Objective:To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis(M.tuberculosis)of a proteoliposome(PL)from Mycobacterium bovis Bacillus Calmette–Guerin(BC...Objective:To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis(M.tuberculosis)of a proteoliposome(PL)from Mycobacterium bovis Bacillus Calmette–Guerin(BCG)with and without alum hydroxide(AL)as adjuvant(PLBCG-AL and PLBCG,respectively)in BALB/c mice.Methods:BALB/c mice were inoculated with phosphate buffer solution,BCG,PLBCG and PLBCG-AL.The humoral immunogenicity was determined by ELISA[immunoglobulin G(Ig G),Ig G1 and Ig G2a]and the cellular immunogenicity was evaluated in vivo by delayed type hypersensitivity.The humoral cross-reactive response against M.tuberculosis was determined by Western blot.Results:Sera from animals immunized with PLBCG-AL and PLBCG showed significant increase in specific total Ig G and Ig G1 antibodies and the presence of cross-reactive antibodies against M.tuberculosis antigens,which were more intense with the use of alum as adjuvant.Mice immunized with PLBCG and PLBCG-AL also showed a specific cellular response in vivo.Conclusions:The cellular and humoral immunogenicity of PLBCG and the capacity to induce cross-reactive responses against M.tuberculosis is in agreement with the protective capacity previously demonstrated by this vaccine candidate and supports the continuation of its evaluation in further stages.展开更多
Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within th...Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas. This treatment is noted for its great effectiveness, minimal invasiveness and local effect. Several studies have been conducted worldwide to evaluate the anfitumoral effect of this therapy. In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained. By this reason, researchers have suggested various mechanisms to explain how direct electric current destroys tumor ceils. Although, it is generally accepted this treatment induces electrolysis, electroosmosis and electroporation in tumoral tissues. However, action mechanism of this alternative modality on the tumor tissue is not well understood. Although the principle of Electrochemical treatment is simple, a standardized method is not yet available. The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process. The present work analyzes the latest and most important research done on the electrochemical treatment of tumors. We conclude with our point of view about the destruction mechanism features of this alternative therapy. Also, we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy. In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done. Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.展开更多
Objective: To evaluate the recognition of NS4 B mimotope, as multiple antigen peptide(MAP), by dengue antibodies presents in serum samples from patients with different serotype infections. Methods: A MAP containing mi...Objective: To evaluate the recognition of NS4 B mimotope, as multiple antigen peptide(MAP), by dengue antibodies presents in serum samples from patients with different serotype infections. Methods: A MAP containing mimotope sequence was synthesized and used to evaluate the recognition of NS4 B mimotope as MAP by a panel of 66 human sera from dengue cases by an indirect ELISA assay. Results: The MAP differentiated between sera from dengue viruses infected patients and sera from healthy individuals and the best reactivity was shown by serum from dengue type 3 virus patients. The recognition was more intense with serum from patients with secondary infection. Conclusions: The findings suggest the potential use of NS4 B mimotope on the development of a multi-epitope diagnostic tool. These results are important for further immunogenicity studies.展开更多
Neisseria meningitidis capsular polysaccharides are the main target of the protective immune response against bacterial meningitis. They are thymus-independent type 2 (TI-2) antigens that are poorly immunogenic and no...Neisseria meningitidis capsular polysaccharides are the main target of the protective immune response against bacterial meningitis. They are thymus-independent type 2 (TI-2) antigens that are poorly immunogenic and not protective in young children, and their administration may impair subsequent challenge with the same polysaccharide. These problems have been addressed using three different vaccines consisting of 1) polysaccharide alone, 2) polysaccharide covalently conjugated to a carrier protein, and 3) polysaccharide with Proteoliposome (PL) adsorbed onto Al(OH)3. VA-MENGOC-BC? is one of the third types of vaccine. It contains PL (detergent-extracted external membrane proteins forming vesicles) and polysaccharide (Ps) from N. meningitidis serogroups B and C (PsC), respectively. Nevertheless, there is a concern that to overcome the TI-2 nature of Ps the covalently conjugation to a carrier is mandatory. Therefore, we evaluated the immune response induced by VA-MENGOC-BC? in infants and toddlers in order to determine whether it stimulates the response against the PsC. High IgG anti PsC and anti PL responses were seen following the administration of two doses in infants and toddlers, after a 3rd dose in pre-teenagers, and after confirmed carrier stages in young adults. The anti PL IgG response persisted longer than anti PsC IgG response and IgM response against both antigens was maintained. An IgG1 anti PL response predominated, as well as IgG4 > IgG3 > IgG1 anti PsC responses. These results suggest that non-covalent incorporation of PsC onto Al(OH)3 containing?PL as adjuvant is immunogenic, primes for memory, and induces long-lasting specific antibody response. The improved PsC immunogenicity of this vaccine may be due to the preferential and potent Th1 response induced in mice and human by the PL as adjuvant.展开更多
