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The cationic dimethyldioctadecylammonium/trehalose 6,6,9-dibehenate (DDA/TDB) liposome is as a strong adjuvant system for vaccines, with remarkable immunostimulatory activity. The mucosal administration of vaccines is a potential strategy for inducing earlier and stronger mucosal immune responses to infectious diseases. In this study, we assessed whether the intranasal administration of cationic DDA/TDB liposomes combined with influenza antigen A (H3N2) can be used as a highly efficacious vaccine to induce mucosal and systemic antibody responses. Confocal laser scanning microscopy and a flow-cytometric analysis showed that the uptake of the cationic DDA/TDB liposome carrier was significantly higher than that of neutral 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (DSPC/Chol) or cationic 1,2-dioleoyl-3-trimethylammonium-propane/3β-(N-[N',N'-dimethylaminoethane]-carbamoyl (DOTAP/DC-Chol) liposomes. Our results indicate that the cationic DDA/TDB liposome is more effective in facilitating its uptake by dendritic cells (DCs) in vitro than the DSPC/Chol or DOTAP/DC-Chol liposome. DCs treated with DDA/TDB liposomes strongly expressed CD80, CD86, and MHC II molecules, whereas those treated with DSPC/Chol or DOTAP/DC-Chol liposomes did not. C57BL/6 mice intranasally immunized with H3N2-encapsulating cationic DDA/TDB liposomes had significantly higher H3N2-specific s-IgA levels in their nasal wash fluid than those treated with other formulations. The DDA/TDB liposomes also simultaneously enhanced the serum IgG IgG2a, IgG1, and IgG2b antibody responses. In summary, DDA/TDB liposomes effectively facilitated their uptake by DCs and DCs maturation in vitro, and induced significantly higher mucosal IgA, systemic IgG, IgG1, and IgG2b antibody titres than other formulations after their intranasal administration in vivo. These results indicate that DDA/TDB liposomes are a promising antigen delivery carrier for clinical antiviral applications.

DDT has enjoyed the reputation of a successful pesticide in disease control programme and agricultural practices along with the serious opposition and ban later on due to its biomagnification and toxic action against non-target organisms. The present work was carried out to develop QSAR models for analysing DDT analogues for their pesticidal activity and in silico validation of these models. A 2D-QSAR model was generated using stepwise with multiple regression, and the model with a value of r(2) = 0.7324; q(2) = 0.6215; pred r(2) = 0.7038, containing five descriptors, was selected for further study. The 3D QSAR with CoMFA analysis showed that steric contribution of 21% and electrostatic contribution of about 79% were required for larvicidal activity of DDT analogues. A set of 3430 molecules was generated using the basic DDT skeleton as template, and these were evaluated for their mosquito larvicidal activity using the generated QSAR models and DDT as standard. Eleven molecules were selected for in silico validation of these models. For this, a docking study of the selected molecules against the homology-modelled voltage-gated sodium channel of Anopheles funestus was conducted. The study showed that the activities of these analogues as predicted by 2D-QSAR, 3D-QSAR with CoMFA and dock score were observed to be well correlated.

The bioconcentration and distribution pattern of p,p'-DDT 1,1,1-1trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)-ethane] and its main metabolites (p,p'-DDD [1,1-dichloro-2,2-bis (4-chlorophenyl) ethane] and p,p'-DDE [1,1-dichloro-2,2-bis (4-chlorophenyl) in adipose tissue, liver, brain, kidney, thymus, and testis were examined in young rats after 10 days of intraperitoneal injection of 50 and 100 mg of p,p'-DDT/kg of body weight. Analyses were performed by high-resolution gas chromatography. p,p'-DDT was found to be accumulated in a dose-dependent manner with the highest concentration in adipose tissue. However, in brain, the accumulation of pesticide was low and remained unchanged at the higher dose. This difference may relate to the protective role of the blood-brain barrier, which limits the access of the xenobiotic in the cerebral compartment, and to the differential tissue lipid composition. Although tissues concentration of p,p'-DDE and p,p'-DDD correlated positively to total p,p'-DDT levels, the active role in detoxification of pollutants may explain why p,p'-DDD is more abundant in liver than in the rest of organs. On the contrary, in brain, the concentration of p,p'-DDE is higher than that of p,p'-DDD, suggesting that the metabolism of the parent insecticide proceeds via more than one pathway.

The potential for anaerobic biodegradation of 1,1,1-trichloro-2,2-bischlorophenylethane (DDT), 1,1-dichloro-2,2,-bischlorophenylethane (DDD), and dichlorodiphenylchloroethylene (DDE) in anoxic sediment slurries collected from the Keelung River was investigated in this study. o,p'- and p,p'-DDT were dechlorinated to o,p'- and p,p'-DDD, respectively, and then transformed to other compound(s). 1-Chloro-2,2-bis (p-chlorophenyl) ethylene (DDMU) and trace amount of dichlorobenzophenone (DBP) were detected in sediment slurries amended with p,p'-DDT or p,p'-DDD. DDMU was also detected in sediment slurries amended with p,p'-DDE. The relative transformation rates for both o,p'- and p,p'-isomers of DDT, DDD, and DDE were DDT>DDD>DDE. Re-addition of DDT, DDD, or DDE to the sediment slurries after initial removal enhanced the respective dechlorination rates. The transformation rates of the p,p'-isomers of both DDT and DDD were faster than those of the respective o,p'-isomers. p,p'-DDT dechlorination in the p,p'-DDT-adapted sediment slurries were inhibited by the addition of molybdate, or molybdate plus sulfate, but not inhibited by the addition of sulfate. Addition of bromoethane-sulfonic acid (BESA) slightly inhibited p,p'-DDT dechlorination. Non-adapted sediment slurries lost the ability to dechlorinate pentachlorophenol during adaptation to p,p'-DDT. p,p'-DDD was the major transformation product of p, p'-DDT in 3,4,4',5-tetrachlorobiphenyl-adapted sediment slurries, which suggested that the microbial community in the 3,4,4',5-CB-adapted sediment was unable to remove chlorine from the aromatic rings of p,p'-DDT.

