Evaluation of an Ultrasonic Insulin Delivery System in Hyperglycemic Rabbits

Directory of Open Access Journals (Sweden)

Ameneh Sazgarnia

2010-03-01

Full Text Available Introduction: Sonophoresis has been assessed as a novel approach to create skin permeability and drug delivery using low frequencies of ultrasound waves in the range of 20 kHz to 3 MHz. In this study, a system including seven 40 kHz piezoelectric transducers and an insulin chamber designed by the Medical Physics Research Center has been evaluated on hyperglycemic rabbits. Materials and Methods: Thirty five rabbits became hyperglycemic through Alloxan monohydrate injection and were divided into five groups. The rabbits were treated in two main groups (with insulin and ultrasound radiation in two radiation periods, one main control group and two further control groups (one group with ultrasound radiation with longer radiation period in absence of insulin and presence of normal saline; and the other group without ultrasound radiation in presence of insulin. By filling the system chamber with insulin and placing it on the skin of the abdomen and activating the piezoelectric transducers, blood samples were drawn from the animals before ultrasound irradiation and after it in specified intervals. The glucose level was measured using a glucometer and the serum insulin level was determined using a radioimmunoassay method. Results: Maximum decrease in glucose level was recorded for a 20 minute irradiation in a 180 minute period, and the highest increase in insulin level was recorded for the10 minute radiation group in a 60 minute period. Discussion and Conclusion: Because rapid uptake and reaching a peak in a short time and its swift decrease make a good scheme for controlling glucose level after meals, the 10 minute radiation seems to be more suitable. Also, it is predicted that irradiation time in the interval between food consumption and use of the instrument is critical.

Additive Construction with Mobile Emplacement (ACME) / Automated Construction of Expeditionary Structures (ACES) Materials Delivery System (MDS)

Science.gov (United States)

Mueller, R. P.; Townsend, I. I.; Tamasy, G. J.; Evers, C. J.; Sibille, L. J.; Edmunson, J. E.; Fiske, M. R.; Fikes, J. C.; Case, M.

2018-01-01

The purpose of the Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) project is to incorporate the Liquid Goods Delivery System (LGDS) into the Dry Goods Delivery System (DGDS) structure to create an integrated and automated Materials Delivery System (MDS) for 3D printing structures with ordinary Portland cement (OPC) concrete. ACES 3 is a prototype for 3-D printing barracks for soldiers in forward bases, here on Earth. The LGDS supports ACES 3 by storing liquid materials, mixing recipe batches of liquid materials, and working with the Dry Goods Feed System (DGFS) previously developed for ACES 2, combining the materials that are eventually extruded out of the print nozzle. Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) is a project led by the US Army Corps of Engineers (USACE) and supported by NASA. The equivalent 3D printing system for construction in space is designated Additive Construction with Mobile Emplacement (ACME) by NASA.

Solid lipid nanoparticles for pulmonary delivery of insulin.

Science.gov (United States)

Liu, Jie; Gong, Tao; Fu, Hualin; Wang, Changguang; Wang, Xiuli; Chen, Qian; Zhang, Qin; He, Qin; Zhang, Zhirong

2008-05-22

Growing attention has been given to the potential of pulmonary route as an alternative for non-invasive systemic delivery of therapeutic agents. In this study, novel nebulizer-compatible solid lipid nanoparticles (SLNs) for pulmonary drug delivery of insulin were developed by reverse micelle-double emulsion method. The influences of the amount of sodium cholate (SC) and soybean phosphatidylcholine (SPC) on the deposition properties of the nanoparticles were investigated. Under optimal conditions, the entrapment delivery (ED), respirable fraction (RF) and nebulization efficiency (NE) of SLNs could reach 96.53, 82.11 and 63.28%, respectively, and Ins-SLNs remained stable during nebulization. Fasting plasma glucose level was reduced to 39.41% and insulin level was increased to approximately 170 microIU/ml 4h after pulmonary administration of 20 IU/kg Ins-SLNs. A pharmacological bioavailability of 24.33% and a relative bioavailability of 22.33% were obtained using subcutaneous injection as a reference. Incorporating fluorescent-labelled insulin into SLNs, we found that the SLNs were effectively and homogeneously distributed in the lung alveoli. These findings suggested that SLNs could be used as a potential carrier for pulmonary delivery of insulin by improving both in vitro and in vivo stability as well as prolonging hypoglycemic effect, which inevitably resulted in enhanced bioavailability.

Silica-Coated Liposomes for Insulin Delivery

Directory of Open Access Journals (Sweden)

Neelam Dwivedi

2010-01-01

Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery.

Science.gov (United States)

Sajeesh, S; Sharma, Chandra P

2006-11-15

Present investigation was aimed at developing an oral insulin delivery system based on hydroxypropyl beta cyclodextrin-insulin (HPbetaCD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles. Nanoparticles were prepared by the free radical polymerization of methacrylic acid in presence of chitosan and polyether in a solvent/surfactant free medium. Dynamic light scattering (DLS) experiment was conducted with particles dispersed in phosphate buffer (pH 7.4) and size distribution curve was observed in the range of 500-800 nm. HPbetaCD was used to prepare non-covalent inclusion complex with insulin and complex was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopic studies. HPbetaCD complexed insulin was encapsulated into PMCP nanoparticles by diffusion filling method and their in vitro release profile was evaluated at acidic/alkaline pH. PMCP nanoparticles displayed good insulin encapsulation efficiency and release profile was largely dependent on the pH of the medium. Enzyme linked immunosorbent assay (ELISA) study demonstrated that insulin encapsulated inside the particles was biologically active. Trypsin inhibitory effect of PMCP nanoparticles was evaluated using N-alpha-benzoyl-L-arginine ethyl ester (BAEE) and casein as substrates. Mucoadhesive studies of PMCP nanoparticles were conducted using freshly excised rat intestinal mucosa and the particles were found fairly adhesive. From the preliminary studies, cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery.

Application of polymeric nanoparticles and micelles in insulin oral delivery

Directory of Open Access Journals (Sweden)

Milind Sadashiv Alai

2015-09-01

Full Text Available Diabetes mellitus is an endocrine disease in which the pancreas does not produce sufficient insulin or the body cannot effectively use the insulin it produces. Insulin therapy has been the best choice for the clinical management of diabetes mellitus. The current insulin therapy is via subcutaneous injection, which often fails to mimic the glucose homeostasis that occurs in normal individuals. This provokes numerous attempts to develop a safe and effective noninvasive route for insulin delivery. Oral delivery is the most convenient administration route. However, insulin cannot be well absorbed orally because of its rapid enzymatic degradation in the gastrointestinal tract. Therefore, nanoparticulate carriers such as polymeric nanoparticles and micelles are employed for the oral delivery of insulin. These nanocarriers protect insulin from degradation and facilitate insulin uptake via a transcellular and/or paracellular pathway. This review article focuses on the application of nanoparticles and micelles in insulin oral delivery. The recent advances in this topic are also reviewed.

Nose-to-Brain delivery of insulin for Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Martina Stützle

2015-09-01

Full Text Available The transport of small molecules, peptides and proteins via the olfactory epithelium and along olfactory and trigeminal nerve pathways from the nasal cavity to the brain is very well known and clinically established for central nervous system (CNS active drugs like oxytocin, sumatriptan or insulin. Insulin is a clinically well-established biopharmaceutical with a validated function in cognition. Central supply with insulin via intranasal administration improves cognition in animal models and in human, making insulin a so-called cognitive enhancer. Furthermore, dysregulation of insulin is implicated in the pathogenesis of Alzheimer’s disease, which is associated with lower levels of insulin in the cerebrospinal fluid and is involved in amyloid-beta (Ab regulation. Clinical trials with intranasal insulin implicate positive effects on learning and memory, but a massive lack of pharmacokinetic and efficacy data hamper a pharmacokinetic – pharmcodynamic relation and a possible clinical development as cognition enhancer. A lack of such data also prevents resolving the mechanisms involved in directing insulin to the central or to the peripheral compartment. Here we discuss the basic mechanism of Nose-to-Brain delivery, evidences for intranasal insulin as cognition enhancer, medical devices for intranasal delivery and safety aspects.

Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system.

Science.gov (United States)

de Araújo, Thiago M; Teixeira, Zaine; Barbosa-Sampaio, Helena C; Rezende, Luiz F; Boschero, Antonio C; Durán, Nelson; Höehr, Nelci F

2013-06-01

The aim of this work was to develop an efficient, biodegradable, biocompatible and safe controlled release system using insulin-loaded poly(epsilon-caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as emulsifier. Using the double emulsion method a high insulin encapsulation efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles showed no toxicity to MIN6 cells. Insulin nanoparticles administered subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels after 15 minutes, and presented a sustainable hypoglycemic effect on insulin-dependent type 1 diabetic rats, showing to be more efficient than unencapsulated insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by the effect over liver cell-death and oxidative stress scavenger system in rats. These results suggest that insulin-loaded PCL nanoparticles prepared by water-in-oil-in-water emulsion method are biocompatible, efficient and safe insulin-delivering system with controlled insulin release, which indicates that it may be a powerful tool for insulin-dependent patients care.

Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides.

Science.gov (United States)

Kamei, Noriyasu; Takeda-Morishita, Mariko

2015-01-10

Intranasal administration is considered as an alternative route to enable effective drug delivery to the central nervous system (CNS) by bypassing the blood-brain barrier. Several reports have proved that macromolecules can be transferred directly from the nasal cavity to the brain. However, strategies to enhance the delivery of macromolecules from the nasal cavity to CNS are needed because of their low delivery efficiencies via this route in general. We hypothesized that the delivery of biopharmaceuticals to the brain parenchyma can be facilitated by increasing the uptake of drugs by the nasal epithelium including supporting and neuronal cells to maximize the potentiality of the intranasal pathway. To test this hypothesis, the CNS-related model peptide insulin was intranasally coadministered with the cell-penetrating peptide (CPP) penetratin to mice. As a result, insulin coadministered with l- or d-penetratin reached the distal regions of the brain from the nasal cavity, including the cerebral cortex, cerebellum, and brain stem. In particular, d-penetratin could intranasally deliver insulin to the brain with a reduced risk of systemic insulin exposure. Thus, the results obtained in this study suggested that CPPs are potential tools for the brain delivery of peptide- and protein-based pharmaceuticals via intranasal administration. Copyright © 2014 Elsevier B.V. All rights reserved.

Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

Science.gov (United States)

Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

2009-02-01

Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery.

Science.gov (United States)

Wang, Jinqiang; Ye, Yanqi; Yu, Jicheng; Kahkoska, Anna R; Zhang, Xudong; Wang, Chao; Sun, Wujin; Corder, Ria D; Chen, Zhaowei; Khan, Saad A; Buse, John B; Gu, Zhen

2018-03-27

A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H 2 O 2 ) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H 2 O 2 -responsive microneedles are coated with a thin-layer embedding H 2 O 2 -scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and protective shell could effectively regulate the blood glucose levels within a normal range with improved biocompatibility.

Silica-Coated Liposomes for Insulin Delivery

OpenAIRE

Neelam Dwivedi; M. A. Arunagirinathan; Somesh Sharma; Jayesh Bellare

2010-01-01

Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evid...

Inkjet printing of insulin microneedles for transdermal delivery.

Science.gov (United States)

Ross, Steven; Scoutaris, Nicolaos; Lamprou, Dimitrios; Mallinson, David; Douroumis, Dennis

2015-08-01

Inkjet printing technology was used to apply insulin polymeric layers on metal microneedles for transdermal delivery. A range of various polymers such as gelatin (GLN), polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol (SOL), poly(2-ethyl-2-oxazoline) (POX) and trehalose (THL) were assessed for their capacity to form thin uniform and homogeneous layers that preserve insulin intact. Atomic force microscopy (AFM) showed homogeneous insulin-polymer layers without any phase separation while SOL demonstrated the best performance. Circular discroism (CD) analysis of rehydrated films showed that insulin's alpha helices and β-sheet were well preserved for THL and SOL. In contrast, GLN and POX insulin layers revealed small band shifts indicating possible conformational changes. Insulin release in Franz diffusion cells from MNs inserted into porcine skin showed rapid release rates for POX and GLN within the first 20 min. Inkjet printing was proved an effective approach for transdermal delivery of insulin in solid state.

Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

Science.gov (United States)

Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

2011-09-01

The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes: Results From a Pilot Study

OpenAIRE

Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

2015-01-01

Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This singl...

Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin.

Science.gov (United States)

Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

2018-02-15

Diabetes mellitus is a chronic metabolic health disease affecting the homeostasis of blood sugar levels. However, subcutaneous injection of insulin can lead to patient non-compliance, discomfort, pain and local infection. Sub-micron sized drug delivery systems have gained attention in oral delivery of insulin for diabetes treatment. In most of the recent literature, the terms "microparticles" and "nanoparticle" refer to particles where the dimensions of the particle are measured in micrometers and nanometers respectively. For instance, insulin-loaded particles are defined as microparticles with size larger than 1 μm by most of the research groups. The size difference between nanoparticles and microparticles proffers numerous effects on the drug loading efficiency, aggregation, permeability across the biological membranes, cell entry and tissue retention. For instance, microparticulate drug delivery systems have demonstrated a number of advantages including protective effect against enzymatic degradation, enhancement of peptide stability, site-specific and controlled drug release. Compared to nanoparticulate drug delivery systems, microparticulate formulations can facilitate oral absorption of insulin by paracellular, transcellular and lymphatic routes. In this article, we review the current status of microparticles, microcapsules and microspheres for oral administration of insulin. A number of novel techniques including layer-by-layer coating, self-polymerisation of shell, nanocomposite microparticulate drug delivery system seem to be promising for enhancing the oral bioavailability of insulin. This review draws several conclusions for future directions and challenges to be addressed for optimising the properties of microparticulate drug formulations and enhancing their hypoglycaemic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system

Directory of Open Access Journals (Sweden)

Paul Pijush Kumar

2017-06-01

Full Text Available In this study, we investigate molecularly imprinted polymers (MIPs, which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7.4 than at pH 1.2. In vivo studies on diabetic Wistar rats showed that the fast onset within 2 h is similar to subcutaneous injection with a maximum at 4 h, giving an engaged function responsible for the duration of glucose reduction for up to 24 h. These MIPs, prepared as nanosized material, may open a new horizon for oral insulin delivery.

Development of glucose-responsive 'smart' insulin systems.

Science.gov (United States)

Rege, Nischay K; Phillips, Nelson F B; Weiss, Michael A

2017-08-01

The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.

Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

Science.gov (United States)

Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

2013-10-01

The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Chitosan nanofibers for transbuccal insulin delivery.

Science.gov (United States)

Lancina, Michael G; Shankar, Roopa Kanakatti; Yang, Hu

2017-05-01

In this work, they aimed at producing chitosan based nanofiber mats capable of delivering insulin via the buccal mucosa. Chitosan was electrospun into nanofibers using poly(ethylene oxide) (PEO) as a carrier molecule in various feed ratios. The mechanical properties and degradation kinetics of the fibers were measured. Insulin release rates were determined in vitro using an ELISA assay. The bioactivity of released insulin was measured in terms of Akt activation in pre-adipocytes. Insulin permeation across the buccal mucosa was measured in an ex-vivo porcine transbuccal model. Fiber morphology, mechanical properties, and in vitro stability were dependent on PEO feed ratio. Lower PEO content blends produced smaller diameter fibers with significantly faster insulin release kinetics. Insulin showed no reduction in bioactivity due to electrospinning. Buccal permeation of insulin facilitated by high chitosan content blends was significantly higher than that of free insulin. Taken together, the work demonstrates that chitosan-based nanofibers have the potential to serve as a transbuccal insulin delivery vehicle. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1252-1259, 2017. © 2017 Wiley Periodicals, Inc.

Designing the modern pump: engineering aspects of continuous subcutaneous insulin infusion software.

Science.gov (United States)

Welsh, John B; Vargas, Steven; Williams, Gary; Moberg, Sheldon

2010-06-01

Insulin delivery systems attracted the efforts of biological, mechanical, electrical, and software engineers well before they were commercially viable. The introduction of the first commercial insulin pump in 1983 represents an enduring milestone in the history of diabetes management. Since then, pumps have become much more than motorized syringes and have assumed a central role in diabetes management by housing data on insulin delivery and glucose readings, assisting in bolus estimation, and interfacing smoothly with humans and compatible devices. Ensuring the integrity of the embedded software that controls these devices is critical to patient safety and regulatory compliance. As pumps and related devices evolve, software engineers will face challenges and opportunities in designing pumps that are safe, reliable, and feature-rich. The pumps and related systems must also satisfy end users, healthcare providers, and regulatory authorities. In particular, pumps that are combined with glucose sensors and appropriate algorithms will provide the basis for increasingly safe and precise automated insulin delivery-essential steps to developing a fully closed-loop system.

Electroreleasing Composite Membranes for Delivery of Insulin and Other Biomacromolecules

Science.gov (United States)

1990-04-05

electrochemistry to control the delivery of a chemical or drug (1, 2). The major advantage of electroreleasing systems (over conventional diffusional drug...used to deliver insulin and vitamin B-12. The composite membrane fabrication procedure is shown schematically in Figure 1. An Anopore ( Alltech ) A1203

Reduction of treatment delivery variances with a computer-controlled treatment delivery system

International Nuclear Information System (INIS)

Fraass, B.A.; Lash, K.L.; Matrone, G.M.; Lichter, A.S.

1997-01-01

Purpose: To analyze treatment delivery variances for 3-D conformal therapy performed at various levels of treatment delivery automation, ranging from manual field setup to virtually complete computer-controlled treatment delivery using a computer-controlled conformal radiotherapy system. Materials and Methods: All external beam treatments performed in our department during six months of 1996 were analyzed to study treatment delivery variances versus treatment complexity. Treatments for 505 patients (40,641 individual treatment ports) on four treatment machines were studied. All treatment variances noted by treatment therapists or quality assurance reviews (39 in all) were analyzed. Machines 'M1' (CLinac (6(100))) and 'M2' (CLinac 1800) were operated in a standard manual setup mode, with no record and verify system (R/V). Machines 'M3' (CLinac 2100CD/MLC) and ''M4'' (MM50 racetrack microtron system with MLC) treated patients under the control of a computer-controlled conformal radiotherapy system (CCRS) which 1) downloads the treatment delivery plan from the planning system, 2) performs some (or all) of the machine set-up and treatment delivery for each field, 3) monitors treatment delivery, 4) records all treatment parameters, and 5) notes exceptions to the electronically-prescribed plan. Complete external computer control is not available on M3, so it uses as many CCRS features as possible, while M4 operates completely under CCRS control and performs semi-automated and automated multi-segment intensity modulated treatments. Analysis of treatment complexity was based on numbers of fields, individual segments (ports), non-axial and non-coplanar plans, multi-segment intensity modulation, and pseudo-isocentric treatments (and other plans with computer-controlled table motions). Treatment delivery time was obtained from the computerized scheduling system (for manual treatments) or from CCRS system logs. Treatment therapists rotate among the machines, so this analysis

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

Science.gov (United States)

Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

2015-02-01

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the p Ka of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yan [Shenyang University, Normal College (China); Lin, Xia; Du, Xuli; Geng, Sicong [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Li, Hongren; Sun, Hong [Shenyang University, Normal College (China); Tang, Xing, E-mail: tanglab@126.com [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Xiao, Wei, E-mail: wzhzh-nj@tom.com [Jiangsu Kanion Pharmaceutical Co., Ltd (China)

2015-02-15

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the pKa of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

International Nuclear Information System (INIS)

Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

2015-01-01

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the pKa of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes

Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

Science.gov (United States)

Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P

2010-08-01

In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel PLGA-based nanoparticles for the oral delivery of insulin

Directory of Open Access Journals (Sweden)

Malathi S

2015-03-01

Full Text Available Sampath Malathi,1 Perumal Nandhakumar,2 Velayudham Pandiyan,2 Thomas J Webster,3 Sengottuvelan Balasubramanian1 1Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India; 2Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India; 3Department of Chemical Engineering, Northeastern University, Boston, USA Background: Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of d-α-tocopherol poly(ethylene glycol 1000 succinate (TPGS-emulsified poly(ethylene glycol (PEG-capped poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs was investigated for sustained delivery of insulin (IS.Objective: To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs as a potential drug carrier for the oral delivery of insulin.Methods: A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6] copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration.Results: The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30 NPs when compared to that of free

Design, Construction, Demonstration and Delivery of an Automated Narrow Gap Welding System.

Science.gov (United States)

1982-06-29

DESIGN, CONSTRUCTION, DEMONSTRATION AND DELIVERY OF WE DA4I &NARROW GAP CONTRACT NO. NOOGOO-81-C-E923 TO DAVID TAYLOR NAVAL RESEARCH AND DEVELOPMENT...the automated * Narrow Gap welding process, is the narrow (3/8 - inch), square-butt joint *design. This narrow joint greatly reduces the volume of weld...AD-i45 495 DESIGN CONSTRUCTION DEMONSTRATION AiND DELIVERY OF RN 1/j AUrOMATED NARROW GAP WELDING SYSTEMI() CRC AUTOMATIC WELDING CO HOUSTON TX 29

Biosynthesis of insulin-silk fibroin nanoparticles conjugates and in vitro evaluation of a drug delivery system

Science.gov (United States)

Yan, Hai-Bo; Zhang, Yu-Qing; Ma, Yong-Lei; Zhou, Li-Xia

2009-11-01

Silk fibroin derived from Bombyx mori is a biomacromolecular protein with outstanding biocompatibility. When it was dissolved in highly concentrated CaCl2 solution and then the mixture of the protein and salt was subjected to desalting treatments for long time in flowing water, the resulting liquid silk was water-soluble polypeptides with different molecular masses, ranging from 8 to 70 kDa. When the liquid silk was introduced rapidly into acetone, silk protein nanoparticles with a range of 40-120 nm in diameter could be obtained. The crystalline silk nanoparticles could be conjugated covalently with insulin alone with cross-linking reagent glutaraldehyde. In vitro properties of the insulin-silk fibroin nanoparticles (Ins-SFN) bioconjugates were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The optimal conditions for the biosynthesis of Ins-SFN bioconjugates were investigated. The Ins-SFN constructs obtained by 8 h of covalent cross-linking with 0.7% cross-linking reagent and the proportion of insulin and SFN being 30 IU: 15 mg showed much higher recoveries (90-115%). When insulin was coupled covalently with silk nanoparticles, the resistance of the modified insulin to trypsin digestion and in vitro stability in human serum were greatly enhanced as compared with insulin alone. The results in human serum indicated that the half-life in vitro of the biosynthesized Ins-SFN derivatives was about 2.5 times more than that of native insulin. Therefore, the silk protein nanoparticles have the potential values for being studied and developed as a new bioconjugate for enzyme/polypeptide drug delivery system.

Sci—Thur PM: Planning and Delivery — 03: Automated delivery and quality assurance of a modulated electron radiation therapy plan

International Nuclear Information System (INIS)

Connell, T; Papaconstadopoulos, P; Alexander, A; Serban, M; Devic, S; Seuntjens, J

2014-01-01

Modulated electron radiation therapy (MERT) offers the potential to improve healthy tissue sparing through increased dose conformity. Challenges remain, however, in accurate beamlet dose calculation, plan optimization, collimation method and delivery accuracy. In this work, we investigate the accuracy and efficiency of an end-to-end MERT plan and automated-delivery workflow for the electron boost portion of a previously treated whole breast irradiation case. Dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. The automated delivery, which covered 4 electron energies, 196 subfields and 6183 total MU was completed in 25.8 minutes, including 6.2 minutes of beam-on time with the remainder of the delivery time spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. The delivery time could be reduced by 5.3 minutes with minor electron collimator modifications and the beam-on time could be reduced by and estimated factor of 2–3 through redesign of the scattering foils. Comparison of the planned and delivered film dose gave 3%/3 mm gamma pass rates of 62.1, 99.8, 97.8, 98.3, and 98.7 percent for the 9, 12, 16, 20 MeV, and combined energy deliveries respectively. Good results were also seen in the delivery verification performed with a MapCHECK 2 device. The results showed that accurate and efficient MERT delivery is possible with current technologies

Insulin delivery through nasal route using thiolated microspheres.

Science.gov (United States)

Nema, Tarang; Jain, Ashish; Jain, Aviral; Shilpi, Satish; Gulbake, Arvind; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

The aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93 µmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62 ± 2.4% and 78.85 ± 3.1% in 6 h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23 ± 2.12% and 75.25 ± 0.93% blood glucose of initial BGL were observed at 6 h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits.

Nanoencapsulation of Insulin into Zirconium Phosphate for Oral Delivery Applications

Science.gov (United States)

Díaz, Agustín; David, Amanda; Pérez, Riviam; González, Millie L.; Báez, Adriana; Wark, Stacey E.; Zhang, Paul; Clearfield, Abraham; Colón, Jorge L.

2010-01-01

The encapsulation of insulin into different kinds of materials for non-invasive delivery is an important field of study because of the many drawbacks of painful needle and syringe delivery such as physiological stress, infection, and local hypertrophy, among others.1 A stable, robust, non-toxic, and viable non-invasive carrier for insulin delivery is needed. We present a new approach for protein nanoencapsulation using layered zirconium phosphate (ZrP) nanoparticles produced without any preintercalator present. The use of ZrP without preintercalators produces a highly pure material, without any kinds of contaminants, such as the preintercalator, which can be noxious. Cytotoxicity cell viability in vitro experiments for the ZrP nanoparticles show that ZrP is not toxic, or harmful, in a biological environment, as previously reported for rats.2 Contrary to previous preintercalator-based methods, we show that insulin can be nanoencapsulated in ZrP if a highly hydrate phase of ZrP with an interlayer distance of 10.3 Å (10.3 Å-ZrP or θ-ZrP) is used as precursor. The intercalation of insulin into ZrP produced a new insulin-intercalated ZrP phase with a ca. 27 Å interlayer distance, as determined by X-ray powder diffraction, demonstrating a successful nanoencapsulation of the hormone. The in vitro release profile of the hormone after the intercalation was determined and circular dichroism was used to study the hormone stability upon intercalation and release. The insulin remains stable in the layered material, at room temperature, for a considerable amount of time, improving the shell life of the peptidic hormone. This type of materials represents a strong candidate to develop a non-invasive insulin carrier for the treatment of diabetes mellitus. PMID:20707305

Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment.

Science.gov (United States)

Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

2017-10-28

Nanoparticles have demonstrated significant advancements in potential oral delivery of insulin. In this publication, we review the current status of polymeric, inorganic and solid-lipid nanoparticles designed for oral administration of insulin. Firstly, the structure and physiological function of insulin are examined. Then, the efficiency and shortcomings of insulin nanoparticle are discussed. These include the susceptibility to digestive enzyme degradation, instability in the acidic pH environment, poor mucus diffusion and inadequate permeation through the gastrointestinal epithelium. In order to optimise the nanocarriers, the following considerations, including polymer nature, surface charge, size, polydispersity index and morphology of nanoparticles, have to be taken into account. Some novel designs such as chitosan-based glucose-responsive nanoparticles, layer by layer technique-based nanoparticles and zwitterion nanoparticles are being adopted to overcome the physiological challenges. The review ends with some future directions and challenges to be addressed for the success of oral delivery of insulin-loaded nanoparticle formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Thiolated Eudragit nanoparticles for oral insulin delivery: preparation, characterization and in vivo evaluation.

Science.gov (United States)

Zhang, Yan; Wu, Xiaorong; Meng, Lingkuo; Zhang, Yu; Ai, Ruiting; Qi, Na; He, Haibing; Xu, Hui; Tang, Xing

2012-10-15

In the present study thiolated Eudragit L100 (Eul) based polymeric nanoparticles (NPs) were employed to develop an oral insulin delivery system. Sulfydryl modification was achieved by grafting cysteine to the carboxylic acid group of Eudragit L100, which displayed maximum conjugate level of 390.3±13.4 μmol thiol groups per gram. Eudragit L100-cysteine (Eul-cys) and Eul nanoparticles were prepared by the precipitation method, in which reversible swelling of pH-sensitive material was used for insulin loading and release. Nanoparticles were characterized in terms of their particle size, morphology, loading efficiency (LE%) and in vitro insulin release behavior. The NPs had an average size of 324.2±39.0 nm and 308.8±35.7 nm, maximal LE% of 92.2±1.7% and 96.4±0.5% for Eul-cys and Eul, respectively. The release profile of NPs in vitro showed pH-dependent behavior. Circular dichroism (CD) spectroscopy analysis proved that the secondary structure of the insulin released from NPs was unchanged compared with native insulin. The mucoadhesion study in vitro showed that Eul-cys NPs produced a 3-fold and 2.8-fold increase in rat jejunum and ileum compared with unmodified polymer NPs, respectively, which was due to the immobilization of thiol groups on Eudragit L100. Oral administration of insulin-loaded Eul-cys NPs produced a higher and prolonged hypoglycemic action, and the corresponding relative bioavailability of insulin was found to be 7.33±0.33%, an increase of 2.8-fold compared with Eul NPs (2.65±0.63%). This delivery system is a promising novel tool to improve the absorption of protein and peptide drugs in the intestinal tract. Copyright © 2012 Elsevier B.V. All rights reserved.

Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

Science.gov (United States)

Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

2016-04-01

In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Glucose-responsive insulin delivery for type 1 diabetes: The artificial pancreas story.

Science.gov (United States)

Bally, Lia; Thabit, Hood; Hovorka, Roman

2018-06-15

Insulin replacement therapy is integral to the management of type 1 diabetes, which is characterised by absolute insulin deficiency. Optimal glycaemic control, as assessed by glycated haemoglobin, and avoidance of hyper- and hypoglycaemic excursions have been shown to prevent diabetes-related complications. Insulin pump use has increased considerably over the past decade with beneficial effects on glycaemic control, quality of life and treatment satisfaction. The advent and progress of ambulatory glucose sensor technology has enabled continuous glucose monitoring based on real-time glucose levels to be integrated with insulin therapy. Low glucose and predictive low glucose suspend systems are currently used in clinical practice to mitigate against hypoglycaemia, and provide the first step towards feedback glucose control. The more advanced technology approach, an artificial pancreas or a closed-loop system, gradually increases and decreases insulin delivery in a glucose-responsive fashion to mitigate against hyper- and hypoglycaemia. Randomised outpatient clinical trials over the past 5 years have demonstrated the feasibility, safety and efficacy of the approach, and the recent FDA approval of the first single hormone closed-loop system establishes a new standard of care for people with type 1 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Biotinylated liposomes as potential carriers for the oral delivery of insulin.

Science.gov (United States)

Zhang, Xingwang; Qi, Jianping; Lu, Yi; He, Wei; Li, Xiaoyang; Wu, Wei

2014-01-01

This study aimed to explore biotinylated liposomes (BLPs) as novel carriers to enhance the oral delivery of insulin. Biotinylation was achieved by incorporating biotin-conjugated phospholipids into the liposome membranes. A significant hypoglycemic effect and enhanced absorption were observed after treating diabetic rats with the BLPs with a relative bioavailability of 12.09% and 8.23%, based on the measurement of the pharmacologic effect and the blood insulin level, respectively; this achieved bioavailability was approximately double that of conventional liposomes. The significance of the biotinylation was confirmed by the facilitated absorption of the BLPs through receptor-mediated endocytosis, as well as by the improved physical stability of the liposomes. Increased cellular uptake and quick gastrointestinal transport further verified the ability of the BLPs to enhance absorption. These results provide a proof of concept that BLPs can be used as potential carriers for the oral delivery of insulin. Diabetes remains a major source of mortality in the Western world, and advances in its management are expected to have substantial socioeconomic impact. In this paper, biotinylated liposomes were utilized as carriers of insulin for local delivery, demonstrating the feasibility of this approach in a rat model. © 2014.

Endothelial Fcγ Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to Cause Insulin Resistance in Mice

Science.gov (United States)

Tanigaki, Keiji; Chambliss, Ken L.; Yuhanna, Ivan S.; Sacharidou, Anastasia; Ahmed, Mohamed; Atochin, Dmitriy N.; Huang, Paul L.

