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Introduction: The cardio-vascular system being the basis of life along with the respiratory system has always been the centre of attention for researchers. Efforts have been made for ages to prop up the failing heart or to regulate its normal beat & rhythm so that life could be extended. A major source of drugs for the heart is the plant kingdom. With this in mind a saponin from a plant called Albizzia chinensis Merr. was taken up to profile its cardiovascular activities. Materials and Methods: Albichinoside (ALB), the test substance was evaluated for its cardio-vascular activities in dogs, rabbits, rats and frogs. The parameters were its effects on the rate, rhythm and tone of heart, blood pressure and studies on the blood vessels. Results: The test substance produced hypotension, increase in tone & force of contraction of the heart, and dilatation of the blood vessels, without any effect on the heart rate. Conclusions: The compound showed immediate and prolonged hypotension along with cardiotonic effect and vasodilatation. Keywords: Saponin, Cardiovascular system, Animals.

Diclofenac is an extensively used nonsteroidal anti-inflammatory drug, but gastrointestinal liabilities and cardiovascular complications take the shine away from such a widely prescribed drug. On the other hand, rutin, a dietary bioflavonoid, has quite a few pharmacological attributes to improve the efficacy and reduce the dose-related toxicities of diclofenac through the intended food-drug/herb-drug interaction. The aim of the present research work was to investigate the role of rutin on pharmacokinetic modulation and the consequent efficacy of diclofenac. At first, pharmacodynamics and pharmacokinetics of diclofenac as alone and in the presence of rutin were investigated orally in a rat model. Then, mechanistic studies were performed to explain the effect of rutin on improvement in oral exposure as well as the efficacy of diclofenac using a battery of in-vitro/in-situ/in-vivo studies. Results displayed that rutin enhanced efficacy as well as oral bioavailability of diclofenac in rats. A marked increase in permeability of diclofenac by rutin was displayed that is linked to inhibition of Breast Cancer Resistance Protein (BCRP) transporters. There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition in human liver microsomes, and CYP2C9/CYP2C11 expression in rat liver tissues to boost the oral exposure of diclofenac. Rutin is found to be an inhibitor for BCRP transporters and can act as an oral bioavailability enhancer for a drug like diclofenac.

The present study is aimed to develop an eco-friendly method to synthesize silver nanoparticles (AgNPs) by the Polygonatum graminifolium (P. graminifolium) leaf extract. Synthesized AgNPs were characterized by using UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM) and Energy dispersive X-ray spectroscopy (EDS). Resultantly, stable and green synthesized AgNPs were formulated. TEM analysis revealed the spherical shape (3–15 nm) of green synthesized AgNPs and were found efficient antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).

Nanostructures of iron oxide and doped iron oxide with cobalt (Co), nickel (Ni) and zinc (Zn) have been prepared by wet chemical methods using sodium dodecyl sulphate (SDS) as capping agent. X-ray diffraction (XRD) and high resolution transmission electron microscopy (HRTEM) results showed that the nanostructures were crystalline with average crystallite size around 20 nm. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images confirmed the granular shape of the nanostructures with ultra small size. The doping was confirmed in the XRD patterns and was well supported by Fourier transform infrared spectroscopy (FTIR). Band gap for iron oxide nanoparticles was found to be 2.2 eV and on doping the band gap found to be increased up to 2.5 eV. Ultra violet-visible (UV–Vis) measurements and blue shift of the optical band gap compliments the ultra small size of nanostructures as suggested by XRD, SEM and TEM studies. Interestingly, few of the compounds showed promising antifungal activity and might be used for antifungal treatment against fungal infection in future.

Rheumatoid arthritis (RA) is a common chronic disease with inflammatory and immunological background where treatments can only improve the symptoms and slow down the progress of the disease. Although there are several drugs with different therapeutic targets available in the market for the treatment of RA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) are the most effective option to date. Methotrexate, azathioprine, hydroxychloroquine, sulfasalazine, leflunomide, minocycline are commonly prescribed DMARDs by rheumatologists but they have the limitations of severe toxicity for which therapeutic drug monitoring is necessary. Many chromatographic methods are available for analysis of these drugs including their metabolites. However, they have not been critically reviewed for pre-chromatographic sample preparation, chromatographic separation and sensitive detection. This review article can be handy for quantitation of DMARDs in diverse biological matrices as it provides comprehensive information on the reported liquid chromatographic methods for last three decades covering all the aspects required for preclinical and clinical studies.

