances. These antioxidative phytophenols are very oxidizable due to their chemical properties, and their oxidation products must accumulate in the oxidizing foods when they are contained as active ingredients. In this investigation, several phytophenols, which are well known as potent antioxidants in food science, were oxidized by oxygen in the presence of a catalytic amount of Ferric ion. Caffeic acid, catechin, chlorogenic acid, rosmarinic acid, and sesamol were quickly oxidized, whereas eugenol, resveratrol, rutin, and quercetin were not under the stated conditions. The oxidation product mixtures of the quickly oxidized phytophenols were next subjected to a cytotoxic assay using normal cells. Among the products, the oxidation product from sesamol showed a remarkably high cytotoxic activity. To clarify the cytotoxic principle of the oxidation products, an assay-guided fractionation and subsequent isolation of the oxidation compound of sesamol was carried out. Structure analysis of the isolated compounds revealed that they are new dimeric compounds (2-5) of sesamol. The cytotoxic activity of the dimers was evaluated from the population of dead cells by a flow cytometric analysis of rat thymocytes in the presence of 100 µM of each compound. Compound 2 showed the most potent cytotoxic activity among them. Compound 2 has a typical conjugated carbonyl moiety and the moiety possibly contributes to its high toxicity from a structure-activity point of view.

Leukocyte distribution in the pseudopregnant mouse uterus.

Pseudopregnancy, induced by mating females with vasectomized males, is a frequently used model for studying pregnancy-like uterine changes in the absence of an embryo. Leukocytes make a significant contribution to uterine cellularity during pregnancy. The present study was designed to determine whether changes in numbers and distribution of leukocytes in the uterus during pseudopregnancy and following intraluminal injection of a deciduogenic stimulus parallel changes observed during the first eight days of pregnancy. Common leukocyte antigen positive (CLA+) cells, macrophages (F4/80+ cells), and granulocytes were assessed between days 1 and 8 of pseudopregnancy using qualitative and quantitative immunohistochemistry. High numbers of CLA+ leukocytes were present on days 1 and 2. Those were comprised primarily by macrophages, polymorphonuclear leukocytes, and eosinophils. High concentrations of leukocytes were detected in the endometrium, and some granulocytes were observed migrating through the luminal epithelium. Leukocytes, principally macrophages, were reduced in number and were distributed throughout the endometrium on days 3 and 4. Introduction of oil to the uterine lumen on day 4 stimulated primary decidualization. Decidual cells were CLA- and F4/80-, and, as decidualization proceeded, CLA+ and F4/80+ cells decreased in number in the anti-mesometrial uterus and were detected primarily in the deep endometrium. Later, a secondary decidualization zone developed in the mesometrial aspect of the uterus. Unlike the initial decidual reaction, which was relatively free of leukocytes, the secondary decidual zone contained very high numbers of CLA+ and F4/80+ cells. The uninjected uterine horn remained relatively unchanged from days 3 through 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse skin tumor model. The anti-oxidant capabilities of these compounds could not solely explain the observed anti-cancer characteristics. Resveratrol is present in grapes. Sesamol, a constituent of sesame oil and sunflower oil are regularly consumed dietary natural products. The observed chemopreventive effect of these products particularly warrants more attention since they already exist in the population with no known adverse effects.