2016-01-01

Modest elevations in C-reactive protein (CRP) are associated with type 2 diabetes. We previously revealed in mice that increased CRP causes insulin resistance and mice globally deficient in the CRP receptor Fcγ receptor IIB (FcγRIIB) were protected from the disorder. FcγRIIB is expressed in numerous cell types including endothelium and B lymphocytes. Here we investigated how endothelial FcγRIIB influences glucose homeostasis, using mice with elevated CRP expressing or lacking endothelial FcγRIIB. Whereas increased CRP caused insulin resistance in mice expressing endothelial FcγRIIB, mice deficient in the endothelial receptor were protected. The insulin resistance with endothelial FcγRIIB activation was due to impaired skeletal muscle glucose uptake caused by attenuated insulin delivery, and it was associated with blunted endothelial nitric oxide synthase (eNOS) activation in skeletal muscle. In culture, CRP suppressed endothelial cell insulin transcytosis via FcγRIIB activation and eNOS antagonism. Furthermore, in knock-in mice harboring constitutively active eNOS, elevated CRP did not invoke insulin resistance. Collectively these findings reveal that by inhibiting eNOS, endothelial FcγRIIB activation by CRP blunts insulin delivery to skeletal muscle to cause insulin resistance. Thus, a series of mechanisms in endothelium that impairs insulin movement has been identified that may contribute to type 2 diabetes pathogenesis. PMID:27207525

NovoPen Echo® insulin delivery device

Directory of Open Access Journals (Sweden)

Hyllested-Winge J

2016-01-01

Full Text Available Jacob Hyllested-Winge,1 Thomas Sparre,2 Line Kynemund Pedersen2 1Novo Nordisk Pharma Ltd, Tokyo, Japan; 2Novo Nordisk A/S, Søborg, Denmark Abstract: The introduction of insulin pen devices has provided easier, well-tolerated, and more convenient treatment regimens for patients with diabetes mellitus. When compared with vial and syringe regimens, insulin pens offer a greater clinical efficacy, improved quality of life, and increased dosing accuracy, particularly at low doses. The portable and discreet nature of pen devices reduces the burden on the patient, facilitates adherence, and subsequently contributes to the improvement in glycemic control. NovoPen Echo® is one of the latest members of the NovoPen® family that has been specifically designed for the pediatric population and is the first to combine half-unit increment (=0.5 U of insulin dosing with a simple memory function. The half-unit increment dosing amendments and accurate injection of 0.5 U of insulin are particularly beneficial for children (and insulin-sensitive adults/elders, who often require small insulin doses. The memory function can be used to record the time and amount of the last dose, reducing the fear of double dosing or missing a dose. The memory function also provides parents with extra confidence and security that their child is taking insulin at the correct doses and times. NovoPen Echo is a lightweight, durable insulin delivery pen; it is available in two different colors, which may help to distinguish between different types of insulin, providing more confidence for both users and caregivers. Studies have demonstrated a high level of patient satisfaction, with 80% of users preferring NovoPen Echo to other pediatric insulin pens. Keywords: NovoPen Echo®, memory function, half-unit increment dosing, adherence, children, adolescents 

Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes

Science.gov (United States)

Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

2015-01-01

Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Results: Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = −5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = −2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. Conclusions: The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. PMID:25670847

Bar-code automated waste tracking system

International Nuclear Information System (INIS)

Hull, T.E.

1994-10-01

The Bar-Code Automated Waste Tracking System was designed to be a site-Specific program with a general purpose application for transportability to other facilities. The system is user-friendly, totally automated, and incorporates the use of a drive-up window that is close to the areas dealing in container preparation, delivery, pickup, and disposal. The system features ''stop-and-go'' operation rather than a long, tedious, error-prone manual entry. The system is designed for automation but allows operators to concentrate on proper handling of waste while maintaining manual entry of data as a backup. A large wall plaque filled with bar-code labels is used to input specific details about any movement of waste

Peptide and protein delivery using new drug delivery systems.

Science.gov (United States)

Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

Effect of adrenomedullin gene delivery on insulin resistance in type 2 diabetic rats

Directory of Open Access Journals (Sweden)

Hoda Y. Henein

2011-01-01

Full Text Available Type 2 diabetes mellitus is one of the common metabolic disorders that ultimately afflicts large number of individuals. Adrenomedullin (AM is a potent vasodilator peptide; previous studies reported development of insulin resistance in aged AM deficient mice. In this study, we employed a gene delivery approach to explore its potential role in insulin resistance. Four groups were included: control, diabetic, non-diabetic injected with the AM gene and diabetic injected with the AM gene. One week following gene delivery, serum glucose, insulin, triglycerides, leptin, adiponectin and corticosterone were measured as well as the insulin resistance index (HOMA-IR. Soleus muscle glucose uptake and RT-PCR of both AM and glucose transporter-4 (GLUT 4 gene expressions were assessed. A single tail vein injection of adrenomedullin gene in type 2 diabetic rats improved skeletal muscle insulin responsiveness with significant improvement of soleus muscle glucose uptake, HOMA-IR, serum glucose, insulin and triglycerides and significant increase in muscle GLUT 4 gene expression (P < 0.05 compared with the non-injected diabetic rats. The beneficial effects of AM gene delivery were accompanied by a significant increase in the serum level of adiponectin (2.95 ± 0.09 versus 2.33 ± 0.17 μg/ml in the non-injected diabetic group as well as a significant decrease in leptin and corticosterone levels (7.51 ± 0.51 and 262.88 ± 10.34 versus 10.63 ± 1.4 and 275.86 ± 11.19 ng/ml respectively in the non-injected diabetic group. The conclusion of the study is that AM gene delivery can improve insulin resistance and may have significant therapeutic applications in type 2 diabetes mellitus.

PROXIMITY TO DELIVERY ALTERS INSULIN SENSITIVITY AND GLUCOSE METABOLISM IN PREGNANT MICE

OpenAIRE

Musial, Barbara; Fernandez-Twinn, Denise S.; Vaughan, Owen R.; Ozanne, Susan E.; Voshol, Peter; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.

2016-01-01

In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and ut...

Update on Mathematical Modeling Research to Support the Development of Automated Insulin Delivery Systems

Science.gov (United States)

2010-05-01

that believed the delay is ≤10–15 min, 50% believed that insulin can cause changes in the blood (i.e., plasma)-to-ISF glucose gradient. Also, 50% still...by the R01HL88448-1 grant, which seeks to establish safe pediatric euglycemia after cardiac surgery in neonates using continuous glucose monitoring...2062–7. 9. Burge MR, Castillo KR, Schade DS. Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. Diabetes Care. 1997;20(2):152–5

Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

OpenAIRE

Mokhamad Nur; Todor Vasiljevic

2018-01-01

Nanoparticles or microparticles created by physical complexation between two polyelectrolytes may have a prospective use as an excipient for oral insulin administration. Natural polymers such as tragacanth, alginate, dextran, pullulan, hyaluronic acid, gelatin and chitosan can be potential candidates for this purpose. In this research, insulin particles were prepared by the inclusion of insulin into a tragacanth hydrogel. The effect of the pH and concentration relationship involving polyelect...

Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

Directory of Open Access Journals (Sweden)

Liu LY

2016-02-01

Full Text Available Liyao Liu, Cuiping Zhou, Xuejun Xia, Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China Purpose: Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery.Methods: Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats.Results: Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant

A Journey to Improved Inpatient Glycemic Control by Redesigning Meal Delivery and Insulin Administration.

Science.gov (United States)

Engle, Martha; Ferguson, Allison; Fields, Willa

2016-01-01

The purpose of this quality improvement project was to redesign a hospital meal delivery process in order to shorten the time between blood glucose monitoring and corresponding insulin administration and improve glycemic control. This process change redesigned the workflow of the dietary and nursing departments. Modifications included nursing, rather than dietary, delivering meal trays to patients receiving insulin. Dietary marked the appropriate meal trays and phoned each unit prior to arrival on the unit. The process change was trialed on 2 acute care units prior to implementation hospital wide. Elapsed time between blood glucose monitoring and insulin administration was analyzed before and after process change as well as evaluation of glucometrics: percentage of patients with blood glucose between 70 and 180 mg/dL (percent perfect), blood glucose greater than 300 mg/dL (extreme hyperglycemia), and blood glucose less than 70 mg/dL (hypoglycemia). Percent perfect glucose results improved from 45% to 53%, extreme hyperglycemia (blood glucose >300 mg/dL) fell from 11.7% to 5%. Hypoglycemia demonstrated a downward trend line, demonstrating that with improving glycemic control hypoglycemia rates did not increase. Percentage of patients receiving meal insulin within 30 minutes of blood glucose check increased from 35% to 73%. In the hospital, numerous obstacles were present that interfered with on-time meal insulin delivery. Establishing a meal delivery process with the nurse performing the premeal blood glucose check, delivering the meal, and administering the insulin improves overall blood glucose control. Nurse-led process improvement of blood glucose monitoring, meal tray delivery, and insulin administration does lead to improved glycemic control for the inpatient population.

A review of the security of insulin pump infusion systems.

Science.gov (United States)

Paul, Nathanael; Kohno, Tadayoshi; Klonoff, David C

2011-11-01

Insulin therapy has enabled patients with diabetes to maintain blood glucose control to lead healthier lives. Today, rather than injecting insulin manually using syringes, a patient can use a device such as an insulin pump to deliver insulin programmatically. This allows for more granular insulin delivery while attaining blood glucose control. Insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result, security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this article, we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components, which include the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues. © 2011 Diabetes Technology Society.

Comparison of standard (self-directed) versus intensive patient training for the human insulin inhalation powder (HIIP) delivery system in patients with type 2 diabetes: efficacy, safety, and training measures.

Science.gov (United States)

Rosenstock, Julio; Nakano, Masako; Silverman, Bernard L; Sun, Bin; de la Peña, Amparo; Suri, Ajit; Muchmore, Douglas B

2007-02-01

The Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system [AIR (a registered trademark of Alkermes, Inc., Cambridge, MA) Inhaled Insulin System] was designed to be easy to use. Training methods were compared in insulin-naive patients with type 2 diabetes. Patients (n = 102) were randomized to standard or intensive training. With standard training, patients learned how to use the HIIP delivery system by reading directions for use (DFU) and trying on their own. Intensive training included orientation to the HIIP delivery system with individual coaching and inspiratory flow rate training. Both groups received preprandial HIIP + metformin with or without a thiazolidinedione for 4 weeks. Overall 2-h postprandial blood glucose (PPBG) excursion was the primary measure. Noninferiority was defined as the upper limit of the two-sided 95% confidence interval of the mean difference between groups being 1.2 training) and 0.23 +/- 0.36 (intensive training) mmol/L. The mean difference (standard minus intensive training) and two-sided 95% confidence interval were -0.35 (-1.02, 0.33) mmol/L. No statistically or clinically significant differences were observed between training methods in premeal, postmeal, or bedtime blood glucose values, HIIP doses at endpoint, or blood glucose values after a test meal. No discontinuations occurred because of difficulty of use or dislike of the HIIP system. DFU compliance was >90% in both training groups. There were no significant differences between training methods in safety measures. The HIIP delivery system is easy to use, and most patients can learn to use it by reading the DFU without assistance from health care professionals.

Insulin and the brain.

Science.gov (United States)

Derakhshan, Fatemeh; Toth, Cory

2013-03-01

Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.

pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.

Science.gov (United States)

Mukhopadhyay, Piyasi; Chakraborty, Souma; Bhattacharya, Sourav; Mishra, Roshnara; Kundu, P P

2015-01-01

Chitosan-alginate (CS/ALG) nanoparticles were prepared by formation of an ionotropic pre-gelation of an alginate (ALG) core entrapping insulin, followed by chitosan (CS) polyelectrolyte complexation, for successful oral insulin administration. Mild preparation process without harsh chemicals is aimed at improving insulin bio-efficiency in in vivo model. The nanoparticles showed an average particle size of 100-200 nm in dynamic light scattering (DLS), with almost spherical or sub-spherical shape and ∼ 85% of insulin encapsulation. Again, retention of almost entire amount of encapsulated insulin in simulated gastric buffer followed by its sustained release in simulated intestinal condition proved its pH sensitivity in in vitro release studies. Significant hypoglycemic effects with improved insulin-relative bioavailability (∼ 8.11%) in in vivo model revealed the efficacy of these core-shell nanoparticles of CS/ALG as an oral insulin carrier. No systemic toxicity was found after its peroral treatment, suggesting these core-shell nanoparticles as a promising device for potential oral insulin delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

In vivo evaluation of thiolated chitosan tablets for oral insulin delivery.

Science.gov (United States)

Millotti, Gioconda; Laffleur, Flavia; Perera, Glen; Vigl, Claudia; Pickl, Karin; Sinner, Frank; Bernkop-Schnürch, Andreas

2014-10-01

Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan-6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6-MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

Science.gov (United States)

Vasiljevic, Todor

2018-01-01

Nanoparticles or microparticles created by physical complexation between two polyelectrolytes may have a prospective use as an excipient for oral insulin administration. Natural polymers such as tragacanth, alginate, dextran, pullulan, hyaluronic acid, gelatin and chitosan can be potential candidates for this purpose. In this research, insulin particles were prepared by the inclusion of insulin into a tragacanth hydrogel. The effect of the pH and concentration relationship involving polyelectrolytes offering individual particle size and zeta potential was assessed by zetasizer and scanning electron microscopy (SEM). Insulin–tragacanth interactions at varying pH (3.7, 4.3, 4.6, or 6), and concentration (0.1%, 0.5%, or 1% w/w) were evaluated by differential scanning calorimetry (DSC) and ATR Fourier transform infrared (ATR-FTIR) analysis. Individual and smaller particles, approximately 800 nm, were acquired at pH 4.6 with 0.5% of tragacanth. The acid gelation test indicated that insulin could be entrapped in the physical hydrogel of tragacanth. DSC thermograms of insulin–tragacanth showed shifts on the same unloaded tragacanth peaks and suggested polyelectrolyte–protein interactions at a pH close to 4.3–4.6. FTIR spectra of tragacanth–insulin complexes exhibited amide absorption bands featuring in the protein spectra and revealed the creation of a new chemical substance. PMID:29304023

New ways of insulin delivery.

Science.gov (United States)

Heinemann, L

2010-02-01

foresee that with most new ways of insulin delivery the bioavailability/biopotency will be lower than with subcutaneous (SC) insulin administration. This in turn requires that more insulin has to be applied to induce the same metabolic (blood glucose lowering) effect in patients with diabetes. If the costs of insulin are of relevance for the price (this clearly depends on the source of insulin the individual company has to use) the price of the product will be higher relative to standard SC insulin therapy. The question is, clearly, what are the advantages of the new product? In times when SC insulin administration was painful and cumbersome it was clear that the ease of swallowing an insulin tablet was a good argument for many patients. With the invention of thin insulin needles that make the SC injection practically pain free in most cases, this argument of being 'convenient' becomes of limited relevance. However, for many patients (especially the public) the avoidance of 'injection' is an argument. The question is, how much is the patient (society) willing to pay for such a psychological 'advantage'? Most probably additional clear-cut clinical advantages must be demonstrable to convince the payers to reimburse a new product, especially when the price is higher than that of SC insulin. If, for example, postprandial glycaemic excursions are considerably better controlled because the pharmacodynamic (PD) effects are better than with SC injection of rapid-acting insulin analogues (this might be possible with inhaled Technosphere insulin), this would be a clinically relevant argument. Without such advantages, new products will have no market success. Most probably it will not be until one of the various ARIA developments (e.g. nasal insulin) makes it into a financially attractive product (sufficient return on investment) that more money will flow again in this area of research. The search for relevant articles about new ways to deliver insulin did not reveal very many

The Relationship between 25-hydroxyvitamin D Levels, Insulin Sensitivity and Insulin Secretion in Women 3 Years after Delivery.

Science.gov (United States)

Tänczer, Tímea; Magenheim, Rita; Fürst, Ágnes; Domján, Beatrix; Janicsek, Zsófia; Szabó, Eszter; Ferencz, Viktória; Tabák, Ádám G

2017-12-01

There is a direct correlation between 25-hydroxyvitamin D (25[OH]D) levels and insulin sensitivity. Furthermore, women with gestational diabetes (GDM) may have lower levels of 25(OH)D compared to controls. The present study intended to investigate 25(OH)D levels and their association with insulin sensitivity and insulin secretion in women with prior GDM and in controls 3.2 years after delivery. A total of 87 patients with prior GDM and 45 randomly selected controls (age range, 22 to 44 years) with normal glucose tolerance during pregnancy nested within a cohort of all deliveries at Saint Margit Hospital, Budapest, between January 1 2005, and December 31 2006, were examined. Their 25(OH) D levels were measured by radioimmunoassay. Insulin sensitivity and fasting insulin secretion were estimated using the homeostasis model asssessment (HOMA) calculator and early insulin secretion by the insulinogenic index based on a 75 g oral glucose tolerance test. There was no significant difference in 25(OH)D levels between cases and controls (27.2±13.1 [±SD] vs. 26.9±9.8 ng/L). There was a positive association between HOMA insulin sensitivity and 25(OH)D levels (beta = 0.017; 95% CI 0.001 to 0.034/1 ng/mL) that was robust to adjustment for age and body mass index. There was a nonsignificant association between HOMA insulin secretion and 25(OH)D (p=0.099), while no association was found with the insulinogenic index. Prior GDM status was not associated with 25(OH)D levels; however, 25(OH) D levels were associated with HOMA insulin sensitivity. It is hypothesized that the association between HOMA insulin secretion and 25(OH)D levels is related to the autoregulation of fasting glucose levels because no association between 25(OH)D and insulinogenic index was found. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

Directory of Open Access Journals (Sweden)

Mokhamad Nur

2018-01-01

Full Text Available Nanoparticles or microparticles created by physical complexation between two polyelectrolytes may have a prospective use as an excipient for oral insulin administration. Natural polymers such as tragacanth, alginate, dextran, pullulan, hyaluronic acid, gelatin and chitosan can be potential candidates for this purpose. In this research, insulin particles were prepared by the inclusion of insulin into a tragacanth hydrogel. The effect of the pH and concentration relationship involving polyelectrolytes offering individual particle size and zeta potential was assessed by zetasizer and scanning electron microscopy (SEM. Insulin–tragacanth interactions at varying pH (3.7, 4.3, 4.6, or 6, and concentration (0.1%, 0.5%, or 1% w/w were evaluated by differential scanning calorimetry (DSC and ATR Fourier transform infrared (ATR-FTIR analysis. Individual and smaller particles, approximately 800 nm, were acquired at pH 4.6 with 0.5% of tragacanth. The acid gelation test indicated that insulin could be entrapped in the physical hydrogel of tragacanth. DSC thermograms of insulin–tragacanth showed shifts on the same unloaded tragacanth peaks and suggested polyelectrolyte–protein interactions at a pH close to 4.3–4.6. FTIR spectra of tragacanth–insulin complexes exhibited amide absorption bands featuring in the protein spectra and revealed the creation of a new chemical substance.

A sensor-based automation system for handling nuclear materials

International Nuclear Information System (INIS)

Drotning, W.; Kimberly, H.; Wapman, W.; Darras, D.

1997-01-01

An automated system is being developed for handling large payloads of radioactive nuclear materials in an analytical laboratory. The automation system performs unpacking and repacking of payloads from shipping and storage containers, and delivery of the payloads to the stations in the laboratory. The system uses machine vision and force/torque sensing to provide sensor-based control of the automation system in order to enhance system safety, flexibility, and robustness, and achieve easy remote operation. The automation system also controls the operation of the laboratory measurement systems and the coordination of them with the robotic system. Particular attention has been given to system design features and analytical methods that provide an enhanced level of operational safety. Independent mechanical gripper interlock and tool release mechanisms were designed to prevent payload mishandling. An extensive Failure Modes and Effects Analysis of the automation system was developed as a safety design analysis tool

How can insulin initiation delivery in a dual-sector health system be optimised? A qualitative study on healthcare professionals' views.

Science.gov (United States)

Lee, Ping Yein; Lee, Yew Kong; Ng, Chirk Jenn

2012-04-30

The prevalence of type 2 diabetes is increasing at an alarming rate in developing countries. However, glycaemia control remains suboptimal and insulin use is low. One important barrier is the lack of an efficient and effective insulin initiation delivery approach. This study aimed to document the strategies used and proposed by healthcare professionals to improve insulin initiation in the Malaysian dual-sector (public-private) health system. In depth interviews and focus group discussions were conducted in Klang Valley and Seremban, Malaysia in 2010-11. Healthcare professionals consisting of general practitioners (n = 11), medical officers (n = 8), diabetes educators (n = 3), government policy makers (n = 4), family medicine specialists (n = 10) and endocrinologists (n = 2) were interviewed. We used a topic guide to facilitate the interviews, which were audio recorded, transcribed verbatim and analysed using a thematic approach. Three main themes emerged from the interviews. Firstly, there was a lack of collaboration between the private and public sectors in diabetes care. The general practitioners in the private sector proposed an integrated system for them to refer patients to the public health services for insulin initiation programmes. There could be shared care between the two sectors and this would reduce the disproportionately heavy workload at the public sector. Secondly, besides the support from the government health authority, the healthcare professionals wanted greater involvement of non-government organisations, media and pharmaceutical industry in facilitating insulin initiation in both the public and private sectors. The support included: training of healthcare professionals; developing and disseminating patient education materials; service provision by diabetes education teams; organising programmes for patients' peer group sessions; increasing awareness and demystifying insulin via public campaigns; and subsidising glucose

How can insulin initiation delivery in a dual-sector health system be optimised? A qualitative study on healthcare professionals’ views

Directory of Open Access Journals (Sweden)

Lee Ping Yein

2012-04-01

Full Text Available Abstract Background The prevalence of type 2 diabetes is increasing at an alarming rate in developing countries. However, glycaemia control remains suboptimal and insulin use is low. One important barrier is the lack of an efficient and effective insulin initiation delivery approach. This study aimed to document the strategies used and proposed by healthcare professionals to improve insulin initiation in the Malaysian dual-sector (public–private health system. Methods In depth interviews and focus group discussions were conducted in Klang Valley and Seremban, Malaysia in 2010–11. Healthcare professionals consisting of general practitioners (n = 11, medical officers (n = 8, diabetes educators (n = 3, government policy makers (n = 4, family medicine specialists (n = 10 and endocrinologists (n = 2 were interviewed. We used a topic guide to facilitate the interviews, which were audio recorded, transcribed verbatim and analysed using a thematic approach. Results Three main themes emerged from the interviews. Firstly, there was a lack of collaboration between the private and public sectors in diabetes care. The general practitioners in the private sector proposed an integrated system for them to refer patients to the public health services for insulin initiation programmes. There could be shared care between the two sectors and this would reduce the disproportionately heavy workload at the public sector. Secondly, besides the support from the government health authority, the healthcare professionals wanted greater involvement of non-government organisations, media and pharmaceutical industry in facilitating insulin initiation in both the public and private sectors. The support included: training of healthcare professionals; developing and disseminating patient education materials; service provision by diabetes education teams; organising programmes for patients’ peer group sessions; increasing awareness and demystifying

Performance of a glucose meter with a built-in automated bolus calculator versus manual bolus calculation in insulin-using subjects.

Science.gov (United States)

Sussman, Allen; Taylor, Elizabeth J; Patel, Mona; Ward, Jeanne; Alva, Shridhara; Lawrence, Andrew; Ng, Ronald

2012-03-01

Patients consider multiple parameters in adjusting prandial insulin doses for optimal glycemic control. Difficulties in calculations can lead to incorrect doses or induce patients to administer fixed doses, rely on empirical estimates, or skip boluses. A multicenter study was conducted with 205 diabetes subjects who were on multiple daily injections of rapid/ short-acting insulin. Using the formula provided, the subjects manually calculated two prandial insulin doses based on one high and one normal glucose test result, respectively. They also determined the two doses using the FreeStyle InsuLinx Blood Glucose Monitoring System, which has a built-in, automated bolus calculator. After dose determinations, the subjects completed opinion surveys. Of the 409 insulin doses manually calculated by the subjects, 256 (63%) were incorrect. Only 23 (6%) of the same 409 dose determinations were incorrect using the meter, and these errors were due to either confirmed or potential deviations from the study instructions by the subjects when determining dose with meter. In the survey, 83% of the subjects expressed more confidence in the meter-calculated doses than the manually calculated doses. Furthermore, 87% of the subjects preferred to use the meter than manual calculation to determine prandial insulin doses. Insulin-using patients made errors in more than half of the manually calculated insulin doses. Use of the automated bolus calculator in the FreeStyle InsuLinx meter minimized errors in dose determination. The patients also expressed confidence and preference for using the meter. This may increase adherence and help optimize the use of mealtime insulin. © 2012 Diabetes Technology Society.

Microencapsulation techniques to develop formulations of insulin for oral delivery: a review.

Science.gov (United States)

Cárdenas-Bailón, Fernando; Osorio-Revilla, Guillermo; Gallardo-Velázquez, Tzayhrí

2013-01-01

Oral insulin delivery represents one of the most challenging goals for pharmaceutical industry. In general, it is accepted that oral administration of insulin would be more accepted by patients and insulin would be delivered in a more physiological way than the parenteral route. From all strategies to deliverer insulin orally, microencapsulation or nanoencapsulation of insulin are the most promising approaches because these techniques protect insulin from enzymatic degradation in stomach, show a good release profile at intestine pH values, maintain biological activity during formulation and enhance intestinal permeation at certain extent. From different microencapsulation techniques, it seems that complex coacervation, multiple emulsion and internal gelation are the most appropriate techniques to encapsulate insulin due to their relative ease of preparation. Besides that, the use of organic solvents is not required and can be scaled up at low cost; however, relative oral bioavailability still needs to be improved.

New ways of insulin delivery.

Science.gov (United States)

Heinemann, L

2011-02-01

mean that more patients are willing to start insulin therapy earlier than with conventional SC insulin therapy? With TI we have a product that has improved pharmacological properties (also in comparison to Exubera) for coverage of prandial insulin requirements. Subsequently, in the clinical trials performed, postprandial glycaemic excursions were lower than with SC injection of RHI or rapid-acting insulin analogues. This only in part (if at all) results in an improved metabolic control in general (= lower HbA1c) (see below). The outlook for 2011 is that there are chances that we shall have an inhaled insulin product on the market. Probably also the first OI will be submitted to the regulatory authorities for market approval or will even be available in less regulated markets. In order to select all relevant publications about new ways of insulin delivery I performed a PUBMED search and also checked the table of contents of a number of journals that publish heavily in this area of research as well references in the publications I found for additional references. Selection of the manuscripts from all publications was predominately based on the fact whether they presented data from clinical studies or not. The selected studies were critically reviewed for novelty and appropriate study design etc. In some cases also reviews about a given topic were selected if they provide relevant novel insights. © 2011 Blackwell Publishing Ltd.

Live demonstration: Screen printed, microwave based level sensor for automated drug delivery

KAUST Repository

Karimi, Muhammad Akram; Arsalan, Muhammad; Shamim, Atif

2018-01-01

Level sensors find numerous applications in many industries to automate the processes involving chemicals. Recently, some commercial ultrasound based level sensors are also being used to automate the drug delivery process [1]. Some of the most

Towards automated construction of dependable software/hardware systems

Energy Technology Data Exchange (ETDEWEB)

Yakhnis, A.; Yakhnis, V. [Pioneer Technologies & Rockwell Science Center, Albuquerque, NM (United States)

1997-11-01

This report contains viewgraphs on the automated construction of dependable computer architecture systems. The outline of this report is: examples of software/hardware systems; dependable systems; partial delivery of dependability; proposed approach; removing obstacles; advantages of the approach; criteria for success; current progress of the approach; and references.

Delivery of Patient-Reported Outcome Instruments by Automated Mobile Phone Text Messaging.

Science.gov (United States)

Anthony, Christopher A; Lawler, Ericka A; Glass, Natalie A; McDonald, Katelyn; Shah, Apurva S

2017-11-01

Patient-reported outcome (PRO) instruments allow patients to interpret their health and are integral in evaluating orthopedic treatments and outcomes. The purpose of this study was to define: (1) correlation between PROs collected by automated delivery of text messages on mobile phones compared with paper delivery; and (2) patient use characteristics of a technology platform utilizing automated delivery of text messages on mobile phones. Paper versions of the 12-Item Short Form Health Survey (SF-12) and the short form of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) were completed by patients in orthopedic hand and upper extremity clinics. Over the next 48 hours, the same patients also completed the mobile phone portion of the study outside of the clinic which included text message delivery of the SF-12 and QuickDASH, assigned in a random order. Correlations between paper and text message delivery of the 2 PROs were assessed. Among 72 patients, the intraclass correlation coefficient (ICC) between the written and mobile phone delivery of QuickDASH was 0.91 (95% confidence interval [CI], 0.85-0.95). The ICC between the paper and mobile phone delivery of the SF-12 physical health composite score was 0.88 (95% CI, 0.79-0.93) and 0.86 (95% CI, 0.75-0.92) for the SF-12 mental health composite score. We find that text message delivery using mobile phones permits valid assessment of SF-12 and QuickDASH scores. The findings suggest that software-driven automated delivery of text communication to patients via mobile phones may be a valid method to obtain other PRO scores in orthopedic patients.

Novel simple insulin delivery device reduces barriers to insulin therapy in type 2 diabetes: results from a pilot study.

Science.gov (United States)

Hermanns, Norbert; Lilly, Leslie C; Mader, Julia K; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R

2015-05-01

The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = -5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = -2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. © 2015 Diabetes Technology Society.

Update on mathematical modeling research to support the development of automated insulin delivery systems.

Science.gov (United States)

Steil, Garry M; Hipszer, Brian; Reifman, Jaques

2010-05-01

One year after its initial meeting, the Glycemia Modeling Working Group reconvened during the 2009 Diabetes Technology Meeting in San Francisco, CA. The discussion, involving 39 scientists, again focused on the need for individual investigators to have access to the clinical data required to develop and refine models of glucose metabolism, the need to understand the differences among the distinct models and control algorithms, and the significance of day-to-day subject variability. The key conclusion was that model-based comparisons of different control algorithms, or the models themselves, are limited by the inability to access individual model-patient parameters. It was widely agreed that these parameters, as opposed to the average parameters that are typically reported, are necessary to perform such comparisons. However, the prevailing view was that, if investigators were to make the parameters available, it would limit their ability (and that of their institution) to benefit from the invested work in developing their models. A general agreement was reached regarding the importance of each model having an insulin pharmacokinetic/pharmacodynamic profile that is not different from profiles reported in the literature (88% of the respondents agreed that the model should have similar curves or be analyzed separately) and the importance of capturing intraday variance in insulin sensitivity (91% of the respondents indicated that this could result in changes in fasting glucose of >or=15%, with 52% of the respondents believing that the variability could effect changes of >or=30%). Seventy-six percent of the participants indicated that high-fat meals were thought to effect changes in other model parameters in addition to gastric emptying. There was also widespread consensus as to how a closed-loop controller should respond to day-to-day changes in model parameters (with 76% of the participants indicating that fasting glucose should be within 15% of target, with 30% of the

Pure Insulin Nanoparticle Agglomerates for Pulmonary Delivery

Science.gov (United States)

Bailey, Mark M.; Gorman, Eric M.; Munson, Eric J.; Berkland, Cory J.

2009-01-01

Diabetes is a set of diseases characterized by defects in insulin utilization, either through autoimmune destruction of insulin-producing cells (Type I) or insulin resistance (Type II). Treatment options can include regular injections of insulin, which can be painful and inconvenient, often leading to low patient compliance. To overcome this problem, novel formulations of insulin are being investigated, such as inhaled aerosols. Sufficient deposition of powder in the peripheral lung to maximize systemic absorption requires precise control over particle size and density, with particles between 1 and 5 μm in aerodynamic diameter being within the respirable range. Insulin nanoparticles were produced by titrating insulin dissolved at low pH up to the pI of the native protein, and were then further processed into microparticles using solvent displacement. Particle size, crystallinity, dissolution properties, structural stability, and bulk powder density were characterized. We have demonstrated that pure drug insulin microparticles can be produced from nanosuspensions with minimal processing steps without excipients, and with suitable properties for deposition in the peripheral lung. PMID:18959432

Design, characterization and ex vivo evaluation of chitosan film integrating of insulin nanoparticles composed of thiolated chitosan derivative for buccal delivery of insulin.

Science.gov (United States)

Mortazavian, Elaheh; Dorkoosh, Farid Abedin; Rafiee-Tehrani, Morteza

2014-05-01

The purpose of this study is to optimize and characterize of chitosan buccal film for delivery of insulin nanoparticles that were prepared from thiolated dimethyl ethyl chitosan (DMEC-Cys). Insulin nanoparticles composed of chitosan and dimethyl ethyl chitosan (DMEC) were also prepared as control groups. The release of insulin from nanoparticles was studied in vitro in phosphate buffer solution (PBS) pH 7.4. Optimization of chitosan buccal films has been carried out by central composite design (CCD) response surface methodology. Independent variables were different amounts of chitosan and glycerol as mucoadhesive polymer and plasticizer, respectively. Tensile strength and bioadhesion force were considered as dependent variables. Ex vivo study was performed on excised rabbit buccal mucosa. Optimized insulin nanoparticles were obtained with acceptable physicochemical properties. In vitro release profile of insulin nanoparticles revealed that the highest solubility of nanoparticles in aqueous media is related to DMEC-Cys nanoparticles. CCD showed that optimized buccal film containing 4% chitosan and 10% glycerol has 5.81 kg/mm(2) tensile strength and 2.47 N bioadhesion forces. Results of ex vivo study demonstrated that permeation of insulin nanoparticles through rabbit buccal mucosa is 17.1, 67.89 and 97.18% for chitosan, DMEC and DMEC-Cys nanoparticles, respectively. Thus, this study suggests that DMEC-Cys can act as a potential enhancer for buccal delivery of insulin.

A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin.

Science.gov (United States)

Seong, Keum-Yong; Seo, Min-Soo; Hwang, Dae Youn; O'Cearbhaill, Eoin D; Sreenan, Seamus; Karp, Jeffrey M; Yang, Seung Yun

2017-11-10

Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm -2 ) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

An artificial pancreas for automated blood glucose control in patients with Type 1 diabetes

DEFF Research Database (Denmark)

Schmidt, Signe; Boiroux, Dimitri; Ranjan, Ajenthen

2015-01-01

Automated glucose control in patients with Type 1 diabetes is much-coveted by patients, relatives and healthcare professionals. It is the expectation that a system for automated control, also know as an artificial pancreas, will improve glucose control, reduce the risk of diabetes complications...... and markedly improve patient quality of life. An artificial pancreas consists of portable devices for glucose sensing and insulin delivery which are controlled by an algorithm residing on a computer. The technology is still under development and currently no artificial pancreas is commercially available....... This review gives an introduction to recent progress, challenges and future prospects within the field of artificial pancreas research....

