Current Issue : April - June Volume : 2012 Issue Number : 2 Articles : 9 Articles
Background: Clotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of\nglycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to\nanalyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles.\nMethodology/Principal Findings: Three cell lines derived from human breast tissue (MCF10A, MCF-7 and MDA-MB-231)\nthat present increasingly aggressive profiles were used. Clotrimazole induces a dose-dependent decrease in glucose uptake\nin all three cell lines, with Ki values of 114.3611.7, 77.167.8 and 37.864.2 mM for MCF10A, MCF-7 and MDA-MB-231,\nrespectively. Furthermore, the drug also decreases intracellular ATP content and inhibits the major glycolytic enzymes,\nhexokinase, phosphofructokinase-1 and pyruvate kinase, especially in the highly metastatic cell line, MDA-MB-231. In this\nlast cell lineage, clotrimazole attenuates the robust migratory response, an effect that is progressively attenuated in MCF-7\nand MCF10A, respectively. Moreover, clotrimazole reduces the viability of breast cancer cells, which is more pronounced on\nMDA-MB-231.\nConclusions/Significance: Clotrimazole presents deleterious effects on two human breast cancer cell lines metabolism,\ngrowth and migration, where the most aggressive cell line is more affected by the drug. Moreover, clotrimazole presents\nlittle or no effect on a non-tumor human breast cell line. These results suggest, at least for these three cell lines studied, that\nthe more aggressive the cell is the more effective clotrimazole is....
A case is made in this article that research on animal models of human age-related cataract has contributed little\nto our understanding of this blinding disease. This surprising conclusion comes about not so much for the reason that\nhumans are different from other animals, although important aspects of human lens biochemistry are not matched by\nexperimental animals, but more so because of the very long periods of time that are required before human cataract\nbecome evident.\nInsidious processes associated with aging are required to establish the conditions necessary for human cataract,\nand laboratory animals simply do not live long enough to act as useful models. In relation to human nuclear cataract, the\nlarge sums of money spent on animal models would have been spent more productively on investigating the processes\nthat underpin human lens aging. Lessons derived from human cataract may apply more widely to other human agerelated\ndiseases....
Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative\ngene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad), serotype 2 adeno-associated\nvirus vectors (rAAV2), or self-complementary (sc) AAV2 vectors carrying green fluorescent protein (GFP). Using 6 horses, bilateral\nmetacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint\ninflammation and neutralizing antibody (NAb) titer in serum and joint fluid. In vitro, the greater transduction efficiency and\nsustained gene expression were achieved by scAAV2 compared to rAAV2 in equine chondrocytes and synovial cells. In vivo, AAV2\ndemonstrated less joint inflammation than Ad, but similar NAb titer. The scAAV2 vectors can induce superior gene transduction\nthan rAAV2 in articular cells, and both rAAV2 and scAAV2 vectors were showed to be safer for intra-articular use than Ad vectors....
Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, acts as a potent stimulator of microglia and has been\r\nused to study the inflammatory process in the pathogenesis of Parkinson�s disease (PD) and anti-inflammatory therapy for PD\r\ntreatment. Here, we review the growing body of literature on both in vitro and in vivo LPS PD models. Primary cell cultures from\r\nmesencephalic tissue were exposed to LPS in vitro; LPS was stereotaxically injected into the substantia nigra, striatum, or globus\r\npallidus of brain or injected into the peritoneal cavity of the animal in vivo. In conclusion, the LPS PD models are summarized\r\nas (1) local and direct LPS treatment and (2) systemic LPS treatment. Mechanisms underlying the PD models are investigated\r\nand indicated that LPS induces microglial activation to release a variety of neurotoxic factors, and damaged neurons may trigger\r\nreactive microgliosis, which lead to progressive dopaminergic neurodegeneration....
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The use of experimental models of DN has\r\nprovided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new\r\ntherapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized\r\nto various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have\r\nnot been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or\r\nglomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes\r\ncontinues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms\r\ninvolving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize\r\nthat the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various\r\nmodels of diabetes....
Animal models are important tools in the development of new drug candidates against the inflammatory bowel diseases (IBDs)\r\nCrohnâ��s disease and ulcerative colitis. In order to increase the translational value of these models, it is important to increase\r\nknowledge relating to standard drugs. Using the SCID adoptive transfer colitis model, we have evaluated the effect of currently\r\nused IBD drugs and IBD drug candidates, that is, anti-TNF-a, TNFR-Fc, anti-IL-12p40, anti-IL-6, CTLA4-Ig, anti-a4�Ÿ7 integrin,\r\nenrofloxacin/metronidazole, and cyclosporine.We found that anti-TNF-a, antibiotics, anti-IL-12p40, anti-a4�Ÿ7 integrin, CTLA4-\r\nIg, and anti-IL-6 effectively prevented onset of colitis, whereas TNFR-Fc and cyclosporine did not. In intervention studies,\r\nantibiotics, anti-IL-12p40, and CTLA4-Ig induced remission, whereas the other compounds did not. The data suggest that the\r\nadoptive transfer model and the inflammatory bowel diseases have some main inflammatory pathways in common. The finding\r\nthat some well-established IBD therapeutics do not have any effect in the model highlights important differences between the\r\nexperimental model and the human disease....
Parkinson’s disease is a disorder of dopaminergic fibres. The extrapyramidal system (Basal Ganglia and Substantia nigra) controls the body movement by a balance between cholinergic excitatory and dopaminergic inhibitory influences. In this disease, there is loss of dopaminergic fibres due to decrease in number of melanin containing neurons in substantia nigra. Most commonly used in vivo screening models are MPTP model in monkey, reserpine antagonism, circling behaviour in lesioned rat while the commonly used in-vitro model is culture of substantia nigra. The drugs used for the treatment of parkinson’s disease have certain limitations in their use because of their side effect such as arrhythmias, headache, migraine, sedation etc. Hence the interest in searching alternative remedies for treatment of parkinson’s disease is greatly increased. The interest in pharmacotherapy of Parkinson’s disease increases so as to reduce side effects of the present drugs. Another interesting area is the search of medicinal plants having antiparkinsonian activity as well as development of new sreening model for Parkinson's disease....
Insomnia is a common problem which includes wide variety of sleep disturbances, like difficulty in falling asleep, early or frequent awaking etc. Sedative-hypnotics are the drugs which reduce anxiety and produce sleep. Use of sedative-hypnotics is one approach to therapy of insomnia. Sedative-hypnotics can induce wide range of central effects from mild sedation to hypnosis. The drugs used as sedative-hypnotics have certain limitations in their use because of their side effect such as idiosyncrasy, hypersensitivity, tolerance and dependence. The interest lies in area of modification of a drug so as to reduce its side effects. Another interesting area is the discovery of herbal remedies producing sedation and hypnosis....
Endothelial dysfunction is one of the main characteristics of chronic hypertension and it is characterized by impaired nitric oxide\n(NO) bioactivity determined by increased levels of reactive oxygen species. Endothelial function is usually evaluated by measuring\nthe vasodilation induced by the local NO production stimulated by external mechanical or pharmacological agent. These vascular\nreactivity tests may be carried out in different models of experimental hypertension such as NO-deficient rats, spontaneously\nhypertensive rats, salt-sensitive rats, and many others. Wire myograph and pressurized myograph are the principal methods used\nfor vascular studies. Usually, increasing concentrations of the vasodilator acetylcholine are added in cumulative manner to perform\nendothelium-dependent concentration-response curves. Analysis of vascular mechanics is relevant to identify arterial stiffness.\nBoth endothelial dysfunction and vascular stiffness have been shown to be associated with increased cardiovascular risk....
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