The effects of in vitro exposure to different organochlorines were evaluated on immune functions of beluga whale peripheral blood leukocytes and splenocytes. The effects of different concentrations of four different congeners of PCBs (138, 153, 180, and 169) as well as two DDT metabolites (p,p'-DDT and p,p'-DDE) were evaluated on phagocytosis and cell proliferation. The effects of dioxins and mixtures of organochlorines were also evaluated on cell proliferation. The different compounds tested had no marked effect on phagocytosis. PCB 138 and p,p'-DDT, but not PCB 153, PCB 180, PCB 169, and p,p'-DDE, reduced significantly the proliferative response of beluga splenocytes cultured either with or without phytohemagglutinin A (PHA). Proliferation of beluga splenocytes was not markedly affected by exposure to 5 ppm of PCB 138, 153, 180, and 169 separately. Exposure to a mixture of congeners 138, 153, and 180 (5 ppm each) significantly reduced splenocytes proliferation, but not the mixture of congeners 138, 153, 180, and 169 (5 ppm each). TCDD did not affect cell proliferation in our study. The reduced proliferation of beluga cells exposed in vitro to mixtures of organochlorines at concentrations in the range of those observed in tissues of St. Lawrence belugas might provide a basis to support the hypothesis that contaminants induce immunosuppression in these animals.

Structure-toxicity relationships for 120 insecticidal DDT-type molecules including diaryl nitropropanes (Prolan analogs), diaryl trichloroethane and other DDT isosters, collected from different literature sources, to Musca domestica. were analysed by regression analysis (RA) and a neural network model (NN). The steric factors are extremely important to the toxicity of all the DDT-type analogs. The lipophilicity is also important for the groups, because it facilitates delivery of these neurotoxicants to the site of action in the nerve. On the basis of training results, the NNs proved to give better results than a regression analysis technique and the most accurate predictions. To describe the role of each of the descriptors we suggested a new method based upon the estimation of the connection weights, the identification and the rationalisation of the residuals.

Some DDT analogs are estrogenic, particularly o,p'-DDT, which comprises approximately 15-20% of the commercial DDT mixture. Whether this compound or its metabolites are active has not been established. In fact, the data obtained thus far are more confusing than enlightening. For example, CCl4 pretreatment of immature female rats has been reported to inhibit or enhance estrogenic activity of o,p'-DDT, and SKF-525A pretreatment has been reported to enhance or not alter the estrogenic effect. Although o,p'-DDT inhibits binding of estradiol to the estrogen receptor from rat or human at low levels (approximately 1-10 micrometer) in vitro, higher levels are required to inhibit nuclear binding of [3H] estradiol in incubated whole uteri. Futhermore, o,p'-DDT appears to be neither estrogenic nor antiestrogenic in an in vitro estrogen assay. Methoxychlor appears to be "activated" by metabolism, and it is probable that phenolic metabolites are responsible for its estrogenic activity. Since chlorinated hydrocarbons often enhance the metabolism of steroids and may reduce circulating levels of steroids, interactions of the exogenous hormonally active agents with steroid receptors may be self-potentiating in vivo.

Laboratory grade methoxychlor (99% pure), base-washed methoxychlor, and a metabolite of methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), were tested for their ability to compete with [3 H] estradiol-17 beta ([3 H]E2) for specific binding to the estrogen receptor from immature rat uterine cytosol. The binding was determined on 10--30% sucrose gradients and by a dextran-coated charcoal assay and subsequent Scatchard plot analysis. On gradients, laboratory grade methoxychlor, but not base-washed methoxychlor, suppressed [3 H]E2 binding to the 8S estrogen receptor. However, the base-soluble fraction from washing of laboratory grade methoxychlor caused suppression o[3 H]E2 binding on sucrose gradients at a concentration as low as 3.6 ppm. Scatchard plot analysis indicated that the inhibition of binding observed with laboratory grade methoxychlor was competitive in nature and not caused by receptor destruction. It was concluded that laboratory grade methoxychlor contained a contaminant that was potentially estrogenic. HPTE, an in vivo metabolite of methoxychlor, caused a marked suppression of [3 H]E2 binding in the 85 region of the gradients. Analysis by Scatchard plot indicated that the effect of HPTE was not to decrease the number of E2 binding sites but merely to alter the affinity of binding to the receptor, presumably in a competitive manner. The low K1 value for HPTE suggested an extremely high affinity for uterine cytosolic E2 receptors.