Diclofenac is an extensively used nonsteroidal anti-inflammatory drug, but gastrointestinal liabilities and cardiovascular complications take the shine away from such a widely prescribed drug. On the other hand, rutin, a dietary bioflavonoid, has quite a few pharmacological attributes to improve the efficacy and reduce the dose-related toxicities of diclofenac through the intended food-drug/herb-drug interaction.The aim of the present research work was to investigate the role of rutin on pharmacokinetic modulation and the consequent efficacy of diclofenac.At first, pharmacodynamics and pharmacokinetics of diclofenac as alone and in the presence of rutin were investigated orally in a rat model. Then, mechanistic studies were performed to explain the effect of rutin on improvement in oral exposure as well as the efficacy of diclofenac using a battery of in-vitro/in-situ/in-vivo studies.Results displayed that rutin enhanced efficacy as well as oral bioavailability of diclofenac in rats. A marked increase in permeability of diclofenac by rutin was displayed that is linked to inhibition of Breast Cancer Resistance Protein (BCRP) transporters. There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition in human liver microsomes, and CYP2C9/CYP2C11 expression in rat liver tissues to boost the oral exposure of diclofenac.Rutin is found to be an inhibitor for BCRP transporters and can act as an oral bioavailability enhancer for a drug like diclofenac. Diclofenac is an extensively used nonsteroidal anti-inflammatory drug, but gastrointestinal liabilities and cardiovascular complications take the shine away from such a widely prescribed drug. On the other hand, rutin, a dietary bioflavonoid, has quite a few pharmacological attributes to improve the efficacy and reduce the dose-related toxicities of diclofenac through the intended food-drug/herb-drug interaction. The aim of the present research work was to investigate the role of rutin on pharmacokinetic modulation and the consequent efficacy of diclofenac. At first, pharmacodynamics and pharmacokinetics of diclofenac as alone and in the presence of rutin were investigated orally in a rat model. Then, mechanistic studies were performed to explain the effect of rutin on improvement in oral exposure as well as the efficacy of diclofenac using a battery of in-vitro/in-situ/in-vivo studies. Results displayed that rutin enhanced efficacy as well as oral bioavailability of diclofenac in rats. A marked increase in permeability of diclofenac by rutin was displayed that is linked to inhibition of Breast Cancer Resistance Protein (BCRP) transporters. There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition in human liver microsomes, and CYP2C9/CYP2C11 expression in rat liver tissues to boost the oral exposure of diclofenac. Rutin is found to be an inhibitor for BCRP transporters and can act as an oral bioavailability enhancer for a drug like diclofenac.

Curcumin, a natural diarylheptanoid, is extensively used as a food additive or dietary supplement on the regular basis. It is known to have potential to encumber the drug transporters and hepatic drug metabolizing enzymes that lead to pharmacokinetic interactions with drug or food. Daclatasvir is a new orally acting drug for the treatment of chronic Hepatitis C Virus infections. This is a substrate of P-glycoprotein and CYP3A4 that are involved in the major pharmacokinetic interaction. Hence, the studies' aim is to assess for any possible pharmacokinetic interactions. Pharmacokinetic studies of daclatasvir in presence or absence of curcumin were carried out in Wistar rats following oral administration. Parallelly, the oral pharmacokinetics of daclatasvir was also determined in the presence of ketoconazole or quinidine. Studies revealed that plasma level of daclatasvir was not altered significantly during concomitant single dose administration of curcumin, whereas significantly decreased upon pretreatment for 7 days with curcumin at high dose level. Ketoconazole and quinidine markedly increase daclatasvir exposure following concomitant administration with daclatasvir. It can be concluded that dose adjustment is unlikely to be required for intermittent use of curcumin at low dose but cautious for chronic and concomitant use of curcumin at a high dose.

Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for new chemical entity (NCE) which can be not only effective against both susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also safe and faster acting with the target, thereby shortening the prolonged TB treatments. We have identified a potential nitrofuranyl methyl piperazine derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory concentration (MIC) value of 0.0072 μM against H37Rv strain. Objective of the present study is to investigate physicochemical, pharmacokinetic, efficacy and toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive manner to assess the likelihood of developing IIIM-MCD-211 as a clinical candidate. Results of computational prediction reveal that compound does not violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays evidence of P-glycoprotein (P-gp) induction but no inhibition ability in rhodamine cell exclusion assay. IIIM-MCD-211 shows high permeability and plasma protein binding based on parallel artificial membrane permeability assay (PAMPA) and rapid equilibrium dialysis (RED) assay model, respectively. IIIM-MCD-211 has adequate metabolic stability in rat liver microsomes (RLM) and favourable pharmacokinetics with admirable correlation during dose escalation study in Swiss mice. IIIM-MCD-211 has capability to appear into highly perfusable tissues. IIIM-MCD-211 is able to actively prevent progression of TB infection in chronic infection mice model. IIIM-MCD-211 shows no substantial cytotoxicity in HepG2 cell line. In acute toxicity study, significant increase of total white blood cell (WBC) count in treatment group as compared to control group is observed. Overall, amenable preclinical data make IIIM-MCD-211 ideal candidate for further development of oral anti-TB agent.

Purpose: Neoadjuvant chemotherapy is recommended in patients with locally advanced breast cancer. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables evaluation of the tumour neovasculature that occurs prior to any volume change, which helps identify early treatment failures and allows prompt implementation of second-line therapy. Material and methods: We conducted a prospective study in 14 patients with histopathologically proven breast cancer. DCE-MRI data were acquired using multisection, T1-weighted, 3D vibe sequences with fat suppression before, during, and after IV bolus injection (0.1 mmol/kg body weight, Gadoversetamide, Optimark). Post-processing of dynamic contrast perfusion data was done with the vendor's Tissue 4D software to generate various dynamic contrast parameters, i.e. Ktrans, Kep, Ve, initial area under the time signal curve (IAUC), apparent diffusion coefficient (ADC), and enhancement curve. Patients underwent MRI examinations at baseline, and then after two cycles, and finally at completion of chemotherapy. Results: Based on Sataloff criteria for pathological responses, four patients out of 14 were responders, and 10 were non-responders. At the 2nd MRI examination, IAUC was significantly smaller in responders than in non-responders (p = 0.023). When the results of the first and second MRI examinations were compared, Kep decreased from baseline to the second MRI (p = 0.03) in non-responders and in responders (p = 0.04). This change was statistically significant in both groups. The ADC values increased significantly in responders from baseline to the third MRI (p = 0.012). Conclusions: In our study, IAUC and ADC were the only parameters that reliably differentiated responders from non-responders after two and three cycles of chemotherapy.

In the present study, a simple, sensitive, specific and rapid liquid chromatography (LC) tandem mass spectrometry (MS/MS) method was developed and validated according to the Food and Drug Administration (FDA) guidelines for estimation of IIIM-MCD-211 (a potent oral candidate with promising action against tuberculosis) in mice plasma using carbamazepine as internal standard (IS). Bioanalytical method consisted of one step protein precipitation for sample preparation followed by quantitation in LC-MS/MS using positive electrospray ionization technique (ESI) operating in multiple reaction monitoring (MRM) mode. Elution was achieved in gradient mode on High Resolution Chromolith RP-18e column with mobile phase comprised of acetonitrile and 0.1% (v/v) formic acid in water at the flow rate of 0.4mL/min. Precursor to product ion transitions (m/z 344.5/218.4 and m/z 237.3/194.2) were used to measure analyte and IS, respectively. All validation parameters were well within the limit of acceptance criteria. The method was successfully applied to assess the pharmacokinetics of the candidate in mice following oral (10mg/kg) and intravenous (IV; 2.5mg/kg) administration. It was also effectively used to quantitate metabolic stability of the compound in mouse liver microsomes (MLM) and human liver microsomes (HLM) followed by its in-vitro-in-vivo extrapolation.

