Current Issue : October - December Volume : 2012 Issue Number : 4 Articles : 6 Articles
The development of animal models of dengue virus (DENV) infection and\r\ndisease has been challenging, as epidemic DENV does not naturally infect non-human\r\nspecies. Non-human primates (NHPs) can sustain viral replication in relevant cell types\r\nand develop a robust immune response, but they do not develop overt disease. In contrast,\r\ncertain immunodeficient mouse models infected with mouse-adapted DENV strains show\r\nsigns of severe disease similar to the ââ?¬Ë?vascular-leakââ?¬â?¢ syndrome seen in severe dengue in\r\nhumans. Humanized mouse models can sustain DENV replication and show some signs of\r\ndisease, but further development is needed to validate the immune response. Classically,\r\nimmunocompetent mice infected with DENV do not manifest disease or else develop\r\nparalysis when inoculated intracranially; however, a new model using high doses of DENV\r\nhas recently been shown to develop hemorrhagic signs after infection. Overall, each\r\nmodel has its advantages and disadvantages and is differentially suited for studies of\r\ndengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs\r\nand vaccines...
Chalcones are chemical compounds that show hopeful obliging efficacy in controlling numerous diseases. The main objective of the study is to evaluate the in vitro human red blood cell membrane stabilization assay of some novel chalcone derivatives. Four different chalcone derivatives were selected for synthesis by Claisen-Schmidt method. The in vitro human red blood cell membrane stabilization assay was performed for the synthesized compounds. The percentage of membrane stabilization activity was calculated for the synthesized compounds. The IC50 values of the compounds, PC-1, PC-2, PC-3 and PC-4 was found to be 113.94±0.42 µg/mL, 87.38±0.67 µg/mL, 146.67±0.35 µg/mL and 67.97±0.27 µg/mL respectively. The order of potency (IC50) of the chalcone and chalcone oxide in HRBC membrane stabilization assay was PC-4 > PC-2 > PC-1 >PC-3. The IC50 of the standard (Diclofenac) was found to be 37.03±0.16 µg/mL. Further in vivo studies are to be carried out for these compounds to confirm their activity thereby develops a potential drug candidate for inflammation....
Depression is a common psychiatric disorder or a mental state or chronic mental disorder characterized by feelings of sadness, loneliness, despair, low self-esteem, and self-reproach; accompanying signs include psychomotor retardation (or less frequently agitation), withdrawal from social contact, and vegetative states such as loss of appetite and insomnia. This disorder is with diverse symptoms and high comorbidity with other brain dysfunctions. Due to this complexity, little is known about the neural and genetic mechanisms involved in depression pathogenesis. Clinical and preclinical trials suggest a disturbance in central nervous system (CNS) serotonin (5-HT) activity as an important factor. Other neurotransmitters implicated include norepinephrine (NE) and dopamine (DA). In a large proportion of patients, current antidepressant treatments are often ineffective and/or have undesirable side effects, fueling the search for more effective drugs. Some drugs used in depression are fluoxetine, amitriptyline, doxepin, impiramine. Animal models mimicking various symptoms of depression are indispensable in studying the biological mechanisms of this disease. In In vivo method, behavior despair model are forced swim test, tail suspension test, Learned Helplessness in Rats, Muricide behavior in rats, Chronic stress model of depression, etc. In in vitro methods, models are inhibition of 3[H]-norepinephrine uptake in rat brain synaptosomes, antagonism of p-chloramphetamine toxicity by inhibitors of serotonin uptake, etc. So, we summarize several popular methods like in vitro & in vivo for assessing depression-like symptoms in mice and their utility in screening antidepressant drugs....
H1 Antihistamines are used widely in the treatment of allergic disorders and are most effective in relieving the symptoms of seasonal rhinitis and conjunctivitis. . Certain allergic dermatoses, such as acute urticaria, respond favorably to H1 antagonists, which help to relieve the itch in atopic dermatitis or contact dermatitis. H2 Antihistamines (e.g., cimetidine and ranitidine) are used primarily to inhibit gastric acid secretion in the treatment of GI disorders. H2 Antagonists are the drug of choice in treatment of peptic ulceration, Zollinger- Ellison syndrome and gastro-oesophageal reflux disease. H3 antagonists have potential use in improving attention and learning, in stimulating arousal, and as antiepileptic agents. H4 antagonists are promising candidates to treat inflammatory conditions such as allergic rhinitis, asthma, and rheumatoid arthritis. Hence there is need of screening methods for screening of this antagonists. This review presents various models to screen various traditional drugs and modern drugs for histamine (H1, H2, H3, and H4) receptor antagonistic activity. This brings a compilation make easy to go through various models at same time and make it easy to screen the drugs. It reveals principle, apparatus and procedure of these models....
Poor response of human malignant melanoma to currently available treatments\r\nrequires a development of innovative therapeutic strategies. Their evaluation should be\r\nbased on animal models that resemble human melanoma with respect to genetics,\r\nhistopathology and clinical features. Here we used a transgenic mouse model of\r\nspontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under\r\nthe control of metallothionein-I promoter. After a short latency, around 25% mice develop\r\nmacroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain,\r\nwhereas other transgenic mice showed only metastatic lesions without visible skin tumors.\r\nWe found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase,\r\ntyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for\r\nthe immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic\r\nmelanomas were able to generate T cell responses not only against a strong model antigen\r\novalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic\r\nprimary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates.\r\nWe suggest that ret transgenic mice could be used as a pre-clinical model for the\r\nevaluation of novel strategies of melanoma immunotherapy....
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