Benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one derivatives as Aurora A kinase inhibitors: LQTA-QSAR analysis and detailed systematic validation of the developed model.

Aurora kinases are sub-divided into Aurora A, Aurora B, and Aurora C kinases that are considered as prospective targets for a new class of anticancer drugs. In this work, a 4-D-QSAR model using an LQTA-QSAR approach with previously reported 31 derivatives of benzo[e]pyrimido[5,4 -b][1,4]diazepin -6(11H)-one as potent Aurora kinase A inhibitors has been created. Instead of single conformation, the conformational ensemble profile generated for each ligand by using trajectories and topology information retrieved from molecular dynamics simulations from GROMACS package were aligned and used for the calculation of intermolecular interaction energies at each grid point. The descriptors generated on the basis of these Coulomb and Lennard-Jones potentials as independent variables were used to perform a PLS analysis using biological activity as dependent variable. A good predictive model was generated with nine field descriptors and five latent variables. The model showed [Formula: see text]; [Formula: see text] and [Formula: see text]. This model was further validated systematically by using different validation parameters. This 4D-QSAR model gave valuable information to recognize features essential to adapt and develop novel potential Aurora kinase inhibitors.

Soluble CD40 ligand: a novel biomarker in the pathogenesis of periodontal disease.

OBJECTIVES: Periodontitis involves a complex interplay of micro-organisms and host immune response via numerous mediator molecules playing strategic roles in its pathogenesis. Soluble CD40L (sCD40L) is one such co-stimulatory molecule which is essential for T-helper cell activation and is a well-known risk indicator of cardiovascular diseases. The levels of this marker in crevicular fluid of patients of chronic periodontitis have been explored in the present study for the first time along with an analysis of its association with levels in serum in otherwise systemically healthy patients. METHODOLOGY: Sixty patients 20 healthy and 40 of chronic periodontitis (18 moderate and 22 severe) participated in the study. Patients of the diseased group underwent non-surgical periodontal therapy. Clinical evaluation and collection of gingival crevicular fluid (GCF) and serum samples was done at baseline, and 6 weeks after phase I periodontal therapy. sCD40L levels were quantified in the fluids using ELISA. RESULTS: Levels of sCD40L in GCF were significantly higher in the diseased group (p ≤ 0.001) and strongly correlated not only with increasing severity of disease but also with levels in serum. In post-treatment, the levels decreased significantly in both the biological fluids (p ≤ 0.001). CONCLUSIONS: The present study brings to light the role of sCD40L as a novel marker in mediating periodontal destruction and disease progression. Evaluation of local treatment outcomes seems promising in minimizing these effects. CLINICAL RELEVANCE: Positive association of its local levels with those in serum further implicates the possibility of widespread systemic effects of this infection.

Mucogingival considerations following orthodontic therapy: a case report.

A healthy periodontium is a prerequisite for any orthodontic intervention to be executed. However, application of orthodontic forces without thoughtful planning can result in not only damage to the attachment apparatus, but also alterations to the associated mucogingival tissues. This article elucidates a case of Miller's Class III gingival recession that developed in relation to the patient's lower right central incisor following orthodontic therapy. Case evaluation pertaining to gingival thickness, the level of underlying alveolar bone, and the inflammatory status of the tissues is critical to avoid the development of such soft-tissue defects. Options for augmentation of such sites prior to application of forces can be explored only if accurate diagnosis and clinical assessment are completed. This concept holds relevance for the treating dentist to identify cases with thin gingival tissue biotype and the propensity for developing dehiscence in order to prevent such mucogingival deformities from becoming established.

Role of oral amino acid supplementation in intra-uterine growth restriction and its outcome.

To compare the perinatal outcome in intra-uterine growth restriction (IUGR) with or without oral amino acid supplementation, a randomised control trial was conducted. Out of 50 mothers having IUGR, 25 received amino acid supplementation, treated as cases (group I) and rest 25 mothers with IUGR who had not received amino acid supplementation treated as controls (group II). The outcome of this study is compared in respect of (a) period of gestation at the time of delivery, (b) birth weight, (c) Apgar score, (d) neonatal intensive care unit (NICU) admission. In group I 88% continued pregnancy beyond 36 weeks and in comparison 48% delivered in between 34 and 36 weeks in group II. In group I 80% babies had birth weight between 2.5 and < 3kg, in comparison 84% babies weighing between 2 and < 2.5kg in group II. Eighty per cent of babies having Apgar score in between 7 and 10 in group I and 92% of group I cases not required any NICU admission. Oral amino acid supplementation commencing from second trimester of pregnancy significantly improves the perinatal outcome in IUGR cases.