Plant derived natural products have been the major source for treatment of diseases traditionally but with the advent of modern systems of medicine, there is need to explore the active constituents present in it followed by modification for better therapeutic activity, low toxicity and favorable pharmacokinetics to become a drug molecule. A simple, rapid and sensitive high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated according to Food and Drug Administration guidelines for determination of IS01957, a derivative of naturally occurring para coumaric acid in mice plasma. The extraction of the analyte and the internal standard (Carbamazepine) from the plasma samples involved protein precipitation using acetonitrile. Results of validation parameters were met with the acceptance criteria of the FDA guidelines. Method was highly sensitive (5 ng/mL) that could determine very low concentration of compound in plasma The developed and validated method was successfully applied to determine compound’s metabolic stability in mouse liver microsomes (MLM) and human liver microsomes (HLM). Test compound was found to be stable in MLM and HLM in the experimental conditions. Metabolic stability data was extrapolated which was further correlated to pharmacokinetics study in mice through oral, intraperitoneal and intravenous administration. In-vitro half life was found to be greater than 2 h in both MLM and HLM. Hepatic extraction ratio of the compound was found to be in the intermediate range. Pharmacokinetic evaluations revealed that it is a suitable candidate for intraperitoneal as well as oral administration.

We report the chemical synthesis of Ofornine mimics from l-vasicine, structure-activity relationship studies and their in vivo screening for anti-hypertensive action in Wistar rats. It was observed that most of the analogs possessed anti-hypertensive effect; however, the duration of the effect was variable and mostly transient. The results demonstrated that the analogs 12, 13, 14, 15, and 16 showed a sharp and significant decrease in systolic and diastolic blood pressure for 30-60min after intravenous administration. Analog (S)-(3-hydroxypyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone (8) showed a significant decrease in blood pressure in a dose dependent manner whose maximal response lowered to 79.29±4.26mmHg of SBP and 62.55±2.9 of DBP at 10mg/kg intravenous dose. Further, the significant anti-hypertensive effect of 8 lasted for about 2.5h at 10mg/kg dose. We also evaluated the acute toxicity of the analog 8 as per the OECD guidelines and the compound was found to be safe up to the dose of 2000mg/kg body weight. These preclinical findings suggest that the analog 8 could be considered as a promising lead and a durable anti-hypertensive drug candidate and deserves further investigation. The SAR studies clearly showed that the amide, hydroxyl and pyridine ring plays important role in showing the activity.

Diclofenac is one of the world's largest selling nonsteroidal anti-inflammatory drugs. The major concerns related to oral diclofenac therapy are gastrointestinal and cardiovascular side effects for which explicitly emphasis has been given to use it at lowest effective dose for the shortest duration. On the other hand, IS01957 has been designed under the purview of anti-inflammatory drug and bioavailability enhancer. IS01957 have dual action on inflammation and nociception with acceptable safety profile. In the quest for a suitable combination with improved therapeutic efficacy and better tolerability, pharmacodynamic and pharmacokinetic interaction studies were performed for diclofenac with or without IS01957 in mice model. Results showed that IS01957 enhanced both anti-inflammatory effect and plasma concentration of diclofenac upon concomitant oral administration. These interesting results steered to enumerate the possible role of IS01957 towards diclofenac pharmacokinetics through a panel of mechanistic investigations: (a) BCRP dependent ATPase activity was markedly interfered by IS01957; (b) IS01957 increased the intestinal permeability of diclofenac in the single pass in-situ perfusion model; (c) IS01957 inhibited the CYP2C9 catalyzed diclofenac 4-hydroxylation in human liver microsomes. Immunoblotting results suggest that diclofenac action was improved significantly in the presence of IS01957 involving MAPK pathways. Finally acute gastric damage study showed that IS01957 in combination with diclofenac was better to improve the desired PGE2 level as compare to alone. In nutshell, IS01957 have potential to augment the efficacy of diclofenac through pharmacokinetic modulation. Further investigations are required for dose reduction of diclofenac to combat its liabilities before going into clinical setting.

