Abstract  The residual fractions remaining after microbial degradation of diesel fuel, different deparaffinized raffinates and extracts from long-term contaminated soils were analyzed by liquid chromatography, gas chromatography, infrared spectrometry and mass spectrometry. The quantity of saturated hydrocarbons decreased after the microbial treatment, whereas the portion of polar compounds increased. The total content of aromatics changed only insignificantly. n-Paraffins < C26 were found to be no longer present in mineral oils degraded to exhaustion. Infrared spectrometry revealed oxygen compounds in the residues, mainly ketones, fatty acids and esters. Elementary analysis confirms the presence of nitrogen, oxygen and sulphur compounds in the degraded products. The gas chromatograms of high boiling oils, as well as of residues and extracts, consist mainly of a large base "envelope" (about 95% of the total area); thus gc/ms coupling reaches the limits of its applicability. However, mass spectrometry with direct inlet gives valuable information regarding hydrocarbon type analysis. The results revealed the preferable degradation of alkanes, 1-ring aliphatics and benzenes and an enrichment of condensed cycloaliphatics and aromatics. The latter compounds are known to be resistant to microbial attack.

Abstract  Gas liquid chromatography was used for analysis of a mixture of seven chlorinated hydrocarbons. Experiments were conducted using columns containing the solvents squalane (111024), di-n-butyl-tetrachlorophthalate (3015665) (DBTP), dinonyl-phthalate (84764) (DNP), tricresyl-phosphate (1330785) (TCP), and polyethylene-glycol (25322683) (PEG) as the stationary phase. Chlorinated hydrocarbons in the mixture tested were: 1-chloropropane (540545), tetrachloromethane (56235), dichloromethane (75092), 1,2-dichloroethane (107062), trichloroethylene (79016), cis-1,2-dichloroethylene (156592), and trichloromethane (67663). Carbon-tetrachloride (56235) was used as the reference solute. The extremes of polarity ran from squalane to PEG, from low to high. Combinations of packings with PEG together with squalane, DBTP, DNP, or TCP were evaluated. Order of elution using squalane was 1-chloropropane, tetrachloromethane, dichloromethane, trichloroethylene, cis-1,2-dichloroethylene, trichloromethane, and 1,2-dichloroethane. For squalane, the most difficult pair to separate was cis-1,2-dichloroethylene and trichloromethane. Efficiencies of the combined stationary phase packings were excellent, better than the optimum loaded squalane column. Analysis was completed in 50 percent of the time required with squalane for all solvent combinations except DBTP with PEG. Helium (7440597) or hydrogen (1333740) as carrier gas improved analysis time. The authors conclude that the window technique for the choice of optimum binary solvent composition is used to attain the shortest possible analysis time, rather than the minimum number of separation plates required for baseline separation.

Abstract  We performed several test methods for safety evaluation of cosmetic ingredients and products. Now we chose guinea pig closed patch test method. This study were performed in the 3 different laboratories. The test mamterials were propylene glycol, 1, 3-butylene glycol, glycerin, liquid paraffin, squalane, and pristane. We chose 100% propylene glycol and pristane as positive control, and distilled water as negative control. We performed this test with the same procedure in each laboratory. The results of this study were as following: (1) In three polyols, only 100% propylene glycol reacted but 1, 3-butylene glycol and glycerin showed no reactions. (2) In three hydrocarbons, the order of positive rate was pristane

Abstract  As the safety evaluation method of cosmetic ingredients and products, we performed human patch tests. The test materials were propylene glycol, 1, 3-butylene glyool, glycerirl, pristane, Iiquid paraffin and squalane We chose propylene glycol and pristane as positive control, and distilled water as negative control. The members of this study were 3 dermatologists in one dermatological office and 2 universities, and 9 researchersin the different cosmetic companies. We performed the tests with the same procedure in each laboratory We could obtain the same results about the order of test materialspositive rates. But test seasons, especially high temperature and high humidity influenced on the reactions of test materials. We have to take a control material when we are going to test the skin irritancy of some chemicals using closed patch test method.

