PREPARATION AND CHARACTERIZATION OF GEMCITABINE LOADED MPEG-PCL POLYMERIC NANOPARTICLES FOR IMPROVED TRANSPORTATION ACROSS BLOOD BRAIN BARRIER

Objective: To prepare Gemcitabine (GCB) loaded Methoxy Polyethylene Glycol-Poly (Caprolactone), (MPEG-PCL) nanoformulations and to carry out the physicochemical characterisation with a primary objective to enhance the transport and penetration of drug across the blood-brain barrier (BBB).Methods: Gemcitabine loaded MPEG-PCL nanoparticles were formulated by using modified nanoprecipitation method. Nanoformulations were prepared by varying drug: polymer ratio. The prepared nanoparticles (NP) were evaluated for particle size, zeta potential, entrapment efficiency, drug content and in-vitro drug release studies. The in vitro cytotoxicity of drug-loaded NPs was evaluated in U-87 MG cells. Results: The prepared nanoformulations indicated a significant increase in particle size with increase in the polymeric concentration. GCB loaded MPEG-PCL nanoformulation (GCBNP 3) exhibited a particle size of 223±1.4 nm. DSC thermo grams indicated that GCB was dispersed as an amorphous state in MPEG NPs. SEM, TEM, and AFM studies indicated that the NPs were spherical, smooth surface without any cracks or pinholes. In vitro studies showed the GCBNP 3 shows an initial burst release followed by a more gradual and sustained-release phase (maximum drug release). The cytotoxicity of GCB loaded MPEG-PCL nanoformulations showed reduction in the IC50 value (4.1 µg). Apoptosis detection assay with Hoechst 33342 dye was carried out and observed an increase in fluorescence in the apoptotic cells. By invasive studies, the GCB loaded MPEG-PCL nanoformulation inhibits the cell migration significantly when compared with the pure drug.Conclusion: The GCB loaded MPEG-PCL nano particles indicated improved cytotoxic activity with minimal concentrations compared with the pure drug in U-87 MG glial cells. Hence, it can be concluded that GCB loaded MPEG-PCL nanoformulation can serve as a potential drug delivery tool for the treatment of brain tumours.Â

IoT Enabled Smart Activity Recognition using Machine Learning Methods

Internet of Things (IoT) enabled architecture-based devices are becoming accessible worldwide irrespective of the area. But functional settings depend on Internet facilities. In this context, the Healthcare industry took a step forward to automate Human Activity Recognition related concepts using IoT and Machine learning methods. This research used a Nodemcu ESP8266 device to track and communicate human activities acquired using ADXL345 accelerometer sensors. Three volunteers participated in this research, and data were acquired using two accelerometer sensors placed on the hand, wrist, and ankle. Data shared to the cloud- thingspeak.com. Acquired data were analyzed and trained with the Random Forest algorithm and tested with the data, achieving 100% accuracy. This model can be helpful in various applications like elderly patient monitoring, I.C.U., dementia, Alzheimer's, etc

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

Overexpression of Pim kinases has an oncogenic/pro-survival role in many hematological and solid cancers. AZD1208 is a pan-Pim kinase inhibitor that has anti-cancer and anti-adipogenic actions. Here, we investigated the effects of AZD1208 on the growth of 93T449 cells, a differentiated human liposarcoma cell line. At 20 µM, AZD1208 was cytotoxic (cytostatic) but not apoptotic, reducing cell survival without DNA fragmentation, caspase activation or increasing cells in the sub G1 phase; known apoptotic parameters. Notably, AZD1208 reduced phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in 93T449 cells. STAT-3 inhibition by AG490, a JAK2/STAT-3 inhibitor similarly reduced cell survival. AZD1208 down-regulated phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal S6 while up-regulated eukaryotic initiation factor-2α (eIF-2α). In addition, AZD1208 induced a LKB-1-independent AMPK activation, which was crucial for its cytostatic effect, as knock-down of AMPK greatly blocked AZD1208s ability to reduce cell survival. AZD1208 had no effect on expression of two members of Pim kinase family (Pim-1 and Pim-3) but inhibited phosphorylation of 4EBP-1, a downstream effector of Pim kinases. Importantly, a central role for Pim-3 in the actions of AZD1208 was confirmed by knock-down, which not only reduced 93T449 cell survival but also led to the inhibition of 4EBP-1, mTOR, eIF-2α and STAT-3, along with the activation of AMPK. In summary, this is the first report demonstrating that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

Overexpression of Pim kinases has an oncogenic/pro-survival role in many hematological and solid cancers. AZD1208 is a pan-Pim kinase inhibitor that has anti-cancer and anti-adipogenic actions. Here, we investigated the effects of AZD1208 on the growth of 93T449 cells, a differentiated human liposarcoma cell line. At 20 µM, AZD1208 was cytotoxic (cytostatic) but not apoptotic, reducing cell survival without DNA fragmentation, caspase activation or increasing cells in the sub G1 phase; known apoptotic parameters. Notably, AZD1208 reduced phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in 93T449 cells. STAT-3 inhibition by AG490, a JAK2/STAT-3 inhibitor similarly reduced cell survival. AZD1208 down-regulated phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal S6 while up-regulated eukaryotic initiation factor-2α (eIF-2α). In addition, AZD1208 induced a LKB-1-independent AMPK activation, which was crucial for its cytostatic effect, as knock-down of AMPK greatly blocked AZD1208s ability to reduce cell survival. AZD1208 had no effect on expression of two members of Pim kinase family (Pim-1 and Pim-3) but inhibited phosphorylation of 4EBP-1, a downstream effector of Pim kinases. Importantly, a central role for Pim-3 in the actions of AZD1208 was confirmed by knock-down, which not only reduced 93T449 cell survival but also led to the inhibition of 4EBP-1, mTOR, eIF-2α and STAT-3, along with the activation of AMPK. In summary, this is the first report demonstrating that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways

An observational study of adverse drug reactions reported in a rural tertiary care hospital

Background: Adverse drug reactions (ADRs) are noxious and unintended effects of a drug that occurs at doses normally used in humans. ADRs may also result in diminished quality of life, increased physician visits, hospitalizations, and even death. The objectives of this study are to analyze and assess the causality and severity of reported ADRs.Methods: A cross sectional study of ADRs reported to Pharmacovigilance cell of MNR Medical College and Hospital Sangareddy in a year. The details of the various ADRs were statistically analyzed to find out pattern of ADRs. The WHO-UMC causality category and Hartwig-Seigel Scale were used to assess causality and severity of ADRs respectively.Results: The study shows, out of 60 suspected ADRs, the majority of ADRs were adults (68.3%) and out of whom 56% were females. According to the WHO-UMC Causality categories, 43.3% of the ADRs were categorized under Probable/likely, followed by possible (35%). The Hartwig-Siegel severity assessment scale shows that the majority (90%) of suspected ADRs were of mild category.Conclusions: The pattern of ADRs reported in our study is comparable to other studies. The commonest organ system affected was gastrointestinal tract, nervous and cutaneous system. Antimicrobial agents were causing maximum ADRs and medicine and allied departments have more number of ADRs. This study provides a valuable database for ADRs due to all commonly used drugs at hospitals and also helps in creating awareness regarding safe & judicious use of drugs to prevent ADRs

Medication adherence and its determinants amongst anti-hypertensive patients in a tertiary care hospital in Navi Mumbai

Background: Anti-hypertensive drugs can effectively control hypertension, subject to good adherence. Uncontrolled hypertension can lead to numerous complications, some even potentially fatal, such as myocardial infarction, atherosclerosis, thromboembolism, shock and stroke.Methods: A cross-sectional prospective study was conducted with the help of a pre-validated questionnaire during the course of 6 months in the medicine outpatient department and the inpatient department (wards) at a tertiary care hospital, Navi Mumbai in 200 hypertensive patients to calculate the correlation of the sociodemographic factors with adherence by the chi-squared test.Results: The overall percentage of adherence to antihypertensive medication was 34.8%. It was the highest (72.1%) in the younger age group, i.e., below 50 years. It was observed that as the age increases, the adherence to treatment decreases. Adherence rates were significantly higher among females and those individuals who had never attended school. Among the employed, 70.3% were adherent to their treatment and among the unemployed, 64.4% were adherent. The percentage of adherence was lower in alcohol consumers (9.5%) as compared to nonusers (76% and 32%, respectively).Conclusions: The clinician advising anti-hypertensive therapy should provide thorough counselling and stress on the issues created due to poor medication adherence as hypertension can be associated with severe outcomes. Treatments should be given in accordance with each patient’s lifestyles in mind such that they may continue taking their medications till the completion of their therapy

Evaluation of anti-ulcer activity of 4-hydrooxy benzalydehide against NSAIDs induced ulcers in rats

Background: The aim of this study was to evaluate antiulcer activity of 4-hydroxybenzaldehyde against NSAIDs induced ulcer in rats based differences in its morphology, distance with other external landmarks and also to sigmoid and transverse sinuses.Methods: The antiulcer activity of 4-HBD was evaluated using pylorus ligation-aspirin induced ulcer method. Animals of this models were treated with 4-HBD (50mg/kg, 100mg/kg and 150mg/kg).Results: It has been observed that 4-HBD at low dose (50mg/kg), intermediate dose (100mg/kg) and high dose (150mg/kg) showed significant increase in pH, significant decrease in gastric volume, significant decrease in ulcer index and significant decrease in total acidity.Conclusions: The impact of 4-HBD therapy with intermediate (100mg/kg, p.o.) dose was observed to be similar with the positive control group. 

Screening of Selected Mulberry (Morus) Germplasm Varieties Through Propagation Parameters.

Nine mulberry varieties along with one check variety M5 were field tested at Bethamangala village of Kolar district, Karnataka. These mulberry varieties were evaluated for the propagation parameters, like sprouting, survival, shoot growth and rooting behaviour. Results showed that, sprouting percentage was above 95% inTR8, TR12 and S1708 mulberry varieties, while survival rate was as high as 93% in S1708. Mulberry variety S1708 recorded highest shoot length of 62.63cm and shorter shoot length was recorded in C6(35.55cm). Mulberry varieties studied exhibited considerable variations in fresh shoot and dry shoot weight. Among the mulberry varieties studied, Matigara black showed the longest root length (25.99cm) followed by TR12 (23.57cm) and TR8 (21.98cm). Numbers of roots / sapling were recorded more in Matigara black (42) and less in TR8 (14). Root volume was significantly high in Matigara black (16.27ml) and Tr20 (14.21ml) when compared to other varieties. Overall the mulberry variety S1708 showed better results in many propagation characters followed by TR8 and TR20 mulberry varieties. Key Words: Growth, mulberry germplasm; sprouting; survival; rooting; root length, root volume