The recent first phase operations of SST-1 in short pulse mode have provided an excellent opportunity for the essential initial tests and benchmark of the SST-1 Data Acquisition System. This paper describes the SST-1 Data Acquisition systems (DAS), which with its heterogeneous composition and distributed architecture, aims to cover a wide range of slow to fast channels interfaced with a large set of diagnostics. The DAS also provides the essential user interface for data acquisition to cater both on and off-line data usage. The central archiving and retrieval service is based on a dual step architecture involving a combination of Network Attached Server (NAS) and a Storage Area Network (SAN). SST-1 Data Acquisition Systems have been reliably operated in the SST-1 experimental campaigns. At present different distributed DAS caters the need of around 130 channels from different SST-1 diagnostics and its subsystems. PXI based DAS and CAMAC based DAS have been chosen to cater the need, with sampling rates varying from 10Ksamples/sec to 1Msamples/sec. For these large sets of channels acquiring from individual diagnostics and subsystems has been a combined setup, subjected to a gradual phase of optimization and tests resulting into a series of improvisations over the recent operations. In order to facilitate a reliable data acquisition, the model further integrates the objects of the systems with the Central Control System of SST-1 using the TCP/IP communication. The associated DAS software essentially addresses the requirement of an active initialization of acquisition from SST-1 Central control and, subsequently, pushing the sampled data into the NAS for data archival using Ethernet. The focus is also on the need and implementation of loss-less data acquisition for various slow and fast SST-1 diagnostics channels along with synchronization of DAS elements with central timing system. The additional aspects of the system include a service subsystem responsible for data retrieval and analysis of diagnostics data, this integrates a facility to view diagnostics/subsystem signals across the network using a centralized MATLAB based plotting and analysis tool for the SST-1 diagnostics data.

We report a case of intracranial hemangiopericytoma of a young male of 22 years who presented with neurological signs of impaired memory, left hemiparesis, headache, and two episodes of focal seizures. A significant history of head trauma 9 years back was given. A space-occupying lesion was identified in the bilateral frontoparietal region. The surgical intervention involved bilateral frontoparietal craniotomy and Simpson Grade II excision of tumor. Postoperative conformal radiotherapy was administered. A marked neurological improvement was subsequently observed. Peak incidence of this disease is in the fourth or fifth decade. However, our case is an exception presenting at an age of 22 years. Associated history of head trauma has only been infrequently reported in the past.

In the present study, we have evaluated the antifungal activity of the seed, root and leaf of Paeonia emodi (commonly known as Himalayan peony) in four common solvents (acetone, chloroform, methanol and water) against six fungal strains. The methanolic seed extract (MSE) showed promising antifungal activity against Candida albicans (6.25mg/mL), Candida glabrata (3.12mg/mL) and Candida parapsilosis (12.50mg/mL) among all the fungal strains tested. Combination of the MSE with the well-known commercial antifungal drugs amphotericin B (Amp B), nystatin (NYS) and fluconazole (FLC) resulted in the killing of C. glabrata at non-inhibitory concentrations, i.e., 0.35μg/mL for Amp B, 0.55μg/mL for NYS and 1.19μg/mL for FLC. Notably, MSE caused cell wall damage of C. glabrata cells, as confirmed by confocal microscopy, flowcytometry and scanning electron microscopy (SEM). The MSE was fractionated by thin layer chromatography (TLC). TLC-bioautography was used to determine the active compounds present in the MSE. Column chromatography was used to separate the potential active compounds from the MSE. Furthermore, gas chromatography-mass spectrometry (GC-MS) andfourier-transform infrared spectroscopy (FTIR) were used to identify the phytocomponents of the MSE. These experiments revealed 13-docosenamide/9-octadecenamide/trans-13-docosenamide (89.70%) as being the predominant compound using a chloroform/methanol solvent system for the separation. Interestingly, the MSE also exhibited less significant cytotoxicity at the minimum inhibitory concentration (MIC) against mammalian cells (HeLa and HEK293). This study suggests that the MSE of P. emodi can be used for the treatment of C. glabrata infection.