Implementation and evaluation of an automated dispensing system.

Science.gov (United States)

Schwarz, H O; Brodowy, B A

1995-04-15

An institution's experience in replacing a traditional unit dose cassette-exchange system with an automated dispensing system is described. A 24-hour unit dose cassette-exchange system was replaced with an automated dispensing system (Pyxis's Medstation Rx) on a 36-bed cardiovascular surgery unit and an 8-bed cardiovascular intensive care unit. Significantly fewer missing doses were reported after Medstation Rx was implemented. No conclusions could be made about the impact of the system on the reporting of medication errors. The time savings for pharmacy associated with the filling, checking, and delivery of new medication orders equated to about 0.5 full-time equivalent (FTE). Medstation Rx also saved substantial nursing time for acquisition of controlled substances and for controlled-substance inventory taking at shift changes. A financial analysis showed that Medstation Rx could save the institution about $1 million over five years if all personnel time savings could be translated into FTE reductions. The automated system was given high marks by the nurses in a survey; 80% wanted to keep the system on their unit. Pilot implementation of an automated dispensing system improved the efficiency of drug distribution over that of the traditional unit dose cassette-exchange system.

Visualization and Quantitative Assessment of the Brain Distribution of Insulin through Nose-to-Brain Delivery Based on the Cell-Penetrating Peptide Noncovalent Strategy.

Science.gov (United States)

Kamei, Noriyasu; Shingaki, Tomotaka; Kanayama, Yousuke; Tanaka, Misa; Zochi, Riyo; Hasegawa, Koki; Watanabe, Yasuyoshi; Takeda-Morishita, Mariko

2016-03-07

Our recent work suggested that intranasal coadministration with the cell-penetrating peptide (CPP) penetratin increased the brain distribution of the peptide drug insulin. The present study aimed to distinctly certify the ability of penetratin to facilitate the nose-to-brain delivery of insulin by quantitatively evaluating the distribution characteristics in brain using radioactive (64)Cu-NODAGA-insulin. Autoradiography and analysis using a gamma counter of brain areas demonstrated that the accumulation of radioactivity was greatest in the olfactory bulb, the anterior part of the brain closest to the administration site, at 15 min after intranasal administration of (64)Cu-NODAGA-insulin with l- or d-penetratin. The brain accumulation of (64)Cu-NODAGA-insulin with penetratin was confirmed by ELISA using unlabeled insulin in which intact insulin was delivered to the brain after intranasal coadministration with l- or d-penetratin. By contrast, quantification of cerebrospinal fluid (CSF) samples showed increased insulin concentration in only the anterior portion of the CSF at 15 min after intranasal coadministration with l-penetratin. This study gives the first concrete proof that penetratin can accelerate the direct transport of insulin from the nasal cavity to the brain parenchyma. Further optimization of intranasal administration with CPP may increase the efficacy of delivery of biopharmaceuticals to the brain while reducing the risk of systemic drug exposure.

Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.

Science.gov (United States)

Yin, Lichen; Ding, Jieying; He, Chunbai; Cui, Liming; Tang, Cui; Yin, Chunhua

2009-10-01

Trimethyl chitosan-cysteine conjugate (TMC-Cys) was synthesized in an attempt to combine the mucoadhesion and the permeation enhancing effects of TMC and thiolated polymers related to different mechanisms for oral absorption. TMC-Cys with various molecular weights (30, 200, and 500 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanoparticles with insulin through self-assembly, which demonstrated particle size of 100-200 nm, zeta potential of +12 to +18 mV, and high encapsulation efficiency. TMC-Cys/insulin nanoparticles (TMC-Cys NP) showed a 2.1-4.7-fold increase in mucoadhesion compared to TMC/insulin nanoparticles (TMC NP), which might be partly attributed to disulfide formation between TMC-Cys and mucin as evidenced by DSC measurement. Compared to insulin solution and TMC NP, TMC-Cys NP induced increased insulin transport through rat intestine by 3.3-11.7 and 1.7-2.6 folds, promoted Caco-2 cell internalization by 7.5-12.7 and 1.7-3.0 folds, and augmented uptake in Peyer's patches by 14.7-20.9 and 1.7-5.0 folds, respectively. Such results were further confirmed by in vivo experiment with the optimal TMC-Cys NP. Biocompatibility assessment revealed lack of toxicity of TMC-Cys NP. Therefore, self-assembled nanoparticles between TMC-Cys and protein drugs could be an effective and safe oral delivery system.

The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

International Nuclear Information System (INIS)

Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke

2015-01-01

Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was

The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

Energy Technology Data Exchange (ETDEWEB)

Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke, E-mail: ksheng@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90024 (United States)

2015-11-15

Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was

The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery.

Science.gov (United States)

Yu, Victoria Y; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A; Sheng, Ke

2015-11-01

Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was attributed to phantom setup

An automated microfluidic multiplexer for fast delivery of C. elegans populations from multiwells.

Directory of Open Access Journals (Sweden)

Navid Ghorashian

Full Text Available Automated biosorter platforms, including recently developed microfluidic devices, enable and accelerate high-throughput and/or high-resolution bioassays on small animal models. However, time-consuming delivery of different organism populations to these systems introduces a major bottleneck to executing large-scale screens. Current population delivery strategies rely on suction from conventional well plates through tubing periodically exposed to air, leading to certain disadvantages: 1 bubble introduction to the sample, interfering with analysis in the downstream system, 2 substantial time drain from added bubble-cleaning steps, and 3 the need for complex mechanical systems to manipulate well plate position. To address these concerns, we developed a multiwell-format microfluidic platform that can deliver multiple distinct animal populations from on-chip wells using multiplexed valve control. This Population Delivery Chip could operate autonomously as part of a relatively simple setup that did not require any of the major mechanical moving parts typical of plate-handling systems to address a given well. We demonstrated automatic serial delivery of 16 distinct C. elegans worm populations to a single outlet without introducing any bubbles to the samples, causing cross-contamination, or damaging the animals. The device achieved delivery of more than 90% of the population preloaded into a given well in 4.7 seconds; an order of magnitude faster than delivery modalities in current use. This platform could potentially handle other similarly sized model organisms, such as zebrafish and drosophila larvae or cellular micro-colonies. The device's architecture and microchannel dimensions allow simple expansion for processing larger numbers of populations.

Development and in vivo evaluation of an oral insulin-PEG delivery system.

Science.gov (United States)

Calceti, P; Salmaso, S; Walker, G; Bernkop-Schnürch, A

2004-07-01

Insulin-monomethoxypoly(ethylene glycol) derivatives were obtained by preparation of mono- and di-terbutyl carbonate insulin derivatives, reaction of available protein amino groups with activated 750 Da PEG and, finally, amino group de-protection. This procedure allowed for obtaining high yield of insulin-1PEG and insulin-2PEG. In vivo studies carried out by subcutaneous injection into diabetic mice demonstrated that the two bioconjugates maintained the native biological activity. In vitro, PEGylation was found to enhance the hormone stability towards proteases. After 1 h incubation with elastase, native insulin, insulin-1PEG and insulin-2PEG undergo about 70, 30 and 10% degradation, respectively, while in the presence of pepsin protein degradation was 100, 70 and 50%, respectively. The attachment of low molecular weight PEG did not significantly (P >0.05) alter insulin permeation behavior across the intestinal mucosa. Insulin-1PEG was formulated into mucoadhesive tablets constituted by the thiolated polymer poly(acrylic acid)-cysteine. The therapeutic agent was sustained released from these tablets within 5 h. In vivo, by oral administration to diabetic mice, the glucose levels were found to decrease of about 40% since the third hour from administration and the biological activity was maintained up to 30 h. According to these results, the combination of PEGylated insulin with a thiolated polymer used as drug carrier matrix might be a promising strategy for oral insulin administration.

Microfluidic perfusion system for automated delivery of temporal gradients to islets of Langerhans.

Science.gov (United States)

Zhang, Xinyu; Roper, Michael G

2009-02-01

A microfluidic perfusion system was developed for automated delivery of stimulant waveforms to cells within the device. The 3-layer glass/polymer device contained two pneumatic pumps, a 12 cm mixing channel, and a 0.2 microL cell chamber. By altering the flow rate ratio of the pumps, a series of output concentrations could be produced while a constant 1.43 +/- 0.07 microL/min flow rate was maintained. The output concentrations could be changed in time producing step gradients and other waveforms, such as sine and triangle waves, at different amplitudes and frequencies. Waveforms were analyzed by comparing the amplitude of output waveforms to the amplitude of theoretical waveforms. Below a frequency of 0.0098 Hz, the output waveforms had less than 20% difference than input waveforms. To reduce backflow of solutions into the pumps, the operational sequence of the valving program was modified, as well as differential etching of the valve seat depths. These modifications reduced backflow to the point that it was not detected. Gradients in glucose levels were applied in this work to stimulate single islets of Langerhans. Glucose gradients between 3 and 20 mM brought clear and intense oscillations of intracellular [Ca(2+)] indicating the system will be useful in future studies of cellular physiology.

Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice.

Science.gov (United States)

Lee, I-Chi; Lin, Wei-Ming; Shu, Jwu-Ching; Tsai, Shau-Wei; Chen, Chih-Hao; Tsai, Meng-Tsan

2017-01-01

Dissolving microneedles (MNs) display high efficiency in delivering poorly permeable drugs and vaccines. Here, two-layer dissolving polymeric MN patches composed of gelatin and sodium carboxymethyl cellulose (CMC) were fabricated with a two-step casting and centrifuging process to localize the insulin in the needle and achieve efficient transdermal delivery of insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine 6G and fluorescein isothiocyanate-labeled insulin (insulin-FITC) can gradually diffuse from the puncture sites to deeper tissue. Ex vivo drug-release profiles showed that 50% of the insulin was released and penetrated across the skin after 1 h, and the cumulative permeation reached 80% after 5 h. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MN patches on diabetic mice for glucose regulation. The total area above the glucose level versus time curve as an index of hypoglycemic effect was 128.4 ± 28.3 (% h) at 0.25 IU/kg. The relative pharmacologic availability and relative bioavailability (RBA) of insulin from MN patches were 95.6 and 85.7%, respectively. This study verified that the use of gelatin/CMC MN patches for insulin delivery achieved a satisfactory RBA compared to traditional hypodermic injection and presented a promising device to deliver poorly permeable protein drugs for diabetic therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 84-93, 2017. © 2016 Wiley Periodicals, Inc.

Development and Evaluation of a Pilot Prototype Automated Online Sampling System

International Nuclear Information System (INIS)

Whitaker, M.J.

2000-01-01

An automated online sampling system has been developed for the BNFL-Hanford Technetium Monitoring Program. The system was designed to be flexible and allows for the collection and delivery of samples to a variety of detection devices that may be used

MICRONEEDLES AS A WAY TO INCREASE THE TRANSDERMAL INSULIN DELIVERY

Directory of Open Access Journals (Sweden)

E. G. Kuznetsova

2016-01-01

Full Text Available Aim: to prove the possibility of increasing the diffusion of insulin through the skin in vitro with pre-applying microneedles.Materials and methods. Microemulsion for transdermal therapeutic system of insulin has been used in vitro studies. Genetically engineered human insulin has been used in this research. Applicators with silicon microneedles (40 and 150 microns long have been used to enhance the diffusion fl ux of drug substance. The dynamics of insulin release from the transdermal therapeutic systems through the rabbit skin has been studied in glass Franz diffusion cells in analyzer diffusion of drugs HDT 1000 (Copley Scientifi c Ltd., UK. Insulin has been labeled with fl uorescein isothiocyanate to separate the insulin absorption spectrum from the spectra of native skin proteins at spectrophotometer measurements.Results. The amounts of insulin delivered through the skin in vitro after previous application of microneedles of 40 and 150 microns are 282.5 ± 61.1 and 372.3 ± 7.0 microgram, respectively. This is 1.4 and 1.9 times more than in the transdermal system without microneedles.Conclusion. The conditions for increasing the diffusion of insulin through the skin in a model transdermal therapeutic system with microneedles (length – 150 microns, duration of pre-application – 1 hour have been found.

Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

Science.gov (United States)

Brankatschk, Marko; Dunst, Sebastian; Nemetschke, Linda; Eaton, Suzanne

2014-10-02

The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

Development and characterisation of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules.

Science.gov (United States)

Giovino, Concetta; Ayensu, Isaac; Tetteh, John; Boateng, Joshua S

2012-05-30

Mucoadhesive chitosan based films, incorporated with insulin loaded nanoparticles (NPs) made of poly(ethylene glycol)methyl ether-block-polylactide (PEG-b-PLA) have been developed and characterised. Blank-NPs were prepared by double emulsion solvent evaporation technique with varying concentrations of the copolymer (5 and 10%, w/v). The optimised formulation was loaded with insulin (model protein) at initial loadings of 2, 5 and 10% with respect to copolymer weight. The developed NPs were analysed for size, size distribution, surface charge, morphology, encapsulation efficiency and drug release. NPs showing negative (ζ)-potential ( 300 nm and a polydispersity index (P.I.) of ≈ 0.2, irrespective of formulation process, were achieved. Insulin encapsulation efficiencies of 70% and 30% for NPs-Insulin-2 and NPs-Insulin-5 were obtained, respectively. The in vitro release behaviour of both formulations showed a classic biphasic sustained release of protein over 5 weeks which was influenced by pH of the release medium. Optimised chitosan films embedded with 3mg of insulin loaded NPs were produced by solvent casting with homogeneous distribution of NPs in the mucoadhesive matrix, which displayed excellent physico-mechanical properties. The drug delivery system has been designed as a novel platform for potential buccal delivery of macromolecules. Copyright © 2012 Elsevier B.V. All rights reserved.

Wireless energizing system for an automated implantable sensor

Energy Technology Data Exchange (ETDEWEB)

Swain, Biswaranjan; Nayak, Praveen P.; Kar, Durga P.; Bhuyan, Satyanarayan; Mishra, Laxmi P. [Department of Electronics and Instrumentation Engineering, Siksha ‘O’ Anusandhan University, Bhubaneswar 751030 (India)

2016-07-15

The wireless drive of an automated implantable electronic sensor has been explored for health monitoring applications. The proposed system comprises of an automated biomedical sensing system which is energized through resonant inductive coupling. The implantable sensor unit is able to monitor the body temperature parameter and sends back the corresponding telemetry data wirelessly to the data recoding unit. It has been observed that the wireless power delivery system is capable of energizing the automated biomedical implantable electronic sensor placed over a distance of 3 cm from the power transmitter with an energy transfer efficiency of 26% at the operating resonant frequency of 562 kHz. This proposed method ensures real-time monitoring of different human body temperatures around the clock. The monitored temperature data have been compared with a calibrated temperature measurement system to ascertain the accuracy of the proposed system. The investigated technique can also be useful for monitoring other body parameters such as blood pressure, bladder pressure, and physiological signals of the patient in vivo using various implantable sensors.

Wireless energizing system for an automated implantable sensor

International Nuclear Information System (INIS)

Swain, Biswaranjan; Nayak, Praveen P.; Kar, Durga P.; Bhuyan, Satyanarayan; Mishra, Laxmi P.

2016-01-01

The wireless drive of an automated implantable electronic sensor has been explored for health monitoring applications. The proposed system comprises of an automated biomedical sensing system which is energized through resonant inductive coupling. The implantable sensor unit is able to monitor the body temperature parameter and sends back the corresponding telemetry data wirelessly to the data recoding unit. It has been observed that the wireless power delivery system is capable of energizing the automated biomedical implantable electronic sensor placed over a distance of 3 cm from the power transmitter with an energy transfer efficiency of 26% at the operating resonant frequency of 562 kHz. This proposed method ensures real-time monitoring of different human body temperatures around the clock. The monitored temperature data have been compared with a calibrated temperature measurement system to ascertain the accuracy of the proposed system. The investigated technique can also be useful for monitoring other body parameters such as blood pressure, bladder pressure, and physiological signals of the patient in vivo using various implantable sensors.

Wireless energizing system for an automated implantable sensor.

Science.gov (United States)

Swain, Biswaranjan; Nayak, Praveen P; Kar, Durga P; Bhuyan, Satyanarayan; Mishra, Laxmi P

2016-07-01

The wireless drive of an automated implantable electronic sensor has been explored for health monitoring applications. The proposed system comprises of an automated biomedical sensing system which is energized through resonant inductive coupling. The implantable sensor unit is able to monitor the body temperature parameter and sends back the corresponding telemetry data wirelessly to the data recoding unit. It has been observed that the wireless power delivery system is capable of energizing the automated biomedical implantable electronic sensor placed over a distance of 3 cm from the power transmitter with an energy transfer efficiency of 26% at the operating resonant frequency of 562 kHz. This proposed method ensures real-time monitoring of different human body temperatures around the clock. The monitored temperature data have been compared with a calibrated temperature measurement system to ascertain the accuracy of the proposed system. The investigated technique can also be useful for monitoring other body parameters such as blood pressure, bladder pressure, and physiological signals of the patient in vivo using various implantable sensors.

Administração oral de peptídios e proteínas: III. Aplicação à insulina Oral delivery systems for peptides and proteins: III. Application to insulin

Directory of Open Access Journals (Sweden)

Catarina Silva

2003-03-01

Full Text Available A insulina é um peptídeo biologicamente ativo, normalmente administrado por via subcutânea, pelos obstáculos que se colocam a sua administração oral. O desenvolvimento de uma forma farmacêutica passível de ser administrada oralmente tem sido razão de uma investigação persistente, acentuada na última década, conforme é descrito. As estratégias utilizadas têm sido muito variadas, a saber, a utilização de inibidores das enzimas proteolíticas, promotores da absorção, modificação química e fórmulas farmacêuticas específicas, como sistemas de partículas, emulsões, sistemas de liberação targeting e sistemas bioadesivos. Embora ainda nenhuma abordagem tenha sido suficientemente eficaz, os resultados são encorajadores. A microencapsulação e, em particular, os métodos que utilizam polímeros naturais, mostram-se promissores neste propósito, pelas características vantajosas que apresentam.Insulin is an important therapeutic protein, generally administered subcutaneously due to the obstacles of oral delivery. A number of different methods have been explored to improve the low oral bioavailability of insulin, particularly in the last decade, namely protease inhibitors, absorption enhancers, chemical modification and the formulation approach which includes particulate systems, emulsions, targeting delivery systems and bioadhesive systems. Although an effective formulation for oral insulin delivery remains to be achieved, the results are encouraging. Microencapsulation has proven to be a promising method of choice, especially when using natural polymers.

Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

Science.gov (United States)

Liu, Liyao; Zhou, Cuiping; Xia, Xuejun; Liu, Yuling

2016-01-01

Purpose Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs) loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery. Methods Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats. Results Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. Conclusion With the aid of phospholipid-complexation techniques, some hydrophilic peptides, such as insulin, can be successfully entrapped into L/C NPs, which could improve oral bioavailability, time-dependent release, and therapeutic activity. PMID:26966360

Treatment planning for SBRT using automated field delivery: A case study

International Nuclear Information System (INIS)

Ritter, Timothy A.; Owen, Dawn; Brooks, Cassandra M.; Stenmark, Matthew H.

2015-01-01

Stereotactic body radiation therapy (SBRT) treatment planning and delivery can be accomplished using a variety of techniques that achieve highly conformal dose distributions. Herein, we describe a template-based automated treatment field approach that enables rapid delivery of more than 20 coplanar fields. A case study is presented to demonstrate how modest adaptations to traditional SBRT planning can be implemented to take clinical advantage of this technology. Treatment was planned for a left-sided lung lesion adjacent to the chest wall using 25 coplanar treatment fields spaced at 11° intervals. The plan spares the contralateral lung and is in compliance with the conformality standards set forth in Radiation Therapy and Oncology Group protocol 0915, and the dose tolerances found in the report of the American Association of Physicists in Medicine Task Group 101. Using a standard template, treatment planning was accomplished in less than 20 minutes, and each 10 Gy fraction was delivered in approximately 5.4 minutes. For those centers equipped with linear accelerators capable of automated treatment field delivery, the use of more than 20 coplanar fields is a viable SBRT planning approach and yields excellent conformality and quality combined with rapid planning and treatment delivery. Although the case study discusses a laterally located lung lesion, this technique can be applied to centrally located tumors with similar results

A sophisticated programmable miniaturised pump for insulin delivery.

Science.gov (United States)

Klein, J C; Slama, G

1980-09-01

We have conceived a truly pre-programmable infusion system usable for intravenous administration of insulin in diabetic subjects. The original system has been built into a small, commercially available, syringe-pump of which only the case and the mechanical parts have been kept. The computing until has a timer, a programmable memory of 512 words by 8 bits and a digital-to-frequency converter to run the motor which drives the syringe. The memory contains 8 profiles of insulin injections stored in digital form over 64 words. Each profile is selected by the patient before eating according to the carbohydrate content of the planned meal and last about two hours, starting from and returning to the basal rate of insulin, at which it remains until next profile selection. Amount, profiles and duration of insulin injection are either mean values deduced from previous studies with a closed-loop artificial pancreas or personally fitted values; they are stored in an instantly replaceable memory cell. This device allows the patient to choose the time, nature and amount of his food intake.

Adsorption and Desorption of Bioactive Proteins on Hydroxyapatite for Protein Delivery Systems

Directory of Open Access Journals (Sweden)

Chie Kojima

2012-01-01

Full Text Available Hydroxyapatite (HA is a precursor of bone and has been studied as a biomaterial. We attempted HA to apply to protein delivery systems. In this study, the association and dissociation properties of two types of bioactive proteins, cytochrom c and insulin, to HA were investigated. Cytochrom c was less associated with HA than insulin, which was easily released from it. However, the release of insulin from HA was slow. Insulin was released from HA at pH 7.4 more rapidly than at pH 3. The association and dissociation properties might be influenced by the size, solubility and net charge of protein. HA is a potential protein carrier with controlled release.

In vivo evaluation of a conjugated poly(lactide-ethylene glycol nanoparticle depot formulation for prolonged insulin delivery in the diabetic rabbit model

Directory of Open Access Journals (Sweden)

Tomar L

2013-02-01

Full Text Available Lomas Tomar,1,2 Charu Tyagi,1,3 Manoj Kumar,2 Pradeep Kumar,1 Harpal Singh,2 Yahya E Choonara,1 Viness Pillay11University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, Johannesburg, Gauteng, South Africa; 2Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, India; 3VSPG College, Chaudhary Charan Singh University, Meerut, IndiaAbstract: Poly(ethylene glycol (PEG and polylactic acid (PLA-based copolymeric nanoparticles were synthesized and investigated as a carrier for prolonged delivery of insulin via the parenteral route. Insulin loading was simultaneously achieved with particle synthesis using a double emulsion solvent evaporation technique, and the effect of varied PEG chain lengths on particle size and insulin loading efficiency was determined. The synthesized copolymer and nanoparticles were analyzed by standard polymer characterization techniques of gel permeation chromatography, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. In vitro insulin release studies performed under simulated conditions provided a near zero-order release pattern up to 10 days. In vivo animal studies were undertaken with varied insulin loads of nanoparticles administered subcutaneously to fed diabetic rabbits and, of all doses administered, nanoparticles containing 50 IU of insulin load per kg body weight controlled the blood glucose level within the physiologically normal range of 90–140 mg/dL, and had a prolonged effect for more than 7 days. Histopathological evaluation of tissue samples from the site of injection showed no signs of inflammation or aggregation, and established the nontoxic nature of the prepared copolymeric nanoparticles. Further, the reaction profiles for PLA-COOH and NH2-PEGDA-NH2 were elucidated using molecular mechanics energy relationships in vacuum and in a solvated system by exploring the spatial disposition of various

Cross-Linked Dependency of Boronic Acid-Conjugated Chitosan Nanoparticles by Diols for Sustained Insulin Release

Directory of Open Access Journals (Sweden)

Nabil A. Siddiqui

2016-10-01

Full Text Available Boronic acids have been widely investigated for their potential use as glucose sensors in glucose responsive polymeric insulin delivery systems. Interactions between cyclic diols and boronic acids, anchored to polymeric delivery systems, may result in swelling of the delivery system, releasing the drug. In this study, 4-formylphenylboronic acid conjugated chitosan was formulated into insulin containing nanoparticles via polyelectrolyte complexation. The nanoparticles had an average diameter of 140 ± 12.8 nm, polydispersity index of 0.17 ± 0.1, zeta potential of +19.1 ± 0.69 mV, encapsulation efficiency of 81% ± 1.2%, and an insulin loading capacity of 46% ± 1.8% w/w. Changes in size of the nanoparticles and release of insulin were type of sugar- and concentration-dependent. High concentration of diols resulted in a sustained release of insulin due to crosslink formation with boronic acid moieties within the nanoparticles. The formulation has potential to be developed into a self-regulated insulin delivery system for the treatment of diabetes.

Insulin regulates brain function, but how does it get there?

Science.gov (United States)

Gray, Sarah M; Meijer, Rick I; Barrett, Eugene J

2014-12-01

We have learned over the last several decades that the brain is an important target for insulin action. Insulin in the central nervous system (CNS) affects feeding behavior and body energy stores, the metabolism of glucose and fats in the liver and adipose, and various aspects of memory and cognition. Insulin may even influence the development or progression of Alzheimer disease. Yet, a number of seemingly simple questions (e.g., What is the pathway for delivery of insulin to the brain? Is insulin's delivery to the brain mediated by the insulin receptor and is it a regulated process? Is brain insulin delivery affected by insulin resistance?) are unanswered. Here we briefly review accumulated findings affirming the importance of insulin as a CNS regulatory peptide, examine the current understanding of how peripheral insulin is delivered to the brain, and identify key gaps in the current understanding of this process. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Simulation of a Schema Theory-Based Knowledge Delivery System for Scientists.

Science.gov (United States)

Vaughan, W. S., Jr.; Mavor, Anne S.

A future, automated, interactive, knowledge delivery system for use by researchers was tested using a manual cognitive model. Conceptualized from schema/frame/script theories in cognitive psychology and artificial intelligence, this hypothetical system was simulated by two psychologists who interacted with four researchers in microbiology to…

pH sensitive thiolated cationic hydrogel for oral insulin delivery.

Science.gov (United States)

Sonia, T A; Sharma, Chandra P

2014-04-01

The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%.

Preparation and Characterization of Water-Soluble Chitosan Microparticles Loaded with Insulin Using the Polyelectrolyte Complexation Method

International Nuclear Information System (INIS)

Wu, S.; Tao, Y.; Zhang, H.; Su, Z.

2011-01-01

Polymeric delivery systems based on microparticles have emerged as a promising approach for peroral insulin delivery. The amount of insulin was quantified by the improved Bradford method. It was shown that water-soluble chitosan/insulin/tripolyphosphate (TPP) mass ratio played an important role in microparticles formation. Stable, uniform, and spherical water-soluble chitosan microparticles (WSC-MPs) with high insulin association efficiency were formed at or close to optimized WSC/insulin/TPP mass ratio. WSC-MPs had higher association efficiency in the ph 4.0 and ph 9.7 of TPP solution. The results showed that association efficiency and loading capacity of insulin-loaded WSC-MPs prepared in 0.01 mol/L HCl of insulin were 48.28 ± 0.90% and 9.52 ± 1.34%. The average size of insulin-loaded WSC-MPs was 292 nm. The presented WSC microparticulate system has promising properties towards the development of an oral delivery system for insulin

Continuous subcutaneous insulin infusion therapy and multiple daily insulin injections in type 1 diabetes mellitus: a comparative overview and future horizons.

Science.gov (United States)

Thabit, Hood; Hovorka, Roman

2016-01-01

Continuous subcutaneous insulin infusion (CSII) therapy is currently accepted as a treatment strategy for type 1 diabetes. Transition from multiple daily injection therapy (MDI; including basal-bolus regimens) to CSII is based on expectations of better metabolic control and fewer hypoglycaemic events. Evidence to date has not been always conclusive. Evidence for CSII and MDI in terms of glycaemic control, hypoglycaemia and psychosocial outcomes is reviewed in the adult and paediatric population with type 1 diabetes. Findings from studies on threshold-based insulin pump suspension and predictive low glucose management (PLGM) are outlined. Limitations of current CSII application and future technological developments are discussed. Glycaemic control and quality of life (QOL) may be improved by CSII compared to MDI depending on baseline HbA1c and hypoglycaemia rates. Future studies are expected to provide evidence on clinical and cost effectiveness in those who will benefit the most. Training, structured education and support are important to benefit from CSII. Novel technological approaches linking continuous glucose monitoring (CGM) and CSII may help mitigate against frequent hypoglycaemia in those at risk. Development of glucose-responsive automated closed-loop insulin delivery systems may reduce the burden of disease management and improve outcomes in type 1 diabetes.

Insulin nanocomplexes formed by self-assembly from amine-modified poly(vinyl alcohol)-graft-poly(L-Lactide) for non-invasive mucosal delivery: Preparation, characterization and in vivo investigations

OpenAIRE

Simon, Michael

2006-01-01

In this work biodegradable DEAPA-PVAL-g-PLLA nanocomplexes were investigated as a colloidal peptide carrier system for non-invasive transmucosal insulin delivery. Chapter 1 describes the basic fundamentals of insulin therapy, current status, problems and future trends. The pathogenesis of diabetes mellitus and the different treatment options are discussed to give an understanding of the necessity for alternative non-invasive ...

The impact of treatment complexity and computer-control delivery technology on treatment delivery errors

International Nuclear Information System (INIS)

Fraass, Benedick A.; Lash, Kathy L.; Matrone, Gwynne M.; Volkman, Susan K.; McShan, Daniel L.; Kessler, Marc L.; Lichter, Allen S.

1998-01-01

Purpose: To analyze treatment delivery errors for three-dimensional (3D) conformal therapy performed at various levels of treatment delivery automation and complexity, ranging from manual field setup to virtually complete computer-controlled treatment delivery using a computer-controlled conformal radiotherapy system (CCRS). Methods and Materials: All treatment delivery errors which occurred in our department during a 15-month period were analyzed. Approximately 34,000 treatment sessions (114,000 individual treatment segments [ports]) on four treatment machines were studied. All treatment delivery errors logged by treatment therapists or quality assurance reviews (152 in all) were analyzed. Machines 'M1' and 'M2' were operated in a standard manual setup mode, with no record and verify system (R/V). MLC machines 'M3' and 'M4' treated patients under the control of the CCRS system, which (1) downloads the treatment delivery plan from the planning system; (2) performs some (or all) of the machine set up and treatment delivery for each field; (3) monitors treatment delivery; (4) records all treatment parameters; and (5) notes exceptions to the electronically-prescribed plan. Complete external computer control is not available on M3; therefore, it uses as many CCRS features as possible, while M4 operates completely under CCRS control and performs semi-automated and automated multi-segment intensity modulated treatments. Analysis of treatment complexity was based on numbers of fields, individual segments, nonaxial and noncoplanar plans, multisegment intensity modulation, and pseudoisocentric treatments studied for a 6-month period (505 patients) concurrent with the period in which the delivery errors were obtained. Treatment delivery time was obtained from the computerized scheduling system (for manual treatments) or from CCRS system logs. Treatment therapists rotate among the machines; therefore, this analysis does not depend on fixed therapist staff on particular

FACTORS AFFECTING THE DEPOSITION OF AEROSOLIZED INSULIN

Science.gov (United States)

AbstractBackground The inhalation of insulin for absorption into the bloodstream via the lung seems to be a promising technique for the treatment of diabetes mellitus. A fundamental issue to be resolved in the development of such insulin aerosol delivery systems is their...

Expression and Purification of C-Peptide Containing Insulin Using Pichia pastoris Expression System

Directory of Open Access Journals (Sweden)

Mohammed N. Baeshen

2016-01-01

Full Text Available Increase in the incidence of Insulin Dependent Diabetes Mellitus (IDDM among people from developed and developing countries has created a large global market for insulin. Moreover, exploration of new methods for insulin delivery including oral or inhalation route which require very high doses would further increase the demand of cost-effective recombinant insulin. Various bacterial and yeast strains have been optimized to overproduce important biopharmaceuticals. One of the approaches we have taken is the production of recombinant human insulin along with C-peptide in yeast Pichia pastoris. We procured a cDNA clone of insulin from Origene Inc., USA. Insulin cDNA was PCR amplified and cloned into yeast vector pPICZ-α. Cloned insulin cDNA was confirmed by restriction analysis and DNA sequencing. pPICZ-α-insulin clone was transformed into Pichia pastoris SuperMan5 strain. Several Zeocin resistant clones were obtained and integration of insulin cDNA in Pichia genome was confirmed by PCR using insulin specific primers. Expression of insulin in Pichia clones was confirmed by ELISA, SDS-PAGE, and Western blot analysis. In vivo efficacy studies in streptozotocin induced diabetic mice confirmed the activity of recombinant insulin. In conclusion, a biologically active human proinsulin along with C-peptide was expressed at high level using Pichia pastoris expression system.

