A REVIEW ON ROLE OF UTTAR BASTI IN THE MANAGEMENT OF ERECTILE DYSFUNCTION

In Ayurveda classics, Klaibya refers to erectile dysfunction i.e., a man who is unable to perform satisfactory sexual intercourse. Various Acharyas has mentioned different causes of the Klabiya likes psychogenic, neurogenic, vascular pathological factors. Male sexual dysfunctions are the most common of the psychosexual disorders in clinical practice. It refers to a problem during any phase of the sexual response cycle that prevents the man from experiencing satisfaction from the activity. Mainly Dhwajabhangaja Klaibya can be compared with the erectile dysfunction on the basis of symptoms. Basti is unique form of treatment modality that not only expels the vitiated Doshas rapidly but also nourishes the body. Charaka considered Basti as Ardhachikitsa, Uttarbasti is an important Panchakarma procedure where the medicated oil, Ghrita or decoction is administered into urinary bladder or uterus and is indicated in genito-urinary disorders of both male and female. Uttarbasti is the prime line of treatment in the case of Klaibya; it deliberates to overcome the Dhatukshaya, Shukrakshaya and Jara-avastha. Probably Uttarbasti acts by following mechanisms first pass metabolism, bladder permeability barrier, neurological stimulation, psychological stimulation. In the results of aphrodisiacs as well as rejuvenation therapy (i.e., Uttarbasti) and medication therapies are more effects on erectile dysfunction that may helps in process of erection

Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2

New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 ( 2 ) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 ( Pf eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline ( 2 ) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency

Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum

In vitro evolution of drug resistance is a powerful approach for identifying antimalarial targets, however, key obstacles to eliciting resistance are the parasite inoculum size and mutation rate. Here we sought to increase parasite genetic diversity to potentiate resistance selections by editing catalytic residues of Plasmodium falciparum DNA polymerase δ. Mutation accumulation assays reveal a ~5–8 fold elevation in the mutation rate, with an increase of 13–28 fold in drug-pressured lines. Upon challenge with the spiroindolone PfATP4-inhibitor KAE609, high-level resistance is obtained more rapidly and at lower inocula than wild-type parasites. Selections also yield mutants with resistance to an “irresistible” compound, MMV665794 that failed to yield resistance with other strains. We validate mutations in a previously uncharacterised gene, PF3D7_1359900, which we term quinoxaline resistance protein (QRP1), as causal for resistance to MMV665794 and a panel of quinoxaline analogues. The increased genetic repertoire available to this “mutator” parasite can be leveraged to drive P. falciparum resistome discovery

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.</p

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Role of Public Library in Making New Dimension in Digital Information and Reference Service

Information being very much essential to the users they opt for those information sources and services which are with ease of accessibility and utility. Giant search engines are playing dominant role in this field with their interface technology. Public libraries are facing intense cruciality in the juncture of their traditional mode of information and reference service. Corporate search engines are driven by the motif of generating more and more revenues for the corporate advertisement providers. They serve such information along with news that base not on, in some cases, reason or experiment. The public library with its splendour of scholarly and rich collection to stand by the true information and reference service and this demands the public libraries to adhere several steps, such as making online availability of its resources, collaboration with academic partners, standing by the principle of equal and free access and taking innovative steps amidst crises to uphold the philosophy ‘people’s local gateway to information

Recent advances in alginate based gastroretentive technologies for drug delivery applications

The efficacy of orally delivered medicines can be maximized through enhancing the gastric residence period and modifying the drug release pattern according to therapeutic need. Several technologies were investigated through recent years for increasing gastric retention of medicines. Biopolymers are one of the widely studied materials for increasing the retention of drug delivery systems in the stomach region. The biodegradability, biocompatibility and non-toxic behavior in combination with the easy fabrication technologies has made biopolymers an interesting option to pharmaceutical scientists for developing gastroretentive drug delivery systems (GRDDS). Several gastroretentive approaches are reported to be efficacious to localize the drug delivery system in the gastric region. Alginates are commonly employed polysaccharide for developing various GRDDS including low density systems, mucoadhesive systems, swellable systems, hydrogel forming systems, in situ gelling systems, raft forming systems, magnetic systems. The abundant availability from marine and bacterial sources in combination with its attractive physicochemical nature has encouraged pharmaceutical researchers to investigate its suitability in developing various drug delivery system. The mucoadhesive, hydrogel forming and raft forming behavior of alginates makes alginate suitable for GRDDS. The attractive properties of alginate makes it a useful biopolymer in the biomedical field. This review focuses on the source and chemistry of alginates and describes the applications of alginates in developing novel gastroretentive drug delivery systems