Aim To compare the compressive strengths of composite resins and resin-modified glass ionomer cements (RMGICs) at different times. Materials and methods A total of 36 samples were prepared, 12 samples of each group, composite resins Filtek Z 250, Filtek Z 350, and resin-modified glass ionomer cement. Compressive strengths of specimens were measured after 1, 24 hours, and 7 days. Test was carried out on a “Universal Testing Machine” with cross-head speed of 5 mm/min. Results There was a significant difference between all the three restorative materials. Analysis of variance showed that mean compressive strengths of Z 250 after 1, 24 hours were higher than Z 350 and RMGIC (p < 0.05). The mean compressive strengths were reduced after 7 days in all the three groups, but after 7 days, the values of Z 250 when compared with the Z 350 and RMGIC were higher. Conclusion The study demonstrated that compressive strengths of hybrid composite resins (Z 250) were significantly higher than that of nanocomposites (Z 350) and RMGIC. How to cite this article Sharma A, Mishra P, Mishra SK. Time-dependent Variation in Compressive Strengths of Three Posterior Esthetic Restorative Materials: An in vitro Study. Int J Prosthodont Restor Dent 2016;6(3):63-65.

Curcumin, a natural diarylheptanoid, is extensively used as a food additive or dietary supplement on the regular basis. It is known to have potential to encumber the drug transporters and hepatic drug metabolizing enzymes that lead to pharmacokinetic interactions with drug or food. Daclatasvir is a new orally acting drug for the treatment of chronic Hepatitis C Virus infections. This is a substrate of P-glycoprotein and CYP3A4 that are involved in the major pharmacokinetic interaction. Hence, the studies' aim is to assess for any possible pharmacokinetic interactions. Pharmacokinetic studies of daclatasvir in presence or absence of curcumin were carried out in Wistar rats following oral administration. Parallelly, the oral pharmacokinetics of daclatasvir was also determined in the presence of ketoconazole or quinidine. Studies revealed that plasma level of daclatasvir was not altered significantly during concomitant single dose administration of curcumin, whereas significantly decreased upon pretreatment for 7 days with curcumin at high dose level. Ketoconazole and quinidine markedly increase daclatasvir exposure following concomitant administration with daclatasvir. It can be concluded that dose adjustment is unlikely to be required for intermittent use of curcumin at low dose but cautious for chronic and concomitant use of curcumin at a high dose.

In the present study, a novel series of 3-pyrimidinylazaindoles were designed and synthesized using a bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription. The present approach gives new dimensions to the existing SAR and opens a new opportunity for the lead optimizations from comparatively inexpensive starting materials. The study led to the identification of the alternative lead candidate 4ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a panel of tested tumor cell lines along with a better safety ratio of ∼33 in comparison to reported leads. In addition, the identified lead 4ab demonstrated a good solubility and an acceptable in vivo PK profile. The identified lead 4ab showed an in vivo efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models with a TGI (tumor growth inhibition) of 90% without any mortality growth inhibition in comparison to reported leads.

In spite of unprecedented advances in modern systems of medicine, there is necessity for exploration of traditional plant based secondary metabolites or their semisynthetic derivatives which may results in better therapeutic activity, low toxicity and favourable pharmacokinetics. In this context, computational model based predictions aid medicinal chemists in rational development of new chemical entity having unfavourable pharmacokinetic properties which is a major hurdle for its further development as a drug molecule. Para-coumaric acid (p-CA) and its derivatives found to be have promising antiinflammatory and analgesic activity. IS01957, a p-CA derivative has been identified as dual acting molecule against inflammation and nociception. Therefore, objective of the present study was to investigate pharmacokinetics, efficacy and safety profile based on in-silico, in-vitro and in-vivo model to assess drug likeliness. In the present study, it has excellent pharmacological action in different animal models for inflammation and nociception. Virtual pharmacokinetics related properties of IS01957 have resemblance between envision and experimentation with a few deviations. It has also acceptable safety pharmacological profile in various animal models for central nervous system (CNS), gastro intestinal tract (GIT)/digestive system and cardiovascular system (CVS). Finally, further development of IS01957 is required based on its attractive preclinical profiles.