Nanogels-particles of polymer gels having the dimensions in the order of nanometers-are gaining attention for their wide application as biomaterials. Mainly, the nanogels are promising novel pharmaceutical carriers fo...Nanogels-particles of polymer gels having the dimensions in the order of nanometers-are gaining attention for their wide application as biomaterials. Mainly, the nanogels are promising novel pharmaceutical carriers for small biologically active agents, bin macromolecules and can be chemically modified to incorporate various ligands for targeted drug delivery. This important factor has stimulated research on dissimilar science field such as nanotechnology and biotechnology, polymer and materials sciences, biochemistry, radiation chemistry and pharmaceutical sciences. A multitude of techniques have been described for the synthesis of this nanomaterial from polymers. However, the use of ionizing radiation （γ, e-） has demonstrated to be especially suitable for obtaining polymeric nanogels with a high degree of purity for biomedical applications, although the gamma radiation has not been widely utilized for these purposes. The aim of this paper is to develop the synthesis of PVP （polyvynilpyrrolidone） nanogels by gamma irradiation, for their evaluation as potential pharmaceutical carriers. Experiments were performed using argon saturated solution of PVP （0.1-1%）. Crosstinking reactions were carried out in a gamma irradiation chamber with a 60Co source （ISOGAMMA LLCo）, at room temperature. The PVP concentration influence was evaluated in PVP solutions （0.1% and 0.25%） at 15 kGy. The SEM （scanning electron microscopy）, ATR （attenuate total reflection spectroscopy）, DLS （dynamic light scattering）, and viscosimetry were used as characterization techniques.展开更多
基金Supported by the Long-Term Research Grant Scheme Grant,Department of Higher Education,Ministry of Education,Malaysia(Grant No.203.PPSK.67212002)as well as the Ministry of Science and Technology,Cuba
文摘Objective:To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis(M.tuberculosis)of a proteoliposome(PL)from Mycobacterium bovis Bacillus Calmette–Guerin(BCG)with and without alum hydroxide(AL)as adjuvant(PLBCG-AL and PLBCG,respectively)in BALB/c mice.Methods:BALB/c mice were inoculated with phosphate buffer solution,BCG,PLBCG and PLBCG-AL.The humoral immunogenicity was determined by ELISA[immunoglobulin G(Ig G),Ig G1 and Ig G2a]and the cellular immunogenicity was evaluated in vivo by delayed type hypersensitivity.The humoral cross-reactive response against M.tuberculosis was determined by Western blot.Results:Sera from animals immunized with PLBCG-AL and PLBCG showed significant increase in specific total Ig G and Ig G1 antibodies and the presence of cross-reactive antibodies against M.tuberculosis antigens,which were more intense with the use of alum as adjuvant.Mice immunized with PLBCG and PLBCG-AL also showed a specific cellular response in vivo.Conclusions:The cellular and humoral immunogenicity of PLBCG and the capacity to induce cross-reactive responses against M.tuberculosis is in agreement with the protective capacity previously demonstrated by this vaccine candidate and supports the continuation of its evaluation in further stages.
基金supported by the Ministry of Superior Education, Republic of Cubaby the Brazilian financial agencies (FAPERJ, CNPq and FUJB)
文摘Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas. This treatment is noted for its great effectiveness, minimal invasiveness and local effect. Several studies have been conducted worldwide to evaluate the anfitumoral effect of this therapy. In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained. By this reason, researchers have suggested various mechanisms to explain how direct electric current destroys tumor ceils. Although, it is generally accepted this treatment induces electrolysis, electroosmosis and electroporation in tumoral tissues. However, action mechanism of this alternative modality on the tumor tissue is not well understood. Although the principle of Electrochemical treatment is simple, a standardized method is not yet available. The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process. The present work analyzes the latest and most important research done on the electrochemical treatment of tumors. We conclude with our point of view about the destruction mechanism features of this alternative therapy. Also, we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy. In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done. Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.
