NOVEL HYDROXYL TERMINATED DENDRIMERS AS POTENTIAL DRUG CARRIERS: SUSTAINED RELEASE, HEMOLYSIS AND CYTOTOXICITY STUDY

Objective: Potential of novel hydroxyl terminated dendrimer generations G1(OH)8, G2(OH)32 and G3(OH)128 as solubility enhancers of model drug ketoprofen was evaluated. G3(OH)128 dendrimer was further explored as the novel carrier for sustained release of ketoprofen. Cytotoxicity and hemolytic potential of G3(OH)128 dendrimer were studied to evaluate toxicity of dendrimer. Methods: Higuchi and Connors method was employed to evaluate improved solubility of ketoprofen at different pH and dendrimer generation. Ketoprofen was loaded into G3(OH)128 dendrimer by inclusion complex method. Ketoprofen loaded dendrimer was characterized by Flourier Transform infrared spectroscopy. Sustained release of ketoprofen from ketoprofen loaded dendrimers was studied and compared to that of free ketoprofen. Cytotoxicity of dendrimers on A-549 cell lines were studied by MTT assay technique. Hemolytic potential of G3 dendrimer was also studied. Results: Solubility of practically insoluble ketoprofen was improved up to 0.77-4.89 mg/ml by dendrimer generations. Solubility of ketoprofen was increased with increase in pH, concentrationand generation number of dendrimer. Ketoprofen was released relatively slowly from ketoprofen loaded dendrimer compared to free ketoprofen. Cytotoxicity and hemolytic assay revealed that dendrimers were less toxic compared to PAMAM dendrimers. Conclusion: Improved solubility of ketoprofen by dendrimer generations, its slow release from G3(OH)128 dendrimer and cytotoxicity and hemolytic assay showed dendrimers have potential as drug carriers. Keywords: Triazine Based Dendrimer, Sustained Release, Cytotoxicity, Hemolysis, Ketoprofen, Encapsulation

Experiences in Implementing an Energy-Driven Task Scheduler in RT-Linux

Dynamic voltage scaling (DVS) is being increasingly used for power management in embedded systems. Energy is a scarce resource in embedded real-time systems and energy consumption must be carefully balanced against realtime responsiveness. We describe our experiences in implementing an energy driven task scheduler in RT-Linux. We attempt to minimize the energy consumed by a taskset while guaranteeing that all task deadlines are met. Our algorithm, which we call LEDF, follows a greedy approach and schedules as many tasks as possible at a low CPU speed in a power-aware manner. We present simulation results on energy savings using LEDF, and we validate our approach using the RT-Linux testbed on the AMD Athlon 4 processor. Power measurements taken on the testbed closely match the power estimates obtained using simulation. Our results show that DVS results in significant energy savings for practical real-life task sets. We also show that when CPU speeds are restricted to only a few discrete values, this approach saves more energy than currently existing methods

Development and Evaluation of Cefadroxil Drug Loaded Biopolymeric Films Based on Chitosan-Furfural Schiff Base

Cefadroxil drug loaded biopolymeric films of chitosan-furfural schiff base were prepared by reacting chitosan with furfural in presence of acetic acid and perchloric acid respectively for the external use. Prepared films were evaluated for their strength, swelling index, thickness, drug content, uniformity, tensile strength, percent elongation, FTIR spectral analysis and SEM. The results of in vitro diffusion studies revealed that the films exhibited enhanced drug diffusion as compared to the films prepared using untreated chitosan. The films also demonstrated good to moderate antibacterial activities against selective gram positive and gram negative bacteria

Assessment of Okra Gum Matrices for Colon Delivery of Theophylline

ABSTRACT Colon targeting would be valuable when such a delay in absorption is therapeutically desirable in treatment of chronic medical conditions like nocturnal asthma. Objective: The major objective was to modulate drug release of prepared matrices to target the nocturnal peak symptoms of asthma. Materials and methods: Colon-specific drug delivery based on a polysaccharide, okra gum, was evaluated using in vitro and in vivo methods. Release kinetics was evaluated by using United States Pharmacopoeia (USP) type I dissolution apparatus. Results and discussion: Dissolution study revealed that okra gum preparation was able to protect the drug from being released under conditions mimicking mouth to colon transit with 27.7 ± 3.1% drug releases. Studies in pH 6.8 phosphate buffered saline (PBS) containing 4% w/v rat cecal contents have demonstrated the susceptibility of okra gum to colonic bacterial enzyme action with consequent drug release. In vivo ingestion in rabbits showed controlled release pharmacokinetic profile of theophylline from the formulation prepared using 400 mg okra gum with Cmax of 22.2 mcg/mL at 4.5 hours (Tmax). Conclusion: Thus the study clearly established that okra gum, in the form of matrix former, is a potential carrier for drug targeting to colon

