Controlled Release of Insulin and Modified Insulin from a Novel Injectable Biodegradable Gel

The objective of the study was to develop a controlled release dosage form of insulin, which can provide basal concentrations of insulin in diabetic rats for 1 to 2 weeks after a single subcutaneous injection. A biodegradable injectable drug delivery gel was prepared by dissolving a biodegradable polymer, polylactic-co-glycolic acid (PLGA), in biocompatible plasticizer(s), triethyl citrate (TEC) and/or acetyl triethyl citrate (ATEC). Insulin was then loaded into the blank gel to form an insulin suspension in the polymer solution. After the insulin-loaded gel was injected subcutaneously, the plasticizer(s) dissolved in the aqueous media and were gradually taken away from the gel. The polymer precipitated after the plasticizer(s) were extracted by the aqueous medium and a solid depot of insulin was formed. The insulin was released slowly from the depot by a combination of drug diffusion and erosion of the polymer. In the first part of this study, the effect of different water-soluble and water- insoluble zinc salts on blood glucose lowering effect of insulin in type-2 diabetic ZDF rats was investigated. Insulin formulations containing varying concentrations of different water-soluble and water-insoluble zinc salts were prepared and injected subcutaneously in type-2 ZDF rats and blood glucose concentration lowering effect was studied. Insulin in presence of water-soluble salts of zinc could suppress blood glucose concentrations in ZDF rats for up to 16 hours. Insulin was loaded into different gel formulations (5% PLGA (i.v. 0.09, acid end group), ATEC:TEC (3:1) and 4% insulin) and tested in vivo. However, these insulin- loaded gel formulations only suppressed the blood glucose concentrations in the ZDF rats for 1 day after a single subcutaneous injection. In order to achieve longer control over the release of insulin from the gels, a water-soluble salt, zinc sulfate was incorporated in these insulin containing gels at different concentrations. A biodegradable injectable gel formulation prepared with zinc sulfate was able to maintain low blood glucose concentrations for up to 8 to 10 days following a single subcutaneous injection. In order to achieve better glucose control after the release of insulin from the gels, insulin glargine particles were purified from commercially available Lantus® formulation. The freeze dried insulin glargine particles were then loaded into the blank gels and tested in vivo. The formulation prepared with 5% PLGA (i.v. 0.09, acid end group), ATEC:TEC (3:1) and 4% insulin glargine was able to suppress the blood glucose concentrations of the ZDF rats significantly for 10 days after a single subcutaneous injection. The concentration of insulin glargine was maintained between 260 ± 134.9 mIU/L and 188 ± 55.9 mIU/L until day 10 after single subcutaneous injection. The addition of zinc sulfate to the formulations prepared with purified insulin glargine particles further slowed down the drop in blood glucose concentrations

A Study of Types of Sensors used in Remote Sensing

Of late, the science of Remote Sensing has been gaining a lot of interest and attention due to its wide variety of applications. Remotely sensed data can be used in various fields such as medicine, agriculture, engineering, weather forecasting, military tactics, disaster management etc. only to name a few. This article presents a study of the two categories of sensors namely optical and microwave which are used for remotely sensing the occurrence of disasters such as earthquakes, floods, landslides, avalanches, tropical cyclones and suspicious movements. The remotely sensed data acquired either through satellites or through ground based- synthetic aperture radar systems could be used to avert or mitigate a disaster or to perform a post-disaster analysis

A Study of Types of Sensors used in Remote Sensing

Of late, the science of Remote Sensing has been gaining a lot of interest and attention due to its wide variety of applications. Remotely sensed data can be used in various fields such as medicine, agriculture, engineering, weather forecasting, military tactics, disaster management etc. only to name a few. This article presents a study of the two categories of sensors namely optical and microwave which are used for remotely sensing the occurrence of disasters such as earthquakes, floods, landslides, avalanches, tropical cyclones and suspicious movements. The remotely sensed data acquired either through satellites or through ground based- synthetic aperture radar systems could be used to avert or mitigate a disaster or to perform a post-disaster analysis

A Wideband Multi Segment Dielectric Resonator Antenna

The present work deals with the design of a wideband multi segment dielectric resonator antenna (DRA) that can be used for various applications.The proposed antenna resonates at a tri-band frequencies of 8.48GHz, 16.8GHz and 23.95GHz giving an impedence bandwidth of 62.99%.The tri-band DRA is excited by a coaxial-cable-feed

Economic Status, Education and Empowerment: Implications for Maternal Health Service Utilization in Developing Countries

, and maternal health service utilization in developing countries. are significantly associated with utilization of maternal health services. The odds of having a skilled attendant at delivery for women in the poorest wealth quintile are 94% lower than that for women in the highest wealth quintile and almost 5 times higher for women with complete primary education relative to those less educated. The likelihood of using modern contraception and attending four or more antenatal care visits are 2.01 and 2.89 times, respectively, higher for women with complete primary education than for those less educated. Women with the highest empowerment score are between 1.31 and 1.82 times more likely than those with a null empowerment score to use modern contraception, attend four or more antenatal care visits and have a skilled attendant at birth.Efforts to expand maternal health service utilization can be accelerated by parallel investments in programs aimed at poverty eradication (MDG 1), universal primary education (MDG 2), and women's empowerment (MDG 3)

Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients

BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients

Characterization of 9-Nitrocamptothecin Liposomes: Anticancer Properties and Mechanisms on Hepatocellular Carcinoma In Vitro and In Vivo

BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼-11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo. CONCLUSIONS/SIGNIFICANCE: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio