Search results for: Kabi Raj Paudyal
6 Low-Density Lipoproteins Mediated Delivery of Paclitaxel and MRI Imaging Probes for Personalized Medicine Applications
Authors: Sahar Rakhshan, Simonetta Geninatti Crich, Diego Alberti, Rachele Stefania
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The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by Flow cytometry analysis. PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 ◦C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel Kabi (PTX Kabi) used in clinical applications. It was possible to demonstrate a high uptake of LDL-Gd in B16-F10 cells. As a consequence of the high cell uptake, melanoma cells showed significantly high cytotoxic effect when incubated in the presence of PTX (LDL-PTX-Gd). Furthermore, B16-F10 have been used to perform Magnetic Resonance Imaging. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone. In conclusion, LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents.Keywords: low density lipoprotein, melanoma cell lines, MRI, paclitaxel, personalized medicine application, theragnostic System
Procedia PDF Downloads 1265 Study of Palung Granite in Central Nepal with Special Reference to Field Occurrence, Petrography and Mineralization
Authors: Narayan Bhattarai, Arjun Bhattarai, Kabi Raj Paudyal, Lalu Paudel
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Palung granite is leucocratic, alkali feldspar granite, which is one of the six major granite bodies of the Lesser Himalaya of Nepal. The Cambro-Ordovician granite body has intruded on the Palaeozoic metasedimentary rock of the Kathmandu Complex in Central Nepal. The granite crystallized from magma that was mainly generated by anatexis of the Precambrian continental crust. The magma is heterogeneous with respect to the primary ages and/or metamorphic histories of the magma source rocks. This indicates either a derivation from (meta-) sediments or an intense mixing of different crustally derived magmas. The genesis of the Palung granite is possibly related to an orogeny which affected the Indian shield in lower Paleozoic times. The granite body has been mapped into different zones with visual inspection and petrographical study: i. Quartz rich granite: Quartz is smokey to grayish, euhedral to subherdal, 0.2 to 0.7 cm, and constitutes 30 to 40%. Feldspar is white to brownish, subhedral to euhedral, more than 3 cm, and constitutes 20–30%. Tourmaline is black, 0.1 to 0.2 cm in size, and consists of 10 to 20%. Biotite is black flakes up to o.2 cm, representing 5-8%. ii. Feldspar rich granite: white to grayish, medium to coarse-grained, containing feldspar, quartz, biotite, muscovite and tourmaline. Feldspar porphyritic crystals up to 2.5 cm subherdral represent 50–60%, quartz is smokey transparent and represents 30–40%, biotite is dark brown to black, crystals are irregular, 0.5 cm and represent 8–20%, tourmaline is black fractured, small needles represent 5–10%, and muscovite is white to brown and represents 1-4%. iii. Biotite granite: grey to white, medium to coarse-grained, containing quartz, feldspar, biotite and tourmaline. Feldspar crystals up to 2.5 cm represent 40–50%, quartz is smokey, representing 30–40%, biotite is dark brown to black, crystal size 0.5cm, representing 10–20%, tourmaline is black, small needle, 5–10%, and muscovite is white to brown, representing 3-5%. and iv. Muscovite granite: medium-coarse-grained, brown and gray, containing quartz, feldspar, muscovite and tourmaline. Feldspar is white to brown; crystal sizes 0.2–0.4 cm represents 40–50%; quartz is brown and white, transparent, crystals up to 1 cm represent 35–50%; tourmaline is black, opaque, needle shaped; size up to 7–20%; and muscovite is brownish to white, with flakes up to 0.3 cm representing 5–10%. The xenoliths are very common and are not genetically related. Xenoliths are composed mostly of fine-grained, grayish quartz biotite (muscovite) schist and garnetiferous quartz mica schist.Keywords: leucocratic granite, cambro-ordovician granite, lesser himalayan granite, pegmatite
Procedia PDF Downloads 734 Vibration Energy Harvesting from Aircraft Structure Using Piezoelectric Transduction
Authors: M. Saifudin Ahmed Atique, Santosh Paudyal, Caixia Yang
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In an aircraft, a great portion of energy is wasted due to its inflight structural vibration. Structural components vibrate due to aeroelastic instabilities, gust perturbations and engine rotation at very high rpm. Energy losses due to mechanical vibration can be utilized by harvesting energy from aircraft structure as electrical energy. This harvested energy can be stored in battery panels built into aircraft fuselage and can be used to power inflight auxiliary accessories i.e., lighting and entertainment systems. Moreover, this power can be used for wireless Structural Health Monitoring System (SHM) for aircraft and as an excellent replacement of aircraft Ground Power Unit (GPU)/Auxiliary Power Unit (APU) during passenger onboard time to power aircraft cabin accessories to reduce aircraft ground operation cost significantly. In this paper, we propose the design of a noble aircraft wing in which Piezoelectric panels placed under the composite skin of aircraft wing will generate electrical charges from any inflight aerodynamics or mechanical vibration and store it into battery to power auxiliary inflight systems/accessories as per requirement. Experimental results show that a well-engineered piezoelectric energy harvester based aircraft wing can produce adequate energy to support in-flight lighting and auxiliary cabin accessories.Keywords: vibration energy, aircraft wing, piezoelectric material, inflight accessories
Procedia PDF Downloads 1593 Contribution of NLRP3 Inflammasome to the Protective Effect of 5,14-HEDGE, A 20-HETE Mimetic, against LPS-Induced Septic Shock in Rats
Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat, Mahesh P. Paudyal, John R. Falck, Kafait U. Malik