Abstract  We investigated the stimulating effect of dietary fiber on fecal excretion of PCDF and PCDD stored in the rat body. Twenty-eight male rats (71-74g body weight) were orally administered with 1ml of the causal rice oil of Yusho desease. The rice oil was contaminated with 2, 3, 4, 7, 8-pentaCDF (691.4ng), 1, 2, 3, 4, 7, 8-hexaCDF (708.6ng), 1, 2, 3, 6, 7, 8-hexaCDF (128.4ng), 1, 2, 3, 7, 8-pentaCDD (7.2ng), 1, 2, 3, 6, 7, 8-hexaCDD (34.1ng), 1, 2, 3, 7, 8, 9-hexaCDD (20.1ng) and 1, 2, 3, 4, 6, 7, 8-heptaCDD (115.9ng). The animals were fed a control diet containing 10% cellulose for seven days. Twenty-eight rats consisting of four rats a group were housed and rats of each group were given a treatment diet containing 10% rice-bran-fiber (RBF), 5% cholestyramine, 10% RBF + 5% cholestyramine, 10% RBF + 5% cholestyramine + 1% squalane, 10% burdock-fiber, 10% corn-fiber and 10% soybean-fiber during a period from eight to twenty-one days. The remaining four rats served as controls. PCDF and PCDD in feces, liver, small intestine and gastrointestinal tract were analyzed by high resolution gas chromatography-mass spectrometry. PCDF level in small intestine of rats administered with RBF + cholestyramine showed a decrease of 40% over the level of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract  The development of a non-toxic selective cytoprotective agent that preferentially protects normal tissues from chemotherapy toxicity, without protecting malignant tissues, is a major challenge in cancer chemotherapy research. The available cytoprotective agents are either toxic or lack selective cytoprotective activity. Here, we report the in vitro selective cytoprotective activity of squalene, an isoprenoid molecule with antioxidant properties. Normal human bone marrow (BM) derived colony-forming unit (CFU) growth was increased by squalene in a dose-dependent manner. Squalene (12.5-25 muM) treatment significantly protected the CFUs from cisplatin-induced toxicity; the protective effect was equivalent to reduced glutathione (GSH), a known cytoprotective agent. Squalene also increased the long-term survival of cisplatin-treated 4-week-old CFUs. Cisplatin-induced apoptosis of CFUs as measured by the TUNEL assay was reduced by squalene. To examine the squalene-induced protection of tumours, several neuroblastoma cell lines, including five MYCN-amplified cell lines, were grown in monolayers, as well as in anchorage-independent cultures, in the presence of squalene and cisplatin. Squalene did not protect the neuroblastoma (NBL) cell lines from cisplatin-induced toxicity. In addition, squalene did not protect the NBL cells from carboplatin, cyclophosphamide, etoposide and doxorubicin-induced toxicity. In conclusion, our results suggest that squalene has a selective in vitro cytoprotective effect on BM-derived haematopoietic stem cells that is equipotent to GSH. (C) 2003 Elsevier Ltd. All rights reserved.

Abstract  A biochemical method was employed to study the response of rabbit skin to isopropyl myristate, squalane, and decane. The results showed that decane damaged the skin so severely that the biosyntheses of lipids, RNA and DNA were reduced markedly for the first 3 days after application, but increased rapidly after that due to the repair. The effect of squalane was found to be weaker than that of isopropyl myristate, though both oils induced the stimulation of biosynthese in the epidermis. The magnitude of the biochemical effects of the 3 oils on the skin was increased in the order of squalane, isopropyl myristate and decane, which was consistent with the results of macroscopic and histological observations. From the profiles of the effects, it is postulated that the repairing processes are controlled by some feedback mechanisms.

