Medical principles and practice : international journal of the Kuwait University, Health Science Centre
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The need for drugs with fewer side effects cannot be overemphasized. Today, most drugs modify the actions of enzymes, receptors, transporters and other molecules by directly binding to their active (orthosteric) sites. However, orthosteric site configuration is similar in several proteins performing related functions and this leads to a lower specificity of a drug for the desired protein. ⋯ Exploitation of allosteric sites has led to the discovery of drugs which can selectively modulate the activation of only 1 (M1 muscarinic) out of the 12 different types of acetylcholine receptors. These drugs are being tested for schizophrenia treatment. It is anticipated that the drug discovery exploiting allosteric sites will lead to more effective therapeutic agents with fewer side effects.
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Comparative analyses of the Mycobacterium tuberculosis genome with the genomes of other mycobacteria have led to the identification of several genomic regions of difference (RDs) between M. tuberculosis and M. bovis BCG. The identification of immunodominant and HLA-promiscuous antigens and peptides encoded by these RDs could be useful for diagnosis and the development of new vaccines against tuberculosis. The analysis of RD proteins and peptides by in silico methods (using computational programs to predict major and HLA-promiscuous antigenic proteins and peptides) and experimental validations (using peripheral blood mononuclear cells and sera from tuberculosis patients and BCG-vaccinated healthy subjects to assess antigen-specific cellular and humoral immune responses in vitro) identified several major antigens and peptides. ⋯ Immunizations of experimental animals with the recombinant constructs induced antigen-specific cellular responses. Further experiments showed that each of these proteins had several T and B cell epitopes scattered throughout their sequence, which confirmed their strong immunogenicity. In conclusion, the bioinformatics-based in silico identification of promiscuous antigens and peptides of M. tuberculosis is a useful approach to identify new candidates important for diagnosis and vaccine applications.
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The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. ⋯ Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible.
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Randomized Controlled Trial
Thoracic paravertebral block for postoperative pain management in percutaneous nephrolithotomy patients: a randomized controlled clinical trial.
To investigate the effect of thoracic paravertebral block (PVB) on pain control and morphine consumption in percutaneous nephrolithotomy operations. ⋯ Thoracic PVB with levobupivacaine provided a good postoperative analgesia and increased patient satisfaction for those who underwent percutaneous nephrolithotomy.
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To investigate the efficacy of coronary stenting in patients with variant angina refractory to medical treatment. ⋯ The present study showed that coronary stenting for severe refractory coronary vasospasm was effective and without serious complications. It can be an alternative and viable option for some patients who are refractory to medical therapy and at a high risk of acute coronary syndrome recurrence.