BACKGROUND The key to success of any root canal therapy is adequate obturation of the prepared root canal space. Root canal sealers are not dimensionally stable and might dissolve partially over a period of time. The objective of this in vitro study is to evaluate the push-out bond strength to intraradicular dentin of two endodontic obturation materials. MATERIAL AND METHODS Forty extracted single rooted permanent teeth were used. Canals orifice was explored, teeth were instrumented. The samples were divided into two groups each containing twenty specimens obturated with different obturation material (Group1 Epiphany/Resilon and Group 2 Gutta Percha/AH Plus).The obturation systems used in this study was Element Obturation unit (Sybron Endo). Each tooth root was horizontally sectioned in approximately 2-mm thick slices from the coronal 1/3rd, middle 1/3rd and apical 1/3rd. The push-out bond strength of each specimen was calculated using Universal Testing Machine. The statistical analysis was done using two way analysis of variance (ANOVA) and tukey's test. RESULTS There was significant difference between push out bond strength of Resilon/Epiphany and AH Plus/Gutta Percha. Gutta percha group was superior with push out bond strength of 2.22 (± 0.16) Mpa in comparison to Resilon/Epiphany group with 1.61 (±0.14) Mpa (p

Asthma is characterized by persistent airway inflammation caused by over expression of pro-inflammatory immune response, predominantly by eosinophils and lymphocytes. Lymphocytes (CD4+ Th2) have been documented to be responsible for the pathogenesis of asthma by secreting Th2 cytokines and activating eosinophils, leading to airway hypersensitivity. Secretion of Th2 cytokines has been shown critical for the induction of the characteristic airway inflammation in humans and animal models of asthma. These cytokines influence the inflammatory response and lead to the pathological changes associated with asthma. In the present study, 10 azepino [2,1-b] quinazolone derivatives (R1 to R10) were synthesised and evaluated for their anti-asthmatic activity using a murine model of asthma. The compounds R2, R4, R6, R7 and R8 caused a notable decrease Th2 cytokine secretion and eosinophilia in asthma-induced animals. However, the decrease was highly significant in case of R8-treated animals. Crystal structure of R8 was made by X-ray crystallography. Molecular modelling studies were done for the compound R8 with transcription factors STAT6 and GATA3 which are the main transcription factors responsible for Th2 cell differentiation. Also the pharmacokinetics of R8 was carried out in mice after oral and intravenous administrations.

Background The key to success of any root canal therapy is adequate obturation of the prepared root canal space. Root canal sealers are not dimensionally stable and might dissolve partially over a period of time. The objective of this in vitro study is to evaluate the push-out bond strength to intraradicular dentin of two endodontic obturation materials. Material and Methods Forty extracted single rooted permanent teeth were used. Canals orifice was explored, teeth were instrumented. The samples were divided into two groups each containing twenty specimens obturated with different obturation material (Group1 Epiphany/Resilon and Group 2 Gutta Percha/AH Plus).The obturation systems used in this study was Element Obturation unit (Sybron Endo). Each tooth root was horizontally sectioned in approximately 2-mm thick slices from the coronal 1/3rd, middle 1/3rd and apical 1/3rd. The push-out bond strength of each specimen was calculated using Universal Testing Machine. The statistical analysis was done using two way analysis of variance (ANOVA) and tukey’s test. Results There was significant difference between push out bond strength of Resilon/Epiphany and AH Plus/Gutta Percha. Gutta percha group was superior with push out bond strength of 2.22 (± 0.16) Mpa in comparison to Resilon/Epiphany group with 1.61 (±0.14) Mpa (p

Progressive inflammatory periodontal disease, if left untreated, it will ultimately result in attachment loss. This can affect the bifurcation or trifurcation of multirooted teeth. Dentists are challenged to save those teeth that earlier would have been extracted without a second thought to save it. Hence, resective therapy has been utilized in the treatment of furcation defects. Hemisection is a removal of compromised root and the associated crown portion. It is one of the treatment options for preserving remaining part of molar having sound periodontium. This case report presents a patient in whom distal half of the carious and periodontally compromised tooth was resected, and after healing, fixed dental prosthesis was given to restore proper form and function.

External cervical resorption (ECR) is a type of external resorption that can be quite devastating for the tooth and in extreme cases can even lead to tooth extraction. Its diagnosis and management present many challenges for a dental practitioner. This case report describes the treatment of an ECR in the upper left central incisor, which was treated surgically following endodontic treatment using the new dental cement Biodentine to repair the cervical defect.