Applying Analytic Hierarchy Process for Identifying Best Management Practices in Erosion Risk Areas of Northwestern Himalayas

Despite the growing importance of soil and water conservation and watershed development projects as an approach to rural development and natural resource management, there has been relatively little research on devising site-specific best management practice (BMP) to check the soil erosion losses within permissible limits, especially in hilly regions. For a sustainable watershed management programme and implementation, site specific BMPs assume importance and hold the promise of making conservation planning and watershed management simpler and more effective. The study was attempted to develop a methodology to obtain BMPs, aiming to reduce the erosion losses in erosion risk areas of the northwestern Himalayas by employing Analytic Hierarchy Process (AHP). The AHP technique was employed to prioritise the potential technologies and select the BMP suitable for a particular land area. The prioritization of technologies was performed with four criteria viz. soil erosion resistance, cost, benefit, maintenance and environment friendliness of conservation measures. The soil erosion scenario of the study area located in the northwestern Himalayas was generated with each selected measure in a SWAT model using DEM, land use maps, a soil map and climate data of the study area. Then, the resultant erosion scenario of the conservation measures was compared and used for the AHP analysis. However, other criteria were assessed based on the judgement of a group of experts as well as farmers. In this study, four conservation measures, viz. Bench Terraces (BT), Vegetative Barrier (VB), Contour Farming (CF) and Zero Tillage + Live Mulch (ZL), were considered for BMP selection. Three scenarios, viz. experts&rsquo; judgement, farmers&rsquo; opinions and combined expert and farmer opinion, were analyzed to uncover the BMP for the different zones. The result revealed that experts and farmers unanimously preferred ZL as a BMP because of its low-cost implementation value and lower maintenance requirement while significantly controlling the erosion level as well as being environment friendly. The BT was the second most preferred technology for the study area. However, BMP was recommended for different zones having high to very severe erosion (soil loss &gt; 10 t/ha/yr). Therefore, ZL was recommended for the areas with low altitude, whereas BT was recommended for the areas having high slopes because of its high capability for erosion control in the high slopping area. The methodology will act as a useful strategy for decision makers to prioritize the technology and recommend the best management for any region after considering suitable criteria. Future work may consider more criteria for inclusion to thus recommend the technology for a region in a more realistic way

Applying Analytic Hierarchy Process for Identifying Best Management Practices in Erosion Risk Areas of Northwestern Himalayas

Despite the growing importance of soil and water conservation and watershed development projects as an approach to rural development and natural resource management, there has been relatively little research on devising site-specific best management practice (BMP) to check the soil erosion losses within permissible limits, especially in hilly regions. For a sustainable watershed management programme and implementation, site specific BMPs assume importance and hold the promise of making conservation planning and watershed management simpler and more effective. The study was attempted to develop a methodology to obtain BMPs, aiming to reduce the erosion losses in erosion risk areas of the northwestern Himalayas by employing Analytic Hierarchy Process (AHP). The AHP technique was employed to prioritise the potential technologies and select the BMP suitable for a particular land area. The prioritization of technologies was performed with four criteria viz. soil erosion resistance, cost, benefit, maintenance and environment friendliness of conservation measures. The soil erosion scenario of the study area located in the northwestern Himalayas was generated with each selected measure in a SWAT model using DEM, land use maps, a soil map and climate data of the study area. Then, the resultant erosion scenario of the conservation measures was compared and used for the AHP analysis. However, other criteria were assessed based on the judgement of a group of experts as well as farmers. In this study, four conservation measures, viz. Bench Terraces (BT), Vegetative Barrier (VB), Contour Farming (CF) and Zero Tillage + Live Mulch (ZL), were considered for BMP selection. Three scenarios, viz. experts’ judgement, farmers’ opinions and combined expert and farmer opinion, were analyzed to uncover the BMP for the different zones. The result revealed that experts and farmers unanimously preferred ZL as a BMP because of its low-cost implementation value and lower maintenance requirement while significantly controlling the erosion level as well as being environment friendly. The BT was the second most preferred technology for the study area. However, BMP was recommended for different zones having high to very severe erosion (soil loss > 10 t/ha/yr). Therefore, ZL was recommended for the areas with low altitude, whereas BT was recommended for the areas having high slopes because of its high capability for erosion control in the high slopping area. The methodology will act as a useful strategy for decision makers to prioritize the technology and recommend the best management for any region after considering suitable criteria. Future work may consider more criteria for inclusion to thus recommend the technology for a region in a more realistic way