Abstract  Environmental investigation of the Early Cambrian is assessed through molecular fossils based from three core samples drilled in the Three Gorges area, South China. The core samples record environmental information dating from the earliest part of the Early Cambrian to nearly the end of the Early Cambrian, making this investigation unique from previous investigations because a more far-reaching temporal record is assessed. This record includes unusually high abundance of longer chain n-alkanes (LCA) around C-n(27), having been recognized in the earliest Cambrian strata. Based on no odd-even preference of the LCA and comparisons to hydrocarbons in cultured cells of microorganisms, the LCA may be derived from hydrocarbons of sulfate reducing bacteria. On the other hand, a phototrophic origin of the SCA is supported by a clear positive correlation with pristane. The relative abundance of LCA to SCA increased in the earliest Cambrian, suggesting predominance of sulfate reducers against phototrophs. This LCA abundance with simultaneous decrease of pristane/phytane may indicate a euxinic condition, where sulfate reducers remineralize organic carbon in the water column. This is consistent with the concomitant decrease of the delta C-13(carb) value probably due to a massive reoxidation of organic carbon. The inferred reducing condition is further supported by the enhanced appearance of squalane that could be derived from an Archeal lipid. Our results suggest the euxinia of the Yangtze platform in the earliest Cambrian that may relate to the emergence of the large nektonic animals which require sufficient level of free oxygen. (C) 2013 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Using a data set for 39 base oils, formulated oil products and pure compounds it was demonstrated that there was a good positive relationship between biodegradation in CEC L-33-T-82 and mineralisation to CO2 in the modified Sturm test. A mathematical model was developed which described this correlation for most of the materials tested. One outlier from the model was di-iso tridecyl adipate (DITA), the well-degradable calibration oil for the CEC test. The measured mineralisation of DITA was much lower than that predicted by the model based on the compound's high biodegradability in the CEC test. A possible reason for this is given and the implications of this result discussed.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. The biodegradation of polycyclic aromatic hydrocarbon pollutants is constrained, in part, by their solid physical state and very low water solubility. Searching for ways to overcome these limitations, we isolated from soil a bacterium capable of growing on pyrene as a sole source of carbon and energy. Acid-fast stain, morphology, and fatty acid profile identified it as a Mycobacterium sp. In a mineral salts solution, the isolate mineralized 50% of a 250-mug/ml concentration of (14C) pyrene in 2 to 3 days. Detergent below the critical micelle concentration increased the pyrene mineralization rate to 154%, but above the critical micelle concentration, the detergent severely inhibited pyrene mineralization. The water-miscible solvent polyethylene glycol was inhibitory. The hydrophobic solvents heptamethylnonane, decalin, phenyldecane, and diphenylmethane were also inhibitory at several concentrations tested, but the addition of paraffin oil, squalene, squalane, tridecylcyc

Abstract  Different adjuvants were assessed for their role in conferring protection against the rodent malarial parasite P. berghei and compared with the classical Freund's complete adjuvant (FCA). Pretreatment of mice with trehalose dimycolate (TDM) mixed with antigen (Ag), sulpholipids (SL) mixed with Ag, muramyl dipeptide (MDP) alone, liposomes containing Ag and phosphomannoinositides (PIM) mixed with Ag were ineffective in conferring protection. However, MDP given with squalane (Sq) and Ag, MDP with incomplete Freund's adjuvant (IFA) and Ag, palmitoyl-MDP with Sq and Ag, aluminium hydroxide adsorbed Ag, and FCA with Ag were effective in conferring varying degrees of protection to mice. Complete protection in rats was obtained with MDP mixed with Sq and Ag, and FCA mixed with Ag, and a partial protection with liposomes containing Ag.