Characterizing Spectral Channels of Visible Emission Line Coronagraph of Aditya-L1

Aditya-L1 is India’s first solar mission with the Visible Emission Line Coronagraph (VELC), which consists of three spectral channels taking high-resolution spectroscopic observations of the inner corona up to 1.5 Rʘ at 5,303, 7,892, and 10,747 Å. In this work, we present a strategy for the slit width optimization of the VELC using synthetic line profiles by taking into account the instrument characteristics and coronal conditions for log(T) varying from 6 to 6.5. The synthetic profiles are convolved with simulated instrumental scattered light and noise to estimate the signal-to-noise ratio (SNR), which will be crucial to designing the future observation plans. We find that the optimum slit width for VELC turns out to be 50 μm, providing sufficient SNR for observations in different solar conditions. We also analyzed the effect of plasma temperature on the SNR at different heights in the VELC field of view for the optimized slit width. We also studied the expected effect of the presence of a CME on the spectral channel observations. This analysis will help to plan the scientific observations of VELC in different solar conditions

The BET inhibitor/degrader ARV-825 prolongs the growth arrest response to Fulvestrant + Palbociclib and suppresses proliferative recovery in ER-positive breast cancer

Anti-estrogens or aromatase inhibitors in combination with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the current standard of care for estrogen receptor-positive (ER+) Her-2 negative metastatic breast cancer. Although these combination therapies prolong progression-free survival compared to endocrine therapy alone, the growth-arrested state of residual tumor cells is clearly transient. Tumor cells that escape what might be considered a dormant or quiescent state and regain proliferative capacity often acquire resistance to further therapies. Our studies are based upon the observation that breast tumor cells arrested by Fulvestrant + Palbociclib enter into states of both autophagy and senescence from which a subpopulation ultimately escapes, potentially contributing to recurrent disease. Autophagy inhibition utilizing pharmacologic or genetic approaches only moderately enhanced the response to Fulvestrant + Palbociclib in ER+ MCF-7 breast tumor cells, slightly delaying proliferative recovery. In contrast, the BET inhibitor/degrader, ARV-825, prolonged the growth arrested state in both p53 wild type MCF-7 cells and p53 mutant T-47D cells and significantly delayed proliferative recovery. In addition, ARV-825 added after the Fulvestrant + Palbociclib combination promoted apoptosis and demonstrated efficacy in resistant RB deficient cell lines. These studies indicate that administration of BET inhibitors/degraders, which are currently being investigated in multiple clinical trials, may potentially improve standard of care therapy in metastatic ER+ breast cancer patients and may further prolong progression-free survival

Examining the Incidence of Human Papillomavirus-Associated Head and Neck Cancers by Race and Ethnicity in the U.S., 1995–2005

Background: Head and neck cancer (HNC) incidence, mortality and survival rates vary by sex and race, with men and African Americans disproportionately affected. Risk factors for HNC include tobacco and alcohol exposure, with a recent implication of human papillomavirus (HPV) in the pathogenesis of HNC. This study describes the epidemiology of HNC in the United States, examining variation of rates by age, sex, race/ethnicity and potential HPV-association. Methods: We used the North American Association of Central Cancer Registries (NAACCR) Cancer in North America (CINA) Deluxe Analytic Data to analyze HNC incidence for 1995–2005 from forty population-based cancer registries. We calculated age-adjusted incidence rates and incidence trends using annual percent change by age, sex, race/ethnicity and HPVassociation. Results: Males and Non-Hispanic Blacks experienced greater HNC incidence compared to women and other race/ethnicity groupings. A significant overall increase in HNC incidence was observed among HPV-associated sites during 1995–2005, while non HPV-associated sites experienced a significant decline in HNC incidence. Overall, younger age groups, Non-Hispanic Whites and Hispanics experienced greater increases in incidence for HPV-associated sites, while HNC incidence declined for Non-Hispanic Blacks independent of HPV-association. In particular, for HPV-associated sites, HNC incidence for Non-Hispanic White males aged 45–54 increased at the greatest rate, with an APC of 6.28 % (p,0.05). Among non HPVassociated sites, Non-Hispanic Black males aged 0–44 years experienced the greatest reduction in incidence (APC, 28.17%

Neuromuscular disease genetics in under-represented populations: increasing data diversity

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses \u27solved\u27 or \u27possibly solved\u27 ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% \u27solved\u27 and ∼13% \u27possibly solved\u27 outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally