PubMed · 3921857
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
L Hutchinson. 1985. Transdermal nitroglycerin.. https://pubmed.ncbi.nlm.nih.gov/3921857/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
DNA vaccines have been shown to elicit both broad humoral and cellular immune responses. Needle-free injection devices and the gene gun have been used to deliver these DNA vaccines to dendritic cells in the viable skin epidermis with some success. However, more cost-effective and dendritic cell (DC)-targeted immunization strategies are sought. To this end, a nanoengineered genetic vaccine for simple topical application was developed. Expressed beta-galactosidase was used as a model antigen. Plasmid DNA was coated on the surface of preformed cationic nanoparticles engineered directly from warm oil-in-water (O/W) microemulsion precursors comprised of emulsifying wax as the oil phase and CTAB as a cationic surfactant. Mannan, a DC ligand, was coated on the nanoparticles with and without entrapped endosomolytic agents, dioleoyl phosphatidylethanolamine (DOPE) and cholesterol. In-vitro cell transfection studies were performed to confirm transgene expression with these pDNA-coated nanoparticles. An in-vitro Concanavalin A (ConA) agglutination assay confirmed the presence of mannan on the surface of nanoparticles. The humoral and proliferative immune responses were assessed after topical application of these nanoengineered systems to the skin of shaved Balb/C mice. All pDNA-coated nanoparticles, especially the mannan-coated pDNA-nanoparticles with DOPE, resulted in significant enhancement in both antigen-specific IgG titers (16-fold) and splenocyte proliferation over 'naked' pDNA alone.
Methemoglobin formation, as well as hemoglobin or DNA adducts, are useful biomarkers of occupational exposure to certain arylamines. It has been suggested that, in liver from animals not treated with a cytochrome P450 (CYP) inducer, hepatic CYP1A2 is the major P450 involved in N-hydroxylation. This is the first step in the metabolic activation of many arylamines, such as the human urinary bladder carcinogen 4-aminobiphenyl (ABP). The product of this catalytic step, N-hydroxy-4-ABP, reacts in the blood with oxyhemoglobin to form methemoglobin and nitrosobiphenyl. We therefore examined the role of CYP1A2 in causing methemoglobinemia in ABP-treated Cyp1a2(-/-) knockout mice. Application of ABP (100 micromol/kg body wt) to the skin resulted in a marked depletion in the levels of the hepatic thiols (reduced glutathione and cysteine) after 2 h, which rebounded to basal levels 24 h later, and we found no differences between the Cyp1a2(-/-) and wild-type Cyp1a2(+/+) animals. Unexpectedly, the methemoglobin levels were significantly (p < 0.05) higher in Cyp1a2(-/-) than Cyp1a2(+/+) mice at 2, 7, and 24 h following topical ABP. Treatment with dioxin, 24 h prior to ABP, decreased methemoglobin levels by about half at each of the time points in both the Cyp1a2(-/-) and Cyp1a2(+/+) mice. These data suggest that CYP1A2 does not play a positive role in methemoglobin formation via the activation of ABP; rather, the absence of CYP1A2 enhances ABP-induced methemoglobinemia. Because liver CYP1A2 levels are known to vary more than 60-fold between humans, our findings may be relevant to patients who are exposed to arylamines in the workplace.
TNF-alpha is a cytokine associated with inflammatory diseases, including asthma. Increased levels of TNF-alpha were found in the bronchoalveolar lavage fluid of mice undergoing a dinitrofluorobenzene (DNFB)-induced non-IgE-mediated pulmonary hypersensitivity reaction. We report in this work that TNF-alpha increases the susceptibility of sensory neurons to dinitrobenzene sulfonic acid (DNS) and capsaicin, leading to a tracheal vascular hyperpermeability response in DNFB-sensitized and DNS-challenged mice. mAb against TNF-alpha or the TNFR1 inhibited this hyperpermeability response in DNFB-sensitized and DNS-challenged mice. Furthermore, the hyperpermeability response after DNS challenge was abolished in DNFB-sensitized mast cell-deficient WBB6F(1)-W/W(V) mice. These animals showed a remarked decrease of TNF-alpha bronchoalveolar lavage fluid levels after a single DNS challenge. The hyperpermeability response after DNS challenge was regained in mast cell-deficient mice after mast cell reconstitution. These findings indicate a prominent role for TNF-alpha and its TNFR1 in the DNFB-induced tracheal hyperpermeability response. We propose that a priming effect of mast cell-derived TNF-alpha on the sensory neurons could be the mechanism of action of TNF-alpha in the vascular hyperpermeability response in tracheas of mice undergoing a pulmonary hypersensitivity reaction.