Abstract  Fossil stromatolites may reveal information about their hydrochemical palaeoenvironment, provided that assignment to a specific microbial community and a corresponding biogeochemical mechanism of formation can be made. Tithonian stromatolites of the Munder Formation at Thuste, north Germany, have traditionally been considered as formed by intertidal cyanobacterial communities. However, thin sections of the stromatolites show elongated angular traces of former gypsum crystals in a dense arrangement, but no algal or cyanobacterial filament traces. Moreover, high Fe(2+) and Mn(2+) contents, oxygen-isotope and sulphur-isotope ratios of carbonate-bound sulphates, and sulphurized hydrocarbon biomarkers of the stromatolitic carbonate indicate that CaCO(3) precipitation occurred near the oxic-anoxic interface as a result of intensive bacterial sulphur cycling rather than photosynthetic activity. Furthermore, anaerobic oxidation of methane by Archaea may have driven CaCO(3) precipitation in deeper parts of the biofilm community, as reflected by high concentrations of squalane with a strongly negative delta(13)C in conjunction with evaporite pseudomorphs showing extremely low delta(13)C(Carb) ratios. Consequently, the Thuste stromatolites are now interpreted as having initially formed by gypsum impregnation of biofilms. Subsequently, early Mg-calcitic calcitization within the biofilms occurred because of combined bacterial iron, manganese and sulphate reduction, with an increasing contribution of anaerobic oxidation of methane with depth. This model plausibly explains the prominent preservation of signals derived from oxygen-independent metabolic pathways, whereas virtually no geochemical record exists for an aerobic community that may, nevertheless, have prevailed at the stromatolite surface. Photic-zone stromatolites with a prominent signal of anaerobic oxidation of methane may be common in, and indicative of, oxygen-depleted sulphate-bearing environments with high rates of methane production, conditions that possibly were fulfilled at the Archaean to Proterozoic transition.

Abstract  In gas liquid chromatography (GLC), the relative retention values log gamma was mainly expressed by van der Waals energy (the sum of the dispersion E(dis) and repulsive E(rep) energies) to the interactions between monosubstituted benzene derivatives and the nonpolar stationary liquid as squalane. The single exception was that of anilines, and it was corrected by the electrostatic energy (E(ES)) due to C-H/pi hydrogen bond. When the stationary liquid changed from the nonpolar to polar, log gamma was estimated by the inductive interaction energy (included in E(ES)) in addition to the sum of E(dis) and E(rep). In the benzene solution, the relative equilibrium values log K/K(o) introduced from the interactions between phenol and substituted benzene derivatives were estimated by E(ES). The E(ES) of COCH(3), CO(2)C(2)H(5) groups is especially originated in the excited dipole moments micro(e). The relative frequency values log nu/nu(o) derived from O-H or O-D stretching vibration of phenol or methanol-D gave the correlation to E(ES) as well as log K/K(o). That of anilines-methanol-D however had been out of a linear relation to E(ES). The cause is concluded that the aniline-methanol-D is making the proton transfer structure from the discussion about the proton affinity (PA) of the base.

Abstract  Compatibility between oligomers and polymers was systematically assessed using differential scanning calorimetry (DSC) and was correlated with similarity in saturation and solubility parameter. These measurements enabled validation of detailed volume of mixing calculations using Statistical Association Fluid Theory (SAFT-γ Mie) and molecular dynamics (MD) simulations, which can be used to predict behaviour beyond the experimentally accessible conditions. These simulations confirmed that squalane is somewhat more compatible with poly(isoprene), "PI" than poly(butadiene), "PB", and further enabled prediction of the temperature dependence of compatibility. Surface and interfacial segregation of a series of deuterated oligomers was quantified in rubbery polymer films: PI, PB and hydrogenated poly(isoprene) "hPI". A striking correlation was established between surface wetting transition and mixtures of low compatibility, such as oligo-dIB in PB or PI. Segregation was quantified normal to the surface by ion beam analysis and neutron reflectometry and in some cases lateral segregation was observable by AFM. While surface segregation is driven by disparity in molecular weight in highly compatible systems this trend reverses as critical point is approached, and surface segregation increases with increasing oligomer molecular weight.