THE METHOD OF FORMING THE PIGGYBACK TECHNOLOGIES USING THE AUTOMATED HEURISTIC SYSTEM

Directory of Open Access Journals (Sweden)

Ye. Nahornyi

2015-07-01

Full Text Available In order to choose a rational piggyback technology there was offered a method that envisages the automated system improvement by giving it a heuristic nature. The automated system is based on a set of methods, techniques and strategies aimed at creating optimal resource saving technologies, which makes it possible to take into account with maximum efficiency the interests of all the participants of the delivery process. When organizing the piggyback traffic there is presupposed the coordination of operations between the piggyback traffic participants to minimize the cargo travel time.

Polymers for Pharmaceutical Packaging and Delivery Systems

DEFF Research Database (Denmark)

Fristrup, Charlotte Juel

materials of interest for pharmaceutical packaging and delivery systems. Confocal fluorescence microscopy studies and stability studies with insulin aspart (AspB28 insulin) were conducted to evaluate the impact of modified PP compared to unmodified PP. In contrast to PEEK, PP did not contain any functional....... In order to decrease the amount of catalyst residual in the modified materials, activator regenerated by electron transfer (ARGET) SI-ATRP was applied in the second experimental round. Two poly(ethylene glycol)methyl ether methacrylate (MPEGMA) monomers with 4 and 23 ethylene oxide units in the side chain......Selection of polymer materials which will be exposed to protein drugs in either containers or medical devices is often very challenging due to the demands on the polymers. Suitable polymer materials should comply with requirements like compatibility with proteins, sterilisability, good barrier...

Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study.

Science.gov (United States)

Bally, Lia; Thabit, Hood; Kojzar, Harald; Mader, Julia K; Qerimi-Hyseni, Jehona; Hartnell, Sara; Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Pieber, Thomas R; Evans, Mark L; Hovorka, Roman

2017-04-01

Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA 1c below 7·5% (58 mmol/mol). In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA 1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed. Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; pday-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA 1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies

Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin.

Science.gov (United States)

He, Zhiyu; Santos, Jose Luis; Tian, Houkuan; Huang, Huahua; Hu, Yizong; Liu, Lixin; Leong, Kam W; Chen, Yongming; Mao, Hai-Quan

2017-06-01

Controlled delivery of protein would find diverse therapeutic applications. Formulation of protein nanoparticles by polyelectrolyte complexation between the protein and a natural polymer such as chitosan (CS) is a popular approach. However, the current method of batch-mode mixing faces significant challenges in scaling up while maintaining size control, high uniformity, and high encapsulation efficiency. Here we report a new method, termed flash nanocomplexation (FNC), to fabricate insulin nanoparticles by infusing aqueous solutions of CS, tripolyphosphate (TPP), and insulin under rapid mixing condition (Re > 1600) in a multi-inlet vortex mixer. In comparison with the bulk-mixing method, the optimized FNC process produces CS/TPP/insulin nanoparticles with a smaller size (down to 45 nm) and narrower size distribution, higher encapsulation efficiency (up to 90%), and pH-dependent nanoparticle dissolution and insulin release. The CS/TPP/insulin nanoparticles can be lyophilized and reconstituted without loss of activity, and produced at a throughput of 5.1 g h -1 when a flow rate of 50 mL min -1 is used. Evaluated in a Type I diabetes rat model, the smaller nanoparticles (45 nm and 115 nm) control the blood glucose level through oral administration more effectively than the larger particles (240 nm). This efficient, reproducible and continuous FNC technique is amenable to scale-up in order to address the critical barrier of manufacturing for the translation of protein nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modular reservoir concept for MEMS-based transdermal drug delivery systems

International Nuclear Information System (INIS)

Cantwell, Cara T; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P

2014-01-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management. (technical note)

Modular reservoir concept for MEMS-based transdermal drug delivery systems

Science.gov (United States)

Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.

2014-11-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

Analysis and Design Information System Logistics Delivery Service in Pt Repex Wahana

Directory of Open Access Journals (Sweden)

Stephanie Surja

2015-12-01

Full Text Available Analysis and Design of Logistic Delivery System in PT Repex Wahana aims to analyze company’s need in existing business process of logistic delivery service. This will then be used in the development of an integrated system that can address the problems in the running process of sending and tracking the whereaboutsor status of the delivered goods which are the core business processes in the enterprise. The result then will be used as basis in the development of integrated information system in pursuit of corporate solution for process business automation, delivery process, inventory, and logistic delivery tracking, which is the core of the company business process, and it will be documented using Unified Modeling Language. The information system is meant to simplify the delivery and tracking process in the company, besides will minimize lost and error of data which is often happened because of the manual and unorganized transaction data processing.

Automatic remote sampling and delivery system incorporating decontamination and disposal of sample bottles

International Nuclear Information System (INIS)

Savarkar, V.K.; Mishra, A.K.; Bajpai, D.D.; Nair, M.K.T.

1990-01-01

The present generation of reprocessing plants have sampling and delivery systems that have to be operated manually with its associated problems. The complete automation and remotisation of sampling system has hence been considered to reduce manual intervention and personnel exposure. As a part of this scheme an attempt to automate and remotise various steps in sampling system has been made. This paper discusses in detail the development work carried out in this area as well as the tests conducted to incorporate the same in the existing plants. (author). 3 figs

Synthesis and characterization of insulin/zirconium phosphate@TiO2 hybrid composites for enhanced oral insulin delivery applications.

Science.gov (United States)

Safari, Mostafa; Kamari, Younes; Ghiaci, Mehran; Sadeghi-Aliabadi, Hojjat; Mirian, Mina

2017-05-01

In this work, a series of composites of insulin (Ins)/zirconium phosphate (ZrP) were synthesized by intercalation method, then, these composites were coated with TiO 2 by sol-gel method to prepare Ins/ZrP@TiO 2 hybrid composites and the drug release of the composites was investigated by using UV-Vis spectroscopy. Ins/ZrP (10, 30, 60 wt%) composites were prepared by intercalation of insulin into the ZrP layers in water. Then Ins/ZrP composites were coated with different amounts of TiO 2 (30, 50, 100 wt %) by using titanium tetra n-butoxide, as precursor. Formation of intercalated Ins/ZrP and Ins/ZrP@TiO 2 hybrid composites was characterized by FT-IR, FE-SEM, BET and XRD analysis. Zeta potential of the optimized Ins/ZrP@TiO 2 hybrid composite was determined -27.2 mV. Cytotoxic effects of the optimized Ins/ZrP@TiO 2 hybrid composite against HeLa and Hek293T cell lines were evaluated using MTT assay and the results showed that designed drug delivery system was not toxic in biological environment. Compared to the Ins/ZrP composites, incorporation of TiO 2 coating enhanced the drug entrapment considerably, and reduced the drug release. The Ins/ZrP composites without TiO 2 coating released the whole drug after 30 min in pH 7.4 (phosphate buffer solution) while the TiO 2 -coated composites released the entrapped drug after 20 h. In addition to increasing the shelf life of hormone, this nanoencapsulation and nanocoating method can convert the insulin utilization from injection to oral and present a painless and more comfortable treatment for diabetics.

World-wide distribution automation systems

International Nuclear Information System (INIS)

Devaney, T.M.

1994-01-01

A worldwide power distribution automation system is outlined. Distribution automation is defined and the status of utility automation is discussed. Other topics discussed include a distribution management system, substation feeder, and customer functions, potential benefits, automation costs, planning and engineering considerations, automation trends, databases, system operation, computer modeling of system, and distribution management systems

Transdermal drug delivery

Science.gov (United States)

Prausnitz, Mark R.; Langer, Robert

2009-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting

Directory of Open Access Journals (Sweden)

Olmos Pablo R

2010-07-01

Full Text Available Abstract Background It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS for inpatient treatment, and tested its stability under simulated clinical conditions. Methods The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions. Results The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. Conclusions When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.

Pitfalls of Insulin Pump Clocks

Science.gov (United States)

Reed, Amy J.

2014-01-01

The objective was to raise awareness about the importance of ensuring that insulin pumps internal clocks are set up correctly at all times. This is a very important safety issue because all commercially available insulin pumps are not GPS-enabled (though this is controversial), nor equipped with automatically adjusting internal clocks. Special attention is paid to how basal and bolus dose errors can be introduced by daylight savings time changes, travel across time zones, and am-pm clock errors. Correct setting of insulin pump internal clock is crucial for appropriate insulin delivery. A comprehensive literature review is provided, as are illustrative cases. Incorrect setting can potentially result in incorrect insulin delivery, with potential harmful consequences, if too much or too little insulin is delivered. Daylight saving time changes may not significantly affect basal insulin delivery, given the triviality of the time difference. However, bolus insulin doses can be dramatically affected. Such problems may occur when pump wearers have large variations in their insulin to carb ratio, especially if they forget to change their pump clock in the spring. More worrisome than daylight saving time change is the am-pm clock setting. If this setting is set up incorrectly, both basal rates and bolus doses will be affected. Appropriate insulin delivery through insulin pumps requires correct correlation between dose settings and internal clock time settings. Because insulin pumps are not GPS-enabled or automatically time-adjusting, extra caution should be practiced by patients to ensure correct time settings at all times. Clinicians and diabetes educators should verify the date/time of insulin pumps during patients’ visits, and should remind their patients to always verify these settings. PMID:25355713

Synthesis and evaluation of temperature- and glucose-sensitive nanoparticles based on phenylboronic acid and N-vinylcaprolactam for insulin delivery

Energy Technology Data Exchange (ETDEWEB)

Wu, Jun-zi [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620 (China); Bremner, David H. [School of Science, Engineering and Technology, Kydd Building, Abertay University, Dundee DD1 1HG, Scotland (United Kingdom); Li, He-yu; Sun, Xiao-zhu [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620 (China); Zhu, Li-Min, E-mail: lzhu@dhu.edu.cn [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620 (China)

2016-12-01

Poly N-vinylcaprolactam-co-acrylamidophenylboronic acid p(NVCL-co-AAPBA) was prepared from N-vinylcaprolactam (NVCL) and 3-acrylamidophenylboronic acid (AAPBA), using 2,2-azobisisobutyronitrile (AIBN) as initiator. The synthesis and structure of the polymer were examined by Fourier Transform infrared spectroscopy (FT-IR) and {sup 1}H-NMR. Dynamic light scattering (DLS), lower critical solution temperature (LCST) and transmission electron microscopy (TEM) were utilized to characterize the nanoparticles, CD spectroscopy was used to determine if there were any changes to the conformation of the insulin, and cell and animal toxicity were also investigated. The prepared nanoparticles were found to be monodisperse submicron particles and were glucose- and temperature-sensitive. In addition, the nanoparticles have good insulin-loading characteristics, do not affect the conformation of the insulin and show low-toxicity to cells and animals. These p(NVCL-co-AAPBA) nanoparticles may have some value for insulin or other hypoglycemic protein delivery. - Highlights: • A comprehensive study of a nanoparticles may have some value for insulin or other hypoglycemic protein delivery. • p(NVCL-co-AAPBA)'s synthetic method is simple, convenient to carry out. • NVCL is low toxic and safe. • The evaluation of acute toxicity and chronic toxicity is the most highlight.

Effect of an Enhanced Nose-to-Brain Delivery of Insulin on Mild and Progressive Memory Loss in the Senescence-Accelerated Mouse.

Science.gov (United States)

Kamei, Noriyasu; Tanaka, Misa; Choi, Hayoung; Okada, Nobuyuki; Ikeda, Takamasa; Itokazu, Rei; Takeda-Morishita, Mariko

2017-03-06

Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia. The pharmacological actions of insulin were investigated at different stages of memory impairment using a senescence-accelerated mouse-prone 8 (SAMP8) model. The results of spatial learning tests suggested that chronic intranasal administration of insulin with l-penetratin to SAMP8 slowed the progression of memory loss in the early stage of memory impairment. However, contrary to expectations, this strategy using penetratin was ineffective in recovering the severe cognitive dysfunction in the progressive stage, which involves brain accumulation of amyloid β (Aβ). Immunohistological examination of hippocampal regions of samples from SAMP8 in the progressive stage suggested that accelerated nose-to-brain insulin delivery had a partial neuroprotective function but unexpectedly increased Aβ plaque deposition in the hippocampus. These findings suggest that the efficient nose-to-brain delivery of insulin combined with noncovalent CPP strategy has different effects on dementia during the mild and progressive stages of cognitive dysfunction.

New Insulin Delivery Recommendations.

Science.gov (United States)

Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

2016-09-01

Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5

International Nuclear Information System (INIS)

Goda, Natsuko; Tenno, Takeshi; Inomata, Kosuke; Shirakawa, Masahiro; Tanaka, Toshiki; Hiroaki, Hidekazu

2008-01-01

Insulin-like growth factor binding proteins (IGFBPs) have various IGF-independent cellular activities, including receptor-independent cellular uptake followed by transcriptional regulation, although mechanisms of cellular entry remain unclear. Herein, we focused on their receptor-independent cellular entry mechanism in terms of protein transduction domain (PTD) activity, which is an emerging technique useful for clinical applications. The peptides of 18 amino acid residues derived from IGFBP-3 and IGFBP-5, which involve heparin-binding regions, mediated cellular delivery of an exogenous protein into NIH3T3 and HeLa cells. Relative protein delivery activities of IGFBP-3/5-derived peptides were approximately 20-150% compared to that of the HIV-Tat peptide, a potent PTD. Heparin inhibited the uptake of the fusion proteins with IGFBP-3 and IGFBP-5, indicating that the delivery pathway is heparin-dependent endocytosis, similar to that of HIV-Tat. The delivery of GST fused to HIV-Tat was competed by either IGFBP-3 or IGFBP-5-derived synthetic peptides. Therefore, the entry pathways of the three PTDs are shared. Our data has shown a new approach for designing protein delivery systems using IGFBP-3/5 derived peptides based on the molecular mechanisms of IGF-independent activities of IGFBPs

The role of insulin-like growth factor in prediction and prevention of preterm delivery

Directory of Open Access Journals (Sweden)

Bogavac Mirjana

2010-01-01

Full Text Available Background/Aim. Prediction and prevention of preterm delivery remain great challenge. It is important to include in everyday medical practice determination of certain markers that could help identifying pregnant women with preterm delivery. Insulin like growth factor (IGF is involved in the control mechanism of fetal and placental growth and development. The aim of this study was to examine the presence of insulin-like growth factor binding protein 1 (IGFBP-1 in cervicovaginal secretion of pregnant women with symptoms of preterm labor, but with apparently intact fetal membranes and to point out a possible application of the strip test for detection of phIGFBP-1 in diagnosis of preterm premature rupture of total membranes (PPROM in everyday medical practice. Methods. The study was performed at the Department for Obstetrics and Gynecology, Clinical Center of Vojvodina between October 2008 and May 2009. The study included 54 pregnant women between 20-35 weeks of gestation (WG, divided into two groups: the study group (16 pregnant women with symptoms of preterm delivery that gave birth before 37 WG and the control group (38 pregnant women with the normal course of pregnancy that gave birth on term. In cervicovaginal secretion of the examined pregnant women the level of IGFBP-1 was determined by the immunochromatographic assay with monoclonal antibodies 6303 as a detecting antibody (Actim PROM test, Medix Biochemica, Kauniainen, Finland. Results. Gestational age (GA at delivery in the study group was 32.6 WG and in the control group it was 38.4 WG. Weight of newborns in the study group was 2,021 g and in the control group 3,430 g. IGFBP test was positive in 15 women (93.75% of the study group, while in the control group it was positive only in 1 woman (2.63%. Conclusion. Test on phIGFBP-1 in cervicovaginal mucus was positive in 93.75% women with preterm delivery, suggesting that this test could be used in diagnosis of silent rupture of fetal

Glucose-Responsive Insulin Delivery by Microneedle-Array Patches Loaded with Hypoxia-Sensitive Vesicles.

Science.gov (United States)

Yu, Jicheng; Zhang, Yuqi; Gu, Zhen

2017-01-01

In this chapter, we describe the preparation of glucose-responsive vesicles (GRVs) and the fabrication of GRV-loaded microneedle-array patches for insulin delivery. The GRVs were formed of hypoxia-sensitive hyaluronic acid (HS-HA), the synthesis of which is presented in detail. We also describe the procedure to evaluate the in vivo efficacy of this smart patch in a mouse model of chemically induced type 1 diabetes through transcutaneous administration.

Poly(ethylene glycol) grafted chitosan as new copolymer material for oral delivery of insulin

International Nuclear Information System (INIS)

Ho, Thanh Ha; Thanh Le, Thi Nu; Nguyen, Tuan Anh; Dang, Mau Chien

2015-01-01

A new scheme of grafting poly (ethylene glycol) onto chitosan was proposed in this study to give new material for delivery of insulin over oral pathway. First, methoxy poly(ethylene glycol) amine (mPEGa MW 2000) were grafted onto chitosan (CS) through multiples steps to synthesize the grafting copolymer PEG-g-CS. After each synthesis step, chitosan and its derivatives were characterized by FTIR, "1H NMR Then, insulin loaded PEG-g-CS nanoparticles were prepared by cross-linking of CS with sodium tripolyphosphate (TPP). Same insulin loaded nanoparticles using unmodified chitosan were also prepared in order to compare with the modified ones. Results showed better protecting capacity of the synthesized copolymer over original CS. CS nanoparticles (10 nm of size) were gel like and high sensible to temperature as well as acidic environment while PEG-g-CS nanoparticles (200 nm of size) were rigid and more thermo and pH stable. (paper)

Updates on smart polymeric carrier systems for protein delivery.

Science.gov (United States)

El-Sherbiny, Ibrahim; Khalil, Islam; Ali, Isra; Yacoub, Magdi

2017-10-01

Smart materials are those materials that are responsive to chemical (organic molecules, chemical agents or specific agents), biochemical (protein, enzymes, growth factors, substrates or ligands), physical (electric field, magnetic field, temperature, pH, ionic strength or radiation) or mechanical (pressure or mechanical stress) signals. These responsive materials interact with the stimuli by changing their properties or conformational structures in a predictable manner. Recently, smart polymers have been utilized in various biomedical applications. Particularly, they have been used as a platform to synthesize stimuli-responsive systems that could deliver therapeutics to a specific site for a specific period with minimal adverse effects. For instance, stimuli-responsive polymers-based systems have been recently reported to deliver different bioactive molecules such as carbohydrates (heparin), chemotherapeutic agents (doxorubicin), small organic molecules (anti-coagulants), nucleic acids (siRNA), and proteins (growth factors and hormones). Protein therapeutics played a fundamental role in treatment of various chronic and some autoimmune diseases. For instance insulin has been used in treatment of diabetes. However, being a protein in nature, insulin delivery is limited by its instability, short half-life, and easy denaturation when administered orally. To overcome these challenges, and as highlighted in this review article, much research efforts have been recently devoted to design and develop convenient smart controlled nanosystems for protein therapeutics delivery.

Advanced fighter technology integration (AFTI)/F-16 Automated Maneuvering Attack System final flight test results

Science.gov (United States)

Dowden, Donald J.; Bessette, Denis E.

1987-01-01

The AFTI F-16 Automated Maneuvering Attack System has undergone developmental and demonstration flight testing over a total of 347.3 flying hours in 237 sorties. The emphasis of this phase of the flight test program was on the development of automated guidance and control systems for air-to-air and air-to-ground weapons delivery, using a digital flight control system, dual avionics multiplex buses, an advanced FLIR sensor with laser ranger, integrated flight/fire-control software, advanced cockpit display and controls, and modified core Multinational Stage Improvement Program avionics.

Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide.

Science.gov (United States)

Boyhan, Diane; Daniell, Henry

2011-06-01

Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene and homoplasmy. Old tobacco leaves accumulated proinsulin up to 47% of total leaf protein (TLP). Old lettuce leaves accumulated proinsulin up to 53% TLP. Accumulation was so stable that up to ~40% proinsulin in TLP was observed even in senescent and dried lettuce leaves, facilitating their processing and storage in the field. Based on the yield of only monomers and dimers of proinsulin (3 mg/g leaf, a significant underestimation), with a 50% loss of protein during the purification process, one acre of tobacco could yield up to 20 million daily doses of insulin per year. Proinsulin from tobacco leaves was purified up to 98% using metal affinity chromatography without any His-tag. Furin protease cleaved insulin peptides in vitro. Oral delivery of unprocessed proinsulin bioencapsulated in plant cells or injectable delivery into mice showed reduction in blood glucose levels similar to processed commercial insulin. C-peptide should aid in long-term treatment of diabetic complications including stimulation of nerve and renal functions. Hyper-expression of functional proinsulin and exceptional stability in dehydrated leaves offer a low-cost platform for oral and injectable delivery of cleavable proinsulin. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Automated Metabolic P System Placement in FPGA

Directory of Open Access Journals (Sweden)

Kulakovskis Darius

2016-07-01

Full Text Available An original Very High Speed Integrated Circuit Hardware Description Language (VHDL code generation tool that can be used to automate Metabolic P (MP system implementation in hardware such as Field Programmable Gate Arrays (FPGA is described. Unlike P systems, MP systems use a single membrane in their computations. Nevertheless, there are many biological processes that have been successfully modeled by MP systems in software. This is the first attempt to analyze MP system hardware implementations. Two different MP systems are investigated with the purpose of verifying the developed software: the model of glucose–insulin interactions in the Intravenous Glucose Tolerance Test (IVGTT, and the Non-Photochemical Quenching process. The implemented systems’ calculation accuracy and hardware resource usage are examined. It is found that code generation tool works adequately; however, a final decision has to be done by the developer because sometimes several implementation architecture alternatives have to be considered. As an archetypical example serves the IVGTT MP systems’ 21–23 bits FPGA implementation manifesting this in the Digital Signal Processor (DSP, slice, and 4-input LUT usage.

Artifical Pancreas

Science.gov (United States)

Fei, Jiangfeng

2013-03-01

In 2006, JDRF launched the Artificial Pancreas Project (APP) to accelerate the development of a commercially-viable artificial pancreas system to closely mimic the biological function of the pancreas individuals with insulin-dependent diabetes, particularly type 1 diabetes. By automating detection of blood sugar levels and delivery of insulin in response to those levels, an artificial pancreas has the potential to transform the lives of people with type 1 diabetes. The 6-step APP development pathway serves as JDRF's APP strategic funding plan and defines the priorities of product research and development. Each step in the plan represents incremental advances in automation beginning with devices that shut off insulin delivery to prevent episodes of low blood sugar and progressing ultimately to a fully automated ``closed loop'' system that maintains blood glucose at a target level without the need to bolus for meals or adjust for exercise.

Live demonstration: Screen printed, microwave based level sensor for automated drug delivery

KAUST Repository

Karimi, Muhammad Akram

2018-01-02

Level sensors find numerous applications in many industries to automate the processes involving chemicals. Recently, some commercial ultrasound based level sensors are also being used to automate the drug delivery process [1]. Some of the most desirable features of level sensors to be used for medical use are their non-intrusiveness, low cost and consistent performance. In this demo, we will present a completely new method of sensing the liquid level using microwaves. It is a common stereotype to consider microwaves sensing mechanism as being expensive. Unlike usual expensive, intrusive and bulky microwave methods of level sensing using guided radars, we will present an extremely low cost printed, non-intrusive microwave sensor to reliably sense the liquid level.

Automated Budget System -

Data.gov (United States)

Department of Transportation — The Automated Budget System (ABS) automates management and planning of the Mike Monroney Aeronautical Center (MMAC) budget by providing enhanced capability to plan,...

The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

LENUS (Irish Health Repository)

Cooley, Sharon M

2010-05-01

To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery.

Insulin-chitosan polyelectrolyte _anocomplexes: preparation ...

African Journals Online (AJOL)

Objectives: To formulate chitosan nanoparticles with specific combinations of molecular weight and degree of deacetylation (DDA) that could be developed into an oral insulin delivery system. Methods: This study was conducted at Jordanian Pharmaceutical Manufacturing Company (JPM), Jordan in the period 2006-2009.

Automated PCB Inspection System

Directory of Open Access Journals (Sweden)

Syed Usama BUKHARI

2017-05-01

Full Text Available Development of an automated PCB inspection system as per the need of industry is a challenging task. In this paper a case study is presented, to exhibit, a proposed system for an immigration process of a manual PCB inspection system to an automated PCB inspection system, with a minimal intervention on the existing production flow, for a leading automotive manufacturing company. A detailed design of the system, based on computer vision followed by testing and analysis was proposed, in order to aid the manufacturer in the process of automation.

The use of dextrose/insulin infusions during labour and delivery in women with gestational diabetes mellitus: Is there any point?

Science.gov (United States)

Farrant, Maritza T; Williamson, Kathryn; Battin, Malcolm; Hague, William M; Rowan, Janet A

2017-06-01

We compared, in 733 women with gestational diabetes mellitus treated with metformin and/or insulin, rates of neonatal hypoglycaemia in those who had received a dextrose/insulin infusion during labour and prior to delivery (n = 132) with those who did not (n = 601). Women who had infusions were more likely to have been treated with insulin (87.1% vs 70.4%, P < 0.01) and have higher mean capillary glucose values (measured four times daily) in the two weeks prior to delivery (P < 0.01). They had lower mean (SD) glucose values in the 12 h prior to delivery (5.1 (1.1) mmol/L vs 5.4 (0.9) mmol/L, P < 0.01). There was no difference between the groups in rates of neonatal hypoglycaemia (glucose <2.6 mmol/L on two or more occasions), 15.9% versus 17.8%, P = 0.78, or of severe neonatal hypoglycaemia (one or more glucose <1.6 mmol/L), 8.3% versus 5.2%, P = 0.15. In the absence of randomised data comparing use of infusions with no infusions, these data are reassuring for clinicians who do not routinely use infusions. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Enhancing effect of bile salts on gastrointestinal absorption of insulin ...

African Journals Online (AJOL)

Purpose: To investigate the effect of co-administration of two absorption enhancing bile alts, sodium glycocholate (NaGc) and sodium salicylate (NaSal), on insulin absorption via intestinal targeted delivery system. Methods: Insulin (10 IU/kg), associated with and without absorption enhancers (5 % enhancer solution of ...

Automated hybrid closed-loop control with a proportional-integral-derivative based system in adolescents and adults with type 1 diabetes: individualizing settings for optimal performance.

Science.gov (United States)

Ly, Trang T; Weinzimer, Stuart A; Maahs, David M; Sherr, Jennifer L; Roy, Anirban; Grosman, Benyamin; Cantwell, Martin; Kurtz, Natalie; Carria, Lori; Messer, Laurel; von Eyben, Rie; Buckingham, Bruce A

2017-08-01

Automated insulin delivery systems, utilizing a control algorithm to dose insulin based upon subcutaneous continuous glucose sensor values and insulin pump therapy, will soon be available for commercial use. The objective of this study was to determine the preliminary safety and efficacy of initialization parameters with the Medtronic hybrid closed-loop controller by comparing percentage of time in range, 70-180 mg/dL (3.9-10 mmol/L), mean glucose values, as well as percentage of time above and below target range between sensor-augmented pump therapy and hybrid closed-loop, in adults and adolescents with type 1 diabetes. We studied an initial cohort of 9 adults followed by a second cohort of 15 adolescents, using the Medtronic hybrid closed-loop system with the proportional-integral-derivative with insulin feed-back (PID-IFB) algorithm. Hybrid closed-loop was tested in supervised hotel-based studies over 4-5 days. The overall mean percentage of time in range (70-180 mg/dL, 3.9-10 mmol/L) during hybrid closed-loop was 71.8% in the adult cohort and 69.8% in the adolescent cohort. The overall percentage of time spent under 70 mg/dL (3.9 mmol/L) was 2.0% in the adult cohort and 2.5% in the adolescent cohort. Mean glucose values were 152 mg/dL (8.4 mmol/L) in the adult cohort and 153 mg/dL (8.5 mmol/L) in the adolescent cohort. Closed-loop control using the Medtronic hybrid closed-loop system enables adaptive, real-time basal rate modulation. Initializing hybrid closed-loop in clinical practice will involve individualizing initiation parameters to optimize overall glucose control. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

LENUS (Irish Health Repository)

Cooley, Sharon M

2012-02-01

AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.

Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors.

Science.gov (United States)

Marks, David R; Tucker, Kristal; Cavallin, Melissa A; Mast, Thomas G; Fadool, Debra A

2009-05-20

The role of insulin pathways in olfaction is of significant interest with the widespread pathology of diabetes mellitus and its associated metabolic and neuronal comorbidities. The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and postsynaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made prediabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors.

Automated System Marketplace 1994.

Science.gov (United States)

Griffiths, Jose-Marie; Kertis, Kimberly

1994-01-01

Reports results of the 1994 Automated System Marketplace survey based on responses from 60 vendors. Highlights include changes in the library automation marketplace; estimated library systems revenues; minicomputer and microcomputer-based systems; marketplace trends; global markets and mergers; research needs; new purchase processes; and profiles…

Flexible automation and the loss of pooling synergy

NARCIS (Netherlands)

Slomp, Jannes; Zee, Durk-Jouke van der

This paper focuses on the effects of flexible automation on the performance of a job shop. Flexible automated machines may significantly improve the delivery performance and the flow time of jobs. The insertion of a flexible automated system in a job shop, however, also has a counter effect on the

Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin.

Science.gov (United States)

Andrade, Fernanda; das Neves, José; Gener, Petra; Schwartz, Simó; Ferreira, Domingos; Oliva, Mireia; Sarmento, Bruno

2015-10-01

Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus®, Pluronic® F68, Pluronic® F108 and Pluronic® F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<6 μm) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic® F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation. The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Insulin pumps and insulin quality--requirements and problems.

Science.gov (United States)

Brange, J; Havelund, S

1983-01-01

In developing insulin solution suitable for delivery devices the chemical and biological stability, as well as the physical stability, must be taken into consideration. Addition of certain mono- and disaccharides increases the physical stability of neutral insulin solutions, but concurrently the chemical and biological stability decrease to an unacceptable degree. Addition of Ca-ions in low concentrations offers a physiologically acceptable method for stabilizing neutral insulin solutions against heat precipitation without affecting the quality, including the chemical and biological stability.

Evaluating the Performance of a Novel Embedded Closed-loop System.

Science.gov (United States)

Leelarathna, Lalantha; Thabit, Hood; Allen, Janet M; Nodale, Marianna; Wilinska, Malgorzata E; Powell, Kevin; Lane, Stephen; Evans, Mark L; Hovorka, Roman

2014-03-01

The objective was to assess the reliability of a novel automated closed-loop glucose control system developed within the AP@home consortium in adults with type 1 diabetes. Eight adults with type 1 diabetes on insulin pump therapy (3 men; ages 40.5 ± 14.3 years; HbA1c 8.2 ± 0.8%) participated in an open-label, single-center, single-arm, 12-hour overnight study performed at the clinical research facility. A standardized evening meal (80 g CHO) accompanied by prandial insulin boluses were given at 19:00 followed by an optional snack of 15 g at 22:00 without insulin bolus. Automated closed-loop glucose control was started at 19:00 and continued until 07:00 the next day. Basal insulin delivery (Accu-Chek Spirit, Roche) was automatically adjusted by Cambridge model predictive control algorithm, running on a purpose-built embedded device, based on real-time continuous glucose monitor readings (Dexcom G4 Platinum). Closed-loop system was operational as intended over 99% of the time. Overnight plasma glucose levels (22:00 to 07:00) were within the target range (3.9 to 8.0 mmol/l) for 75.4% (37.5, 92.9) of the time without any time spent in hypoglycemia (system. The time spent in target glucose level overnight was comparable to results of previously published studies. Further developments to miniaturize the system for home studies are warranted. © 2014 Diabetes Technology Society.

Low Molecular Weight Chitosan–Insulin Polyelectrolyte Complex: Characterization and Stability Studies

Directory of Open Access Journals (Sweden)

Zakieh I. Al-Kurdi

2015-03-01

Full Text Available The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC in a reverse micelle (RM system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity.

Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation.

Directory of Open Access Journals (Sweden)

J Eduardo Rico

Full Text Available Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition. Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in

Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation

Science.gov (United States)

Rico, J. Eduardo; Saed Samii, Sina; Mathews, Alice T.; Lovett, Jacqueline; Haughey, Norman J.; McFadden, Joseph W.

2017-01-01

Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition). Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in peripartal sphingolipids

Systematically In Silico Comparison of Unihormonal and Bihormonal Artificial Pancreas Systems

Directory of Open Access Journals (Sweden)

Xiaoteng Gao

2013-01-01

Full Text Available Automated closed-loop control of blood glucose concentration is a daily challenge for type 1 diabetes mellitus, where insulin and glucagon are two critical hormones for glucose regulation. According to whether glucagon is included, all artificial pancreas (AP systems can be divided into two types: unihormonal AP (infuse only insulin and bihormonal AP (infuse both insulin and glucagon. Even though the bihormonal AP is widely considered a promising direction, related studies are very scarce due to this system’s short research history. More importantly, there are few studies to compare these two kinds of AP systems fairly and systematically. In this paper, two switching rules, P-type and PD-type, were proposed to design the logic of orchestrates switching between insulin and glucagon subsystems, where the delivery rates of both insulin and glucagon were designed by using IMC-PID method. These proposed algorithms have been compared with an optimal unihormonal system on virtual type 1 diabetic subjects. The in silico results demonstrate that the proposed bihormonal AP systems have outstanding superiorities in reducing the risk of hypoglycemia, smoothing the glucose level, and robustness with respect to insulin/glucagon sensitivity variations, compared with the optimal unihormonal AP system.