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We hypothesized that 20-hydroxyeicosatetraenoic acid (20-HETE) mimetics such as N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE) may be beneficial for preventing mortality due to inflammation induced by lipopolysaccharide (LPS). This study aims to assess the effect of 5,14-HEDGE on the LPS-induced changes in nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3)/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome. Rats were injected with saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg/kg) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta, and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC, and β-actin proteins as well as interleukin-1β (IL-1β) levels. Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3, and ASC in addition to IL-1β levels were increased. 5,14-HEDGE prevented the LPS-induced changes. Our findings suggest that inhibition of renal, cardiac, and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involved in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats. This work was financially supported by the Mersin University (2015-AP3-1343) and USPHS NIH (PO1 HL034300).Keywords: 5, 14-HEDGE, lipopolysaccharide, NLRP3, inflammasome, septic shock
Procedia PDF Downloads 2962 Tax System Reform in Nepal: Analysis of Contemporary Issues, Challenges, and Ways Forward
Authors: Dilliram Paudyal
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The history of taxation in Nepal dates back to antiquity. However, the modern tax system gained its momentum after the establishment of democracy in 1951, which initially focused only land tax and tariff on foreign trade. In the due time, several taxes were introduced, such as direct taxes, indirect taxes, and non-taxes. However, the tax structure in Nepal is heavily dominated by indirect taxes that contribute more than 60 % of the total revenue. The government has been mobilizing revenues through a series of tax reforms during the Tenth Five-year Plan (2002 – 2007) and successive Three-year Interim Development Plans by introducing several tax measures. However, these reforms are regressive in nature, which does not lead the overall economy towards short-run stability as well as in the long run development. Based on the literature review and discussion among government officials and few taxpayers individually and groups, this paper aims to major issues and challenges that hinder the tax reform effective in Nepal. Additionally, this paper identifies potential way and process of tax reform in Nepal. The results of the study indicate that transparency in a major problem in Nepalese tax system in Nepal, where serious structural constraints with administrative and procedural complexities envisaged in the Income Tax Act and taxpayers are often unaware of the specific size of tax which is to comply them. Some other issues include high tax rate, limited tax base, leakages in tax collection, rigid and complex Income Tax Act, inefficient and corrupt tax administration, limited potentialities of direct taxes and negative responsiveness of land tax with higher administrative costs. In the context, modality of tax structure and mobilize additional resources is to be rectified on a greater quantum by establishing an effective, dynamic and highly power driven Autonomous Revenue Board.Keywords: corrupt, development, inefficient, taxation
Procedia PDF Downloads 1801 Maternal and Neonatal Outcome: Comparison between Adolescents and Adult Pregnancy at Selected Hospital, Hetauda, Nepal
Authors: Laxmi Paudyal, Indira Adhikari Poudel, Muna Bhattarai
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Introduction: Numerous factors can affect how pregnancies and births turn out. One of these is adolescent pregnancy, which is a worldwide issue with known causes, harmful impacts on both the mother's and the child's health, as well as various negative social and economic consequences. Objective: The study was carried out to compare the maternal and neonatal outcomes between adolescents and adult pregnancy. Methods: This retrospective hospital-based cohort study was conducted at Madan Bhandari Academy of Health of Health Sciences, Hetauda Hospital at Makwanpur. The study population was pregnant women who delivered at selected hospital within 1 year study period from 2079 Shrawan (July 2022) to 2080 Ashad (June 2023). A total of 479 mothers aged 20-30 years and 53 mothers aged 15-19 years were study participants, and they were selected using a simple random sampling lottery method. Data were collected from the hospital’s electronic database and the register maintained at the maternity ward and neonatal ward. Result: The findings indicate that 6.51% of the 3273 mothers who gave birth in a single year were in the adolescent age range. When comparing the two mother groups, more adult mothers than teenage mothers skipped the complete antenatal checkup. Compared to adult mothers, the mothers of adolescents were found to be underweight and to have less iron and folic acid supplement intake. Anaemia, UTI, and placental abnormalities during pregnancy have been reported by a greater percentage of teenage mothers than adult mothers, with p=0.032, p=0.025, and p=0.041, respectively. When compared to adult pregnancies, vaginal delivery and complicated delivery were both shown to be more common in teenage pregnancies (p=0.001 and p=0.012, respectively). Adolescent pregnancies were associated with higher rates of NICU admission (p=0.037), low birth weight (p=0.034), premature birth (p=0.001), and fetal deaths (p=0.024) than adult pregnancies. Conclusion: According to this study, there are some notable variations in obstetric and neonatal outcomes by the age of the mother. It was discovered that there were a considerable number of adverse effects on adolescent mothers both during their pregnancies and after giving birth. Need for strategic planning in preventing adolescent females from getting pregnant is recommended.Keywords: adolescent, antenatal, natal, postnatal, neonatal, outcome
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