ABSTRACT
Translational research using small laboratory animals is being done to demonstrate proof of concept, to study pharmacokinetics as well as to understand efficacy and safety of new drug molecules. During the evaluation of a drug candidate, the assessment of efficacy and safety is normally performed in different experiments using various animal models. In such experiments, efficacy is assessed by mimicking the disease state in animal model while safety is investigated in healthy animals. Inventing new drugs using biotechnological and nanotechnological approaches is becoming a major thrust area in drug research. Apart from this, the development of medicine from traditional knowledge like Ayurveda has emerged as major area for drug industry. Use of conventional in-vivo approaches may not prove useful to answer many questions. Transgenic/knock-out/knock-in animals are now getting space in pharmaceutical research for target identification and validation. Predictability of in-vivo research depends on scientific protocols and methods adopted for model selection and development. Various alternative approaches for in-vivo research are being followed. It is a fact that no animal model is 100 % capable of mimicking the complex human body but still, researchers have not yet found any alternative model which can completely replace in-vivo models. This review is a holistic approach explaining the various animal models being used for translational research, animal ethical issues, alternative approaches available and provides a critical analysis of major issues/challenges faced in translational research using in-vivo approaches.
ABSTRACT
Airway remodeling in asthma is recognized as irreversible structural change. However, several recent reports revealed that remodeling might be the process of repair from injury. Airway remodeling is increasingly recognised to be a serious consequence of chronic asthma.Stat3 and Cytokines play an integral role in the coordination and persistence of inflammation. However, exact role of Stat3 in airway inflammation is lacking. In the present study BALB/c mice were sensitized and challenged with OVA (OVA/OVA) after validation these mice models were further studied to check silencing effect of Stat3 .mRNA and ELISA studies revealed alteration in IL-4, IL-5, IL-13 and TGF-β in BALF and lung with blood eosinophilia also airway hyperresponsiveness in OVA/OVA mice. Airway hyperresponsiveness was studied by methacholine-induced specific airway resistance in a plethysmogrpah while eosinophils study was done using automatic blood analyser. Total and OVA-specific IgG and IgE antibodies depicted significant rise among mice sensitized and challenged with OVA. Studies pertaining to histology revealed fibrous tissue proliferation along with other inflammatory changes in airway structure among OVA/OVA mice and it are the characteristic of human model of asthma. Heightened expression of TGF-β and proliferation of fibrous tissue in lungs are directly related. On the contrary SAL/SAL mice revealed normal blood eosinophils. There was no change in IL-4, IL-5, IL-13 and TGF-β also OVA-specific IgG and IgE antibodies in SAL/SAL mice presented normal range. Our earlier studies showed downregulation of Stat3 gene in airway tissues is related with airway inflammation in a mouse model of asthma using this background we tried to study airway histology after silencing Stat3 gene in OVA/OVA mice interestingly our results showed that silencing Stat3 did not help in restoring airway histology in OVA/OVA mice in addition to this investigations pertaining to cytokines, immunoglobulins, blood eosinophils, sRAW and mRNA studies did not depicted any sign of restoration.
ABSTRACT
Thirty-two bacterial isolates were obtained from wheat rhizosphere in black cotton soils of North Maharashtra region and subsequently tested for in-vitro siderophore production. Wheat isolate SCW1, being a strong siderophore producer, was selected, identified and confirmed as Acinetobacter calcoaceticus. The strain produced catechol type of siderophores during exponential phase which was influenced by iron content of medium. Seed bacterization with siderophoregenic A.calcoaceticus improved plant growth in pot and field studies. Such PGPR activity was attributed to the ability of strain to solubilise phosphates and produce IAA. Siderophore mediated antagonism was observed against common phytopathogens viz., Aspergillus flavus, A. niger, Colletotrichum capsicum and Fusarium oxysporum