Buying Program of the Standard Automated Materiel Management System. Automated Small Purchase System: Defense Supply Center Philadelphia

National Research Council Canada - National Science Library

2001-01-01

The Standard Automated Materiel Management System Automated Small Purchase System is a fully automated micro-purchases system used by the General and Industrial Directorate at the Defense Supply Center Philadelphia...

Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.

Science.gov (United States)

Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Zhang, Hongbo; Mäkilä, Ermei M; Kauppila, Jussi; Sarmento, Bruno; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

2014-08-01

Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. Copyright © 2014 Elsevier Ltd. All rights reserved.

Legionnaires' Disease Outbreak at a Long-Term Care Facility Caused by a Cooling Tower Using an Automated Disinfection System--Ohio, 2013.

Science.gov (United States)

Quinn, Celia; Demirjian, Alicia; Watkins, Louise Francois; Tomczyk, Sara; Lucas, Claressa; Brown, Ellen; Kozak-Muiznieks, Natalia; Benitez, Alvaro; Garrison, Laurel E; Kunz, Jasen; Brewer, Scott; Eitniear, Samantha; DiOrio, Mary

2015-12-01

On July 9, 2013, an outbreak of Legionnaires' disease (LD) was identified at Long-Term Care Facility A in central Ohio. This article describes the investigation of the outbreak and identification of the outbreak source, a cooling tower using an automated biocide delivery system. In total, 39 outbreak LD cases were identified; among these, six patients died. Water samples from a cooling tower were positive for Legionella pneumophila serogroup 1, reactive to monoclonal antibody 2, with matching sequence type to a patient isolate. An electronic control system turned off cooling tower pumps during low-demand periods, preventing delivery of disinfectant by a timed-release system, and leading to amplification of Legionella in the cooling tower. Guidelines for tower maintenance should address optimal disinfection when using automated systems.

Automation System Products and Research

OpenAIRE

Rintala, Mikko; Sormunen, Jussi; Kuisma, Petri; Rahkala, Matti

2014-01-01

Automation systems are used in most buildings nowadays. In the past they were mainly used in industry to control and monitor critical systems. During the past few decades the automation systems have become more common and are used today from big industrial solutions to homes of private customers. With the growing need for ecologic and cost-efficient management systems, home and building automation systems are becoming a standard way of controlling lighting, ventilation, heating etc. Auto...

Automation systems for radioimmunoassay

International Nuclear Information System (INIS)

Yamasaki, Paul

1974-01-01

The application of automation systems for radioimmunoassay (RIA) was discussed. Automated systems could be useful in the second step, of the four basic processes in the course of RIA, i.e., preparation of sample for reaction. There were two types of instrumentation, a semi-automatic pipete, and a fully automated pipete station, both providing for fast and accurate dispensing of the reagent or for the diluting of sample with reagent. Illustrations of the instruments were shown. (Mukohata, S.)

Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

Science.gov (United States)

Brandt, Benny; Mazaki-Tovi, Shali; Hemi, Rina; Yinon, Yoav; Schiff, Eyal; Mashiach, Roy; Kanety, Hannah; Sivan, Eyal

2015-05-01

Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, Pinsulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Peroral insulin delivery : new concepts and excipients

NARCIS (Netherlands)

Sadeghi, Assal M.M.

2008-01-01

A number of chitosan derivatives were synthesized and compared to the previously synthesized derivatives for their permeation enhancing activity. Using these derivatives insulin nanoparticles were prepared and their effect was compared to the free polymer and insulin in Caco-2 cells. The results

Automated Parallel Capillary Electrophoretic System

Science.gov (United States)

Li, Qingbo; Kane, Thomas E.; Liu, Changsheng; Sonnenschein, Bernard; Sharer, Michael V.; Kernan, John R.

2000-02-22

An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths. An off-line capillary reconditioner thoroughly cleans a capillary cartridge to enable simultaneous execution of electrophoresis with another capillary cartridge. The streamlined nature of the off-line capillary reconditioner offers the advantage of increased system throughput with a minimal increase in system cost.

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P

NILDE, Network Inter Library Document Exchange: An Italian Document Delivery System

Science.gov (United States)

Brunetti, F.; Gasperini, A.; Mangiaracina, S.

2007-10-01

This poster presents NILDE, a document delivery system supporting the exchange of documents via the internet. The system has been set up by the Central Library of the National Research Council of Bologna (Italy) in order to make use of new internet technology, to promote cooperation between Italian university libraries and research libraries, and to achieve quick response times in satisfying DD requests. The Arcetri Astrophysical Observatory Library was the first astronomical library to join the NILDE project from its earliest days in 2002. Many were the reasons for this choice: automation of the DD processes, security and reliability of the network, creation of usage statistics and reports, reduction of DD System management costs and so on. This work describes the benefits of NILDE and discusses the role of an organized document delivery system as an important tool to cope with the difficult constraints of the publishing market.

Fasting in Ramadan with an insulin pump.

Science.gov (United States)

Kesavadev, Jothydev

2015-05-01

A good majority of subjects with diabetes on insulin therapies observe fasting during Ramadan. The challenge for the physician and the patient is to manage diabetes without an interruption to fasting by avoiding hypoglycaemia and simultaneously ensuring that blood glucose remain at acceptable safe levels. Insulin Pumps differ from syringes and insulin pens in that it offers a variable basal rate, different type of boluses and associated calculators. The technological advances that pumps offer, help educated subjects pre-programme a reduced basal rate throughout the day. Pumps ensure avoidance of hypoglycaemia and hyperglycaemia and preserve quality of life and enhance confidence in patients during fasting. Due to multiple benefits, insulin pumps are considered the best delivery systems for insulin during the holy month of Ramadan, despite the prerequisites for its optimal output and cost concerns.

Oral delivery of insulin using pH-sensitive hydrogels based on polyvinyl alcohol grafted with acrylic acid/methacrylic acid by radiation

Energy Technology Data Exchange (ETDEWEB)

Nho, Young-Chang [Radiation Application Research Division, Korea Atomic Energy Research Institute, Daejeon 305-600 (Korea, Republic of)]. E-mail: ycnho@kaeri.re.kr; Park, Sung-Eun [Radiation Application Research Division, Korea Atomic Energy Research Institute, Daejeon 305-600 (Korea, Republic of); Kim, Hyung-Il [College of Engineering, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Hwang, Taek-Sung [College of Engineering, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

2005-07-01

The pH-responsive hydrogels were studied as a drug carrier for the protection of insulin from the acidic environment of the stomach before releasing in the small intestine. Hydrogels based on poly(vinyl alcohol) networks grafted with acrylic acid or methacrylic acid were prepared via a two-step process. Poly(vinyl alcohol) hydrogels were prepared by gamma ray irradiation (50 kGy) and then followed by grafting either acrylic acid or methacrylic acid onto this poly(vinyl alcohol) hydrogels with subsequent irradiation (5-20 kGy). These graft hydrogels showed pH-sensitive swelling behavior. These hydrogels were used as carrier for the controlled release of insulin. The in vitro release of insulin was observed for the insulin-loaded hydrogels in a simulated intestinal fluid (pH 6.8) but not in a simulated gastric fluid (pH 1.2). The release behavior of insulin in vivo in a rat model confirmed the effectiveness of the oral delivery of insulin to control the level of glucose.

Oral delivery of insulin using pH-sensitive hydrogels based on polyvinyl alcohol grafted with acrylic acid/methacrylic acid by radiation

International Nuclear Information System (INIS)

Nho, Young-Chang; Park, Sung-Eun; Kim, Hyung-Il; Hwang, Taek-Sung

2005-01-01

The pH-responsive hydrogels were studied as a drug carrier for the protection of insulin from the acidic environment of the stomach before releasing in the small intestine. Hydrogels based on poly(vinyl alcohol) networks grafted with acrylic acid or methacrylic acid were prepared via a two-step process. Poly(vinyl alcohol) hydrogels were prepared by gamma ray irradiation (50 kGy) and then followed by grafting either acrylic acid or methacrylic acid onto this poly(vinyl alcohol) hydrogels with subsequent irradiation (5-20 kGy). These graft hydrogels showed pH-sensitive swelling behavior. These hydrogels were used as carrier for the controlled release of insulin. The in vitro release of insulin was observed for the insulin-loaded hydrogels in a simulated intestinal fluid (pH 6.8) but not in a simulated gastric fluid (pH 1.2). The release behavior of insulin in vivo in a rat model confirmed the effectiveness of the oral delivery of insulin to control the level of glucose

A fully automated Drosophila olfactory classical conditioning and testing system for behavioral learning and memory assessment.

Science.gov (United States)

Jiang, Hui; Hanna, Eriny; Gatto, Cheryl L; Page, Terry L; Bhuva, Bharat; Broadie, Kendal

2016-03-01

Aversive olfactory classical conditioning has been the standard method to assess Drosophila learning and memory behavior for decades, yet training and testing are conducted manually under exceedingly labor-intensive conditions. To overcome this severe limitation, a fully automated, inexpensive system has been developed, which allows accurate and efficient Pavlovian associative learning/memory analyses for high-throughput pharmacological and genetic studies. The automated system employs a linear actuator coupled to an odorant T-maze with airflow-mediated transfer of animals between training and testing stages. Odorant, airflow and electrical shock delivery are automatically administered and monitored during training trials. Control software allows operator-input variables to define parameters of Drosophila learning, short-term memory and long-term memory assays. The approach allows accurate learning/memory determinations with operational fail-safes. Automated learning indices (immediately post-training) and memory indices (after 24h) are comparable to traditional manual experiments, while minimizing experimenter involvement. The automated system provides vast improvements over labor-intensive manual approaches with no experimenter involvement required during either training or testing phases. It provides quality control tracking of airflow rates, odorant delivery and electrical shock treatments, and an expanded platform for high-throughput studies of combinational drug tests and genetic screens. The design uses inexpensive hardware and software for a total cost of ∼$500US, making it affordable to a wide range of investigators. This study demonstrates the design, construction and testing of a fully automated Drosophila olfactory classical association apparatus to provide low-labor, high-fidelity, quality-monitored, high-throughput and inexpensive learning and memory behavioral assays. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimuli sensitive polymethacrylic acid microparticles (PMAA)--oral insulin delivery.

Science.gov (United States)

Victor, Sunita Prem; Sharma, Chandra P

2002-10-01

This study investigated polymethacrylic acid (PMAA) microparticles for controlled release of Insulin in oral administration. The microparticles were characterised by scanning electron microscopy (SEM) for morphological studies. The swelling behaviour and drug release profile in various pH media were studied. The % swelling of gels was found to be inversely related to the amount of crosslinker added. Inclusion complex of betaCD and Insulin was studied using polyacrylamide gel electrophoresis (PAGE). Optimum complexation was obtained in the ratio 100 mg betaCD: 200 IU Insulin. The release pattern of Insulin from Insulin-betaCD complex encapsulated PMAA microparticles showed release of Insulin for more than seven hours.

Automated Status Notification System

Science.gov (United States)

2005-01-01

NASA Lewis Research Center's Automated Status Notification System (ASNS) was born out of need. To prevent "hacker attacks," Lewis' telephone system needed to monitor communications activities 24 hr a day, 7 days a week. With decreasing staff resources, this continuous monitoring had to be automated. By utilizing existing communications hardware, a UNIX workstation, and NAWK (a pattern scanning and processing language), we implemented a continuous monitoring system.

Programmable automation systems in PSA

International Nuclear Information System (INIS)

Pulkkinen, U.

1997-06-01

The Finnish safety authority (STUK) requires plant specific PSAs, and quantitative safety goals are set on different levels. The reliability analysis is more problematic when critical safety functions are realized by applying programmable automation systems. Conventional modeling techniques do not necessarily apply to the analysis of these systems, and the quantification seems to be impossible. However, it is important to analyze contribution of programmable automation systems to the plant safety and PSA is the only method with system analytical view over the safety. This report discusses the applicability of PSA methodology (fault tree analyses, failure modes and effects analyses) in the analysis of programmable automation systems. The problem of how to decompose programmable automation systems for reliability modeling purposes is discussed. In addition to the qualitative analysis and structural reliability modeling issues, the possibility to evaluate failure probabilities of programmable automation systems is considered. One solution to the quantification issue is the use of expert judgements, and the principles to apply expert judgements is discussed in the paper. A framework to apply expert judgements is outlined. Further, the impacts of subjective estimates on the interpretation of PSA results are discussed. (orig.) (13 refs.)

Wireless Android Based Home Automation System

Directory of Open Access Journals (Sweden)

Muhammad Tanveer Riaz

2017-01-01

Full Text Available This manuscript presents a prototype and design implementation of an advance home automation system that uses Wi-Fi technology as a network infrastructure connecting its parts. The proposed system consists of two main components; the first part is the server, which presents system core that manages and controls user’s home. Users and system administrator can locally (Local Area Network or remotely (internet manage and control the system. Second part is the hardware interface module, which provides appropriate interface to sensors and actuator of home automation system. Unlike most of the available home automation system in the market, the proposed system is scalable that one server can manage many hardware interface modules as long as it exists within network coverage. System supports a wide range of home automation devices like appliances, power management components, and security components. The proposed system is better in terms of the flexibility and scalability than the commercially available home automation systems

Insulin aspart in diabetic pregnancy

DEFF Research Database (Denmark)

Mathiesen, Elisabeth R

2008-01-01

in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery.

Science.gov (United States)

Schiffter, Heiko; Condliffe, Jamie; Vonhoff, Sebastian

2010-08-06

The feasibility of preparing microparticles with high insulin loading suitable for needle-free ballistic drug delivery by spray-freeze-drying (SFD) was examined in this study. The aim was to manufacture dense, robust particles with a diameter of around 50 microm, a narrow size distribution and a high content of insulin. Atomization using ultrasound atomizers showed improved handling of small liquid quantities as well as narrower droplet size distributions over conventional two-fluid nozzle atomization. Insulin nanoparticles were produced by SFD from solutions with a low solid content (300 mg ml(-1)) consisting of trehalose, mannitol, dextran (10 kDa) and dextran (150 kDa) (abbreviated to TMDD) in order to maximize particle robustness and density after SFD. With the increase in insulin content, the viscosity of the nanosuspensions increased. Liquid atomization was possible up to a maximum of 250 mg of nano-insulin suspended in a 1.0 g matrix. However, if a narrow size distribution with a good correlation between theoretical and measurable insulin content was desired, no more than 150 mg nano-insulin could be suspended per gram of matrix formulation. Particles were examined by laser light diffraction, scanning electron microscopy and tap density testing. Insulin stability was assessed using size exclusion chromatography (SEC), reverse phase chromatography and Fourier transform infrared (FTIR) spectroscopy. Densification of the particles could be achieved during primary drying if the product temperature (T(prod)) exceeded the glass transition temperature of the freeze concentrate (T(g)') of -29.4 degrees C for TMDD (3331) formulations. Particles showed a collapsed and wrinkled morphology owing to viscous flow of the freeze concentrate. With increasing insulin loading, the d (v, 0.5) of the SFD powders increased and particle size distributions got wider. Insulin showed a good stability during the particle formation process with a maximum decrease in insulin monomer of

Laboratory automation: trajectory, technology, and tactics.

Science.gov (United States)

Markin, R S; Whalen, S A

2000-05-01

Laboratory automation is in its infancy, following a path parallel to the development of laboratory information systems in the late 1970s and early 1980s. Changes on the horizon in healthcare and clinical laboratory service that affect the delivery of laboratory results include the increasing age of the population in North America, the implementation of the Balanced Budget Act (1997), and the creation of disease management companies. Major technology drivers include outcomes optimization and phenotypically targeted drugs. Constant cost pressures in the clinical laboratory have forced diagnostic manufacturers into less than optimal profitability states. Laboratory automation can be a tool for the improvement of laboratory services and may decrease costs. The key to improvement of laboratory services is implementation of the correct automation technology. The design of this technology should be driven by required functionality. Automation design issues should be centered on the understanding of the laboratory and its relationship to healthcare delivery and the business and operational processes in the clinical laboratory. Automation design philosophy has evolved from a hardware-based approach to a software-based approach. Process control software to support repeat testing, reflex testing, and transportation management, and overall computer-integrated manufacturing approaches to laboratory automation implementation are rapidly expanding areas. It is clear that hardware and software are functionally interdependent and that the interface between the laboratory automation system and the laboratory information system is a key component. The cost-effectiveness of automation solutions suggested by vendors, however, has been difficult to evaluate because the number of automation installations are few and the precision with which operational data have been collected to determine payback is suboptimal. The trend in automation has moved from total laboratory automation to a

An Inventory-Routing Problem with Pickups and Deliveries Arising in the Replenishment of Automated Teller Machines

NARCIS (Netherlands)

van Anholt, Roel G.; Coelho, Leandro C.; Laporte, Gilbert; Vis, Iris F. A.

The purpose of this paper is to introduce, model, and solve a rich multiperiod inventory-routing problem with pickups and deliveries motivated by the replenishment of automated teller machines in the Netherlands. Commodities can be brought to and from the depot, as well as being exchanged among

An inventory-routing problem with pickups and deliveries arising in the replenishment of automated teller machines

NARCIS (Netherlands)

Van Anholt, Roel G.; Coelho, Leandro C.; Laporte, Gilbert; Vis, Iris F.A.

2016-01-01

The purpose of this paper is to introduce, model, and solve a rich multiperiod inventory-routing problem with pickups and deliveries motivated by the replenishment of automated teller machines in the Netherlands. Commodities can be brought to and from the depot, as well as being exchanged among

Glucagon-Like Peptide 1 Recruits Muscle Microvasculature and Improves Insulin’s Metabolic Action in the Presence of Insulin Resistance

Science.gov (United States)

Chai, Weidong; Zhang, Xingxing; Barrett, Eugene J.

2014-01-01

Glucagon-like peptide 1 (GLP-1) acutely recruits muscle microvasculature, increases muscle delivery of insulin, and enhances muscle use of glucose, independent of its effect on insulin secretion. To examine whether GLP-1 modulates muscle microvascular and metabolic insulin responses in the setting of insulin resistance, we assessed muscle microvascular blood volume (MBV), flow velocity, and blood flow in control insulin-sensitive rats and rats made insulin-resistant acutely (systemic lipid infusion) or chronically (high-fat diet [HFD]) before and after a euglycemic-hyperinsulinemic clamp (3 mU/kg/min) with or without superimposed systemic GLP-1 infusion. Insulin significantly recruited muscle microvasculature and addition of GLP-1 further expanded muscle MBV and increased insulin-mediated glucose disposal. GLP-1 infusion potently recruited muscle microvasculature in the presence of either acute or chronic insulin resistance by increasing muscle MBV. This was associated with an increased muscle delivery of insulin and muscle interstitial oxygen saturation. Muscle insulin sensitivity was completely restored in the presence of systemic lipid infusion and significantly improved in rats fed an HFD. We conclude that GLP-1 infusion potently expands muscle microvascular surface area and improves insulin’s metabolic action in the insulin-resistant states. This may contribute to improved glycemic control seen in diabetic patients receiving incretin-based therapy. PMID:24658303

Insulin is essential for in vitro chondrogenesis of mesenchymal progenitor cells and influences chondrogenesis in a dose-dependent manner.

Science.gov (United States)

Mueller, Michael B; Blunk, Torsten; Appel, Bernhard; Maschke, Angelika; Goepferich, Achim; Zellner, Johannes; Englert, Carsten; Prantl, Lukas; Kujat, Richard; Nerlich, Michael; Angele, Peter

2013-01-01

Insulin is a commonly used additive in chondrogenic media for differentiating mesenchymal stem cells (MSCs). The indispensability of other bioactive factors like TGF-β or dexamethasone in these medium formulations has been shown, but the role of insulin is unclear. The purpose of this study was to investigate whether insulin is essential for MSC chondrogenesis and if there is a dose-dependent effect of insulin on MSC chondrogenesis. We cultivated human MSCs in pellet culture in serum-free chondrogenic medium with insulin concentrations between 0 and 50 μg/ml and assessed the grade of chondrogenic differentiation by histological evaluation and determination of glycosaminoglycan (GAG), total collagen and DNA content. We further tested whether insulin can be delivered in an amount sufficient for MSC chondrogenesis via a drug delivery system in insulin-free medium. Chondrogenesis was not induced by standard chondrogenic medium without insulin and the expression of cartilage differentiation markers was dose-dependent at insulin concentrations between 0 and 10 μg/ml. An insulin concentration of 50 μg/ml had no additional effect compared with 10 μg/ml. Insulin was delivered by a release system into the cell culture under insulin-free conditions in an amount sufficient to induce chondrogenesis. Insulin is essential for MSC chondrogenesis in this system and chondrogenic differentiation is influenced by insulin in a dose-dependent manner. Insulin can be provided in a sufficient amount by a drug delivery system. Therefore, insulin is a suitable and inexpensive indicator substance for testing drug release systems in vitro.

Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery

Science.gov (United States)

Schiffter, Heiko; Condliffe, Jamie; Vonhoff, Sebastian

2010-01-01

The feasibility of preparing microparticles with high insulin loading suitable for needle-free ballistic drug delivery by spray-freeze-drying (SFD) was examined in this study. The aim was to manufacture dense, robust particles with a diameter of around 50 µm, a narrow size distribution and a high content of insulin. Atomization using ultrasound atomizers showed improved handling of small liquid quantities as well as narrower droplet size distributions over conventional two-fluid nozzle atomization. Insulin nanoparticles were produced by SFD from solutions with a low solid content (ballistic injection, the insulin nanoparticles were suspended in matrix formulations with a high excipient content (>300 mg ml−1) consisting of trehalose, mannitol, dextran (10 kDa) and dextran (150 kDa) (abbreviated to TMDD) in order to maximize particle robustness and density after SFD. With the increase in insulin content, the viscosity of the nanosuspensions increased. Liquid atomization was possible up to a maximum of 250 mg of nano-insulin suspended in a 1.0 g matrix. However, if a narrow size distribution with a good correlation between theoretical and measurable insulin content was desired, no more than 150 mg nano-insulin could be suspended per gram of matrix formulation. Particles were examined by laser light diffraction, scanning electron microscopy and tap density testing. Insulin stability was assessed using size exclusion chromatography (SEC), reverse phase chromatography and Fourier transform infrared (FTIR) spectroscopy. Densification of the particles could be achieved during primary drying if the product temperature (Tprod) exceeded the glass transition temperature of the freeze concentrate (Tg′) of −29.4°C for TMDD (3∶3∶3∶1) formulations. Particles showed a collapsed and wrinkled morphology owing to viscous flow of the freeze concentrate. With increasing insulin loading, the d (v, 0.5) of the SFD powders increased and particle size distributions got wider

Iontophoresis of monomeric insulin analogues in vitro: effects of insulin charge and skin pretreatment.

Science.gov (United States)

Langkjaer, L; Brange, J; Grodsky, G M; Guy, R H

1998-01-23

The aim of this study was to investigate the influence of association state and net charge of human insulin analogues on the rate of iontophoretic transport across hairless mouse skin, and the effect of different skin pretreatments on said transport. No insulin flux was observed with anodal delivery probably because of degradation at the Ag/AgCl anode. The flux during cathodal iontophoresis through intact skin was insignificant for human hexameric insulin, and only low and variable fluxes were observed for monomeric insulins. Using stripped skin on the other hand, the fluxes of monomeric insulins with two extra negative charges were 50-100 times higher than that of hexameric human insulin. Introducing three additional charges led to a further 2-3-fold increase in flux. Wiping the skin gently with absolute alcohol prior to iontophoresis resulted in a 1000-fold increase in transdermal transport of insulin relative to that across untreated skin, i.e. to almost the same level as stripping the skin. The alcohol pretreatment reduced the electrical resistance of the skin, presumably by lipid extraction. In conclusion, monomeric insulin analogues with at least two extra negative charges can be iontophoretically delivered across hairless mouse skin, whereas insignificant flux is observed with human, hexameric insulin. Wiping the skin with absolute alcohol prior to iontophoresis gave substantially improved transdermal transport of monomeric insulins resulting in clinically relevant delivery rates for basal treatment.

Evaluation of an Automated Keywording System.

Science.gov (United States)

Malone, Linda C.; And Others

1990-01-01

Discussion of automated indexing techniques focuses on ways to statistically document improvements in the development of an automated keywording system over time. The system developed by the Joint Chiefs of Staff to automate the storage, categorization, and retrieval of information from military exercises is explained, and performance measures are…

QA Issues for Computer-Controlled Treatment Delivery: This Is Not Your Old R/V System Any More!

International Nuclear Information System (INIS)

Fraass, Benedick A.

2008-01-01

State-of-the-art radiotherapy treatment delivery has changed dramatically during the past decade, moving from manual individual field setup and treatment to automated computer-controlled delivery of complex treatments, including intensity-modulated radiotherapy and other similarly complex delivery strategies. However, the quality assurance methods typically used to ensure treatment is performed precisely and correctly have not evolved in a similarly dramatic way. This paper reviews the old manual treatment process and use of record-and-verify systems, and describes differences with modern computer-controlled treatment delivery. The process and technology used for computer-controlled treatment delivery are analyzed in terms of potential (and actual) problems, as well as relevant published guidance on quality assurance. The potential for improved quality assurance for computer-controlled delivery is discussed

Programmable Automated Welding System (PAWS)

Science.gov (United States)

Kline, Martin D.

1994-01-01

An ambitious project to develop an advanced, automated welding system is being funded as part of the Navy Joining Center with Babcock & Wilcox as the prime integrator. This program, the Programmable Automated Welding System (PAWS), involves the integration of both planning and real-time control activities. Planning functions include the development of a graphical decision support system within a standard, portable environment. Real-time control functions include the development of a modular, intelligent, real-time control system and the integration of a number of welding process sensors. This paper presents each of these components of the PAWS and discusses how they can be utilized to automate the welding operation.

Autonomy, Automation, and Systems

Science.gov (United States)

Turner, Philip R.

1987-02-01

Aerospace industry interest in autonomy and automation, given fresh impetus by the national goal of establishing a Space Station, is becoming a major item of research and technology development. The promise of new technology arising from research in Artificial Intelligence (AI) has focused much attention on its potential in autonomy and automation. These technologies can improve performance in autonomous control functions that involve planning, scheduling, and fault diagnosis of complex systems. There are, however, many aspects of system and subsystem design in an autonomous system that impact AI applications, but do not directly involve AI technology. Development of a system control architecture, establishment of an operating system within the design, providing command and sensory data collection features appropriate to automated operation, and the use of design analysis tools to support system engineering are specific examples of major design issues. Aspects such as these must also receive attention and technology development support if we are to implement complex autonomous systems within the realistic limitations of mass, power, cost, and available flight-qualified technology that are all-important to a flight project.

21 CFR 862.2900 - Automated urinalysis system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated urinalysis system. 862.2900 Section 862....2900 Automated urinalysis system. (a) Identification. An automated urinalysis system is a device... that duplicate manual urinalysis systems. This device is used in conjunction with certain materials to...

Flexible automation and the loss of pooling synergy

OpenAIRE

Slomp, Jannes; Zee, Durk-Jouke van der

2001-01-01

This paper focuses on the effects of flexible automation on the performance of a job shop. Flexible automated machines may significantly improve the delivery performance and the flow time of jobs. The insertion of a flexible automated system in a job shop, however, also has a counter effect on the manufacturing performance. This is caused by the reduction of pooling synergy due to the dedication implied by flexible automated machines. This paper investigates by means of a simulation study to ...

Can a tool that automates insulin titration be a key to diabetes management?

Science.gov (United States)

Bergenstal, Richard M; Bashan, Eran; McShane, Margaret; Johnson, Mary; Hodish, Israel

2012-08-01

Most patients who use insulin do not achieve optimal glycemic control and become susceptible to complications. Numerous clinical trials have shown that frequent insulin dosage titration is imperative to achieve glycemic control. Unfortunately, implementation of such a paradigm is often impractical. We hypothesized that the Diabetes Insulin Guidance System (DIGS™) (Hygieia, Inc., Ann Arbor, MI) software, which automatically advises patients on adjustment of insulin dosage, would provide safe and effective weekly insulin dosage adjustments. In a feasibility study we enrolled patients with type 1 and type 2 diabetes, treated with a variety of insulin regimens and having suboptimal glycemic control. The 12-week intervention period followed a 4-week baseline run-in period. During the intervention, DIGS processed patients' glucose readings and provided insulin dosage adjustments on a weekly basis. If approved by the study team, the adjusted insulin dosage was communicated to the patients. Insulin formulations were not changed during the study. The primary outcome was the fraction of DIGS dosage adjustments approved by the study team, and the secondary outcome was improved glycemic control. Forty-six patients were recruited, and eight withdrew. The DIGS software recommended 1,734 insulin dosage adjustments, of which 1,731 (99.83%) were approved. During the run-in period the weekly average glucose was stable at 174.2±36.7 mg/dL (9.7±2.0 mmol/L). During the following 12 weeks, DIGS dosage adjustments resulted in progressive improvement in average glucose to 163.3±35.1 mg/dL (9.1±1.9 mmol/L) (P<0.03). Mean glycosylated hemoglobin decreased from 8.4±0.8% to 7.9±0.9% (P<0.05). Concomitantly, the frequency of hypoglycemia decreased by 25.2%. The DIGS software provided patients with safe and effective weekly insulin dosage adjustments. Widespread implementation of DIGS may improve the outcome and reduce the cost of implementing effective insulin therapy.

Enhancing Effect of Bile Salts on Gastrointestinal Absorption of Insulin

African Journals Online (AJOL)

glycocholate (NaGc) and sodium salicylate (NaSal), on insulin absorption via intestinal targeted delivery system. ... medication in diabetes mellitus treatment but ... emulsion, then the temperature was dropped to 4 ... using abdominal incision.

Control and automation systems

International Nuclear Information System (INIS)

Schmidt, R.; Zillich, H.

1986-01-01

A survey is given of the development of control and automation systems for energy uses. General remarks about control and automation schemes are followed by a description of modern process control systems along with process control processes as such. After discussing the particular process control requirements of nuclear power plants the paper deals with the reliability and availability of process control systems and refers to computerized simulation processes. The subsequent paragraphs are dedicated to descriptions of the operating floor, ergonomic conditions, existing systems, flue gas desulfurization systems, the electromagnetic influences on digital circuits as well as of light wave uses. (HAG) [de

Automated radiochemical processing for clinical PET

International Nuclear Information System (INIS)

Padgett, H.C.; Schmidt, D.G.; Bida, G.T.; Wieland, B.W.; Pekrul, E.; Kingsbury, W.G.

1991-01-01

With the recent emergence of positron emission tomography (PET) as a viable clinical tool, there is a need for a convenient, cost-effective source of the positron emitter-labeled radiotracers labeled with carbon-11, nitrogen-13, oxygen-15, and fluorine-18. These short-lived radioisotopes are accelerator produced and thus, require a cyclotron and radiochemistry processing instrumentation that can be operated 3 in a clinical environment by competant technicians. The basic goal is to ensure safety and reliability while setting new standards for economy and ease of operation. The Siemens Radioisotope Delivery System (RDS 112) is a fully automated system dedicated to the production and delivery of positron-emitter labeled precursors and radiochemicals required to support a clinical PET imaging program. Thus, the entire RDS can be thought of as an automated radiochemical processing apparatus

Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

Science.gov (United States)

Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

2014-10-01

To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

Enteric-coated capsules filled with mono-disperse micro-particles containing PLGA-lipid-PEG nanoparticles for oral delivery of insulin.

Science.gov (United States)

Yu, Fei; Li, Yang; Liu, Chang Sheng; Chen, Qin; Wang, Gui Huan; Guo, Wei; Wu, Xue E; Li, Dong Hui; Wu, Winston Duo; Chen, Xiao Dong

2015-04-30

The success of the oral delivery of insulin (INS) as a therapeutic protein drug would significantly improve the quality of life of diabetic patients who would otherwise receive multiple daily INS injections. The oral delivery of INS, however, is still limited in its delivery efficiency, which could be due to the chemical, enzymatic, and adsorption barriers. In this work, in an attempt to improve the delivery efficiency, the INS-loaded polymer-lipid hybrid nanoparticles (INS-PLGA-lipid-PEG NPs) were designed and constructed through a double-emulsion solvent evaporation technique, followed by formulation of the spherical micro-particles using a spray freeze dryer (SFD). This kind of dryers has a uniquely designed microfluidic aerosol nozzle (MFAN), ensuring the formation of uniform particles. The resulted particles of ∼212 μm could easily be reverted to discrete INS-PLGA-lipid-PEG NPs in an aqueous solution. The INS-PLGA-lipid-PEG NPs created in this work showed a highly negative surface charge, excellent entrapment efficiency (92.3%) and a sustained drug release (∼24 h). Confocal laser scanning microscopy and flow cytometer were used to show that the cellular uptake efficiency for the INS-PLGA-lipid-PEG NPs was more effective than the INS in Caco-2 cells. More importantly, the in vivo pharmacodynamics demonstrated that the orally delivered system induced a prolonged decrease in blood glucose levels among diabetic rats. The relative bioavailability of INS compared with subcutaneous injection in diabetic rats was found to be approximately 12%. These results suggested that the encapsulated INS-PLGA-lipid-PEG NPs are promising and should be investigated further in the near future as an effective INS oral delivery system. Copyright © 2015. Published by Elsevier B.V.