Abstract  Gelatin capsules containing squalane partially purified bone morphogenetic protein (BMP) complex were placed on the perimuscular membrane of rats. Two kinds of control, gelatin capsules containing only BMP and those bearing squalane only, were used. The embedded areas were histopathologically examined at 3 and 6 wk after the operation. The observations revealed that the squalane/BMP complex elicited wide heterotopic bone formation with bone marrow tissue, suggesting that squalane is a possible carrier of BMP for clinical applications.

Abstract  Over the past several years, we have conducted a variety of elastic neutron diffraction and quasielastic neutron scattering experiments to study the structure and the dynamics of films of two intermediate-length alkane molecules (C sub( n)H sub(2n+2)), adsorbed on a graphite basal-plane surface. The two molecules are the normal alkane n-tetracosane [n-CH sub( 3)(CH sub(2)) sub(22)CH sub(3)] and the branched alkane squalane (C sub(30)H sub(62) or 2, 6, 10, 15, 19, 23-hexamethyltetracosane) whose carbon backbone is the same length as teteracosane. The temperature dependence of the monolayer structure of tetracosane and squalane was investigated using elastic neutron diffraction and evidence of two phase transitions was observed. Both the low-coverage tetracosane (C sub( 24)H sub(50)) and squalane (C sub(30)H sub(62)) monolayers have crystalline-to-"smectic" and "smectic"-to-isotropic fluid phase transitions upon heating. The diffusive motion in the tetracosane and squalane monolayers has been investigated by quasielastic neutron scattering. Two different quasielastic neutron scattering spectrometers at the Center for Neutron Research, National Institute of Standards and Technology (NIST) have been used. The spectrometers differ in both their dynamic range and energy resolution allowing molecular motions to be investigated on time scales in the range 10 super(-13)--10 super( -9) s. On these time scales, we observe evidence of translational, rotational, and intermolecular diffusive motions in the tetracosane and squalane monolayers. We conclude that the molecular diffusive motion in the two monolayers is qualitatively similar. Thus, despite the three methyl sidegroups at each end of the squalane molecule, its monolayer structure, phase transitions, and dynamics are qualitatively similar to that of a monolayer of the unbranched tetracosane molecules. With the higher resolution spectrometer at NIST, we have also investigated the molecular diffusive motion in multilayer tetracosane films. The analysis of our measurements indicates slower diffusive motion in the bottom layer of a bilayer tetracosane film compared to that in a monolayer, while the rate of diffusive motion in the bottom two layers of the trilayer film is comparable to that in a monolayer.

Abstract  Squalane is obtained by hydrogenation from squalene, an unsaturated terpene hydrocarbon found mainly in shark liver oil. It is a very stable liquid, and has a remarkably low capacity to irritate the skin. Squalane is used as an important component in various kinds of cosmetics and has a considerably beneficial effect on faecal excretion of the highly toxic 2, 3, 4, 7, 8-pentachlorodibenzofuran (PenCDF). The distribution, excretion and subacute toxicity of squalane after oral administration has already been examined. We considered that squalane, applied subcutaneously, might be an effective carrier of drugs. Furthermore, we found an application of squalane as a carrier of bone morphogenetic protein (BMP). As there were no data on the tissue reaction to squalane administered subcutaneously, we decided to make a histopathological evaluation of squalane fluid in vivo (DBO).

