Ischemic stroke is a leading cause of disability worldwide. In cerebral ischemia there is an enhanced expression of matrix metallo-proteinase-9 (MMP-9), which has been associated with various complications including excitotoxicity, neuronal damage, apoptosis, blood–brain barrier (BBB) opening leading to cerebral edema, and hemorrhagic transformation. Moreover, the tissue plasminogen activator (tPA), which is the only US-FDA approved treatment of ischemic stroke, has a brief 3 to 4 h time window and it has been proposed that detrimental effects of tPA beyond the 3 h since the onset of stroke are derived from its ability to activate MMP-9 that in turn contributes to the breakdown of BBB. Therefore, the available literature suggests that MMP-9 inhibition can be of therapeutic importance in ischemic stroke. Hence, combination therapies of MMP-9 inhibitor along with tPA can be beneficial in ischemic stroke. In this review we will discuss the current status of various strategies which have shown neuroprotection and extension of thrombolytic window by directly or indirectly inhibiting MMP-9 activity. In the introductory part of the review, we briefly provide an overview on ischemic stroke, commonly used models of ischemic stroke and a role of MMP-9 in ischemia. In next part, the literature is organized as various approaches which have proven neuroprotective effects through direct or indirect decrease in MMP-9 activity, namely, using biotherapeutics, involving MMP-9 gene inhibition using viral vectors; using endogenous inhibitor of MMP-9, repurposing of old drugs such as minocycline, new chemical entities like DP-b99, and finally other approaches like therapeutic hypothermia.

Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive learning and positive emotions motivating appetitive learning. The amygdala is a key component of the brain emotional system; however, an understanding of how various emotions are differentially processed in the amygdala has yet to be achieved. We report that matrix metalloproteinase-9 (MMP-9, extracellularly operating enzyme) in the central nucleus of the amygdala (CeA) is crucial for appetitive, but not for aversive, learning in mice. The knock-out of MMP-9 impairs appetitively motivated conditioning, but not an aversive one. MMP-9 is present at the excitatory synapses in the CeA with its activity greatly enhanced after the appetitive training. Finally, blocking extracellular MMP-9 activity with its inhibitor TIMP-1 provides evidence that local MMP-9 activity in the CeA is crucial for the appetitive, but not for aversive, learning.

This update review is on mucoadhesive polymers used in nasal dosage forms. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The various new technology uses in development of nasal drug delivery dosage forms are discussed. The various dosage forms are vesicular carriers (liposome, noisome), nanostructured particles, prodrugs, in situ gelling system with special attention to in vivo studies.

Aim The aim of this study was to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for delivery of a protein – tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) – across the blood–brain barrier (BBB) to inhibit deleterious matrix metalloproteinases (MMPs). Materials and methods The NPs were formulated by multiple-emulsion solvent-evaporation, and for enhancing BBB penetration, they were coated with polysorbate 80 (Ps80). We compared Ps80-coated and uncoated NPs for their toxicity, binding, and BBB penetration on primary rat brain capillary endothelial cell cultures and the rat brain endothelial 4 cell line. These studies were followed by in vivo studies for brain delivery of these NPs. Results Results showed that neither Ps80-coated nor uncoated NPs caused significant opening of the BBB, and essentially they were nontoxic. NPs without Ps80 coating had more binding to endothelial cells compared to Ps80-coated NPs. Penetration studies showed that TIMP-1 NPs + Ps80 had 11.21%±1.35% penetration, whereas TIMP-1 alone and TIMP-1 NPs without Ps80 coating did not cross the endothelial monolayer. In vivo studies indicated BBB penetration of intravenously injected TIMP-1 NPs + Ps80. Conclusion The study demonstrated that Ps80 coating of NPs does not cause significant toxic effects to endothelial cells and that it can be used to enhance the delivery of protein across endothelial cell barriers, both in vitro and in vivo.

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Water quality monitoring exercise was carried out with water quality index (WQI) method by using water characteristics data for bore wells and a water treatment plant in Delhi city from December 2006 to August 2007. The water treatment plant received surface water as raw water, and product water is supplied after treatment. The WQI is used to classify water quality as excellent, good, medium, bad, and very bad. The National Sanitation Foundation WQI procedure was used to calculate the WQI. The index ranges from 0 to 100, where 100 represents an excellent water quality condition. Water samples were collected monthly from a bore well in Nehru Camp (site 1), a bore well in Sanjay Gandhi pumping station (site 2), and water treatment plant in Haiderpur (site 3). Five parameters were analyzed, namely, nitrate, pH, total dissolved solids, turbidity, and temperature. We found that the WQI was around 73-80 in site 3, which corresponds to "good," and it decreased to 54.32-60.19 and 59.93-70.63 in site 1 and site 2, respectively, indicating that these bore wells were classified as "medium" quality.

Background A study was carried out to classify municipal solid waste (MSW) compost produced in Delhi, India for their marketability and use in different area with respect to physico-chemical properties, fertilizing and heavy metal polluting potentials. Results The pH of the compost was slightly alkaline (8.4 ± 0.02) and C:N ratio (9.46 ± 0.91) was low as compared to Fertilizer Control Order (FCO) Standard, Government of India, 1985. Sample analysis was carried out using standard methods. The concentrations of some selected heavy metals, e.g., Zn, Cd and Ni were within the permissible limit of FCO standard. However, the concentrations of Cu, Pb and Cr exceeded (66.7 %) the permissible limit of FCO standard. Further, the compost was characterized to know the fertilizing potential and its potential to contaminate the soil. Fertilizing index (FI) was calculated from the values of TOC, TN, TP, TK and C:N ratio and clean index (CI) was also calculated using heavy metal concentrations. FI value of compost was varied from 4.47 to 4.60, whereas CI value of compost was varied from 2.33 to 2.87, respectively. Conclusions The study results indicated that majority of MSW compost produced in Delhi failed to achieve quality control guidelines of FCO standard. The compost has fertilizing potential, however, certain risk to the environment.Hence, the prepared compost in Delhi was not suitable for its intended purpose. Post-treatment of compost is required to improve the quality of compost, which can be utilized for agricultural purposes.

Orthodontic treatment need among 33.4% calls for developing school based oral health promotion programmes for children with an inculcation of orthodontic treatment and educational programmes for parents (fishermen) addressing prevention and early interceptive treatment of malocclusion.