Modulation of immune response to group C meningococcal conjugate vaccine given intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl chitosan delivery system

Previous work had shown that the immunogenicity of conjugate vaccine against group C meningococci (CRM-MenC) is enhanced when it is delivered intranasally (inl) with mucosal adjuvants, such as mutants of the Escherichia coli enterotoxin (LT), and with delivery systems such as chitosan derivatives. We show, in mice, that the concomitant use of limiting doses of the fully nontoxic LTK63 mutant as a mucosal adjuvant and of the trimethyl derivative of chitosan as a delivery system allows the reduction of each of the components for the induction of antibody and bactericidal responses to CRM-MenC conjugate vaccine delivered inl at titers similar to or higher than those induced by parenteral immunization. These data could affect the design of efficacious mucosal vaccines and their safety.     

The evaluation of gastrointestinal function in diabetic patients

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Electrochemical and optoelectronic properties of terthiophene- and bithiophene-based polybenzofulvene derivatives

The electrochemical behavior of some polybenzofulvene derivatives bearing bithiophene (BT) or terthiophene (TT) side chains was investigated by cyclic voltammetry. Very interestingly, the presence of unsubstituted terminal thiophene moieties allowed poly-6-BT-BF3k and poly-6-TT-BF3k to be cross-linked by electrochemical procedures. Conductive films were obtained by electrodeposition from solutions of these polymers onto electrode surfaces through the formation of covalent cross-linking due to dimerization (i.e. electrochemical oxidation) of the BT or TT side chains. The films showed electrochromic features and switched from yellow-orange (neutral) to green (positively charged) by switching the potential, and were stable to tenths of cycles, without degradation in the wet state in the electrolyte solution. Finally, the thin film obtained by electrodeposition of poly-6-TT-BF3k on a indium tin oxide (ITO) glass substrate showed in the neutral state a significantly red-shifted photoluminescence (PL) emission (∼40 nm red-shifted with respect to that of the corresponding film obtained by casting procedures), which was consistent with the presence of more conjugated moieties produced by the oxidative dimerization of the TT side chains. The innovative architecture and the easy preparation could lead to a broad range of applications in optoelectronics and bioelectronics for these cross-linked hybrid materials based on π-stacked polybenzofulvene backbones bearing oligothiophene side chains.

The electrochemical behavior of some polybenzofulvene derivatives bearing bithiophene (BT) or terthiophene (TT) side chains was investigated by cyclic voltammetry and cross-linked materials were obtained by dimerization of the BT or TT side chains.     

Effects of Enteral Nutrition on the Barrier Function of the Intestinal Mucosa and Dopamine Receptor Expression in Rats With Traumatic Brain Injury

Background: Impaired intestinal mucosal barrier (IMB) function is common in traumatic brain injury (TBI), but dopamine receptors (DRs) change in intestinal mucosa after TBI, and effects of enteral nutrition (EN) and supplements on IMB function remain unclear. Our purpose was to study the effects of EN and supplements on intestinal mucosal permeability (IMPB) and the expression of DRs DRD1 and DRD2 in the intestinal mucosa of rats with TBI. Methods: Forty‐eight rats were divided into 8 groups; control, animals with TBI, dopamine group, animals with TBI treated with dopamine antagonist, EN alone, or EN combined with glutamine, probiotics, or a combination of probiotics and glutamine daily after TBI. Results: The IMPB was improved in the glutamine, probiotics, and combination groups. Including probiotics improved IMPB more than adding glutamine, and bacterial translocation in the intestines after TBI was reduced in the probiotics and combination groups (all Ps < .01). TBI led to elevated DRD1 and DRD2 mRNA and protein levels, which were reduced in the DA antagonist, glutamine, probiotics, and combination groups. DRD2 mRNA and protein levels in the probiotics and combination groups were decreased more than in the DA antagonist group (all Ps < .01). The increased IMPB after TBI correlated with increased DRD1 and DRD2 levels in the rat intestinal mucosa. Conclusion: EN supplemented with probiotics or combining glutamine and probiotics lowers the increased IMPB, bacterial translocation, and DRD1 and DRD2 mRNA and protein expression in rat intestinal mucosa caused by TBI.     

Cellular and molecular pharmacology of 4′-epidoxorubicin in HeLa Cells

Summary The effects on cellular DNA and cytotoxicity produced by doxorubicin (Dx) and its epimer 4-epidoxorubicin (4E-Dx) were investigated in cultured HeLa cells. 4E-Dx was 2.3 times more cytotoxic than Dx after 1 h of treatment, but the two anthracyclines were equally cytotoxic on longer-term (24h) drug exposure. The different kinetics of cell lethality were related to pharmacodynamic differences between the two drugs. In fact, cellular uptake and efflux rates of 4E-Dx were faster than those of Dx on 1 h of drug exposure but similar after 24 h of treatment. 4E-Dx caused more protein-concealed strand breaks in DNA (single and double) than did Dx, despite a lower potency for free-radical formation. The degree of strand breakage by 4E-Dx was not a linear function of exposure time and, in fact, the rate of strand-break induction declined continuously with time. In contrast, Dx caused an almost linear increase in DNA single-strand breaks with time during 1 h of drug exposure; this was apparently due to its slower uptake. There was little repair of the DNA single-strand breaks produced by Dx upon postincubation for 5 h in a drug-free medium, whereas DNA lesions caused by 4E-Dx were removed with a t _1/2 of about 1.7h. These findings underline the importance of the cellular pharmacokinetics of anthracyclines in relation to their cytotoxic and DNA-damaging effects.Abbreviations used DX doxorubicin - 4E-Dx 4-epidoxorubicin     

The pipeline of new anticancer agents for breast cancer treatment in 2003

In recent years, strategy in cancer therapy in general, and breast cancer in particular, has been the use of maximum tolerated doses of toxic non-specific agents as well as the investigation of a range of new agents that specifically target tumor-related molecules, in a variety of biological pathways. The trial of chemotherapy (CT) versus chemotherapy+trastuzumab (Herceptin) in HER-2-overexpressing metastatic breast cancer (MBC) was one of the first to use a biological agent in combination with chemotherapy with success and, together with some trials of taxanes in anthracycline-resistance patients one of the few to demonstrate an overall survival (OS) advantage in MBC. Five main molecular pathways are of particular interest in terms of new drug development in breast cancer: the estrogen receptor (ER) pathway, the tyrosine kinase signal transduction pathway, the cell cycle regulation pathway, the apoptosis pathway and the angiogenesis pathway. This review will focus on new agents, cytotoxic, hormonal and molecular-targeted, which are in advanced clinical stages of development for the treatment of MBC.