26 research outputs found

    RHEOLOGICAL BEHAVIOR OF DSPC-, DBPC-, AND DPPC-OXYGEN MICROBUBBLES AND THEIR EFFECTIVENESS IN IMPROVING SURVIVAL IN A RAT MODEL OF LIPOPOLYSACCHARIDE-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME

    Get PDF
    Acute respiratory distress syndrome (ARDS) causes 75,000 deaths in the U.S., annually. It is characterized by hypoxemia and damage to the lung alveoli. ARDS Management strategies involve extracorporeal membrane oxygenation (ECMO) and mechanical ventilation, but none of these methods improve the mortality rates. Oxygen microbubbles (OMBs) consist of a lipid shell with an oxygen core and have potential to augment oxygenation to manage ARDS. Previous studies demonstrated significant improvements in systemic oxygenation and mortality upon administering OMBs. We replicated an ARDS rat model by intratracheal administration of lipopolysaccharide at a 24 mg/kg dose. After inducing the disease in rats, the distearoylphosphatidylcholine (DSPC), dibehenoylphosphatidylcholine (DBPC), or dipalmitoylphosphatidylcholine (DPPC) OMBs were administered intraperitoneally at a 100 mL/kg dose every 12 h, up to 36 h. Arterial blood gas analysis and pulse oximetry were then performed. Results showed 77.8%, 20%, and 10% survival in the DSPC, DBPC, and DPPC groups. Rats in the first group had significantly greater survival than others. Beyond 12 hours, the mean %SpO2 and PaO2 of rats was greater in the DSPC group. Additionally, the mean edema score, wet/dry ratio, and inflammation scores were lower in the DSPC group. The rheological behavior was characterized using a rotating rheometer. The oxygen microbubbles showed a shear-thinning behavior. The results also showed that the viscosity decreased with a decreasing volume fraction and increasing temperature. Lipids with longer chain lengths showed greater viscosities and greater storage and loss moduli. The viscoelastic behavior at lower angular frequencies was predominantly viscous. At greater frequencies, the behavior was predominantly elastic. These results explain the behavior of OMBs when acted upon by a stress. Non-Newtonian fluid models (Casson, Herschell-Bulkley, Power-law) were fit to the shear stress-shear strain data and the R2 and best-fit parameters were obtained to assess the fit. The viscoelastic behavior provides insight into the structure, molecular weight, and temperature-dependent properties of a material. Advisor: Benjamin S. Terr

    Phytochemical screening, free radical scavenging, antioxidant activity and phenolic content of Dodonaea viscosa

    Get PDF
    The purpose of this study was to evaluate the antioxidant potential of Dodonaea viscosa Jacq. Methanolic extract of the plant was dissolved in distilled water and partitioned with n-hexane, chloroform, ethyl acetate and nbutanol sequentially. Phytochemical screening showed presence of phenolics, flavonoides and cardiac glycosides in large amount in chloroform, ethyl acetate and n-butanol fraction. The antioxidant potential of all these fractions and remaining aqueous fraction was evaluated by four methods: 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, total antioxidant activity, Ferric Reducing Antioxidant Power (FRAP) assay and ferric thiocyanate assay along with determination of their total phenolics. The results revealed that ethyl acetate soluble fraction exhibited highest percent inhibition of DPPH radical as compared to other fractions. It showed 81.14 ± 1.38% inhibition of DPPH radical at a concentration of 60 μg/ml. The IC50 of this fraction was found to be 33.95 ± 0.58 μg/ml, relative to butylated hydroxytoluene (BHT), having IC50 of 12.54 ± 0.89 μg/mL. It also showed highest FRAP value (380.53 ± 0.74 μM of trolox equivalents) as well as highest total phenolic contents (208.58 ± 1.83 GAE μg/g) and highest value of inhibition of lipid peroxidation (58.11 ± 1.49% at concentration of 500 μg/ml) as compared to the other studied fractions. The chloroform fraction showed highest total antioxidant activity i.e.1.078 ± 0.59 (eq. to BHT)

    Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome

    Get PDF
    With a mortality rate of 46% before the onset of COVID-19, acute respiratory distress syndrome (ARDS) affected 200,000 people in the US, causing 75,000 deaths. Mortality rates in COVID-19 ARDS patients are currently at 39%. Extrapulmonary support for ARDS aims to supplement mechanical ventilation by providing life-sustaining oxygen to the patient. A new rapid-onset, human-sized pig ARDS model in a porcine intensive care unit (ICU) was developed. The pigs were nebulized intratracheally with a high dose (4 mg/kg) of the endotoxin lipopolysaccharide (LPS) over a 2 h duration to induce rapid-onset moderate-to- severe ARDS. They were then catheterized to monitor vitals and to evaluate the therapeutic effect of oxygenated microbubble (OMB) therapy delivered by intrathoracic (IT) or intraperitoneal (IP) administration. Post-LPS administration, the PaO2 value dropped below 70 mmHg, the PaO2/FiO2 ratio dropped below 200 mmHg, and the heart rate increased, indicating rapidly developing (within 4 h) moderate-to- severe ARDS with tachycardia. The SpO2 and PaO2 of these LPS-injured pigs did not show significant improvement after OMB administration, as they did in our previous studies of the therapy on small animal models of ARDS injury. Furthermore, pigs receiving OMB or saline infusions had slightly lower survival than their ARDS counterparts. The OMB administration did not induce a statistically significant or clinically relevant therapeutic effect in this model; instead, both saline and OMB infusion appeared to lower survival rates slightly. This result is significant because it contradicts positive results from our previous small animal studies and places a limit on the efficacy of such treatments for larger animals under more severe respiratory distress. While OMB did not prove efficacious in this rapid-onset ARDS pig model, it may retain potential as a novel therapy for the usual presentation of ARDS in humans, which develops and progresses over days to weeks

    Nonordered dendritic mesoporous silica nanoparticles as promising platforms for advanced methods of diagnosis and therapies

    Get PDF
    Dendritic mesoporous silica nanoparticles (DMSNs) are a new generation of porous materials that have gained great attention compared to other mesoporous silicas due to attractive properties, including straightforward synthesis methods, modular surface chemistry, high surface area, tunable pore size, chemical inertness, particle size distribution, excellent biocompatibility, biodegradability, and high pore volume compared with conventional mesoporous materials. The last years have witnessed a blooming growth of the extensive utilization of DMSNs as an efficient platform in a broad spectrum of biomedical and industrial applications, such as catalysis, energy harvesting, biosensing, drug/gene delivery, imaging, theranostics, and tissue engineering. DMSNs are considered great candidates for nanomedicine applications due to their ease of surface functionalization for targeted and controlled therapeutic delivery, high therapeutic loading capacity, minimizing adverse effects, and enhancing biocompatibility. In this review, we will extensively detail state-of-the-art studies on recent advances in synthesis methods, structure, properties, and applications of DMSNs in the biomedical field with an emphasis on the different delivery routes, cargos, and targeting approaches and a wide range of therapeutic, diagnostic, tissue engineering, vaccination applications and challenges and future implications of DMSNs as cuttingedge technology in medicine

    Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

    Get PDF
    Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

    Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

    Get PDF
    BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation

    Rheological Behavior of DSPC-, DBPC-, and DPPC-Oxygen Microbubbles and Their Effectiveness in Improving Survival in a Rat Model of Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

    Get PDF
    Acute respiratory distress syndrome (ARDS) causes 75,000 deaths in the U.S., annually. It is characterized by hypoxemia and damage to the lung alveoli. ARDS Management strategies involve extracorporeal membrane oxygenation (ECMO) and mechanical ventilation, but none of these methods improve the mortality rates. Oxygen microbubbles (OMBs) consist of a lipid shell with an oxygen core and have potential to augment oxygenation to manage ARDS. Previous studies demonstrated significant improvements in systemic oxygenation and mortality upon administering OMBs. We replicated an ARDS rat model by intratracheal administration of lipopolysaccharide at a 24 mg/kg dose. After inducing the disease in rats, the distearoylphosphatidylcholine (DSPC), dibehenoylphosphatidylcholine (DBPC), ordipalmitoylphosphatidylcholine (DPPC) OMBs were administered intraperitoneally at a100 mL/kg dose every 12 h, up to 36 h. Arterial blood gas analysis and pulse oximetry were then performed. Results showed 77.8%, 20%, and 10% survival in the DSPC,DBPC, and DPPC groups. Rats in the first group had significantly greater survival than others. Beyond 12 hours, the mean %SpO2 and PaO2 of rats was greater in the DSPC group. Additionally, the mean edema score, wet/dry ratio, and inflammation scores were lower in the DSPC group. The rheological behavior was characterized using a rotating rheometer. The oxygen microbubbles showed a shear-thinning behavior. The results also showed that the viscosity decreased with a decreasing volume fraction and increasing temperature. Lipids with longer chain lengths showed greater viscosities and greater storage and loss moduli. The viscoelastic behavior at lower angular frequencies was predominantly viscous. At greater frequencies, the behavior was predominantly elastic. These results explain the behavior of OMBs when acted upon by a stress. Non-Newtonian fluid models (Casson, Herschell-Bulkley, Power-law) were fit to the shear stress-shear strain data and the R2 and best-fit parameters were obtained to assess the fit. The viscoelastic behavior provides insight into the structure, molecular weight, and temperature-dependent properties of a material
    corecore