Dual Modified Liposomes for Drug and Gene Delivery to Brain

The overall goal of our research was to design a vector for efficient delivery of therapeutic genes/drugs to brain. Specifically, this research work was focused on designing PEGylated liposomes surface modified with the receptor targeting protein, transferrin and cell penetrating peptides (CPPs) for targeting and improving the delivery of desired therapeutic agent to brain. Various CPPs including poly-L-arginine, TAT, Penetratin and Mastoparan were investigated for their influence on transport of transferrin receptor targeted liposomes across brain endothelial cells. The dual-modified liposomes were synthesized using thin film hydration and post-insertion technique. The biocompatibility of the liposomes was evaluated at increasing concentrations to obtain an optimum value for safe and effective delivery of drugs or genes. The liposomes showed excellent cellular, blood and tissue compatibility at the optimized concentration. In addition, the combination of targeting ligand transferrin and CPPs resulted in considerable translocation of the therapeutic agent across cellular and brain endothelial barriers both in vitro and in vivo. Among different Tf-CPP liposomes, the Tf-Penetratin liposomes showed maximum translocation of the drug across the brain endothelial barrier (approximately 15% across in vitro and 4% across in vivo BBB) and efficient cellular transport of the encapsulated drug (approximately 90-98%) in various cell lines. In addition, Tf-poly-L-arginine and Tf-Penetratin liposomes showed improved transfection efficiencies in various cell lines. The Tf-Penetratin and Tf-TAT liposomes demonstrated excellent cellular biocompatibility and no hemolytic activity upto 200nM phospholipid concentration. In vivo efficacy of the liposomes was evaluated by performing biodistribution studies in in adult Sprague Dawley rats. The liposomes were intended for delivery of small molecule drug, doxorubicin and pDNA to brain. The dual modified liposomes showed significantly (p<0.05) higher transport of encapsulated agents in rat brain as compared to single ligand (Tf) or plain liposomes. Histological examination of the tissues, from various organs, did not show any signs of toxicity including necrosis, inflammation, fibrosis etc. The study underlines the potential of bifunctional liposomes as high-efficiency and low-toxicity gene delivery system for the treatment of central nervous system disorders

Flexible Denture: A Hope for Partial Edentulous Patient- A Case Report

The various treatment options for the aesthetic and functional rehabilitation of partially edentulous patients are conventional fixed partial dentures, implant supported fixed partial dentures and removable partial dentures. In some cases, removable partial dentures may be the only choice which is available other than implants and fixed partial denture. Removable cast partial dentures are used as definitive removable prostheses when indicated, but location of clasps is not aesthetically pleasant. So, when patient is concerned about aesthetics, flexible partial dentures which is aesthetically superior may be considered. But for the success of flexible removable partial denture, proper diagnosis, treatment planning, insertion, wearing and maintenance of this prosthesis is very important

Post-operative rehabilitation of displaced-proximal radius fracture: a case study

Proximal radial fractures typically occur after a fall on the outstretched hand. Elbow trauma is usually followed by post-traumatic elbow stiffness, which has been recognized as a major cause of functional impairment. A stiff elbow restricts patient’s ability to position hand in space required, for desired use of the upper extremities during activity of daily living. The goal of rehabilitation, post-traumatic elbow stiffness is to restore functional arc of motion. The patient treatment should be designed depending on the severity, type and time course of the arthrofibrosis. Since, there is no universally recognized treatment algorithm, treatment must be personalized/customized and stipulated through a shared decision-making process with each patient. Fourty four-year female was diagnosed with post – operative elbow stiffness following a displaced proximal one-third of radius fracture (right side). The patient had decreased muscle strength and limited shoulder, elbow and wrist range of motion, hypersensitivity around the scar and wrist and elbow pain. Progressive multi-treatment rehabilitation approach was given to the patient. Physical therapy intervention improved range of motion, strength, decreased hypersensitivity and pain of the patient as well as aided in quick recovery from stiff elbow

DFT Investigation of the mechanism of hydrogenation by borenium based chiral FLPs

In this thesis, hydrogenation of olefins and carbonyl compounds by borenium compounds based on camphor scaffolds “Frustrated Lewis Pairs” (FLPs) has been investigated using density functional theory. FLPs provide a novel substitute to the conventional catalysts that are quite expensive and sometimes toxic. The main aim of the present study was to design some new FLPs employing main group elements, as sustainable alternatives to transition metal catalysts for industry. The study has been done in three phases. The first part of the thesis (Chapter-3) deals with the design of chiral intramolecular FLPs. During this study various methods in DFT have been screened to find the most suitable method. M06-2X/6-31G(d) level of theory has been utilized to study the newly designed FLPs. The most stable FLPs were then selected for further studies. In the second part (Chapter-4) selected FLP systems were explored as possible catalyst for the hydrogenation of small achiral molecules of olefins and carbonyl compounds. The results demonstrated that the activation barriers for these reactions were quite moderate. In the third part of the study (Chapter-5), FLPs were used to study the hydrogenation of some prochiral olefins and carbonyls. Stereochemistry of these reactions was also investigated to understand the stereochemical preferences towards the substrate. The results indicated that the FLPs indeed have preference for specific face of the substrate. These observations open up a possibility of further exploration of FLPs for preparation of industrially useful chiral compounds by hydrogenation of prochiral substrates

