Physical pegylation enhances the cytotoxicity of 5-fluorouracil-loaded PLGA And PCL nanoparticles.

Purpose : The main goal of this study is to evaluate the impact of physical incorporation of polyethylene glycol (PEG) into 5-fluorouracil (5-FU)-loaded polymeric nanoparticles (NPs). METHODS: The 5-FU-loaded NPs were prepared utilizing a simple double emulsion method using polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) with or without PEG 6000. The surface charge, particle size, and shape of NPs were evaluated by standard procedures. Both Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra of the 5-FU loaded NPs were compared against the pure 5-FU. The in vitro release profile of 5-FU from the NPs was monitored by the dialysis tubing method. Cell death and apoptosis induction in response to 5-FU NP exposure were measured by MTT and Annexin-V/7-amino-actinomycin D (7-AAD) assays, respectively, in Daoy, HepG2, and HT-29 cancer cell lines. RESULTS: The 5-FU loaded NPs were found to be spherical in shape with size ranging between 176±6.7 and 253.9±8.6 nm. The zeta potential varied between -7.13± 0.13 and -27.06±3.18 mV, and the entrapment efficiency was between 31.96% and 74.09%. The in vitro release of the drug followed a two-phase mode characterized by rapid release in the first 8 hrs followed by a period of slow release up to 72 hrs with composition-based variable extents. Cells exposed to NPs demonstrated a significant cell death which correlated with the ratio of PEG in the formulations in Daoy and HepG2 cells but not in HT-29 cells. Formulations (F1-F3) significantly induced early apoptosis in HT-29 cell lines. CONCLUSION: The physical PEGylation significantly enhanced the entrapment and loading efficiencies of 5-FU into NPs formulated with PLGA and PCL. It also fostered the in vitro cytotoxicity of 5-FU-loaded NPs in both Daoy and HepG2 cells. Induction of early apoptosis was confirmed for some of the formulations

Influence of blend ratio on the electrical characteristics of vulcanized SBR/NBR blends compatibilized by Cis-polybutadiene rubber

Blends composed of styrene butadiene rubber (SBR) and acrylonitrile-butadiene rubber (NBR) have been fabricated by melt-blending technique using two-roll mill blend machine. Cis-polybutadiene rubber (CBR) was used as a compatibilizer for enhancing the homogeneity between blend phases. No previous reports were found to discuss improving electrical properties of vulcanized SBR/NBR blends using unfilled rubber system (i.e. no fillers incorporation). SEM micrographs were utilized to verify the compatibility between two rubber ingredients in various blends, owing to the use of compatibilizer. Thermal stability of blends was investigated by differential thermal analysis (DTA) and differential scanning calorimetric (DSC) to evaluate the influence of blend ratio on the compatibility of investigated samples. Results revealed that the dielectric properties of blends are dramatically influenced by altering the blend ratio. The results revealed that the SEM observations confirmed the compatibilization effect of CBR on vulcanized SBR/NBR blends. Meanwhile, thermal properties of vulcanized SBR/NBR blends were enhanced with increasing of SBR contents in blends. The complex impedance graphs showed circular arcs showing the bulk contribution to overall electrical behavior for investigated vulcanized SBR/NBR blends. During I-V characteristics have been presented, where a remarkably change from linear behavior to nonlinear conduction at lower temperatures was found for 0SBR/100NBR blends. These findings supported and confirmed that the compatibilization effect and the blend ratio between rubber compositions have strongly influenced on their thermal and electrical properties of vulcanized blends

PEGylation of PLGA and PCL nanoparticles enhanced the cytotoxicity of loaded 5-flurouracil

Introduction: The high metabolic rate and the short biological half-life of 5-flourouracil (5-FU) required a continuous administration of large doses and consequently resulting in high profile of adverse effects. Incorporation of 5-FU into biodegradable nanoparticles (NPs) would enhance the therapeutic efficacy through prolongation of the biological half-life and the duration of tumour exposure to 5-FU. This study aimed to monitor the effect of physical incorporation of PEG on the attributes of 5-FU-loaded polymeric NPs. Methods: An emulsification-solvent evaporation technique was employed for the preparation of 5-FU-loaded NPs using polylactic-co-glycolic acid (PLGA) and polycaprolactone (PCL). The effect of incorporating polyethylene glycol (PEG6000) was also investigated. The prepared NPs were evaluated for their particle sizes and morphology and characterized by FTIR and X-ray diffraction. The in vitro drug release profiles were evaluated and the anticancer activity was assessed utilizing MTT assay Daoy, HepG2, and HT29 cancer-cell-lines. Results: The NPs average sizes were between 176±6.7-253.9±8.6 nm and zeta potential between -7.13± 0.13 and -27.06±3.18 mV. The 5-FU %EE of ranged between 31.96-73.54% and enhanced significantly by PEG incorporation. The SEM images showed spherical particles with smooth surfaces. The in vitro release studies showed an initial rapid 5-FU release up to 8 h followed by a slow release ranging from 36 to 84% after 72 h. The higher was the ratio of PEG, the faster was the drug release rate. Significant % cell death was achieved with all the prepared NPs in the three tested cancer cell lines after 48 and 72 hours incubations. The PEG ratio correlated well with the magnitude of cell death in both Doay and HepG cells only. Conclusion: The physical PEGylation resulted in significant increase in the entrapment and loading efficiency of 5-FU in both PLGA and PCL NPs. They also improved both the drug release profile and the extent of in vitro cytotoxicity in both Doay and HepG2 cancer cell lines