Abstract  In the previous papers, we demonstrated, by using rats, that squalane (2,6,10,15,19,23-hexamethyltetracosane) could stimulate the fecal excretion of 2,3,4,7,8-pentachlorodibenzofuran, which was regarded as the most important etiologic agent of yusho among PCB and PCDF congeners found in the causal rice oil. We also reported that, in rats, squalane was not essentially absorbed from the gastrointestinal tract, and did not show any appreciable side effects during the 3-month treatment. In the present paper, we have investigated the distribution, excretion and subacute toxicity of squalane in beagle dogs. The fecal excretion of squalane accounted for about 83% of dose during the initial 2 days after administration at a single oral dose of 1,200 mg/kg to male dogs. On day 3, absorbed squalane was mostly distributed to the hair and the skin, and the concentrations in these tissues were decreased on day 6. These results suggested that most of squalane administered orally was not absorbed from the gastrointestinal tract, but a part was absorbed and excreted through the hair. In addition, squalane distributed into the liver was found to be eliminated rather slowly. A long-term (13-week) treatments with squalane orally at doses of 400 mg/kg/day or 1,200 mg/kg/day in male and female dogs, resulted also in accumulation of squalane in the liver at a level of about 3% (400 mg/kg) or about 6% (1,200 mg/kg) of the daily dose. This accumulation of squalane in the liver was highest among all the tissues. Nevertheless, no appreciable toxic signs were observed in the serum biochemical tests and the hepatic functional test for squalane groups. Therefore, squalane accumulating in the liver, did not seem to disturb the hepatic physiological functions. It was suggested also in a long-term treatment that the skin and the hair played the most important role in the elimination of squalane. In conclusion, the present studies on subacute toxicity tests suggested that squalane did not give any significant toxic effects on dogs as well as rats.

Abstract  Female mice were given 100 mg HCB/kg body weight i.p. and fed diets containing 0, 2.5, 5.0, and 7.5% of squalane. After 3 weeks samples of liver, blood and abdominal fat were analysed for HCB as well as for squalane. HCB concentrations were significantly lowered as compared to controls in all tissues and at all dietary concentrations of squalane to a maximum of about 36% in fat, 44% in liver and 47% in blood. The effect of squalane upon HCB concentrations was strongly dose dependent in abdominal fat. In contrast, no significant differences were seen with liver and blood between animals fed 5.0 or 7.5% of squalane. Squalane was detected in considerable amounts in the livers (50-100 ppm) but not in abdominal fat (less than 1 ppm) of mice fed squalane.

Abstract  Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen. Antigens are added after emulsification so that conformational epitopes are not lost by denaturation and to facilitate manufacture. A Pluronic block copolymer can be added to the squalane or squalene emulsion. Soluble antigens administered in such emulsions generate cytotoxic T lymphocytes able to lyse target cells expressing the antigen in a genetically restricted fashion. Optionally a relatively nontoxic analog of muramyl dipeptide (MDP) or another immunomodulator can be added; however, the dose of MDP must be restricted to avoid systemic side effects in humans. Squalene or squalane emulsions without copolymers or MDP have very little toxicity and elicit potent antibody responses to several antigens in nonhuman primates. They could be used to improve a wide range of vaccines. Squalene or squalane emulsions have been administered in human cancer vaccines, with mild side effects and evidence of efficacy, in terms of both immune responses and antitumor activity.

Abstract  This study focused on an investigation into the experimental quantities inherent in the determination of partition coefficients from gas-liquid chromatographic measurements through the use of capillary columns. We prepared several squalane a (2,6,10,15,19,23-hexamethyltetracosane) a containing columns with very precisely known phase ratios and determined solute retention and hold-up times at 30, 40, 50 and 60 degree C. We calculated infinite dilution partition coefficients from the slopes of the linear regression of retention factors as a function of the reciprocal of the phase ratio by means of fundamental chromatographic equations. In order to minimize gasasolid and liquid-solid interface contributions to retention, the surface of the capillary inner wall was pretreated to guarantee a uniform coat of stationary phase. The validity of the proposed approach was first tested by estimating the partition coefficients of n-alkanes between n-pentane and n-nonane, for which compounds data from the literature were available. Then partition coefficients of sixteen aliphatic alcohols in squalane were determined at those four temperatures. We deliberately chose these highly challenging systems: alcohols in the reference paraffinic stationary phase. These solutes exhibited adsorption in the gas-liquid interface that contributed to retention. The corresponding adsorption constant values were estimated. We fully discuss here the uncertainties associated with each experimental measurement and how these fundamental determinations can be performed precisely by circumventing the main drawbacks.

Abstract  Among several bacterial species belonging to the general Gordonia, Mycobacterium, Micromonospora, Pseudomonas, and Rhodococcus, only two mycobacterial isolates, Mycobacterium fortuitum strain NF4 and the new isolate Mycobacterium ratisbonense strain SD4, which was isolated from a sewage treatment plant, were capable of utilizing the multiply branched hydrocarbon squalane (2,6,10,15,19, 23-hexamethyltetracosane) and its analogous unsaturated hydrocarbon squalene as the sole carbon source for growth. Detailed degradation studies and high-pressure liquid chromatography analysis showed a clear decrease of the concentrations of squalane and squalene during biomass increase. These results were supported by resting-cell experiments using strain SD4 and squalane or squalene as the substrate. The degradation of acyclic isoprenoids and alkanes as well as of acids derived from these compounds was also investigated. Inhibition of squalane and squalene degradation by acrylic acid indicated the possible involvement of beta-oxidation in the degradation route. To our knowledge, this is the first report demonstrating the biodegradation of squalane by using defined axenic cultures.

Abstract  1. The intestinal excretion of hexachlorobenzene (HCB) was studied in rats using the method of pendular perfusion. One and four weeks after i.p. application of 100 micrograms HCB/kg body weight segments of jejunum, ileum and colon were perfused with light liquid paraffin or squalane for 5 h. 2. The highest amount of HCB was excreted into jejunum, followed by ileum and colon. After 5 h HCB concentration in jejunal perfusion medium equals that in plasma. 3. Serosal tissue of intestinal segments contained higher HCB concentrations as compared to mucosa. 4. Paraffin treatment decreased the HCB content in both serosal and mucosal tissue of jejunum and ileum but not of colon.

Abstract  The efficacy of a new vaccine preparation against Epstein-Barr (EB) virus was investigated in cotton-top tamarins. The vaccine consists of fast protein liquid chromatography-purified EB virus membrane antigen glycoprotein of 340 Kd (MA gp340) mixed with a synthetic muramyl dipeptide adjuvant emulsified in squalane containing a pluronic polymer; it is suitable for both scaled-up batch production and eventual administration to man. Vaccinated tamarins rapidly developed ELISA detectable high titre antibodies to MA gp340, and their sera became strongly EB virus-neutralising. After challenge with a massive 100% carcinogenic dose of EB virus, the vaccinated tamarins had a strikingly low level of circulating EB virus-carrying mononuclear cells, in contrast to a control animal, and remained entirely free of tumours. This first-generation vaccine has thus been validated in experimental animals and the way opened for a phase I human trial.

Abstract  The ability of nontoxic monophosphoryl lipid A (MPL) to stimulate nonspecific resistance against viral infection was investigated. Mice pretreated intravenously with squalane-in-water emulsions of MPL, alone or in combination with other immunostimulants, were given an aerosol of influenza virus three weeks after the pretreatment. Complete protection against lethal influenza virus infection was conferred when MPL was combined with trehalose dimycolate (TDM). The protective activity of MPL plus TDM combination was corroborated by a significant reduction of the lung virus titers. Combination of lower doses of MPL with TDM extracted from Mycobacterium bovis, but not with that of M. phlei, induced significant resistance to influenza virus. Preparations containing MPL alone, or combined with mycobacterial cell wall skeleton or muramyl dipeptide, were not effective. The adjuvant activity of MPL on bivalent influenza subunit vaccine was also studied. The primary antibody responses to influenza A and influenza B antigens were enhanced by the addition of MPL and were higher than the vaccine associated with aluminum hydroxide. The adjuvant activity of MPL was confirmed by the elevated secondary response. High levels of circulating antibodies were still present in the MPL group when antibody titers in the controls were waning.