Disassembly automation automated systems with cognitive abilities

CERN Document Server

Vongbunyong, Supachai

2015-01-01

This book presents a number of aspects to be considered in the development of disassembly automation, including the mechanical system, vision system and intelligent planner. The implementation of cognitive robotics increases the flexibility and degree of autonomy of the disassembly system. Disassembly, as a step in the treatment of end-of-life products, can allow the recovery of embodied value left within disposed products, as well as the appropriate separation of potentially-hazardous components. In the end-of-life treatment industry, disassembly has largely been limited to manual labor, which is expensive in developed countries. Automation is one possible solution for economic feasibility. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

An evaluation of prefilled insulin pens: a focus on the Next Generation FlexPen®

Directory of Open Access Journals (Sweden)

Estella M Davis

2010-08-01

Full Text Available Estella M Davis, Emily L Sexson, Mikayla L Spangler, Pamela A ForalDepartment of Pharmacy Practice, Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska, USAAbstract: Insulin pen delivery systems are preferred by patients over the traditional vial and syringe method for insulin delivery because they are simple and easy to use, improve confidence in dosing insulin, and have less interference with activities and improved discretion with use. Insulin manufacturers have made numerous improvements to their first marketed pen devices and are now introducing their next generation of devices. Design modifications to the newest generation of prefilled insulin pen devices are intended to improve the ease of use and safety and continue to positively impact adherence to insulin. This review focuses on the Next Generation FlexPen® with regard to design considerations to reduce injection force, improve accuracy and ease of use, and evaluate the preference of patient and health-care provider compared with other disposable, prefilled insulin pen devices.Keywords: diabetes, dose accuracy, injection force, patient preference, insulin pen device

Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

Science.gov (United States)

Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

2014-09-28

Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

Insulin sensitivity and insulin secretion at birth in intrauterine growth retarded infants.

Science.gov (United States)

Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Lata; Vinayagamoorti, R; John, Mathew

2006-06-01

To study insulin sensitivity, secretion and relation of insulin levels with birth weight and ponderal index in intrauterine growth retarded (IUGR) infants at birth. We studied 30 IUGR and 30 healthy newborns born at term by vaginal delivery in Jipmer, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of plasma glucose and insulin. When compared with healthy newborns, IUGR newborns had lower plasma glucose levels (mean 2.3+/-0.98 versus 4.1+/-0.51 mmol/L, p<0.001); lower plasma insulin levels (mean 4.5+/-2.64 versus 11.03+/-1.68 microU/L, p<0.001); higher insulin sensitivity calculated using G/I ratio (mean 11.6+/-5.1 versus 6.7+/-0.31, p<0.001), HOMA IS (mean 5.5+/-6.0 versus 0.53+/-0.15, p<0.001), and QUICKI (mean 0.47+/-0.12 versus 0.34+/-0.02, p<0.001); and decreased pancreatic beta-cell function test measured as I/G (mean 0.10+/-0.037 versus 0.15+/-0.006, p<0.001). A positive correlation was identified between insulin levels and birth weight in both the healthy control group (r2 = 0.17, p = 0.024) and IUGR group (r2 = 0.13, p = 0.048). However correlation of insulin levels with ponderal index was much more confident in both healthy control (r2 = 0.90, p<0.001) and IUGR groups (r2 = 0.28, p = 0.003). Insulin status correlated both with birth weight and ponderal index more confidently in control group than in IUGR group. At birth, IUGR infants are hypoglycaemic, hypoinsulinaemic and display increased insulin sensitivity and decreased pancreatic beta-cell function. Insulin levels correlate with ponderal index much more confidently than with birth weight.

Robotics/Automated Systems Technicians.

Science.gov (United States)

Doty, Charles R.

Major resources exist that can be used to develop or upgrade programs in community colleges and technical institutes that educate robotics/automated systems technicians. The first category of resources is Economic, Social, and Education Issues. The Office of Technology Assessment (OTA) report, "Automation and the Workplace," presents analyses of…

TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

OpenAIRE

Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

2012-01-01

Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

A system-level approach to automation research

Science.gov (United States)

Harrison, F. W.; Orlando, N. E.

1984-01-01

Automation is the application of self-regulating mechanical and electronic devices to processes that can be accomplished with the human organs of perception, decision, and actuation. The successful application of automation to a system process should reduce man/system interaction and the perceived complexity of the system, or should increase affordability, productivity, quality control, and safety. The expense, time constraints, and risk factors associated with extravehicular activities have led the Automation Technology Branch (ATB), as part of the NASA Automation Research and Technology Program, to investigate the use of robots and teleoperators as automation aids in the context of space operations. The ATB program addresses three major areas: (1) basic research in autonomous operations, (2) human factors research on man-machine interfaces with remote systems, and (3) the integration and analysis of automated systems. This paper reviews the current ATB research in the area of robotics and teleoperators.

UAV Delivery Monitoring System

Directory of Open Access Journals (Sweden)

San Khin Thida

2018-01-01

Full Text Available UAV-based delivery systems are increasingly being used in the logistics field, particularly to achieve faster last-mile delivery. This study develops a UAV delivery system that manages delivery order assignments, autonomous flight operation, real time control for UAV flights, and delivery status tracking. To manage the delivery item assignments, we apply the concurrent scheduler approach with a genetic algorithm. The present paper describes real time flight data based on a micro air vehicle communication protocol (MAVLink. It also presents the detailed hardware components used for the field tests. Finally, we provide UAV component analysis to choose the suitable components for delivery in terms of battery capacity, flight time, payload weight and motor thrust ratio.

Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

Science.gov (United States)

Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

2013-12-05

Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth. Published by Elsevier Ireland Ltd.

Launch Control System Software Development System Automation Testing

Science.gov (United States)

Hwang, Andrew

2017-01-01

The Spaceport Command and Control System (SCCS) is the National Aeronautics and Space Administration's (NASA) launch control system for the Orion capsule and Space Launch System, the next generation manned rocket currently in development. This system requires high quality testing that will measure and test the capabilities of the system. For the past two years, the Exploration and Operations Division at Kennedy Space Center (KSC) has assigned a group including interns and full-time engineers to develop automated tests to save the project time and money. The team worked on automating the testing process for the SCCS GUI that would use streamed simulated data from the testing servers to produce data, plots, statuses, etc. to the GUI. The software used to develop automated tests included an automated testing framework and an automation library. The automated testing framework has a tabular-style syntax, which means the functionality of a line of code must have the appropriate number of tabs for the line to function as intended. The header section contains either paths to custom resources or the names of libraries being used. The automation library contains functionality to automate anything that appears on a desired screen with the use of image recognition software to detect and control GUI components. The data section contains any data values strictly created for the current testing file. The body section holds the tests that are being run. The function section can include any number of functions that may be used by the current testing file or any other file that resources it. The resources and body section are required for all test files; the data and function sections can be left empty if the data values and functions being used are from a resourced library or another file. To help equip the automation team with better tools, the Project Lead of the Automated Testing Team, Jason Kapusta, assigned the task to install and train an optical character recognition (OCR

Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

Science.gov (United States)

de la Monte, Suzanne M

Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

Insulin-egg yolk dispersions in self microemulsifying system

OpenAIRE

Singnurkar P; Gidwani S

2008-01-01

Formulation of insulin into a microemulsion very often presents a physicochemical instability during their preparation and storage. In order to overcome this lack of stability and facilitate the handling of these colloidal systems, stabilization of insulin in presence of hydrophobic components of a microemulsion appears as the most promising strategy. The present paper reports the use of egg yolk for stabilization of insulin in self microemulsifying dispersions. Insulin loaded egg yolk self m...

Insulin-egg yolk dispersions in self microemulsifying system.

Science.gov (United States)

Singnurkar, P S; Gidwani, S K

2008-11-01

Formulation of insulin into a microemulsion very often presents a physicochemical instability during their preparation and storage. In order to overcome this lack of stability and facilitate the handling of these colloidal systems, stabilization of insulin in presence of hydrophobic components of a microemulsion appears as the most promising strategy. The present paper reports the use of egg yolk for stabilization of insulin in self microemulsifying dispersions. Insulin loaded egg yolk self microemulsifying dispersions were prepared by lyophilization followed by dispersion into self microemulsifying vehicle. The physicochemical characterization of selfmicroemulsifying dispersions includes such as insulin encapsulation efficiency, in vitro stability of insulin in presence of proteolytic enzymes and in vitro release. The biological activity of insulin from the dispersion was estimated by enzyme-linked immunosorbant assay and in vivo using Wistar diabetic rats. The particle size ranged 1.023±0.316 μm in diameter and insulin encapsulation efficiency was 98.2±0.9 %. Insulin hydrophobic self microemulsifying dispersions suppressed insulin release in pH 7.4 phosphate buffer and shown to protect insulin from enzymatic degradation in vitro in presence of chymotripsin. Egg yolk encapsulated insulin was bioactive, demonstrated through both in vivo and in vitro.

Grizzli mobile systems and LPG delivery management; Grizzli mobile systems

Energy Technology Data Exchange (ETDEWEB)

Anon.

2000-07-01

Complete text of publication follows: Grizzli Mobile Systems (and its sister companies) specialists in data communications and system solutions, offer their complete management solution for LPG deliveries, right through from remote reading of the gas level in the tank, through route management, management of the delivery itself and finally on-site invoicing and payment. The system permits a supplier to really differentiate itself from its competitors in terms of customer service and control of its operations. Domestic gas tanks are often difficult to access; visual reading of the gauge is not always easy and often leads to the customer re-ordering in panic mode. The supplier has also to react in panic mode to the customer. Grizzli Mobile Systems has developed a radio module that is fitted to the gas tank that calls, at regular set intervals with the tank level to a Call Rider gateway plug. The Call Rider is a small box plugged into the regular telephone socket (also supplying multiple operator telephony and other home automation services). As soon as the gas level reaches a predetermined minimum level, this radio information is relayed via the Internet to the LPG supplier. The supplier can then arrange (in non-panic mode) to deliver gas to the customer, via conventional means or by use of an interactive radio display (attached to a refrigerator or similar by magnets) that communicates with the Call Rider by radio. Once a delivery date has been set, a Grizzli Mobile Systems' dispatch system, installed at the supplier's headquarters creates and transfers routes via GSM communications to its fleet of delivery vehicles. A main-frame mapping software provides real-time follow-up and status checks of the vehicles using the GPS functionality and imports data back from the vehicles and updates databases. The driver is also assisted in localizing delivery sites. Inside the cabin of the vehicle the driver has available a Fujitsu PenCentra pen computer, a Microsoft

Using observational data to inform the design of a prospective effectiveness study for a novel insulin delivery device

Directory of Open Access Journals (Sweden)

Grabner M

2013-09-01

Full Text Available Michael Grabner,1 Yong Chen,2 Matthew Nguyen,3 Scott D Abbott,3 Ralph Quimbo1 1HealthCore, Inc., Wilmington, DE, USA; 2Merck and Co., Inc., Whitehouse Station, NJ, USA; 3Valeritas, Inc., Bridgewater, NJ, USA Objective: To inform the design and assess the feasibility of a prospective effectiveness study evaluating an insulin delivery device for patients with diabetes mellitus to be conducted within the membership of a large US commercial insurer. Methods: Providers who issued ≥1 insulin prescription between January 1, 2011 and September 30, 2011 were selected from administrative claims contained in the HealthCore Integrated Research DatabaseSM. Adult diabetes patients with visits to these providers were identified. Providers were dichotomized into high- [HVPs] and low-volume providers [LVPs] based on median number of diabetes patients per provider. Results: We identified 15,349 HVPs and 15,313 LVPs (median number of patients = 14. Most HVPs were located in the Midwest (6,291 [41.0%] and South (5,092 [33.2%], while LVPs were evenly distributed across regions. Over 80% (12,769 of HVPs practiced family or internal medicine; 6.4% (989 were endocrinologists. HVPs prescribed insulin to an average of 25% of patients. Patients of HVPs (522,527 had similar characteristics as patients of LVPs (80,669, except for geographical dispersion, which followed that of providers. Approximately 65% of patients were aged 21-64 years and 97% had type 2 diabetes. Among patients with ≥1 available HbA1C result during 2011 (103,992, 48.3% (50,193 had an average HbA1C ≥7.0%. Among patients initiating insulin, 79.6% (22,205 had an average HbA1C ≥7.0%. Conclusion: The observed provider and patient populations support the feasibility of the prospective study. Sampling of patients from HVPs is efficient while minimizing bias as patient characteristics are similar to those from LVPs. The study also highlights unmet needs for improved glycemic control since approximately

Automating Mapping Production for the Enterprise: from Contract to Delivery

Science.gov (United States)

Uebbing, R.; Xie, C.; Beshah, B.; Welter, J.

2012-07-01

also view their data, much of the design and development was focused on work flow automation, scalability and security. Ideally, users will interact with the system to retrieve a specific project status and summaries while the work flow processes are triggered automatically by modeling their dependencies. The enterprise system is built using open source technologies (PostGIS, Hibernate, OpenLayers, GWT and others) and adheres to OGC web services for data delivery (WMS/WFS/WCS) to third party applications.

Systems integration (automation system). System integration (automation system)

Energy Technology Data Exchange (ETDEWEB)

Fujii, K; Komori, T; Fukuma, Y; Oikawa, M [Nippon Steal Corp., Tokyo (Japan)

1991-09-26

This paper introduces business activities on an automation systems integration (SI) started by a company in July,1988, and describes the SI concepts. The business activities include, with the CIM (unified production carried out on computers) and AMENITY (living environment) as the mainstays, a single responsibility construction ranging from consultation on structuring optimal systems for processing and assembling industries and intelligent buildings to system design, installation and after-sales services. With an SI standing on users {prime} position taken most importantly, the business starts from a planning and consultation under close coordination. On the conceptual basis of structuring optimal systems using the ompany {prime}s affluent know-hows and tools and adapting and applying with multi-vendors, open networks, centralized and distributed systems, the business is promoted with the accumulated technologies capable of realizing artificial intelligence and neural networks in its background, and supported with highly valuable business results in the past. 10 figs., 1 tab.

Structural properties and release of insulin-loaded reverse hexagonal (HII) liquid crystalline mesophase.

Science.gov (United States)

Mishraki-Berkowitz, Tehila; Aserin, Abraham; Garti, Nissim

2017-01-15

Insulin loading into the H II mesophases was examined as a function of its concentration, with addition of glycerol as a cosolvent and with addition of phosphatidylcholine (PC) as a structural stabilizer. The structural properties, the molecular interactions, the viscoelastic properties, and the dynamic behavior were investigated by SAXS, ATR-FTIR, and rheological measurements. Insulin release was then monitored and analyzed. Insulin incorporation into the H II systems shrank the cylinders as it competed with the lipids in water-bonding. Insulin interrupted the interface while increasing τ max and creating a more solid-like response. Upon addition of PC, cooperative flow behavior was detected, which is probably the reason for increase in insulin cumulative release from 28% to 52% after 300 min. In the presence of glycerol, the system was less cooperative but insulin was more compactly folded, resulting in a slight improvement in insulin release (up to 6%). Addition of both PC and glycerol caused the maximum release (55%). The addition of additives into the H II system demonstrates how structural modifications can improve insulin release, and influence future design of encapsulated drug delivery systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in vivo characterizations.

Science.gov (United States)

Mahjub, Reza; Radmehr, Moojan; Dorkoosh, Farid Abedin; Ostad, Seyed Naser; Rafiee-Tehrani, Morteza

2014-12-01

from quaternized aromatic derivatives of chitosan. In vivo data showed significantly higher insulin intestinal absorption in nanoparticles prepared from methylated N-(4-N, N-dimethylaminobenzyl) chitosan nanoparticles compared to trimethyl chitosan. These data obtained demonstrated that as the result of optimized physico-chemical properties, drug release rate, cytotoxicity profile, ex vivo permeation enhancement and increased in vivo absorption, nanoparticles prepared from N-aryl derivatives of chitosan can be considered as valuable method for the oral delivery of insulin.

New automated pellet/powder assay system

International Nuclear Information System (INIS)

Olsen, R.N.

1975-01-01

This paper discusses an automated, high precision, pellet/ powder assay system. The system is an active assay system using a small isotopic neutron source and a coincidence detection system. The handling of the pellet powder samples has been automated and a programmable calculator has been integrated into the system to provide control and data analysis. The versatile system can assay uranium or plutonium in either active or passive modes

Effect of formulation variables on insulin localisation within solid lipid nanoparticles

OpenAIRE

Thong, Li Ming

2016-01-01

There has been a lot of interest on solid lipid nanoparticles (SLNs) as these colloidal submicron drug dosage forms present a promising frontier in drug delivery. It is possible to incorporate susceptible drugs such as protein intended for oral delivery. Here, we aim to develop an oral delivery system based on SLNs to deliver the peptide hormone, insulin using the double emulsion (W/O/W) solvent evaporation technique for formulating the SLNs. The choice of lipids was carefully selected to inc...

System reliability, performance and trust in adaptable automation.

Science.gov (United States)

Chavaillaz, Alain; Wastell, David; Sauer, Jürgen

2016-01-01

The present study examined the effects of reduced system reliability on operator performance and automation management in an adaptable automation environment. 39 operators were randomly assigned to one of three experimental groups: low (60%), medium (80%), and high (100%) reliability of automation support. The support system provided five incremental levels of automation which operators could freely select according to their needs. After 3 h of training on a simulated process control task (AutoCAMS) in which the automation worked infallibly, operator performance and automation management were measured during a 2.5-h testing session. Trust and workload were also assessed through questionnaires. Results showed that although reduced system reliability resulted in lower levels of trust towards automation, there were no corresponding differences in the operators' reliance on automation. While operators showed overall a noteworthy ability to cope with automation failure, there were, however, decrements in diagnostic speed and prospective memory with lower reliability. Copyright © 2015. Published by Elsevier Ltd.

A rapid-acting, long-acting insulin formulation based on a phospholipid complex loaded PHBHHx nanoparticles.

Science.gov (United States)

Peng, Qiang; Zhang, Zhi-Rong; Gong, Tao; Chen, Guo-Qiang; Sun, Xun

2012-02-01

The application of poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) for sustained and controlled delivery of hydrophilic insulin was made possible by preparing insulin phospholipid complex loaded biodegradable PHBHHx nanoparticles (INS-PLC-NPs). The INS-PLC-NPs produced by a solvent evaporation method showed a spherical shape with a mean particle size, zeta potential and entrapment efficiency of 186.2 nm, -38.4 mv and 89.73%, respectively. In vitro studies demonstrated that only 20% of insulin was released within 31 days with a burst release of 5.42% in the first 8 h. The hypoglycaemic effect in STZ induced diabetic rats lasted for more than 3 days after the subcutaneous injection of INS-PLC-NPs, which significantly prolonged the therapeutic effect compared with the administration of insulin solution. The pharmacological bioavailability (PA) of INS-PLC-NPs relative to insulin solution was over 350%, indicating that the bioavailability of insulin was significantly enhanced by INS-PLC-NPs. Therefore, the INS-PLC-NPs system is promising to serve as a long lasting insulin release formulation, by which the patient compliance can be enhanced significantly. This study also showed that phospholipid complex loaded biodegradable nanoparticles (PLC-NPs) have a great potential to be used as a sustained delivery system for hydrophilic proteins to be encapsulated in hydrophobic polymers. Copyright © 2011 Elsevier Ltd. All rights reserved.

Automated packing systems: review of industrial implementations

Science.gov (United States)

Whelan, Paul F.; Batchelor, Bruce G.

1993-08-01

A rich theoretical background to the problems that occur in the automation of material handling can be found in operations research, production engineering, systems engineering and automation, more specifically machine vision, literature. This work has contributed towards the design of intelligent handling systems. This paper will review the application of these automated material handling and packing techniques to industrial problems. The discussion will also highlight the systems integration issues involved in these applications. An outline of one such industrial application, the automated placement of shape templates on to leather hides, is also discussed. The purpose of this system is to arrange shape templates on a leather hide in an efficient manner, so as to minimize the leather waste, before they are automatically cut from the hide. These pieces are used in the furniture and car manufacturing industries for the upholstery of high quality leather chairs and car seats. Currently this type of operation is semi-automated. The paper will outline the problems involved in the full automation of such a procedure.

Automation of analytical systems in power cycles

International Nuclear Information System (INIS)

Staub Lukas

2008-01-01

'Automation' is a widely used term in instrumentation and is often applied to signal exchange, PLC and SCADA systems. Common use, however, does not necessarily described autonomous operation of analytical devices. We define an automated analytical system as a black box with an input (sample) and an output (measured value). In addition we need dedicated status lines for assessing the validities of the input for our black box and the output for subsequent systems. We will discuss input parameters, automated analytical processes and output parameters. Further considerations will be given to signal exchange and integration into the operating routine of a power plant. Local control loops (chemical dosing) and the automation of sampling systems are not discussed here. (author)

Laboratory automation in clinical bacteriology: what system to choose?

Science.gov (United States)

Croxatto, A; Prod'hom, G; Faverjon, F; Rochais, Y; Greub, G

2016-03-01

Automation was introduced many years ago in several diagnostic disciplines such as chemistry, haematology and molecular biology. The first laboratory automation system for clinical bacteriology was released in 2006, and it rapidly proved its value by increasing productivity, allowing a continuous increase in sample volumes despite limited budgets and personnel shortages. Today, two major manufacturers, BD Kiestra and Copan, are commercializing partial or complete laboratory automation systems for bacteriology. The laboratory automation systems are rapidly evolving to provide improved hardware and software solutions to optimize laboratory efficiency. However, the complex parameters of the laboratory and automation systems must be considered to determine the best system for each given laboratory. We address several topics on laboratory automation that may help clinical bacteriologists to understand the particularities and operative modalities of the different systems. We present (a) a comparison of the engineering and technical features of the various elements composing the two different automated systems currently available, (b) the system workflows of partial and complete laboratory automation, which define the basis for laboratory reorganization required to optimize system efficiency, (c) the concept of digital imaging and telebacteriology, (d) the connectivity of laboratory automation to the laboratory information system, (e) the general advantages and disadvantages as well as the expected impacts provided by laboratory automation and (f) the laboratory data required to conduct a workflow assessment to determine the best configuration of an automated system for the laboratory activities and specificities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

An Automated Mouse Tail Vascular Access System by Vision and Pressure Feedback.

Science.gov (United States)

Chang, Yen-Chi; Berry-Pusey, Brittany; Yasin, Rashid; Vu, Nam; Maraglia, Brandon; Chatziioannou, Arion X; Tsao, Tsu-Chin

2015-08-01

This paper develops an automated vascular access system (A-VAS) with novel vision-based vein and needle detection methods and real-time pressure feedback for murine drug delivery. Mouse tail vein injection is a routine but critical step for preclinical imaging applications. Due to the small vein diameter and external disturbances such as tail hair, pigmentation, and scales, identifying vein location is difficult and manual injections usually result in poor repeatability. To improve the injection accuracy, consistency, safety, and processing time, A-VAS was developed to overcome difficulties in vein detection noise rejection, robustness in needle tracking, and visual servoing integration with the mechatronics system.

Automated Subsystem Control for Life Support System (ASCLSS)

Science.gov (United States)

Block, Roger F.

1987-01-01

The Automated Subsystem Control for Life Support Systems (ASCLSS) program has successfully developed and demonstrated a generic approach to the automation and control of space station subsystems. The automation system features a hierarchical and distributed real-time control architecture which places maximum controls authority at the lowest or process control level which enhances system autonomy. The ASCLSS demonstration system pioneered many automation and control concepts currently being considered in the space station data management system (DMS). Heavy emphasis is placed on controls hardware and software commonality implemented in accepted standards. The approach demonstrates successfully the application of real-time process and accountability with the subsystem or process developer. The ASCLSS system completely automates a space station subsystem (air revitalization group of the ASCLSS) which moves the crew/operator into a role of supervisory control authority. The ASCLSS program developed over 50 lessons learned which will aide future space station developers in the area of automation and controls..

Automated measuring systems. Automatisierte Messsysteme

Energy Technology Data Exchange (ETDEWEB)

1985-01-01

Microprocessors have become a regular component of automated measuring systems. Experts offer their experience and basic information in 24 lectures and 10 poster presentations. The focus is on the following: Automated measuring, computer and microprocessor use, sensor technique, actuator technique, communication, interfaces, man-system interaction, distrubance tolerance and availability as well as uses. A discussion meeting is dedicated to the theme complex sensor digital signal, sensor interface and sensor bus.

Building Automation Systems.

Science.gov (United States)

Honeywell, Inc., Minneapolis, Minn.

A number of different automation systems for use in monitoring and controlling building equipment are described in this brochure. The system functions include--(1) collection of information, (2) processing and display of data at a central panel, and (3) taking corrective action by sounding alarms, making adjustments, or automatically starting and…

Project delivery system (PDS)

CERN Document Server

2001-01-01

As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.

Synthetic sustained gene delivery systems.

Science.gov (United States)

Agarwal, Ankit; Mallapragada, Surya K

2008-01-01

Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

Review and Update of Insulin Dependent Diabetes Mellitus

OpenAIRE

Gorrell, Jennifer Justice; Williams, Jennifer Schoelles; Powell, Paula

2003-01-01

The purpose of this article is to provide the health care practitioner with a comprehensive review of the pathophysiology and treatment of Type 1 Diabetes Mellitus. Traditionally, insulin has been administered via an insulin syringe. In the recent past, diabetes research has focused on developing more convenient insulin delivery devices and longer acting insulin's in hopes of increasing compliance with insulin therapy and improving the management of Type 1 diabetes in both children and adults...

Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

Science.gov (United States)

Chu, Michael Kok Loon

Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

Colloidal drug delivery system: amplify the ocular delivery.

Science.gov (United States)

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

2016-01-01

The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

Automated Information System (AIS) Alarm System

International Nuclear Information System (INIS)

Hunteman, W.

1997-01-01

The Automated Information Alarm System is a joint effort between Los Alamos National Laboratory, Lawrence Livermore National Laboratory, and Sandia National Laboratory to demonstrate and implement, on a small-to-medium sized local area network, an automated system that detects and automatically responds to attacks that use readily available tools and methodologies. The Alarm System will sense or detect, assess, and respond to suspicious activities that may be detrimental to information on the network or to continued operation of the network. The responses will allow stopping, isolating, or ejecting the suspicious activities. The number of sensors, the sensitivity of the sensors, the assessment criteria, and the desired responses may be set by the using organization to meet their local security policies

Automated Information System (AIS) Alarm System

Energy Technology Data Exchange (ETDEWEB)

Hunteman, W.

1997-05-01

The Automated Information Alarm System is a joint effort between Los Alamos National Laboratory, Lawrence Livermore National Laboratory, and Sandia National Laboratory to demonstrate and implement, on a small-to-medium sized local area network, an automated system that detects and automatically responds to attacks that use readily available tools and methodologies. The Alarm System will sense or detect, assess, and respond to suspicious activities that may be detrimental to information on the network or to continued operation of the network. The responses will allow stopping, isolating, or ejecting the suspicious activities. The number of sensors, the sensitivity of the sensors, the assessment criteria, and the desired responses may be set by the using organization to meet their local security policies.

21 CFR 864.9300 - Automated Coombs test systems.

Science.gov (United States)

2010-04-01

... Blood and Blood Products § 864.9300 Automated Coombs test systems. (a) Identification. An automated Coombs test system is a device used to detect and identify antibodies in patient sera or antibodies bound... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated Coombs test systems. 864.9300 Section...

15 CFR 758.2 - Automated Export System (AES).

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Automated Export System (AES). 758.2... CLEARANCE REQUIREMENTS § 758.2 Automated Export System (AES). The Census Bureau's Foreign Trade Statistics...) electronically using the Automated Export System (AES). In order to use AES, you must apply directly to the...

Automated drawing generation system

International Nuclear Information System (INIS)

Yoshinaga, Toshiaki; Kawahata, Junichi; Yoshida, Naoto; Ono, Satoru

1991-01-01

Since automated CAD drawing generation systems still require human intervention, improvements were focussed on an interactive processing section (data input and correcting operation) which necessitates a vast amount of work. As a result, human intervention was eliminated, the original objective of a computerized system. This is the first step taken towards complete automation. The effects of development and commercialization of the system are as described below. (1) The interactive processing time required for generating drawings was improved. It was determined that introduction of the CAD system has reduced the time required for generating drawings. (2) The difference in skills between workers preparing drawings has been eliminated and the quality of drawings has been made uniform. (3) The extent of knowledge and experience demanded of workers has been reduced. (author)

Highly stable and degradable multifunctional microgel for self-regulated insulin delivery under physiological conditions

Science.gov (United States)

Zhang, Xinjie; Lü, Shaoyu; Gao, Chunmei; Chen, Chen; Zhang, Xuan; Liu, Mingzhu

2013-06-01

The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors.The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size

Spaceport Command and Control System Automation Testing

Science.gov (United States)

Hwang, Andrew

2017-01-01

The Spaceport Command and Control System (SCCS) is the National Aeronautics and Space Administrations (NASA) launch control system for the Orion capsule and Space Launch System, the next generation manned rocket currently in development. This large system requires high quality testing that will properly measure the capabilities of the system. Automating the test procedures would save the project time and money. Therefore, the Electrical Engineering Division at Kennedy Space Center (KSC) has recruited interns for the past two years to work alongside full-time engineers to develop these automated tests, as well as innovate upon the current automation process.

Spaceport Command and Control System Automated Testing

Science.gov (United States)

Stein, Meriel

2017-01-01

The Spaceport Command and Control System (SCCS) is the National Aeronautics and Space Administrations (NASA) launch control system for the Orion capsule and Space Launch System, the next generation manned rocket currently in development. This large system requires high quality testing that will properly measure the capabilities of the system. Automating the test procedures would save the project time and money. Therefore, the Electrical Engineering Division at Kennedy Space Center (KSC) has recruited interns for the past two years to work alongside full-time engineers to develop these automated tests, as well as innovate upon the current automation process.

An Improved PID Algorithm Based on Insulin-on-Board Estimate for Blood Glucose Control with Type 1 Diabetes.

Science.gov (United States)

Hu, Ruiqiang; Li, Chengwei

2015-01-01

Automated closed-loop insulin infusion therapy has been studied for many years. In closed-loop system, the control algorithm is the key technique of precise insulin infusion. The control algorithm needs to be designed and validated. In this paper, an improved PID algorithm based on insulin-on-board estimate is proposed and computer simulations are done using a combinational mathematical model of the dynamics of blood glucose-insulin regulation in the blood system. The simulation results demonstrate that the improved PID algorithm can perform well in different carbohydrate ingestion and different insulin sensitivity situations. Compared with the traditional PID algorithm, the control performance is improved obviously and hypoglycemia can be avoided. To verify the effectiveness of the proposed control algorithm, in silico testing is done using the UVa/Padova virtual patient software.

Multilayered pyramidal dissolving microneedle patches with flexible pedestals for improving effective drug delivery.

Science.gov (United States)

Lau, Shinying; Fei, Jie; Liu, Haoran; Chen, Weixing; Liu, Ran

2017-11-10

Dissolving microneedles have been employed as a safe and convenient transdermal delivery system for drugs and vaccines. To improve effective drug delivery, a multilayered pyramidal dissolving microneedle patch, composed of silk fibroin tips with the ability of robust mechanical strength, rapid dissolution and drug release supported on a flexible polyvinyl alcohol (PVA) pedestal is reported. To show the utility of this approach the ability of the fabricated microneedles to deliver insulin is demonstrated. The dissolving microneedles have sufficient mechanical strength to be inserted into abdomen skin of mice to a depth of approximately 150μm, and release their encapsulated insulin into the skin to cause a hypoglycemic effect. The fabrication of microneedles avoids high temperature which benefits storage stability at room temperature for 20d. This result indicates >99.4% of insulin remained in the microneedles. In comparison to traditional needle-based administration, the proposed multilayered pyramidal dissolving microneedle patches enable self-administration, miniaturization, pain-free administration, drug delivery and drug stability, all being important features in needle free drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

How to Evaluate Integrated Library Automation Systems.

Science.gov (United States)

Powell, James R.; Slach, June E.

1985-01-01

This paper describes methodology used in compiling a list of candidate integrated library automation systems at a corporate technical library. Priorities for automation, identification of candidate systems, the filtering process, information for suppliers, software and hardware considerations, on-site evaluations, and final system selection are…

Computerized automated remote inspection system

International Nuclear Information System (INIS)

The automated inspection system utilizes a computer to control the location of the ultrasonic transducer, the actual inspection process, the display of the data, and the storage of the data on IBM magnetic tape. This automated inspection equipment provides two major advantages. First, it provides a cost savings, because of the reduced inspection time, made possible by the automation of the data acquisition, processing, and storage equipment. This reduced inspection time is also made possible by a computerized data evaluation aid which speeds data interpretation. In addition, the computer control of the transducer location drive allows the exact duplication of a previously located position or flaw. The second major advantage is that the use of automated inspection equipment also allows a higher-quality inspection, because of the automated data acquisition, processing, and storage. This storage of data, in accurate digital form on IBM magnetic tape, for example, facilitates retrieval for comparison with previous inspection data. The equipment provides a multiplicity of scan data which will provide statistical information on any questionable volume or flaw. An automatic alarm for location of all reportable flaws reduces the probability of operator error. This system has the ability to present data on a cathode ray tube as numerical information, a three-dimensional picture, or ''hard-copy'' sheet. One important advantage of this system is the ability to store large amounts of data in compact magnetic tape reels

Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells.

