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1.
Toxins (Basel) ; 13(9)2021 08 26.
Article in English | MEDLINE | ID: mdl-34564599

ABSTRACT

The alpha (CPA), beta (CPB) and epsilon (ETX) toxins of Clostridium perfringens are responsible for causing diseases that are difficult to eradicate and have lethal potential in production animals. Vaccination of herds is still the best control strategy. Recombinant clostridial vaccines have shown good success at inducing neutralizing antibody titers and appear to be a viable alternative to the conventional production of commercial clostridial toxoids. Research is still needed on the longevity of the humoral immune response induced by recombinant proteins in immunized animals, preferably in target species. The objective of this study was to measure the humoral immune response of cattle immunized with trivalent vaccines containing the recombinant proteins alpha (rCPA), beta (rCPB) and epsilon (rETX) of C. perfringens produced in Escherichia coli at three different concentrations (100, 200, and 400 µg) of each protein for 12 months. The recombinant vaccines containing 200 (RV2) and 400 µg (RV3) yielded statistically similar results at 56 days. They performed better throughout the study period because they induced higher neutralizing antibody titers and were detectable for up to 150 and 180 days, respectively. Regarding industrial-scale production, RV2 would be the most economical and viable formulation as it achieved results similar to RV3 at half the concentration of recombinant proteins in its formulation. However, none of the vaccines tested induced the production of detectable antibody titers on day 365 of the experiment, the time of revaccination typically recommended in vaccination protocols. Thus, reiterating the need for research in the field of vaccinology to achieve greater longevity of the humoral immune response against these clostridial toxins in animals, in addition to the need to discuss the vaccine schedules and protocols adopted in cattle production.


Subject(s)
Antibodies, Neutralizing/blood , Bacterial Toxins/immunology , Cattle Diseases/immunology , Cattle Diseases/prevention & control , Clostridium Infections/immunology , Clostridium Infections/prevention & control , Clostridium perfringens/immunology , Recombinant Proteins/immunology , Animals , Antibodies, Neutralizing/immunology , Bacterial Toxins/toxicity , Bacterial Vaccines/administration & dosage , Bacterial Vaccines/immunology , Brazil , Cattle , Cattle Diseases/blood , Cattle Diseases/microbiology , Clostridium Infections/veterinary , Recombinant Proteins/administration & dosage
2.
Eur J Med Chem ; 45(12): 5671-7, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20884094

ABSTRACT

2-acetylpyridine N(4)-phenyl thiosemicarbazone (H2Ac4Ph), and its N(4)-ortho-tolyl (H2Ac4oT), N(4)-meta-tolyl (H2Ac4mT), N(4)-para-tolyl (H2Ac4pT), N(4)-ortho-chlorophenyl (H2Ac4oClPh), N(4)-meta-chlorophenyl (H2Ac4mClPh) and N(4)-para-chlorophenyl (H2Ac4pClPh) derivatives were assayed for their cytotoxicity against RT2 (expressing p53 protein) and against T98 (expressing mutant p53 protein) glioma cells. The compounds were highly cytotoxic against RT2 (IC50=24-1.4 nM) and T98 cells (IC50=50-1.0 nM). IC50 for cisplatin=5 (RT2) and 17 µM (T98). The thiosemicarbazones presented haemolytic activity with IC50>10(-3)M, indicating a very good therapeutic index. SAR studies suggested that stereo properties are critical to define the potential activity of the studied compounds against the RT2 cell line, while electronic properties seem to be important for interaction with the biological target in T98 cells.


Subject(s)
Apoptosis/drug effects , Glioma/drug therapy , Thiosemicarbazones/pharmacology , Animals , Crystallography, X-Ray , Dose-Response Relationship, Drug , Glioma/pathology , Models, Molecular , Molecular Structure , Rats , Stereoisomerism , Structure-Activity Relationship , Thiosemicarbazones/chemistry , Tumor Cells, Cultured
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