Creationa and Assessment of Dry Powder Inhalation Formulations of Gamma Oryzanol Based on Chitosan Nanoparticles

Gamma oryzanol is an antioxidant and anticancer medication that is taken orally by a traditional method. It comes from plants. Its utility is nonetheless restricted by its erratic absorption and frequent administration. An alternative method that can maintain the release of Gamma Oryzanol in the lungs for several hours was considered: giving the drug via the pulmonary route as nanoparticles. Gamma Oryzanol was coated with chitosan, a biodegradable polymer, and then freeze-dried to create a dry powder inhaler (DPI) with an aerodynamic particle size of 1.54μm. Initial burst release was seen in an in vitro release investigation, which was followed by continuous release up to 97.51% in 24 hours. In vivo research and in vitro release showed further correlation. After a single dosage was administered, the prepared DPI enhanced the Gamma Oryzanol via pulmonary route residence in the lung tissue for more than 24 hours and sustained the Gamma Oryzanol through pulmonary pathway concentration above MIC for more than 12 hours. A decrease in the amount administered in the lungs was also seen in an animal investigation; this will help with tumour treatment

Synthesis and characterization of interpenetrating polymer networks from transesterified castor oil based polyurethane and polystyrene

AbstractA series of two component interpenetrating polymer networks (IPN) of modified castor oil based polyurethane (PU) and polystyrene (PS) were prepared by the sequential method. Castor oil was modified by triethanolamine by means of transesterification and designated as transesterified castor oil (TCO). The polyurethane network was prepared from transesterified castor oil (TCO) with the isophoronediisocyanates (IPDI) by using dibutyltindilaurate (DBTDL) as catalyst. Simultaneously styrene was added with benzoyl peroxide (BPO) as initiator and N,N′-Dimehtylaniline as coinitiator. Diallylphthalate was added as a crosslinking agent to form IPN and finally cast into films. To cast the film, the mixture (IPN) was poured in the glass cavity with pourable viscosity free from air bubbles. A series of two component interpenetrating polymer networks were prepared by varying % weight ratio of both polyurethane and polystyrene. These films were characterized by FT-IR, dynamic mechanical analysis (DMA), thermogravimetry analysis (TGA), morphology was measured by scanning electron microscopy (SEM). FT-IR have given the conformation of IPN formation. DMA results have shown much increase in the value of tanδ and a decrease in the value of Tg by increasing the anount of Styrene

Study of feto-maternal outcome in patients with intra uterine fetal death

Background: Intra Uterine Fetal Death (IUFD) is an important issue in modern obstetrics. This study has been undertaken to find out the incidence of IUFD, socio-demographic factors, probable etiological factors, mode of delivery, its outcome and complications if any.Methods: This retrospective observational study was carried out at a tertiary care hospital. Data was collected from case papers of patients who have delivered beyond 20 weeks and/or baby weighing more than 500 grams and having IUFD prior to onset of labor or during labor with singleton pregnancy.Results: Incidence of IUFD was 17.2 per 1000 births. Majority of the patients 93 (48.1%) were in age group of 26-30 years, 115 (59.5%) came as an emergency and 94 (48.7%) were primi gravida. Majority 89 (46.1%) patients had not taken any antenatal visit. IUFD occurred due to unexplained etiology, pre-eclampsia-eclampsia, anemia, uncontrolled diabetes, jaundice, antepartum haemorrhage and congenital malformation in 77 (39.9%), 51 (26.4%), 10 (5.1%), 7 (3.6%), 4 (2%), 29 (15%) and 2 (1%) respectively. Vaginal delivery occurred in 151 (78.2%). Majority of dead babies 111 (57.5%) were male, 71 (36.7%) were weighing 1kg or less and 92 (47.6%) were macerated. Emotional upset, DIC, PPH and ARF occurred in 193 (100%), 21 (10.8%), 15 (7.7%) and 1 (0.5%) respectively.Conclusions: Majority of patients were unregistered and had not taken antenatal care or had inadequate antenatal care. Pre-eclampsia-eclampsia, APH, anemia and diabetes were the leading cause of IUFD along with unknown causes. A significant proportion of IUFD can be prevented by health education regarding adequate antenatal care, warning signs and institutional deliveries

Multi-Response Optimization of WEDM Process Parameters for Machining of Superelastic Nitinol Shape-Memory Alloy Using a Heat-Transfer Search Algorithm

Nitinol, a shape-memory alloy (SMA), is gaining popularity for use in various applications. Machining of these SMAs poses a challenge during conventional machining. Henceforth, in the current study, the wire-electric discharge process has been attempted to machine nickel-titanium (Ni55.8Ti) super-elastic SMA. Furthermore, to render the process viable for industry, a systematic approach comprising response surface methodology (RSM) and a heat-transfer search (HTS) algorithm has been strategized for optimization of process parameters. Pulse-on time, pulse-off time and current were considered as input process parameters, whereas material removal rate (MRR), surface roughness, and micro-hardness were considered as output responses. Residual plots were generated to check the robustness of analysis of variance (ANOVA) results and generated mathematical models. A multi-objective HTS algorithm was executed for generating 2-D and 3-D Pareto optimal points indicating the non-dominant feasible solutions. The proposed combined approach proved to be highly effective in predicting and optimizing the wire electrical discharge machining (WEDM) process parameters. Validation trials were carried out and the error between measured and predicted values was negligible. To ensure the existence of a shape-memory effect even after machining, a differential scanning calorimetry (DSC) test was carried out. The optimized parameters were found to machine the alloy appropriately with the intact shape memory effect

Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy.

Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of combined mTOR inhibitor sirolimus (1 mg-5 mg PO daily) and HDAC inhibitor vorinostat (100 mg-400 mg PO daily) in patients with advanced cancer. Seventy patients were enrolled and 46 (66%) were evaluable for DLT assessment since they completed cycle 1 without dose modification unless they had DLT. DLTs comprised grade 4 thrombocytopenia (n = 6) and grade 3 mucositis (n = 1). Sirolimus 4 mg and vorinostat 300 mg was declared RP2D because MTD with sirolimus 5 mg caused significant thrombocytopenia. The grade 3 and 4 drug-related toxic effects (including DLTs) were thrombocytopenia (31%), neutropenia (8%), anemia (7%), fatigue (3%), mucositis (1%), diarrhea (1%), and hyperglycemia (1%). Of the 70 patients, 35 (50%) required dose interruption or modification and 61 were evaluable for response. Partial responses were observed in refractory Hodgkin lymphoma (-78%) and perivascular epithelioid tumor (-54%), and stable disease in hepatocellular carcinoma and fibromyxoid sarcoma. In conclusion, the combination of sirolimus and vorinostat was feasible, with thrombocytopenia as the main DLT. Preliminary anticancer activity was observed in patients with refractory Hodgkin lymphoma, perivascular epithelioid tumor, and hepatocellular carcinoma

Multicenter research priorities in pediatric CMR: results of a collaborative wiki survey

Multicenter studies in pediatric cardiovascular magnetic resonance (CMR) improve statistical power and generalizability. However, a structured process for identifying important research topics has not been developed. We aimed to (1) develop a list of high priority knowledge gaps, and (2) pilot the use of a wiki survey to collect a large group of responses. Knowledge gaps were defined as areas that have been either unexplored or under-explored in the research literature. High priority goals were: (1) feasible and answerable from a multicenter research study, and (2) had potential for high impact on the field of pediatric CMR. Seed ideas were contributed by a working group and imported into a pairwise wiki survey format which allows for new ideas to be uploaded and voted upon (https://allourideas.org). Knowledge gaps were classified into 2 categories: ‘Clinical CMR Practice’ (16 ideas) and ‘Disease Specific Research’ (22 ideas). Over a 2-month period, 3,658 votes were cast by 96 users, and 2 new ideas were introduced. The 3 highest scoring sub-topics were myocardial disorders (9 ideas), translating new technology & techniques into clinical practice (7 ideas), and normal reference values (5 ideas). The highest priority gaps reflected strengths of CMR (e.g., myocardial tissue characterization; implementation of technologic advances into clinical practice), and deficiencies in pediatrics (e.g., data on normal reference values). The wiki survey format was effective and easy to implement, and could be used for future surveys

Ongoing Exercise Intolerance Following COVID‐19: A Magnetic Resonance–Augmented Cardiopulmonary Exercise Test Study

Background: Ongoing exercise intolerance of unclear cause following COVID‐19 infection is well recognized but poorly understood. We investigated exercise capacity in patients previously hospitalized with COVID‐19 with and without self‐reported exercise intolerance using magnetic resonance–augmented cardiopulmonary exercise testing. / Methods and Results: Sixty subjects were enrolled in this single‐center prospective observational case‐control study, split into 3 equally sized groups: 2 groups of age‐, sex‐, and comorbidity‐matched previously hospitalized patients following COVID‐19 without clearly identifiable postviral complications and with either self‐reported reduced (COVIDreduced) or fully recovered (COVIDnormal) exercise capacity; a group of age‐ and sex‐matched healthy controls. The COVIDreducedgroup had the lowest peak workload (79W [Interquartile range (IQR), 65–100] versus controls 104W [IQR, 86–148]; P=0.01) and shortest exercise duration (13.3±2.8 minutes versus controls 16.6±3.5 minutes; P=0.008), with no differences in these parameters between COVIDnormal patients and controls. The COVIDreduced group had: (1) the lowest peak indexed oxygen uptake (14.9 mL/minper kg [IQR, 13.1–16.2]) versus controls (22.3 mL/min per kg [IQR, 16.9–27.6]; P=0.003) and COVIDnormal patients (19.1 mL/min per kg [IQR, 15.4–23.7]; P=0.04); (2) the lowest peak indexed cardiac output (4.7±1.2 L/min per m2) versus controls (6.0±1.2 L/min per m2; P=0.004) and COVIDnormal patients (5.7±1.5 L/min per m2; P=0.02), associated with lower indexed stroke volume (SVi:COVIDreduced 39±10 mL/min per m2 versus COVIDnormal 43±7 mL/min per m2 versus controls 48±10 mL/min per m2; P=0.02). There were no differences in peak tissue oxygen extraction or biventricular ejection fractions between groups. There were no associations between COVID‐19 illness severity and peak magnetic resonance–augmented cardiopulmonary exercise testing metrics. Peak indexed oxygen uptake, indexed cardiac output, and indexed stroke volume all correlated with duration from discharge to magnetic resonance–augmented cardiopulmonary exercise testing (P<0.05). / Conclusions: Magnetic resonance–augmented cardiopulmonary exercise testing suggests failure to augment stroke volume as a potential mechanism of exercise intolerance in previously hospitalized patients with COVID‐19. This is unrelated to disease severity and, reassuringly, improves with time from acute illness