Cytotoxic activity of eurycoma longifolia jack root extract against nasopharyngeal carcinoma cell line

Background: Eurycoma longifolia (E. longifolia) or Tongkat Ali is a tree that grows in southeast Asia, the roots of which contain bioactive components that exhibit cytotoxic properties against various cancer cell lines. However, no study has been conducted to relate the cytotoxic properties against nasopharyngeal carcinoma (NPC), a type of cancer that shows poor prognosis for metastatic disease. The purpose of this study was to determine whether the E. longifolia root extract exerts cytotoxic activity against nasopharyngeal carcinoma (ORL-115) cell lines. Materials and Method: E. longifolia root extracts were obtained through Soxhlet extraction method and by using two different solvents; ethanol and dicholoromethane. MTS assay was used to evaluate the cytotoxic effect of the root extracts against ORL-115 cell line for three different incubation time which were 24-hour, 48-hour and 72-hour. Results: Ethanol extract was significantly more potent compared to DCM extract. Ethanol extract exhibited lower IC50 value compared to DCM extract. The IC50 of ethanol extract were 232.1 µg/ml, 66.86 µg/ml and 42.6 µg/ml. Meanwhile the IC50 of DCM extract were 678.87 µg/ml, 136.71 µg/ml, 73.72 µg/ml for 24-hour, 48-hour and 72-hour incubation period respectively. The cytotoxic activity of both extracts increased as the incubation time prolonged. The cytotoxic activity of ethanol extract at each incubation time was significantly different from DCM extract except at 72 hours. Conclusion: E. longifolia root extracts exerted cytotoxic activity against the nasopharyngeal carcinoma (ORL-115) cell line. Ethanol extract exhibited lower IC50 value compared to DCM extract. The cytotoxic activity of both extracts were dose dependent and time dependent

Is quadratus lumborum block combined with low dose-spinal anesthesia an effective alternative to general anesthesia in patients undergoing percutaneous nephrolithotomy?

Background: General anesthesia in high-risk patients has many complications and needs long preoperative preparations and postoperative intensive care unit (ICU). Therefore the present study aimed to evaluate the efficacy of combined low-dose spinal anesthesia with quadratus lumborum block (QLB) as an alternative to general anesthesia for patients undergoing percutaneous nephrolithotomy. Patients and methods: A prospective study was conducted at the urology department of Al-Azhar University Hospitals in Cairo, Egypt, from January 2021 to January 2022. The study included 60 patients of ASA ll-lll scheduled for percutaneous nephrolithotomy. All patients received low-dose spinal anesthesia (5 mg bupivacaine) and QLB (QL1-QL2-QL3) approaches. The primary observation parameter was the efficacy of this technique as an alternative to general anesthesia. The secondary parameters measured were evaluation of need for intraoperative narcotics, postoperative pain score (VAS), and patients satisfaction as assessed using a 5-point Likert Scale. Results: None of the patients was given general anesthesia, and intraoperative sedation was given to nineteen patients (32.2%). No hemodynamic changes were observed in all patients. There was a significant correlation between the use of intraoperative sedation and stone site, intraoperative blood loss, and hospital stay. Pain intensity on VAS at rest and movement was low until the 24th postoperative hour. Patient satisfaction score was 3, 4, and 5 in 1 (1.7%), 4 (6.7%), and 55 (91.6%) patients, respectively. Conclusions: Combined low-dose spinal anesthesia with quadratus lumborum block is an effective alternative to general anesthesia in patients undergoing PCNL procedures with good postoperative analgesia. Patients with lower calyceal punctures have a lower incidence of intraoperative sedation requirements

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

An experimental and computational study of the effect of ambient turbulence on fuel injection sprays

This thesis focuses on the effect of initial ambient turbulence on the spray characteristics of fuel injected into a constant volume. The investigation is performed experimentally and computationally. The spray axial penetration length and radial penetration width, area and velocity are used as key parameters to characterise the spray in the experimental work together with vapour fuel mass fraction, mean droplet diameters and number of droplets in the computational work. In the experimental study, the liquid fuel (iso-octane) is injected, using a high pressure swirl atomiser, into ambient nitrogen with different prescribed nearly isotropic turbulence levels, characterised by the root mean square (RMS) turbulence velocity. Mie scattering laser sheet and Schlieren techniques are combined with a high speed camera to capture images of the vapour and liquid phases simultaneously as a function of injection pressure and ambient turbulence. These indicate that the latter has a significant influence on tip penetration length, penetration width, cross sectional area and velocity. Increased initial ambient turbulence levels lead to reductions in the penetration length in the axial direction and increases in the penetration width in the radial direction; it is also shown to improve fuel evaporation and mixing. In the computational investigation, the commercial Computational Fluid Dynamics code Fluent is used to explore the effect of the RMS turbulence velocity in a constant volume vessel on the spray characteristics of liquid fuel injected into it. The theoretical results are compared with corresponding experimental data obtained for the case of iso- octane fuel injected into nitrogen; the main features of sprays are successfully predicted. The results show how increased ambient turbulence level in the gas into which fuel is injected influences spray atomisation, break-up and evaporation and leads to reduced vapour penetration length and sauter mean droplet diameter, together with increasing vapour penetration width and number of fuel droplets. Additionally, the effect of injection pressure, ambient density and ambient temperature on spray characteristics is investigated at quiescent and turbulent ambient conditions; in which case increasing the injection pressure leads to increases in both the penetration length and the number of droplets, and a corresponding reduction in the sauter mean diameter.EThOS - Electronic Theses Online ServiceGBUnited Kingdo