文摘Objective: To evaluate the recognition of NS4 B mimotope, as multiple antigen peptide(MAP), by dengue antibodies presents in serum samples from patients with different serotype infections. Methods: A MAP containing mimotope sequence was synthesized and used to evaluate the recognition of NS4 B mimotope as MAP by a panel of 66 human sera from dengue cases by an indirect ELISA assay. Results: The MAP differentiated between sera from dengue viruses infected patients and sera from healthy individuals and the best reactivity was shown by serum from dengue type 3 virus patients. The recognition was more intense with serum from patients with secondary infection. Conclusions: The findings suggest the potential use of NS4 B mimotope on the development of a multi-epitope diagnostic tool. These results are important for further immunogenicity studies.
文摘Neisseria meningitidis capsular polysaccharides are the main target of the protective immune response against bacterial meningitis. They are thymus-independent type 2 (TI-2) antigens that are poorly immunogenic and not protective in young children, and their administration may impair subsequent challenge with the same polysaccharide. These problems have been addressed using three different vaccines consisting of 1) polysaccharide alone, 2) polysaccharide covalently conjugated to a carrier protein, and 3) polysaccharide with Proteoliposome (PL) adsorbed onto Al(OH)3. VA-MENGOC-BC? is one of the third types of vaccine. It contains PL (detergent-extracted external membrane proteins forming vesicles) and polysaccharide (Ps) from N. meningitidis serogroups B and C (PsC), respectively. Nevertheless, there is a concern that to overcome the TI-2 nature of Ps the covalently conjugation to a carrier is mandatory. Therefore, we evaluated the immune response induced by VA-MENGOC-BC? in infants and toddlers in order to determine whether it stimulates the response against the PsC. High IgG anti PsC and anti PL responses were seen following the administration of two doses in infants and toddlers, after a 3rd dose in pre-teenagers, and after confirmed carrier stages in young adults. The anti PL IgG response persisted longer than anti PsC IgG response and IgM response against both antigens was maintained. An IgG1 anti PL response predominated, as well as IgG4 > IgG3 > IgG1 anti PsC responses. These results suggest that non-covalent incorporation of PsC onto Al(OH)3 containing?PL as adjuvant is immunogenic, primes for memory, and induces long-lasting specific antibody response. The improved PsC immunogenicity of this vaccine may be due to the preferential and potent Th1 response induced in mice and human by the PL as adjuvant.
文摘Nanogels-particles of polymer gels having the dimensions in the order of nanometers-are gaining attention for their wide application as biomaterials. Mainly, the nanogels are promising novel pharmaceutical carriers for small biologically active agents, bin macromolecules and can be chemically modified to incorporate various ligands for targeted drug delivery. This important factor has stimulated research on dissimilar science field such as nanotechnology and biotechnology, polymer and materials sciences, biochemistry, radiation chemistry and pharmaceutical sciences. A multitude of techniques have been described for the synthesis of this nanomaterial from polymers. However, the use of ionizing radiation （γ, e-） has demonstrated to be especially suitable for obtaining polymeric nanogels with a high degree of purity for biomedical applications, although the gamma radiation has not been widely utilized for these purposes. The aim of this paper is to develop the synthesis of PVP （polyvynilpyrrolidone） nanogels by gamma irradiation, for their evaluation as potential pharmaceutical carriers. Experiments were performed using argon saturated solution of PVP （0.1-1%）. Crosstinking reactions were carried out in a gamma irradiation chamber with a 60Co source （ISOGAMMA LLCo）, at room temperature. The PVP concentration influence was evaluated in PVP solutions （0.1% and 0.25%） at 15 kGy. The SEM （scanning electron microscopy）, ATR （attenuate total reflection spectroscopy）, DLS （dynamic light scattering）, and viscosimetry were used as characterization techniques.