The paperless partograph: can it be effective to replace the WHO modified partograph

Background: The partograph is a graphical representation of the various events of labour plotted against time. The main aim was to determine whether the paperless partograph can replace the WHO partograph to monitor labour and aid in decision making.Methods: It is a hospital based prospective analytical study. The course of labour in 400 women with term singleton uncomplicated pregnancies were studied by using either partographs. 12 resident doctors were included to assess the user friendliness and asked to fill 240 separate partographs (120 each of WHO Modified and Paperless partograph).Results: The maternal and perinatal outcome was comparable between both the partographs. The Paperless partograph was however more user-friendly than the WHO partograph (p&lt;0.0001).Conclusions: The Paperless partograph was found to be as effective as the WHO partograph in the effective management of labour. It is more user-friendly and has promising prospects to replace the WHO partograph

Platinum(iv) azido complexes undergo copper-free click reactions with alkynes

We report our investigations into the first examples of copper-free 1,3-dipolar cycloaddition (click) reactions of electrophiles with a PtIV azido complex. The Pt-IV azido complex trans, trans, trans-[PtIV(py)2(N3)2(OH)2] (1) was reactive towards dimethyl acetylenedicarboxylate (DMAD) (2), diethyl acetylenedicarboxylate DEACD (3), N-[(1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonyl]-1,8-diamino-3,6-dioxaoctane (BCN) (11) and dibenzocyclooctyne-amine (DBCO) (12) resulting in formation of the corresponding mono (a) and bis-substituted (b) complexes. Complexes of 2 undergo further reactions between the Pt centre and the carbonyl group to form 2a′ and 2b′. This is not seen for the products of the corresponding PtII azido complex trans-[Pt(py)2(N3)2] with acetylene 2. Novel complexes 2a′, 2b′, 11a and 11b have been characterised by multinuclear NMR, IR and UV-vis spectroscopy and ESI-MS. These reactions represent new synthetic routes to novel Pt(IV) complexes

Computational design of an intramolecular frustrated Lewis pair catalyst for enantioselective hydrogenation

We report DFT calculations on potential intramolecular, enantioselective hydrogenation catalysts based around borenium-carbenes based on a camphor scaffold. Using the M06-2X meta-hybrid functional, we find frustrated Lewis pair (FLP) behaviour with suitably chosen linkers that prevent association of Lewis bases with the borenium centre. These intramolecular FLPs are predicted to be able to heterolytically dissociate H2. Barriers to dissociation and the and endo/exo-ergic nature of the reaction can be tuned by the nature of the base and substituent on B. The reactivity of the hydrogenated FLP catalyst with olefin and carbonyl substrates is then explored: we predict concerted reactions for all substrates considered with relatively low barriers and large exoergic character. Hydrogenation of both faces of a prochiral substrate is also examined, indicating a small but significant variation in reaction barrier in favour of the Si-face, ascribed to stronger interactions with the aromatic π-system in the TS compared to the Re-face

High resolution mapping of QTLs for fruit color and firmness in Amrapali/Sensation mango hybrids

IntroductionMango (Mangifera indica L.), acclaimed as the ‘king of fruits’ in the tropical world, has historical, religious, and economic values. It is grown commercially in more than 100 countries, and fresh mango world trade accounts for ~3,200 million US dollars for the year 2020. Mango is widely cultivated in sub-tropical and tropical regions of the world, with India, China, and Thailand being the top three producers. Mango fruit is adored for its taste, color, flavor, and aroma. Fruit color and firmness are important fruit quality traits for consumer acceptance, but their genetics is poorly understood.MethodsFor mapping of fruit color and firmness, mango varieties Amrapali and Sensation, having contrasting fruit quality traits, were crossed for the development of a mapping population. Ninety-two bi-parental progenies obtained from this cross were used for the construction of a high-density linkage map and identification of QTLs. Genotyping was carried out using an 80K SNP chip array.Results and discussionInitially, we constructed two high-density linkage maps based on the segregation of female and male parents. A female map with 3,213 SNPs and male map with 1,781 SNPs were distributed on 20 linkages groups covering map lengths of 2,844.39 and 2,684.22cM, respectively. Finally, the integrated map was constructed comprised of 4,361 SNP markers distributed on 20 linkage groups, which consisted of the chromosome haploid number in Mangifera indica (n =20). The integrated genetic map covered the entire genome of Mangifera indica cv. Dashehari, with a total genetic distance of 2,982.75 cM and an average distance between markers of 0.68 cM. The length of LGs varied from 85.78 to 218.28 cM, with a mean size of 149.14 cM. Phenotyping for fruit color and firmness traits was done for two consecutive seasons. We identified important consistent QTLs for 12 out of 20 traits, with integrated genetic linkages having significant LOD scores in at least one season. Important consistent QTLs for fruit peel color are located at Chr 3 and 18, and firmness on Chr 11 and 20. The QTLs mapped in this study would be useful in the marker-assisted breeding of mango for improved efficiency