Science.gov (United States)

Kwon, Kwang-Chul; Nityanandam, Ramya; New, James S; Daniell, Henry

2013-01-01

Glucagon-like peptide (GLP-1) increases insulin secretion but is rapidly degraded (half-life: 2 min in circulation). GLP-1 analogue, exenatide (Byetta) has a longer half-life (3.3-4 h) with potent insulinotropic effects but requires cold storage, daily abdominal injections with short shelf life. Because patients with diabetes take >60 000 injections in their life time, alternative delivery methods are highly desired. Exenatide is ideal for oral delivery because insulinotropism is glucose dependent, with reduced risk of hypoglycaemia even at higher doses. Therefore, exendin-4 (EX4) was expressed as a cholera toxin B subunit (CTB)-fusion protein in tobacco chloroplasts to facilitate bioencapsulation within plant cells and transmucosal delivery in the gut via GM1 receptors present in the intestinal epithelium. The transgene integration was confirmed by PCR and Southern blot analysis. Expression level of CTB-EX4 reached up to 14.3% of total leaf protein (TLP). Lyophilization of leaf material increased therapeutic protein concentration by 12- to 24-fold, extended their shelf life up to 15 months when stored at room temperature and eliminated microbes present in fresh leaves. The pentameric structure, disulphide bonds and functionality of CTB-EX4 were well preserved in lyophilized materials. Chloroplast-derived CTB-EX4 showed increased insulin secretion similar to the commercial EX4 in beta-TC6, a mouse pancreatic cell line. Even when 5000-fold excess dose of CTB-EX4 was orally delivered, it stimulated insulin secretion similar to the intraperitoneal injection of commercial EX4 but did not cause hypoglycaemia in mice. Oral delivery of the bioencapsulated EX4 should eliminate injections, increase patient compliance/convenience and significantly lower their cost. © 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Fluid Delivery System For Capillary Electrophoretic Applications.

Science.gov (United States)

Li, Qingbo; Liu, Changsheng; Kane, Thomas E.; Kernan, John R.; Sonnenschein, Bernard; Sharer, Michael V.

2002-04-23

An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths. An off-line capillary reconditioner thoroughly cleans a capillary cartridge to enable simultaneous execution of electrophoresis with another capillary cartridge. The streamlined nature of the off-line capillary reconditioner offers the advantage of increased system throughput with a minimal increase in system cost.

Smart GSM Based Home Automation System

OpenAIRE

Teymourzadeh, Rozita

2013-01-01

This research work investigates the potential of ‘Full Home Control’, which is the aim of the Home Automation Systems in near future. The analysis and implementation of the home automation technology using Global System for Mobile Communication (GSM) modem to control home appliances such as light, conditional system, and security system via Short Message Service (SMS) text messages is presented in this paper. The proposed research work is focused on the functionality of the GSM protocol, whic...

47 CFR 80.54 - Automated Maritime Telecommunications System (AMTS)-System Licensing.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Automated Maritime Telecommunications System (AMTS)-System Licensing. 80.54 Section 80.54 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... § 80.54 Automated Maritime Telecommunications System (AMTS)—System Licensing. AMTS licensees will be...

A communication and information technology infrastructure for real time monitoring and management of type 1 diabetes patients.

Science.gov (United States)

Skevofilakas, Marios; Mougiakakou, Stavroula G; Zarkogianni, Konstantia; Aslanoglou, Erika; Pavlopoulos, Sotiris A; Vazeou, Andriani; Bartsocas, Christos S; Nikita, Konstantina S

2007-01-01

This paper is focused on the integration of state-of-the-art technologies in the fields of telecommunications, simulation algorithms, and data mining in order to develop a Type 1 diabetes patient's semi to fully-automated monitoring and management system. The main components of the system are a glucose measurement device, an insulin delivery system (insulin injection or insulin pumps), a mobile phone for the GPRS network, and a PDA or laptop for the Internet. In the medical environment, appropriate infrastructure for storage, analysis and visualizing of patients' data has been implemented to facilitate treatment design by health care experts.

Survey and comparison of automated UT systems

International Nuclear Information System (INIS)

Neeley, V.I.; Avioli, M.J.

1988-01-01

In the past decade, the limitations of manual UT inspections have become more severe and adverse. Perhaps the best evidence of this has been the problem of intergranular stress corrosion cracking (IGSCC) in boiling water reactors (BWR). The onset of this problem clearly showed that better and more sophisticated UT inspection methods must be developed to assure the industry that an appropriate level of inspection integrity could be maintained. While automated UT inspection systems have been under development for some time, this event certainly spurred this activity and has resulted in a variety of commercial systems. The intent of this project, sponsored by EPRI, is to develop a utility engineer's 'Buyer guide' to automated UT systems. Comparison of different automated UT systems along with results of questionnaires on manual UT versus automated UT costs and effectiveness are reviewed. (author)

A control system verifier using automated reasoning software

International Nuclear Information System (INIS)

Smith, D.E.; Seeman, S.E.

1985-08-01

An on-line, automated reasoning software system for verifying the actions of other software or human control systems has been developed. It was demonstrated by verifying the actions of an automated procedure generation system. The verifier uses an interactive theorem prover as its inference engine with the rules included as logical axioms. Operation of the verifier is generally transparent except when the verifier disagrees with the actions of the monitored software. Testing with an automated procedure generation system demonstrates the successful application of automated reasoning software for verification of logical actions in a diverse, redundant manner. A higher degree of confidence may be placed in the verified actions of the combined system

Implantable batteryless device for on-demand and pulsatile insulin administration

Science.gov (United States)

Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

2017-04-01

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Computer automation and artificial intelligence

International Nuclear Information System (INIS)

Hasnain, S.B.

1992-01-01

Rapid advances in computing, resulting from micro chip revolution has increased its application manifold particularly for computer automation. Yet the level of automation available, has limited its application to more complex and dynamic systems which require an intelligent computer control. In this paper a review of Artificial intelligence techniques used to augment automation is presented. The current sequential processing approach usually adopted in artificial intelligence has succeeded in emulating the symbolic processing part of intelligence, but the processing power required to get more elusive aspects of intelligence leads towards parallel processing. An overview of parallel processing with emphasis on transputer is also provided. A Fuzzy knowledge based controller for amination drug delivery in muscle relaxant anesthesia on transputer is described. 4 figs. (author)

Polymer matrices obtained by ionizing radiation for using in controlled drug delivery systems

International Nuclear Information System (INIS)

Martellini, Flavia

1998-01-01

Two kinds of controlled drug delivery system were obtained by gamma radiation induced polymerization. One of the system was obtained from an acrylic derivative of acetaminophen (40-hydroxyacetanilide), by copolymerization of 4-(acryloyloxy) acetanilide and N,N-dimethylacrylamide (DMAA) in dimethylformamide solution with 0,16 kGy/h dose rate and 54 Gy dose. The values of reactivity rate, r-D MAA = 0,31 ± 0,02 e r AOA -0,07 ± 0,12, were determined by Fineman-Ross method. The acetaminophen hydrolysis was carried out in alkaline and enzymatic (trypsin) media. Another kind of drug delivery system studied was solvent controlled type, being the drug immobilized in the hydrogel,. The hydrogels prepared by radiation polymerization of acryloyl-L-propine methylester (A-Pro-OMe) with 10 Gy dose, showed thermosensible property, swelling or shrinking in water with decreased or increased temperatures. The hydrogels were obtained with different crosslink density, trimethylolpropane trimethacrylate, and the monomers N, N-dimethyl acrylamide (DMAA) and 2-cyanoethyl acrylate to study the influence of the composition in the drug delivery rate. It was verified that the porous size besides being a characteristic of the matrix composition, it was also temperature dependent (thermosensible). The analgesic drug acetaminophen was immobilized by entrapment and by physical adsorption into the hydrogels matrices for 'in vitro' study. The insulin was immobilized by adsorption for 'in vivo' study. (author)

Automated imaging system for single molecules

Science.gov (United States)

Schwartz, David Charles; Runnheim, Rodney; Forrest, Daniel

2012-09-18

There is provided a high throughput automated single molecule image collection and processing system that requires minimal initial user input. The unique features embodied in the present disclosure allow automated collection and initial processing of optical images of single molecules and their assemblies. Correct focus may be automatically maintained while images are collected. Uneven illumination in fluorescence microscopy is accounted for, and an overall robust imaging operation is provided yielding individual images prepared for further processing in external systems. Embodiments described herein are useful in studies of any macromolecules such as DNA, RNA, peptides and proteins. The automated image collection and processing system and method of same may be implemented and deployed over a computer network, and may be ergonomically optimized to facilitate user interaction.

Automated analysis of images acquired with electronic portal imaging device during delivery of quality assurance plans for inversely optimized arc therapy

DEFF Research Database (Denmark)

Fredh, Anna; Korreman, Stine; Rosenschöld, Per Munck af

2010-01-01

This work presents an automated method for comprehensively analyzing EPID images acquired for quality assurance of RapidArc treatment delivery. In-house-developed software has been used for the analysis and long-term results from measurements on three linacs are presented....

Facilitating Automation Development in Internal Logistics Systems

OpenAIRE

Granlund, Anna

2014-01-01

The internal logistics system includes all activities connected with managing the flow of materials within the physical limits of a facility. This system is an important part of operations in need of increased focus and continuous improvements. Automation is one possible tool with a previously confirmed great potential to improve internal logistics. Despite this great potential and a growing trend of using automation in the area, internal logistics activities are still not automated to the sa...

Longwall automation 2

Energy Technology Data Exchange (ETDEWEB)

David Hainsworth; David Reid; Con Caris; J.C. Ralston; C.O. Hargrave; Ron McPhee; I.N. Hutchinson; A. Strange; C. Wesner [CSIRO (Australia)

2008-05-15

This report covers a nominal two-year extension to the Major Longwall Automation Project (C10100). Production standard implementation of Longwall Automation Steering Committee (LASC) automation systems has been achieved at Beltana and Broadmeadow mines. The systems are now used on a 24/7 basis and have provided production benefits to the mines. The LASC Information System (LIS) has been updated and has been implemented successfully in the IT environment of major coal mining houses. This enables 3D visualisation of the longwall environment and equipment to be accessed on line. A simulator has been specified and a prototype system is now ready for implementation. The Shearer Position Measurement System (SPMS) has been upgraded to a modular commercial production standard hardware solution.A compact hardware solution for visual face monitoring has been developed, an approved enclosure for a thermal infrared camera has been produced and software for providing horizon control through faulted conditions has been delivered. The incorporation of the LASC Cut Model information into OEM horizon control algorithms has been bench and underground tested. A prototype system for shield convergence monitoring has been produced and studies to identify techniques for coal flow optimisation and void monitoring have been carried out. Liaison with equipment manufacturers has been maintained and technology delivery mechanisms for LASC hardware and software have been established.

22 CFR 120.30 - The Automated Export System (AES).

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false The Automated Export System (AES). 120.30... DEFINITIONS § 120.30 The Automated Export System (AES). The Automated Export System (AES) is the Department of... system for collection of export data for the Department of State. In accordance with this subchapter U.S...

21 CFR 864.5620 - Automated hemoglobin system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

Thiomers: potential excipients for non-invasive peptide delivery systems.

Science.gov (United States)

Bernkop-Schnürch, Andreas; Krauland, Alexander H; Leitner, Verena M; Palmberger, Thomas

2004-09-01

In recent years thiolated polymers or so-called thiomers have appeared as a promising alternative in the arena of non-invasive peptide delivery. Thiomers are generated by the immobilisation of thiol-bearing ligands to mucoadhesive polymeric excipients. By formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of these polymers are improved up to 130-fold. Due to formation of inter- and intramolecular disulfide bonds within the thiomer itself, dosage forms such as tablets or microparticles display strong cohesive properties resulting in comparatively higher stability, prolonged disintegration times and a more controlled release of the embedded peptide drug. The permeation of peptide drugs through mucosa can be improved by the use of thiolated polymers. Additionally some thiomers exhibit improved inhibitory properties towards peptidases. The efficacy of thiomers in non-invasive peptide delivery could be demonstrated by various in vivo studies. Tablets comprising a thiomer and pegylated insulin, for instance, resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Furthermore, a pharmacological efficacy of 1.3% was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Human growth hormone in a thiomer-gel was applied nasally to rats and led to a bioavailability of 2.75%. In all these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. According to these results drug carrier systems based on thiomers seem to be a promising tool for non-invasive peptide drug delivery.

Peripheral nervous system insulin resistance in ob/ob mice

Science.gov (United States)

2013-01-01

Background A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. Results The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. Conclusions These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy. PMID:24252636

Insulin analogues with improved absorption characteristics.

Science.gov (United States)

Brange, J; Hansen, J F; Langkjaer, L; Markussen, J; Ribel, U; Sørensen, A R

1992-01-01

The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

Voice-Controlled and Wireless Solid Set Canopy Delivery (VCW-SSCD System for Mist-Cooling

Directory of Open Access Journals (Sweden)

Yiannis Ampatzidis

2018-02-01

Full Text Available California growers in the San Joaquin Valley believe that climate change will affect the pistachio yield dramatically. As the central valley fog disappears, insufficient dormant chill accumulation results in poor flowering synchrony, flower quality, and fruit set in this dioecious species. We have developed a novel, user-friendly, and low-cost Voice-Controlled Wireless Solid Set Canopy Delivery (VCW-SSCD system to increase bud chill accumulation with evaporative cooling on sunny (winter days. This system includes: (i an automated solid-state canopy delivery (SSCD system; (ii a wireless weather-, crop-related data acquisition system; (iii a Voice-Controlled (VC system using Amazon Alexa; (iv a mobile application to visualize the collected data and wirelessly control the SSCD system; and (v a smart control system. The proposed system was deployed and evaluated in a commercial pistachio orchard in Bakersfield, CA. The system worked well with no reported errors. Results demonstrated the system’s ability to cool bud temperatures in a low relative humidity climate. At an ambient temperature of 10–20 °C, bud temperatures were lowered 5–10 °C.

Influence of deposition and spray pattern of nasal powders on insulin bioavailability.

Science.gov (United States)

Pringels, E; Callens, C; Vervaet, C; Dumont, F; Slegers, G; Foreman, P; Remon, J P

2006-03-09

The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

Automated Vehicle Monitoring System

OpenAIRE

Wibowo, Agustinus Deddy Arief; Heriansyah, Rudi

2014-01-01

An automated vehicle monitoring system is proposed in this paper. The surveillance system is based on image processing techniques such as background subtraction, colour balancing, chain code based shape detection, and blob. The proposed system will detect any human's head as appeared at the side mirrors. The detected head will be tracked and recorded for further action.

Test Results for the Automated Rendezvous and Capture System

Science.gov (United States)

Cruzen, Craig; Dabney, Richard; Lomas, James

1999-01-01

The Automated Rendezvous and Capture (AR&C) system was designed and tested at NASA's Marshall Space Flight Center (MSFC) to demonstrate technologies and mission strategies for automated rendezvous and docking of spacecraft in Earth orbit, The system incorporates some of the latest innovations in Global Positioning, System space navigation, laser sensor technologies and automated mission sequencing algorithms. The system's initial design and integration was completed in 1998 and has undergone testing at MSFC. This paper describes the major components of the AR&C system and presents results from the official system tests performed in MSFC's Flight Robotics Laboratory with digital simulations and hardware in the loop tests. The results show that the AR&C system can safely and reliably perform automated rendezvous and docking missions in the absence of system failures with 100 percent success. When system failures are included, the system uses its automated collision avoidance maneuver logic to recover in a safe manner. The primary objective of the AR&C project is to prove that by designing a safe and robust automated system, mission operations cost can be reduced by decreasing the personnel required for mission design, preflight planning and training required for crewed rendezvous and docking missions.

Automated pH Control of Nutrient Solution in a Hydroponic Plant Growth System

Science.gov (United States)

Smith, B.; Dogan, N.; Aglan, H.; Mortley, D.; Loretan, P.

1998-01-01

Over, the years, NASA has played an important role in providing to and the development of automated nutrient delivery and monitoring, systems for growing crops hydroponically for long term space missions. One example are the systems used in the Biomass Production Chamber (BPC) at Kennedy Space Center (KSC). The current KSC monitoring system is based on an engineering workstation using standard analog/digital input/output hardware and custom written software. The monitoring system uses completely separate sensors to provide a check of control sensor accuracy and has the ability to graphically display and store data form past experiment so that they are available for data analysis [Fortson, 1992]. In many cases, growing systems have not been fitted with the kind of automated control systems as used at KSC. The Center for Food and Environmental Systems for Human Exploration of Space (CFESH) located on the campus of Tuskegee University, has effectively grown sweetpotatoes and peanuts hydroponically for the past five years. However they have adjusted the pH electrical conductivity and volume of the hydroponic nutrient solution only manually at times when the solution was to be replenished or changed out according to its protocol (e.g. one-week, two-week, or two-day cycle). But the pH of the nutrient solution flowing through the channel is neither known nor controlled between the update, change out, or replenishment period. Thus, the pH of the nutrient solution is not held at an optimum level over the span of the plant's growth cycle. To solve this dilemma, an automated system for the control and data logging of pH data relative to sweetpotato production using the nutrient film technique (NFT) has been developed, This paper discusses a microprocessor-based system, which was designed to monitor, control, and record the pH of a nutrient solution used for growing sweetpotatoes using NFT.

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

Science.gov (United States)

Petrak, Frank; Herpertz, Stephan; Stridde, Elmar; Pfützner, Andreas

2013-08-01

"Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but

Status of automated nuclear scanning systems

International Nuclear Information System (INIS)

Gold, R.; Roberts, J.H.; Preston, C.C.; McNeece, J.P.; Ruddy, F.H.

1983-07-01

Present day minicomputers and microprocessors enable a range of automation, from partial to total, of tasks once thought beyond approach. The status of three computer controlled systems for quantitative track measurements is reviewed. Two systems, the Hanford optical track scanner (HOTS) and an automated scanning electron microscope (ASEM) are used for scanning solid state track recorders (SSTR). The third systems, the emulsion scanning processor (ESP), is an interactive system used to measure the length of proton tracks in nuclear research emulsions (NRE). Current limitations of these systems for quantitative track scanning are presented. Experimental uncertainties attained with these computer controlled systems are described using results obtained from reactor neutron dosimetry

Preparing and evaluating delivery systems for proteins

DEFF Research Database (Denmark)

Jorgensen, L; Moeller, E H; van de Weert, M

2006-01-01

From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping...... and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge...... for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions....

Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice.

Science.gov (United States)

Coomans, Claudia P; Biermasz, Nienke R; Geerling, Janine J; Guigas, Bruno; Rensen, Patrick C N; Havekes, Louis M; Romijn, Johannes A

2011-12-01

Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated tissue-specific glucose uptake. Tolbutamide, an inhibitor of ATP-sensitive K(+) channels (K(ATP) channels), or vehicle was infused into the lateral ventricle in the basal state and during hyperinsulinemic-euglycemic conditions in postabsorptive, chow-fed C57Bl/6J mice and in postabsorptive C57Bl/6J mice with diet-induced obesity. Whole-body glucose uptake was measured by d-[(14)C]glucose kinetics and tissue-specific glucose uptake by 2-deoxy-d-[(3)H]glucose uptake. During clamp conditions, intracerebroventricular administration of tolbutamide impaired the ability of insulin to inhibit EGP by ∼20%. In addition, intracerebroventricular tolbutamide diminished insulin-stimulated glucose uptake in muscle (by ∼59%) but not in heart or adipose tissue. In contrast, in insulin-resistant mice with diet-induced obesity, intracerebroventricular tolbutamide did not alter the effects of insulin during clamp conditions on EGP or glucose uptake by muscle. Insulin stimulates glucose uptake in muscle in part through effects via K(ATP) channels in the central nervous system, in analogy with the inhibitory effects of insulin on EGP. High-fat diet-induced obesity abolished the central effects of insulin on liver and muscle. These observations stress the role of central insulin resistance in the pathophysiology of diet-induced insulin resistance.

Personal computer based home automation system

OpenAIRE

Hellmuth, George F.

1993-01-01

The systems engineering process is applied in the development of the preliminary design of a home automation communication protocol. The objective of the communication protocol is to provide a means for a personal computer to communicate with adapted appliances in the home. A needs analysis is used to ascertain that a need exist for a home automation system. Numerous design alternatives are suggested and evaluated to determine the best possible protocol design. Coaxial cable...

Hydrometeorological Automated Data System

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Office of Hydrologic Development of the National Weather Service operates HADS, the Hydrometeorological Automated Data System. This data set contains the last 48...

An automated thermoluminescence dosimetry (TLD) system

International Nuclear Information System (INIS)

Kicken, P.J.H.; Huyskens, C.J.

1979-01-01

In the Health Physics Division of the Eindhoven University of Technology work is going on in developing an automated TLD-system. Process automization, statistical computation, dose calculation as well as dose recording are carried out, using a microcomputer and floppy disk unit. The main features of this TLD-system are its low costs, flexibility, easy to operate, and the feasibility for use in routine dosimetry as well as in complex TLD research. Because of its modular set-up several components of the system are multifunctional in other operations. The system seems suited for medium sized Health Physics groups. (Auth.)

METHOD OF CHOOSING THE TECHNOLOGY OF VEHICLE OPERATION ON DELIVERY ROUTES

Directory of Open Access Journals (Sweden)

Ye. Nagornyi

2014-10-01

Full Text Available A method for determining the technology of vehicles operation on delivery (team routes, which allows to determine the optimal sequence of cargo delivery to customers by vehicles of certain capacity in order to meet the requirements of cargo owners regarding the conditions of service is offered. Recommendations for creation of an automated system of forming the technology of vehicles operation on delivery routes are developed.

pH-Dependent Release of Insulin from Layer-by-Layer-Deposited Polyelectrolyte Microcapsules

Directory of Open Access Journals (Sweden)

Kentaro Yoshida

2015-07-01

Full Text Available Insulin-containing microcapsules were prepared by a layer-by-layer (LbL deposition of poly(allylamine hydrochloride (PAH and polyanions, such as poly(styrenesulfonate (PSS, poly(vinyl sulfate (PVS, and dextran sulfate (DS on insulin-containing calcium carbonate (CaCO3 microparticles. The CaCO3 core was dissolved in diluted HCl solution to obtain insulin-containing hollow microcapsules. The microcapsules were characterized by scanning electron microscope (SEM and atomic force microscope (AFM images and ζ-potential. The release of insulin from the microcapsules was faster at pH 9.0 and 7.4 than in acidic solutions due to the different charge density of PAH. In addition, insulin release was suppressed when the microcapsules were constructed using PAH with a lower molecular weight, probably owing to a thicker shell of the microcapsules. The results suggested a potential use of the insulin-containing microcapsules for developing insulin delivery systems.

Cross talk between insulin and bone morphogenetic protein signaling systems in brown adipogenesis

DEFF Research Database (Denmark)

Zhang, Hongbin; Schulz, Tim J; Espinoza, Daniel O

2010-01-01

Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin...... BMP7's suppressive effect on pref-1 transcription. Together, these data suggest cross talk between the insulin and BMP signaling systems by which BMP7 can rescue brown adipogenesis in cells with insulin resistance....

Home Automation System Using Capacitive Touchscreen

OpenAIRE

Yash Inaniya; Naresh Kumari

2014-01-01

Technology has been constantly evolving and with the advent of touchscreen in human life , devices are much easier and simple to operate. This work is mainly focused on building home automation system which is more user friendly and thus can be operated by anyone. Earlier home automation systems were completely mechanically operated and thus required a lot of maintenance and were costly also. Now that human and computer interaction has been developed into a more wide and sophi...

In Vivo Experimental Study of Noninvasive Insulin Microinjection through Hollow Si Microneedle Array

Directory of Open Access Journals (Sweden)

Drago Resnik

2018-01-01

Full Text Available An experimental study of in vivo insulin delivery through microinjection by using hollow silicon microneedle array is presented. A case study was carried out on a healthy human subject in vivo to determine the influence of delivery parameters on drug transfer efficiency. As a microinjection device, a hollow microneedle array (13 × 13 mm2 having 100 microneedles (220 µm high, 130 µm-outer diameter and 50 µm-inner diameter was designed and fabricated using classical microfabrication techniques. The efficiency of the delivery process was first characterized using methylene blue and a saline solution. Based on these results, the transfer efficiency was found to be predominantly limited by the inability of viable epidermis to absorb and allow higher drug transport toward the capillary-rich region. Two types of fast-acting insulin were used to provide evidence of efficient delivery by hollow MNA to a human subject. By performing blood analyses, infusion of more-concentrated insulin (200 IU/mL, international units (IU exhibited similar blood glucose level drop (5–7% compared to insulin of standard concentration (100 IU/mL, however, significant increase of serum insulin (40–50% with respect to the preinfusion values was determined. This was additionally confirmed by a distinctive increase of insulin to C-peptide ratio as compared to preinfusion ratio. Moreover, we noticed that this route of administration mimics a multiple dose regimen, able to get a “steady state” for insulin plasma concentration.

Application of automated reasoning software: procedure generation system verifier

International Nuclear Information System (INIS)

Smith, D.E.; Seeman, S.E.

1984-09-01

An on-line, automated reasoning software system for verifying the actions of other software or human control systems has been developed. It was demonstrated by verifying the actions of an automated procedure generation system. The verifier uses an interactive theorem prover as its inference engine with the rules included as logic axioms. Operation of the verifier is generally transparent except when the verifier disagrees with the actions of the monitored software. Testing with an automated procedure generation system demonstrates the successful application of automated reasoning software for verification of logical actions in a diverse, redundant manner. A higher degree of confidence may be placed in the verified actions gathered by the combined system

Wireless Home Automation System using IoT

Directory of Open Access Journals (Sweden)

Alexandra MIHALACHE

2017-01-01

Full Text Available Nowadays, the chance of having an automated home is no longer a fancy luxury, but a reality accessible to a wide range of consumers, because smart home systems have replaced those that only automated the home in the past. More and more solutions based on IoT are being devel-oped to transform homes into smart ones, but the problem is that the benefits of home automa-tion are still not clear to everyone as they are not promoted enough, so we cannot talk about a broad mass of consumers already using integrated or DIY solutions to improve their lives. In this paper, I will present a home automation system using Arduino Uno integrated with rele-vant modules which are used to allow remote control of lights or fans, changes being made on the basis of different sensors data. The system is designed to be low cost and expandable, bring-ing accessibility, convenience and energy efficiency.

A Systems Approach to Nitrogen Delivery

Energy Technology Data Exchange (ETDEWEB)

Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States)

2017-10-23

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

A Systems Approach to Nitrogen Delivery

Energy Technology Data Exchange (ETDEWEB)

Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

2017-10-17

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

Automation in an addiction treatment research clinic: computerised contingency management, ecological momentary assessment and a protocol workflow system.

Science.gov (United States)

Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Epstein, David H; Preston, Kenzie L

2009-01-01

A challenge in treatment research is the necessity of adhering to protocol and regulatory strictures while maintaining flexibility to meet patients' treatment needs and to accommodate variations among protocols. Another challenge is the acquisition of large amounts of data in an occasionally hectic environment, along with the provision of seamless methods for exporting, mining and querying the data. We have automated several major functions of our outpatient treatment research clinic for studies in drug abuse and dependence. Here we describe three such specialised applications: the Automated Contingency Management (ACM) system for the delivery of behavioural interventions, the transactional electronic diary (TED) system for the management of behavioural assessments and the Protocol Workflow System (PWS) for computerised workflow automation and guidance of each participant's daily clinic activities. These modules are integrated into our larger information system to enable data sharing in real time among authorised staff. ACM and the TED have each permitted us to conduct research that was not previously possible. In addition, the time to data analysis at the end of each study is substantially shorter. With the implementation of the PWS, we have been able to manage a research clinic with an 80 patient capacity, having an annual average of 18,000 patient visits and 7300 urine collections with a research staff of five. Finally, automated data management has considerably enhanced our ability to monitor and summarise participant safety data for research oversight. When developed in consultation with end users, automation in treatment research clinics can enable more efficient operations, better communication among staff and expansions in research methods.

Automated 741 document preparation: Oak Ridge National Laboratory's Automated Safeguards Information System (OASIS)

International Nuclear Information System (INIS)

Austin, H.C.; Gray, L.M.

1982-01-01

OASIS has been providing for Oak Ridge National Laboratory's total safeguards needs since being place on line in April 1980. The system supports near real-time nuclear materials safeguards and accountability control. The original design of OASIS called for an automated facsimile of a 741 document to be prepared as a functional by-product of updating the inventory. An attempt was made to utilize, intact, DOE-Albuquerque's automated 741 system to generate the facsimile; however, the five page document produced proved too cumbersome. Albuquerque's programs were modified to print an original 741 document utilizing standard DOE/NRC 741 forms. It is felt that the best features of both the automated and manually generated 741 documents have been incorporated. Automation of the source data for 741 shipping documents produces greater efficiency while reducing possible errors. Through utilization of the standard DOE/NRC form, continuity within the NMMSS system is maintained, thus minimizing the confusion and redundancy associated with facsimiles. OASIS now fulfills the original concept of near real-time accountability by furnishing a viable 741 document as a function of updating the inventory

Automated activation-analysis system

International Nuclear Information System (INIS)

Minor, M.M.; Hensley, W.K.; Denton, M.M.; Garcia, S.R.

1981-01-01

An automated delayed neutron counting and instrumental neutron activation analysis system has been developed at Los Alamos National Laboratory's Omega West Reactor (OWR) to analyze samples for uranium and 31 additional elements with a maximum throughput of 400 samples per day. The system and its mode of operation for a large reconnaissance survey are described

Development of design principles for automated systems in transport control.

Science.gov (United States)

Balfe, Nora; Wilson, John R; Sharples, Sarah; Clarke, Theresa

2012-01-01

This article reports the results of a qualitative study investigating attitudes towards and opinions of an advanced automation system currently used in UK rail signalling. In-depth interviews were held with 10 users, key issues associated with automation were identified and the automation's impact on the signalling task investigated. The interview data highlighted the importance of the signallers' understanding of the automation and their (in)ability to predict its outputs. The interviews also covered the methods used by signallers to interact with and control the automation, and the perceived effects on their workload. The results indicate that despite a generally low level of understanding and ability to predict the actions of the automation system, signallers have developed largely successful coping mechanisms that enable them to use the technology effectively. These findings, along with parallel work identifying desirable attributes of automation from the literature in the area, were used to develop 12 principles of automation which can be used to help design new systems which better facilitate cooperative working. The work reported in this article was completed with the active involvement of operational rail staff who regularly use automated systems in rail signalling. The outcomes are currently being used to inform decisions on the extent and type of automation and user interfaces in future generations of rail control systems.

Automated clearing system and the banking sector performance: the ...

African Journals Online (AJOL)

Automated clearing system and the banking sector performance: the Nigerian experience. ... Abstract. This study investigated the impact of automated clearing system on the Nigerian banking system. ... AJOL African Journals Online. HOW TO ...

STRATEGIES AND PROSPECTS OF NASAL DRUG DELIVERY SYSTEMS

OpenAIRE

Gannu Praveen Kumar

2012-01-01

The recent advancement of nasal drug delivery systems has increased enormously and is gaining significant importance. Intranasal therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The non-invasive delivery of nasal drug delivery systems made to exploit for the development of successful treatment. The advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, nasal vaccines and CNS...

Adoption of automated livestock production systems in Northern Europe

DEFF Research Database (Denmark)

Pedersen, Søren Marcus; Lind, Kim Martin Hjorth

2014-01-01

In the last decades the development of automated systems in livestock production has gained increasing interest among farmers. A combined use of computers and sensor systems has lead the development into new research areas with automated milking systems, grain drying systems and automated feeding...... on the relationship and adoption patterns among these countries. The paper presents the results of the surveyed population, demography, farm structure with livestock production characteristics and farmers use of selected automated systems in livestock production....... systems. The aim of this paper is to present the results of a farm survey and cluster analysis that have been made among 4 countries in Europe. This study is based on replies from 413 respondents in Germany (eastern part), Greece, Finland and Denmark, respectively, and the study comments...

IDAPS (Image Data Automated Processing System) System Description

Science.gov (United States)

1988-06-24

This document describes the physical configuration and components used in the image processing system referred to as IDAPS (Image Data Automated ... Processing System). This system was developed by the Environmental Research Institute of Michigan (ERIM) for Eglin Air Force Base. The system is designed

21 CFR 864.5700 - Automated platelet aggregation system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated platelet aggregation system. 864.5700 Section 864.5700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices...

Fiber coupled optical spark delivery system

Science.gov (United States)

Yalin, Azer; Willson, Bryan; Defoort, Morgan

2008-08-12

A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

Economic Model Predictive Control of Bihormonal Artificial Pancreas System Based on Switching Control and Dynamic R-parameter.

