Polymeric Nanocarriers for Delivery of Small Molecules and miRNAs for the Treatment of Liver Fibrosis and Pancreatic Cancer

The aim of this thesis is to develop combination therapy of small molecules and miRNAs for treating liver fibrosis and pancreatic cancer. New amphiphilic biodegradable polymers capable of carrying small hydrophobic molecules and hydrophilic anionic nucleic acids were synthesized, characterized and evaluated in vitro and in vivo liver fibrosis and pancreatic cancer mouse models. In Chapter 1, an overview of liver fibrosis, current treatments and the role of miRNAs in liver fibrosis as well as the design of their delivery systems is given. Further, a general introduction to pancreatic cancer and role of miRNAs in pancreatic cancer is given. In Chapter 2, small molecules GDC-0449 and rosiglitazone were encapsulated into nanoparticles prepared using a biodegradable copolymer mPEG-b-p(CB-co-LA) and used for the treatment of common bile duct ligation (CBDL) induced liver-fibrotic rats. GDC-0449 and rosiglitazone loaded nanoparticles could reverse early stage liver fibrosis by reducing ECM deposition in the liver and inhibiting Hh signaling pathway. Chapter 3 reports the design of a cationic biodegradable copolymer methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft-tetraethylene-pentamine) (mPEG-b-PCC-g-DC-g-TEPA) for encapsulation of GDC-0449 into the micelle core and complexation of miR-let7b via electrostatic interaction with TEPA. These micelles were characterized for particle size, surface morphology, drug loading, cytotoxicity and transfection efficiency in vitro. Micelles containing both these drugs were evaluated in a subcutaneous pancreatic tumor model. The combination therapy effectively inhibited tumor growth compared to micelles carrying either GDC-0449 or miR-let7b. Immunohistochemical analysis of tumor sections revealed decreased tumor cell proliferation and increased apoptosis of tumor cells of the animals treated with miR-let7b and GDC-0449 combination. Chapter 4 describes the use of mPEG-b-PCC-g-DC-g-TEPA copolymer for delivery of miR-29b1 and GDC-0449 in CBDL mice. Systemic administration of these micelles into CBDL liver fibrotic mice resulted in high concentrations of GDC-0449 and miR-29b1 to the liver cells as determined by in situ liver perfusion. We observed a significant decrease in collagen deposition in the liver and serum injury markers, leading to improvement in liver morphology and disease condition. Combination therapy was effective in providing hepatoprotection, lowering liver injury related serum enzyme levels and reducing fibrotic protein markers such as collagen, α-SMA, FN-1 and p-AKT compared to monotherapy. Finally, Chapter 5 summarizes the results of this thesis and gives suggestions for future research

Monitoring paneer for Listeria monocytogenes- A high risk food pathogen by multiplex PCR

A multiplex polymerase chain reaction (PCR) assay was developed and applied to spiked and natural paneer samples to detect Listeria monocytogenes, a high risk food pathogen. The sensitivity of the assay on L. monocytogenes spiked paneer samples was 104 cells prior to enrichment, was improved to 103 cells after 4 h enrichment and one to 10 cells after 6 h enrichment as indicated by the amplification of 1.2 kb and 713 bp PCR products. The multiplex PCR assay when applied to 10 randomly sampled natural paneer products did not reveal any amplification products, indicating the absence of this organism from these samples.Key words: Listeria monocytogenes, multiplex PCR, 16S rRNA, hemolysin, paneer products

The physiological and performance responses with a water cooled hood in a heat stress environment while doing creative mental work

Call number: LD2668 .T4 1969 G78Master of Scienc

Impact of Nuclear Deformation on Neutron Dripline Prediction: A Study of Mg Isotopes

We have employed the relativistic Hartree-Bogoliubov (RHB) model with density-dependent meson-exchange interaction and separable pairing to investigate neutron dripline mechanisms for heavy Mg isotopes. In the present study, 40Mg is predicted to be dripline nuclei. The calculations are carried out by taking axial deformation into account. An investigation of shape transition is also done for even-even 32-42Mg isotopes. Our prediction for neutron dripline for 40Mg is consistent with some recent studies

