Our results indicate that n-3 PUFA from seal oils is safe and efficacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confirm these results.

Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

We report here that animals can be protected against lethal infection by Clostridium tetani cells and Bacillus anthracis spores following topical application of intact particles of live or ␥-irradiated Escherichia coli vectors overproducing tetanus and anthrax antigens, respectively. Cutaneous ␥␦T cells were rapidly recruited to the administration site. Live E. coli cells were not found in nonskin tissues after topical application, although fragments of E. coli DNA were disseminated transiently. Evidence suggested that intact E. coli particles in the outer layer of skin may be disrupted by a ␥␦T-cell-mediated innate defense mechanism, followed by the presentation of E. coli ligand-adjuvanted intravector antigens to the immune system and rapid degradation of E. coli components. The nonreplicating E. coli vector overproducing an exogenous immunogen may foster the development of a new generation of vaccines that can be manufactured rapidly and administered noninvasively in a wide variety of disease settings.Noninvasive epicutaneous vaccination without pain, fear, and tissue damage (35, 38) offers distinct advantages over conventional vaccination regimens in that it can be administered by nonmedical personnel and potentially has a higher compliance rate. Administration of vaccines to the surface of skin may also trigger efficient antigen presentation, as the outer layer of skin is more immunocompetent than deep tissue (9, 29). To date, both animals and humans have been immunized against a wide variety of antigens and pathogens by topical application of adenovirus-vectored vaccines (4,17,22,29,35,38) and bacterial toxin-adjuvanted proteins (11-13).To counteract unpredicted disease outbreaks and bioterrorist attacks, vaccines have to be not only safe and efficacious but also amenable to rapid, large-scale production. The Escherichia coli bacterium is fully defined at the molecular level (3) and has proven to be a simple and efficient vector system for the production of exogenous proteins since its first use, which marked the advent of the recombinant DNA era (1, 19). Recombinant plasmid DNA isolated from transformed E. coli vectors is also effective in eliciting an immune response when used as a genetic vaccine (33, 37). We report here that there is no need to biochemically purify recombinant protein or DNA as a vaccine from E. coli vectors. Topical application of intact E. coli particles overproducing pathogen-derived antigens can effectively mobilize the immune repertoire toward beneficial immune protection against relevant pathogens through the controlled activation of an E. coli-targeted defense mechanism in the outer layer of skin. Production and administration of this new class of vaccines are less dependent upon medical resources than any other vaccination regimens. Moreover, this demonstration provides compelling evidence that a cutaneous defense mechanism that rapidly disrupts invading bacterial cells indeed exists along the precarious skin barrier to ward off infections. MATERIALS AND METHODSRecombinant E. c...

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Hemostasis devices have comparative advantages over the conventional pressure dressing. The presence of radial artery flow during compression represents a strong predictor of radial artery patency during follow-up periods.