Finite element analysis (FEA) of stress distribution in platform-switched short dental implants.

The distribution of stress on short platform switched dental implants is of interest. Hence, the mandibular posterior molar area was modelled using a three-dimensional finite element method (FEM) with a continuous 1.5 mm cortical bone thickness and an inner cancellous bone core. The implants used in the study were 5 mm long, 4.5 mm wide and 3.5 mm wide at the abutments. 120 N of force was applied in both the vertical and oblique (20° and 35°) directions to create a realistic simulation. ANSYS Workbench was generated for each model. Von Mises stress was assessed in the cortical and cancellous bones at varying depths. Ten noded tetrahedron elements with three degrees of freedom per node were employed to interpret translations on the x, y, and z axes. The stress-based biomechanical behaviour of platform switched short osseo-integrated implants varied across all 5 positions in FEM simulations, based on the depth of implant placement, the direction of applied force, and the shape of the bone. Data shows that opposite forces to the vertical forces caused more damage. Thus, the implantation of subcrestal implants resulted in reduced stress on the cortical and cancellous bone.

Safe Polycationic Dendrimers as Potent Oral In Vivo Inhibitors of Mycobacterium tuberculosis: A New Therapy to Take Down Tuberculosis.

The long-term treatment of tuberculosis (TB) sometimes leads to nonadherence to treatment, resulting in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. Inadequate bioavailability of the drug is the main factor for therapeutic failure, which leads to the development of drug-resistant cases. Therefore, there is an urgent need to design and develop novel antimycobacterial agents minimizing the period of treatment and reducing the propagation of resistance at the same time. Here, we report the development of original and noncytotoxic polycationic phosphorus dendrimers essentially of generations 0 and 1, but also of generations 2-4, with pyrrolidinium, piperidinium, and related cyclic amino groups on the surface, as new antitubercular agents active per se, meaning with intrinsic activity. The strategy is based on the phenotypic screening of a newly designed phosphorus dendrimer library (generations 0-4) against three bacterial strains: attenuated Mycobacterium tuberculosis H37Ra, virulent M. tuberculosis H37Rv, and Mangora bovis BCG. The most potent polycationic phosphorus dendrimers 1G0,HCl and 2G0,HCl are active against all three strains with minimum inhibitory concentrations (MICs) between 3.12 and 25.0 µg/mL. Both are irregularly shaped nanoparticles with highly mobile branches presenting a radius of gyration of 7 Å, a diameter of maximal 25 Å, and a solvent-accessible surface area of dominantly positive potential energy with very localized negative patches arising from the central N3P3 core, which steadily interacts with water molecules. The most interesting is 2G0,HCl, showing relevant efficacy against single-drug-resistant (SDR) M. tuberculosis H37Rv, resistant to rifampicin, isoniaid, ethambutol, or streptomycin. Importantly, 2G0,HCl displayed significant in vivo efficacy based on bacterial counts in lungs of infected Balb/C mice at a dose of 50 mg/kg oral administration once a day for 2 weeks and superior efficacy in comparison to ethambutol and rifampicin. This series of polycationic phosphorus dendrimers represents first-in-class drugs to treat TB infection, could fulfill the clinical candidate pipe of this high burden of infectious disease, and play a part in addressing the continuous demand for new drugs.

Identification of N-Hydroxycinnamamide analogues and their bio-evaluation against breast cancer cell lines.

The present study demonstrates the identification of N-hydroxycinnamamide derivatives and their anticancer potential against human triple-negative breast cancer cell line MDA-MB­231, MCF-7 and non-malignant origin cell line, HEK-293 (human embryonic kidney). MTT assay was studied with HEK-293 cell line. Anticancer potential of the N-hydroxycinnamamide derivatives were compared with marked drug Tamoxifen through in vitro study. The compound numbers 3b and 3h exhibit most potent activity against antagonistic breast cancer cells (MDA-MB-231) with IC5013µM and 5µM respectively. Compound 3h promotes DNA fragmentation and induction of apoptosis. Furthermore, loss of mitochondrial membrane potential induced by compound 3h. The major mechanism of compound 3h for anti-breast cancer activity was probably initiation of reactive oxygen species (ROS) in cancer cells thereby persuading apoptotic cell deaths in cancer cells.

Isolated tubercular liver abscess in an elderly diabetic successfully treated with systemic antitubercular drugs.

Tubercular liver abscess is a rare extrapulmonary manifestation of tuberculosis. We are presenting a case of isolated tubercular liver abscess in a 70 year old diabetic male without any evidence of tuberculosis in the lungs or abdomen. Diagnosis was made on the basis of radiological findings along with PCR for Mycobacterium tuberculosis in pus aspirated from abscess under CT guidance. Systemic antitubercular drugs were given for 6 months. On follow up patient improved clinically with radiological evidence of resolution of abscess.

Design and synthesis of 1,3-biarylsulfanyl derivatives as new anti-breast cancer agents.

A new series of 1,3-biarylsulfanyl derivatives (homodibenzyl core motif) have been designed and synthesized as new estrogen receptor ligands by chopping benzothiophene core of raloxifene to engender seco-raloxifene scaffold. All the synthesized compounds were screened for anti-proliferative, anti-osteoporotic, and anti-implantation activity. Compounds (35, 36) having basic amino anti-estrogenic side chain were exhibiting potential anti-proliferative activity in MCF-7, MDA-MB-231 and ishikawa cell lines. Some of the synthesized compounds having homodibenzyl motif (5, 8, 10) have shown moderate anti-osteoporotic activity.

Design and synthesis of 2,4-disubstituted polyhydroquinolines as prospective antihyperglycemic and lipid modulating agents.

A series of 2,4-disubstituted polyhydroquinoline were synthesized and evaluated for their in vivo antihyperglycemic as well as antidyslipidemic activities. Several synthesized compounds have exhibited promising in vivo antihyperglycemic in SLM, STZ-S, and db/db mice model along with significant lipid and TG modulating activity. All these compounds were evaluated in various in vitro models of diabetes to know the possible mechanism of their antihyperglycemic action. Interestingly, compounds 3a-r (diaryl substitution) have exhibited promising protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity whereas, compounds 5a-d (acid substituted) have shown significant glycogen phosphorylase activity.