Rehabilitation of Maxillary defect using Removable Maxillary Cast Partial Denture Hollow Prosthesis for managing Mucomycosis patient: A Clinical Case Report

  Introduction: Mucormycosis is the fungal infection which especially affects immunocompromised patients. Case Report: In this case report, prosthetic rehabilitation of maxillary defect due to past mucormycosis in an uncontrolled diabetic patient was discussed by means of lightweight prosthesis by attaching a hollow occlusal shim to cast partial denture framework as absence of alveolar ridge on the defect side tends to increase the weight of the prosthesis which would have compromised the retention of the prosthesis. Conclusion: This technique is simple, economical and less time-consuming

Enhanced photocatalytic and disinfection activities of silver loaded ordered mesoporous titanium dioxide for water treatment

In the present paper ordered mesoporous titanium dioxide (TiO2) has been synthesized by using the nanocasting method with SBA-15 as a hard template and titanium alkoxide as the precursor. The silver has been loaded onto the obtained ordered mesoporous TiO2 using photoreduction method. The physicochemical properties of as-prepared and calcined silver loaded mesoporous titanium dioxide (SMTO) have been characterized by various techniques. The XRD pattern confirms the existence of tetragonal anatase-rutile mixed phases of TiO2 with a crystallite size of the range of 12-15 nm. SEM and TEM images show that the aggregation of nanocrystalline phase results in the formation of nanometer sized mesoporous TiO2 with a well-defined spherical morphology and retained ordered structure. The as-obtained samples exhibit good photocatalytic degradation of rhodamine B, Congo red and methyl orange dyes as model water contaminant at room temperature with UV light irradiation. The samples under study also show substantial disinfection properties against E. coli & S. aureus used as a model strain. The significant enhancement of the photocatalytic and disinfection activities of the SMTO materials is mainly attributed to their absorbed more photons and reduced electron-hole pair recombination due to synergic effect of porosity of the ordered structure and Ag-impregnated nanoparticles, respectively

Nuclear shape evolution and shape coexistence in Zr and Mo isotopes

The phenomena of shape evolution and shape coexistence in even-even $^{88-126}$Zr and $^{88-126}$Mo isotopes is studied by employing covariant density functional theory (CDFT) with density-dependent point coupling parameter sets DD-PCX and DD-PC1, and with separable pairing interaction. The results for rms deviation in binding energies, two-neutron separation energy, the differential variation of two-neutron separation energy, and rms charge radii, as a function of neutron number, are presented and compared with available experimental data. In addition to the oblate-prolate shape coexistence in $^{96-110}$Zr isotopes, the correlation between shape transition and discontinuity in the observables are also examined. A smooth trend of charge radii in Mo isotopes is found to be due to the manifestation of triaxiality softness. The observed oblate and prolate minima are related to the low single-particle energy level density around the Fermi level of neutron and proton respectively. The present calculations also predict a deformed bubble structure in $^{100}$Zr isotope.Comment: this preprint contains incomplete data and some mistake

Assessment of endothelial dysfunction in diabetes mellitus in Indian population by color Doppler

Background: Endothelial dysfunction is regarded as a systemic marker of cardiovascular disease. Brachial artery flow-mediated dilation (FMD) is a mode of evaluating endothelial function and for early diagnosis of atherosclerotic diseases. We studied whether there is a difference in vascular endothelial function between type 1 and 2 diabetes mellitus and normal population.Methods: We assessed %FMD of 50 patients with diabetes mellitus and 50 control populations without diabetes mellitus or other risk factors. SPSSS version 13 was used for statistical analysis. Students T test was used for comparison of means of the two groups.Results: The %FMD was significantly lower in patients with type1 and 2 diabetes mellitus compared to normal population.Conclusions: Diabetes mellitus is associated with endothelial dysfunction irrespective of Type 1 or Type 2 diabetes mellitus, as suggested by impairment in vascular reactivity to hyperemia in both. Monitoring FMD may help in assessment of progression of atherosclerosis