Science.gov (United States)

Tang, Fengna; Wang, Youqing

2017-11-01

Blood glucose (BG) regulation is a long-term task for people with diabetes. In recent years, more and more researchers have attempted to achieve automated regulation of BG using automatic control algorithms, called the artificial pancreas (AP) system. In clinical practice, it is equally important to guarantee the treatment effect and reduce the treatment costs. The main motivation of this study is to reduce the cure burden. The dynamic R-parameter economic model predictive control (R-EMPC) is chosen to regulate the delivery rates of exogenous hormones (insulin and glucagon). It uses particle swarm optimization (PSO) to optimize the economic cost function and the switching logic between insulin delivery and glucagon delivery is designed based on switching control theory. The proposed method is first tested on the standard subject; the result is compared with the switching PID and the switching MPC. The effect of the dynamic R-parameter on improving the control performance is illustrated by comparing the results of the EMPC and the R-EMPC. Finally, the robustness tests on meal change (size and timing), hormone sensitivity (insulin and glucagon), and subject variability are performed. All results show that the proposed method can improve the control performance and reduce the economic costs. The simulation results verify the effectiveness of the proposed algorithm on improving the tracking performance, enhancing robustness, and reducing economic costs. The method proposed in this study owns great worth in practical application.

Sterile Product Packaging and Delivery Systems.

Science.gov (United States)

Akers, Michael J

2015-01-01

Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood.

Science.gov (United States)

Lee, Seung-Hwan; Zabolotny, Janice M; Huang, Hu; Lee, Hyon; Kim, Young-Bum

2016-08-01

Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders.

Automated activation-analysis system

International Nuclear Information System (INIS)

Minor, M.M.; Garcia, S.R.; Denton, M.M.

1982-01-01

An automated delayed neutron counting and instrumental neutron activation analysis system has been developed at Los Alamos National Laboratory's Omega West Reactor (OWR) to analyze samples for uranium and 31 additional elements with a maximum throughput of 400 samples per day

An automated digital imaging system for environmental monitoring applications

Science.gov (United States)

Bogle, Rian; Velasco, Miguel; Vogel, John

2013-01-01

Recent improvements in the affordability and availability of high-resolution digital cameras, data loggers, embedded computers, and radio/cellular modems have advanced the development of sophisticated automated systems for remote imaging. Researchers have successfully placed and operated automated digital cameras in remote locations and in extremes of temperature and humidity, ranging from the islands of the South Pacific to the Mojave Desert and the Grand Canyon. With the integration of environmental sensors, these automated systems are able to respond to local conditions and modify their imaging regimes as needed. In this report we describe in detail the design of one type of automated imaging system developed by our group. It is easily replicated, low-cost, highly robust, and is a stand-alone automated camera designed to be placed in remote locations, without wireless connectivity.

MINI-SLAR delivery system

International Nuclear Information System (INIS)

Alstein, D.

1996-01-01

In the Spring of 1993, a need to complete Spacer Location and Repositioning (SLAR) on the Bruce 'A', Unit 1 Reactor was identified. An alternate SLAR delivery system was required due to conversion constraints that prevented the existing Bruce SLAR System from being used in Unit 1. A Portable SLAR Delivery System called MINI-SLAR Delivery System was developed, designed and fabricated in a 14 month period, then used to successfully SLAR 109 channels. The system is a portable remotely operated Nuclear Class 1 registered fitting that is independent of the Fuelling Machine, allowing the station to continue normal Fuelling and Maintenance activities. It is designed to a Level 'D' faulted condition of HPECI Pressure thus minimizing PHT Heat Sink configuration requirements and minimizing outage set-up times. The system is based on a modular design allowing for easy fabrication, assembly and repair. It consists of a Snout Assembly, a Closure Plug Assembly, Shield Plug Assembly, SLAR Ram assembly, Work Table Assembly and Control Panel. Controls are through a Programmable Logic Controller with software tested and certified to a Software Quality Assurance of Level Ill. (author). 2 refs., 2 figs

MINI-SLAR delivery system

Energy Technology Data Exchange (ETDEWEB)

Alstein, D [Ontario Hydro, Tiverton, ON (Canada). Bruce Nuclear Generating Station-A; Dalton, K [Spectrum Engineering, Peterborough, ON (Canada)

1997-12-31

In the Spring of 1993, a need to complete Spacer Location and Repositioning (SLAR) on the Bruce `A`, Unit 1 Reactor was identified. An alternate SLAR delivery system was required due to conversion constraints that prevented the existing Bruce SLAR System from being used in Unit 1. A Portable SLAR Delivery System called MINI-SLAR Delivery System was developed, designed and fabricated in a 14 month period, then used to successfully SLAR 109 channels. The system is a portable remotely operated Nuclear Class 1 registered fitting that is independent of the Fuelling Machine, allowing the station to continue normal Fuelling and Maintenance activities. It is designed to a Level `D` faulted condition of HPECI Pressure thus minimizing PHT Heat Sink configuration requirements and minimizing outage set-up times. The system is based on a modular design allowing for easy fabrication, assembly and repair. It consists of a Snout Assembly, a Closure Plug Assembly, Shield Plug Assembly, SLAR Ram assembly, Work Table Assembly and Control Panel. Controls are through a Programmable Logic Controller with software tested and certified to a Software Quality Assurance of Level Ill. (author). 2 refs., 2 figs.

Health care delivery systems.

NARCIS (Netherlands)

Stevens, F.; Zee, J. van der

2007-01-01

A health care delivery system is the organized response of a society to the health problems of its inhabitants. Societies choose from alternative health care delivery models and, in doing so, they organize and set goals and priorities in such a way that the actions of different actors are effective,

AUTOMATION DESIGN FOR MONORAIL - BASED SYSTEM PROCESSES

Directory of Open Access Journals (Sweden)

Bunda BESA

2016-12-01

Full Text Available Currently, conventional methods of decline development put enormous cost pressure on the profitability of mining operations. This is the case with narrow vein ore bodies where current methods and mine design of decline development may be too expensive to support economic extraction of the ore. According to studies, the time it takes to drill, clean and blast an end in conventional decline development can be up to 224 minutes. This is because once an end is blasted, cleaning should first be completed before drilling can commence, resulting in low advance rates per shift. Improvements in advance rates during decline development can be achieved by application of the Electric Monorail Transport System (EMTS based drilling system. The system consists of the drilling and loading components that use monorail technology to drill and clean the face during decline development. The two systems work simultaneously at the face in such a way that as the top part of the face is being drilled the pneumatic loading system cleans the face. However, to improve the efficiency of the two systems, critical processes performed by the two systems during mining operations must be automated. Automation increases safety and productivity, reduces operator fatigue and also reduces the labour costs of the system. The aim of this paper is, therefore, to describe automation designs of the two processes performed by the monorail drilling and loading systems during operations. During automation design, critical processes performed by the two systems and control requirements necessary to allow the two systems execute such processes automatically have also been identified.

Home Automation and Security System

OpenAIRE

Surinder Kaur,; Rashmi Singh; Neha Khairwal; Pratyk Jain

2016-01-01

Easy Home or Home automation plays a very important role in modern era because of its flexibility in using it at different places with high precision which will save money and time by decreasing human hard work. Prime focus of this technology is to control the household equipment’s like light, fan, door, AC etc. automatically. This research paper has detailed information on Home Automation and Security System using Arduino, GSM and how we can control home appliances using Android application....

Radioimmunoassay test system for detection of anti-insulin antibodies

International Nuclear Information System (INIS)

Dudko, N.V.; Piven', N.V.; Ibragimova, G.V.; Kasatkin, Yu.N.

1995-01-01

A radiodiagnostic test system has been developed and commercial kit for radioimmunoassay of anti-insulin antibodies in human blood serum created. Clinical trials of the kit in patients (150 diabetics with types 1 and 2 condition) and normal subjects (n=100) demonstrated the possibility of using this kit for the detection of preclinical forms of diabetes and for distinguishing groups at risk of diabetes among children and adults, for the detection of insulin resistance, for the differential diagnosis of diabetes, and for monitoring the efficacy of insulin therapy. 9 refs.; 1 tab

DEVELOPMENT OF AUTOMATED SYSTEM OF CLIMATE CONDITIONS MANAGEMENT

Directory of Open Access Journals (Sweden)

Novikova L.V.

2017-12-01

Full Text Available The scientific work is devoted to the analysis and development of the automated control system of the climatic conditions of the minites. The analysis of existing automated control systems is carried out, in particular attention is paid to the systems of climate control of greenhouses. The technical means of the control system are determined. As a platform, Arduino®Uno is selected.

Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

Science.gov (United States)

Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

2009-01-01

We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

Preparation and characterization of insulin-surfactant complexes for loading into lipid-based drug delivery systems

DEFF Research Database (Denmark)

Li, Ping; Nielsen, Hanne Mørck; Fano, Mathias

2013-01-01

of surfactants, but also a nonnative secondary structure in the solid state. Finally, circular dichroism analysis of rehydrated complexes showed that the processing did not irreversibly alter the secondary structure of insulin. In short, the present study demonstrates changes in the secondary structure...

Automated Cryocooler Monitor and Control System Software

Science.gov (United States)

Britchcliffe, Michael J.; Conroy, Bruce L.; Anderson, Paul E.; Wilson, Ahmad

2011-01-01

This software is used in an automated cryogenic control system developed to monitor and control the operation of small-scale cryocoolers. The system was designed to automate the cryogenically cooled low-noise amplifier system described in "Automated Cryocooler Monitor and Control System" (NPO-47246), NASA Tech Briefs, Vol. 35, No. 5 (May 2011), page 7a. The software contains algorithms necessary to convert non-linear output voltages from the cryogenic diode-type thermometers and vacuum pressure and helium pressure sensors, to temperature and pressure units. The control function algorithms use the monitor data to control the cooler power, vacuum solenoid, vacuum pump, and electrical warm-up heaters. The control algorithms are based on a rule-based system that activates the required device based on the operating mode. The external interface is Web-based. It acts as a Web server, providing pages for monitor, control, and configuration. No client software from the external user is required.

Inhaled insulin for controlling blood glucose in patients with diabetes

Directory of Open Access Journals (Sweden)

Bernard L Silverman

2008-01-01

Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

Partial Automated Alignment and Integration System

Science.gov (United States)

Kelley, Gary Wayne (Inventor)

2014-01-01

The present invention is a Partial Automated Alignment and Integration System (PAAIS) used to automate the alignment and integration of space vehicle components. A PAAIS includes ground support apparatuses, a track assembly with a plurality of energy-emitting components and an energy-receiving component containing a plurality of energy-receiving surfaces. Communication components and processors allow communication and feedback through PAAIS.

Driver support and automated driving systems : Acceptance and effects on behavior

NARCIS (Netherlands)

De Waard, D.; Brookhuis, K.A.; Scerbo, MW; Mouloua, M

1999-01-01

Automation in driving ranges from simple in-vehicle information systems to completely automated driving in the Automated Highway System (AHS). An increased level of automation and increased restriction in behavioural freedom, as well as decreased control over tasks, have serious consequences for

Recent advances in automated system model extraction (SME)

International Nuclear Information System (INIS)

Narayanan, Nithin; Bloomsburgh, John; He Yie; Mao Jianhua; Patil, Mahesh B; Akkaraju, Sandeep

2006-01-01

In this paper we present two different techniques for automated extraction of system models from FEA models. We discuss two different algorithms: for (i) automated N-DOF SME for electrostatically actuated MEMS and (ii) automated N-DOF SME for MEMS inertial sensors. We will present case studies for the two different algorithms presented

Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin

DEFF Research Database (Denmark)

O'Harte, F P; Boyd, A C; McKillop, A M

2000-01-01

Human insulin was glycated under hyperglycemic reducing conditions and a novel diglycated form (M(r) 6135.1 Da) was purified by RP-HPLC. Endoproteinase Glu-C digestion combined with mass spectrometry and automated Edman degradation localized glycation to Gly(1) and Phe(1) of the insulin A- and B-...

Using collaborative technologies in remote lab delivery systems for topics in automation

Science.gov (United States)

Ashby, Joe E.

communication tools for remote labs involving automation equipment, the results of this work points to making voice chat the default method of communication; but the webcam video with voice chat option should be included. Standards are only beginning to be developed for the design of remote lab systems. Research, design and innovation involving collaboration and presence should be included.

Automated metabolic gas analysis systems: a review.

Science.gov (United States)

Macfarlane, D J

2001-01-01

The use of automated metabolic gas analysis systems or metabolic measurement carts (MMC) in exercise studies is common throughout the industrialised world. They have become essential tools for diagnosing many hospital patients, especially those with cardiorespiratory disease. Moreover, the measurement of maximal oxygen uptake (VO2max) is routine for many athletes in fitness laboratories and has become a defacto standard in spite of its limitations. The development of metabolic carts has also facilitated the noninvasive determination of the lactate threshold and cardiac output, respiratory gas exchange kinetics, as well as studies of outdoor activities via small portable systems that often use telemetry. Although the fundamental principles behind the measurement of oxygen uptake (VO2) and carbon dioxide production (VCO2) have not changed, the techniques used have, and indeed, some have almost turned through a full circle. Early scientists often employed a manual Douglas bag method together with separate chemical analyses, but the need for faster and more efficient techniques fuelled the development of semi- and full-automated systems by private and commercial institutions. Yet, recently some scientists are returning back to the traditional Douglas bag or Tissot-spirometer methods, or are using less complex automated systems to not only save capital costs, but also to have greater control over the measurement process. Over the last 40 years, a considerable number of automated systems have been developed, with over a dozen commercial manufacturers producing in excess of 20 different automated systems. The validity and reliability of all these different systems is not well known, with relatively few independent studies having been published in this area. For comparative studies to be possible and to facilitate greater consistency of measurements in test-retest or longitudinal studies of individuals, further knowledge about the performance characteristics of these

Some Recent Advances in Transdermal Drug Delivery Systems ...

African Journals Online (AJOL)

Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells.

Science.gov (United States)

Lizunov, Vladimir A; Stenkula, Karin; Troy, Aaron; Cushman, Samuel W; Zimmerberg, Joshua

2013-01-01

Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.

Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells.

Directory of Open Access Journals (Sweden)

Vladimir A Lizunov

Full Text Available Insulin-stimulated delivery of glucose transporter-4 (GLUT4 to the plasma membrane (PM is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm. GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.

Automation in an Addiction Treatment Research Clinic: Computerized Contingency Management, Ecological Momentary Assessment, and a Protocol Workflow System

Science.gov (United States)

Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Epstein, David H.; Preston, Kenzie L.

2009-01-01

Issues A challenge in treatment research is the necessity of adhering to protocol and regulatory strictures while maintaining flexibility to meet patients’ treatment needs and accommodate variations among protocols. Another challenge is the acquisition of large amounts of data in an occasionally hectic environment, along with provision of seamless methods for exporting, mining, and querying the data. Approach We have automated several major functions of our outpatient treatment research clinic for studies in drug abuse and dependence. Here we describe three such specialized applications: the Automated Contingency Management (ACM) system for delivery of behavioral interventions, the Transactional Electronic Diary (TED) system for management of behavioral assessments, and the Protocol Workflow System (PWS) for computerized workflow automation and guidance of each participant’s daily clinic activities. These modules are integrated into our larger information system to enable data sharing in real time among authorized staff. Key Findings ACM and TED have each permitted us to conduct research that was not previously possible. In addition, the time to data analysis at the end of each study is substantially shorter. With the implementation of the PWS, we have been able to manage a research clinic with an 80-patient capacity having an annual average of 18,000 patient-visits and 7,300 urine collections with a research staff of five. Finally, automated data management has considerably enhanced our ability to monitor and summarize participant-safety data for research oversight. Implications and conclusion When developed in consultation with end users, automation in treatment-research clinics can enable more efficient operations, better communication among staff, and expansions in research methods. PMID:19320669

Drug delivery systems with modified release for systemic and biophase bioavailability.

Science.gov (United States)

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Healthcare Blockchain System Using Smart Contracts for Secure Automated Remote Patient Monitoring.

Science.gov (United States)

Griggs, Kristen N; Ossipova, Olya; Kohlios, Christopher P; Baccarini, Alessandro N; Howson, Emily A; Hayajneh, Thaier

2018-06-06

As Internet of Things (IoT) devices and other remote patient monitoring systems increase in popularity, security concerns about the transfer and logging of data transactions arise. In order to handle the protected health information (PHI) generated by these devices, we propose utilizing blockchain-based smart contracts to facilitate secure analysis and management of medical sensors. Using a private blockchain based on the Ethereum protocol, we created a system where the sensors communicate with a smart device that calls smart contracts and writes records of all events on the blockchain. This smart contract system would support real-time patient monitoring and medical interventions by sending notifications to patients and medical professionals, while also maintaining a secure record of who has initiated these activities. This would resolve many security vulnerabilities associated with remote patient monitoring and automate the delivery of notifications to all involved parties in a HIPAA compliant manner.

Automated delivery of codes for charge in radiotherapy

International Nuclear Information System (INIS)

Sauer, Michael; Volz, Steffen; Hall, Markus; Roehner, Fred; Frommhold, Hermann; Grosu, Anca-Ligia; Heinemann, Felix

2010-01-01

Background and purpose: for the medical billing of Radiotherapy every fraction has to be encoded, including date and time of all administered treatments. With fractions averaging 30 per patient and about 2,500 new patients every year the number of Radiotherapy codes reaches an amount of 70,000 and more. Therefore, an automated proceeding for transferring and processing therapy codes has been developed at the Department of Radiotherapy Freiburg, Germany. This is a joint project of the Department of Radiotherapy, the Administration Department, and the Central II Department of the University Hospital of Freiburg. Material and methods: the project consists of several modules whose collaboration makes the projected automated transfer of treatment codes possible. The first step is to extract the data from the department's Clinical Information System (MOSAIQ). These data are transmitted to the Central IT Department via an HL7 interface, where a check for corresponding hospitalization data is performed. In the further processing of the data, a matching table plays an important role allowing the transformation of a treatment code into a valid medical billing code. In a last step, the data are transferred to the medical billing system. Results and conclusion: after assembling and implementing the particular modules successfully, a first beta test was launched. In order to test the modules separately as well as the interaction of the components, extensive tests were performed during March 2006. Soon it became clear that the tested procedure worked efficiently and accurately. In April 2006, a pilot project with a few qualities of treatment (e.g., computed tomography, simulation) was put into practice. Since October 2006, nearly all Radiation Therapy codes (∝ 75,000) are being transferred to the comprehensive Hospital Information System (HIS) automatically in a daily routine. (orig.)

Saturn facility oil transfer automation system

Energy Technology Data Exchange (ETDEWEB)

Joseph, Nathan R.; Thomas, Rayburn Dean; Lewis, Barbara Ann; Malagon, Hector Ricardo.

2014-02-01

The Saturn accelerator, owned by Sandia National Laboratories, has been in operation since the early 1980s and still has many of the original systems. A critical legacy system is the oil transfer system which transfers 250,000 gallons of transformer oil from outside storage tanks to the Saturn facility. The oil transfer system was iden- ti ed for upgrade to current technology standards. Using the existing valves, pumps, and relay controls, the system was automated using the National Instruments cRIO FGPA platform. Engineered safety practices, including a failure mode e ects analysis, were used to develop error handling requirements. The uniqueness of the Saturn Oil Automated Transfer System (SOATS) is in the graphical user interface. The SOATS uses an HTML interface to communicate to the cRIO, creating a platform independent control system. The SOATS was commissioned in April 2013.

Diminished hepatic insulin removal in obesity

International Nuclear Information System (INIS)

Cano, I.; Salvador, J.; Rodriguez, R.; Arraiza, M.C.; Goena, M.; Barberia, J.J.; Moncada, E.

1986-01-01

Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out

Diminished hepatic insulin removal in obesity

Energy Technology Data Exchange (ETDEWEB)

Cano, I; Salvador, J; Rodriguez, R; Arraiza, M C; Goena, M; Barberia, J J; Moncada, E

1986-01-01

Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out.

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

Science.gov (United States)

Davis, Michael E.; Hsieh, Patrick C. H.; Takahashi, Tomosaburo; Song, Qing; Zhang, Shuguang; Kamm, Roger D.; Grodzinsky, Alan J.; Anversa, Piero; Lee, Richard T.

2006-05-01

Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy. engineering | maturation | scaffold

DESIGN OF SMALL AUTOMATION WORK CELL SYSTEM DEMONSTRATIONS

International Nuclear Information System (INIS)

TURNER, C.; PEHL, J.

2000-01-01

The introduction of automation systems into many of the facilities dealing with the production, use and disposition of nuclear materials has been an ongoing objective. Many previous attempts have been made, using a variety of monolithic and, in some cases, modular technologies. Many of these attempts were less than successful, owing to the difficulty of the problem, the lack of maturity of the technology, and over optimism about the capabilities of a particular system. Consequently, it is not surprising that suggestions that automation can reduce worker Occupational Radiation Exposure (ORE) levels are often met with skepticism and caution. The development of effective demonstrations of these technologies is of vital importance if automation is to become an acceptable option for nuclear material processing environments. The University of Texas Robotics Research Group (UTRRG) has been pursuing the development of technologies to support modular small automation systems (each of less than 5 degrees-of-freedom) and the design of those systems for more than two decades. Properly designed and implemented, these technologies have a potential to reduce the worker ORE associated with work in nuclear materials processing facilities. Successful development of systems for these applications requires the development of technologies that meet the requirements of the applications. These application requirements form a general set of rules that applicable technologies and approaches need to adhere to, but in and of themselves are generally insufficient for the design of a specific automation system. For the design of an appropriate system, the associated task specifications and relationships need to be defined. These task specifications also provide a means by which appropriate technology demonstrations can be defined. Based on the requirements and specifications of the operations of the Advanced Recovery and Integrated Extraction System (ARIES) pilot line at Los Alamos National

Adaptive Liver Stereotactic Body Radiation Therapy: Automated Daily Plan Reoptimization Prevents Dose Delivery Degradation Caused by Anatomy Deformations

Energy Technology Data Exchange (ETDEWEB)

Leinders, Suzanne M. [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Delft University of Technology, Delft (Netherlands); Breedveld, Sebastiaan; Méndez Romero, Alejandra [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Schaart, Dennis [Delft University of Technology, Delft (Netherlands); Seppenwoolde, Yvette, E-mail: y.seppenwoolde@erasmusmc.nl [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Heijmen, Ben J.M. [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

2013-12-01

Purpose: To investigate how dose distributions for liver stereotactic body radiation therapy (SBRT) can be improved by using automated, daily plan reoptimization to account for anatomy deformations, compared with setup corrections only. Methods and Materials: For 12 tumors, 3 strategies for dose delivery were simulated. In the first strategy, computed tomography scans made before each treatment fraction were used only for patient repositioning before dose delivery for correction of detected tumor setup errors. In adaptive second and third strategies, in addition to the isocenter shift, intensity modulated radiation therapy beam profiles were reoptimized or both intensity profiles and beam orientations were reoptimized, respectively. All optimizations were performed with a recently published algorithm for automated, multicriteria optimization of both beam profiles and beam angles. Results: In 6 of 12 cases, violations of organs at risk (ie, heart, stomach, kidney) constraints of 1 to 6 Gy in single fractions occurred in cases of tumor repositioning only. By using the adaptive strategies, these could be avoided (<1 Gy). For 1 case, this needed adaptation by slightly underdosing the planning target volume. For 2 cases with restricted tumor dose in the planning phase to avoid organ-at-risk constraint violations, fraction doses could be increased by 1 and 2 Gy because of more favorable anatomy. Daily reoptimization of both beam profiles and beam angles (third strategy) performed slightly better than reoptimization of profiles only, but the latter required only a few minutes of computation time, whereas full reoptimization took several hours. Conclusions: This simulation study demonstrated that replanning based on daily acquired computed tomography scans can improve liver stereotactic body radiation therapy dose delivery.

Automated system for crack detection using infrared thermograph

International Nuclear Information System (INIS)

Starman, Stanislav

2009-01-01

The objective of this study was the development of the automated system for crack detection on square steel bars used in the automotive industry for axle and shaft construction. The automated system for thermographic crack detection uses brief pulsed eddy currents to heat steel components under inspection. Cracks, if present, will disturb the current flow and so generate changes in the temperature profile in the crack area. These changes of temperature are visualized using an infrared camera. The image acquired by the infrared camera is evaluated through an image processing system. The advantages afforded by the system are its inspection time, its excellent flaw detection sensitivity and its ability to detect hidden, subsurface cracks. The automated system consists of four IR cameras (each side of steel bar is evaluated at a time), coil, high frequency generator and control place with computers. The system is a part of the inspection line where the subsurface and surface cracks are searched. If the crack is present, the cracked place is automatically marked. The components without cracks are then deposited apart from defective blocks. The system is fully automated and its ability is to evaluate four meter blocks within 20 seconds. This is the real reason for using this system in real industrial applications. (author)

Automated transmission system operation and management : meeting stakeholder information needs

Energy Technology Data Exchange (ETDEWEB)

Peelo, D.F.; Toom, P.O. [British Columbia Hydro, Vancouver, BC (Canada)

1998-12-01

Information monitoring is considered to be the fundamental basis for moving beyond substation automation and into automated transmission system operation and management. Information monitoring was defined as the acquisition of data and processing the data into decision making. Advances in digital technology and cheaper, more powerful computing capability has made it possible to capture all transmission stakeholder needs in a shared and automated operation and management system. Recognizing that the key to success in the development of transmission systems is automation, BC Hydro has initiated a long-term research and development project to develop the structure and detail of transmission system automation. The involvement of partners, be they utility or equipment suppliers, is essential in order to deal with protocol and similar issues. 3 refs., 1 tab., 3 figs.

Self-assembling bubble carriers for oral protein delivery.

Science.gov (United States)

Chuang, Er-Yuan; Lin, Kun-Ju; Lin, Po-Yen; Chen, Hsin-Lung; Wey, Shiaw-Pyng; Mi, Fwu-Long; Hsiao, Hsu-Chan; Chen, Chiung-Tong; Sung, Hsing-Wen

2015-09-01

Successful oral delivery of therapeutic proteins such as insulin can greatly improve the quality of life of patients. This study develops a bubble carrier system by loading diethylene triamine pentaacetic acid (DTPA) dianhydride, a foaming agent (sodium bicarbonate; SBC), a surfactant (sodium dodecyl sulfate; SDS), and a protein drug (insulin) in an enteric-coated gelatin capsule. Following oral administration to diabetic rats, the intestinal fluid that has passed through the gelatin capsule saturates the mixture; concomitantly, DTPA dianhydride produces an acidic environment, while SBC decomposes to form CO2 bubbles at acidic pH. The gas bubbles grow among the surfactant molecules (SDS) owing to the expansion of the generated CO2. The walls of the CO2 bubbles consist of a self-assembled film of water that is in nanoscale and may serve as a colloidal carrier to transport insulin and DTPA. The grown gas bubbles continue to expand until they bump into the wall and burst, releasing their transported insulin, DTPA, and SDS into the mucosal layer. The released DTPA and SDS function as protease inhibitors to protect the insulin molecules as well as absorption enhancers to augment their epithelial permeability and eventual absorption into systemic circulation, exerting their hypoglycemic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automated Car Park Management System

Science.gov (United States)

Fabros, J. P.; Tabañag, D.; Espra, A.; Gerasta, O. J.

2015-06-01

This study aims to develop a prototype for an Automated Car Park Management System that will increase the quality of service of parking lots through the integration of a smart system that assists motorist in finding vacant parking lot. The research was based on implementing an operating system and a monitoring system for parking system without the use of manpower. This will include Parking Guidance and Information System concept which will efficiently assist motorists and ensures the safety of the vehicles and the valuables inside the vehicle. For monitoring, Optical Character Recognition was employed to monitor and put into list all the cars entering the parking area. All parking events in this system are visible via MATLAB GUI which contain time-in, time-out, time consumed information and also the lot number where the car parks. To put into reality, this system has a payment method, and it comes via a coin slot operation to control the exit gate. The Automated Car Park Management System was successfully built by utilizing microcontrollers specifically one PIC18f4550 and two PIC16F84s and one PIC16F628A.

Pitfalls of insulin pump clocks: technical glitches that may potentially affect medical care in patients with diabetes.

Science.gov (United States)

Aldasouqi, Saleh A; Reed, Amy J

2014-11-01

The objective was to raise awareness about the importance of ensuring that insulin pumps internal clocks are set up correctly at all times. This is a very important safety issue because all commercially available insulin pumps are not GPS-enabled (though this is controversial), nor equipped with automatically adjusting internal clocks. Special attention is paid to how basal and bolus dose errors can be introduced by daylight savings time changes, travel across time zones, and am-pm clock errors. Correct setting of insulin pump internal clock is crucial for appropriate insulin delivery. A comprehensive literature review is provided, as are illustrative cases. Incorrect setting can potentially result in incorrect insulin delivery, with potential harmful consequences, if too much or too little insulin is delivered. Daylight saving time changes may not significantly affect basal insulin delivery, given the triviality of the time difference. However, bolus insulin doses can be dramatically affected. Such problems may occur when pump wearers have large variations in their insulin to carb ratio, especially if they forget to change their pump clock in the spring. More worrisome than daylight saving time change is the am-pm clock setting. If this setting is set up incorrectly, both basal rates and bolus doses will be affected. Appropriate insulin delivery through insulin pumps requires correct correlation between dose settings and internal clock time settings. Because insulin pumps are not GPS-enabled or automatically time-adjusting, extra caution should be practiced by patients to ensure correct time settings at all times. Clinicians and diabetes educators should verify the date/time of insulin pumps during patients' visits, and should remind their patients to always verify these settings. © 2014 Diabetes Technology Society.

Oral Insulin – Fact or Fiction? - Possibilities of Achieving Oral ...

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 5. Oral Insulin – Fact or Fiction? - Possibilities of Achieving Oral Delivery of Insulin. K Gowthamarajan Giriraj T Kulkarni. General Article Volume 8 Issue 5 May 2003 pp 38-46 ...

Home Automation and Security System Using Android ADK

OpenAIRE

Deepali Javale; Mohd. Mohsin; Shreerang Nandanwar; Mayur Shingate

2013-01-01

Today we are living in 21st century where automation is playing important role in human life. Home automation allows us to control household appliances like light, door, fan, AC etc. It also provides home security and emergency system to be activated. Home automation not only refers to reduce human efforts but also energy efficiency and time saving. The main objective of home automation and security is to help handicapped and old aged people which will enable them to control home appliances a...

DOMOTICS Aplicability and home automation systems

Directory of Open Access Journals (Sweden)

César Luiz de Azevedo Dias

2010-05-01

Full Text Available This article discusses the benefits and applicability of domestic automation, also known as Domotics. According to Domotics Integration Project (DIP, Domotics or smart house technology is the integration of services and technologies applied to homes, flats, apartments, houses and small buildings with the purpose of automating them and obtaining and increasing safety and security, comfort, communication and technical management. This papper also presents a summary of the elements which may be part of a “smart home”, the advantages given by its integration and, illustrations of various systems and technologies applied to domestic automation that have achieved both national and international commercial relevance.

Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy

Directory of Open Access Journals (Sweden)

Jacques Lepercq

2012-01-01

Full Text Available As glargine, an analog of human insulin, is increasingly used during pregnancy, a meta-analysis assessed its safety in this population. A systematic literature search identified studies of gestational or pregestational diabetes comparing use of insulin glargine with human NPH insulin, with at least 15 women in both arms. Data was extracted for maternal outcomes (weight at delivery, weight gain, 1st/3rd trimester HbA1c, severe hypoglycemia, gestation/new-onset hypertension, preeclampsia, and cesarean section and neonatal outcomes (congenital malformations, gestational age at delivery, birth weight, macrosomia, LGA, 5 minute Apgar score >7, NICU admissions, respiratory distress syndrome, neonatal hypoglycemia, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were determined using a random effect model. Eight studies of women using glargine (331 or NPH (371 were analyzed. No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during pregnancy.

Secure Automated Microgrid Energy System

Science.gov (United States)

2016-12-01

O&M Operations and Maintenance PSO Power System Optimization PV Photovoltaic RAID Redundant Array of Independent Disks RBAC Role...elements of the initial study and operational power system model (feeder size , protective devices, generation sources, controllable loads, transformers...EW-201340) Secure Automated Microgrid Energy System December 2016 This document has been cleared for public release; Distribution Statement A

Automated systems to identify relevant documents in product risk management

Science.gov (United States)

2012-01-01

Background Product risk management involves critical assessment of the risks and benefits of health products circulating in the market. One of the important sources of safety information is the primary literature, especially for newer products which regulatory authorities have relatively little experience with. Although the primary literature provides vast and diverse information, only a small proportion of which is useful for product risk assessment work. Hence, the aim of this study is to explore the possibility of using text mining to automate the identification of useful articles, which will reduce the time taken for literature search and hence improving work efficiency. In this study, term-frequency inverse document-frequency values were computed for predictors extracted from the titles and abstracts of articles related to three tumour necrosis factors-alpha blockers. A general automated system was developed using only general predictors and was tested for its generalizability using articles related to four other drug classes. Several specific automated systems were developed using both general and specific predictors and training sets of different sizes in order to determine the minimum number of articles required for developing such systems. Results The general automated system had an area under the curve value of 0.731 and was able to rank 34.6% and 46.2% of the total number of 'useful' articles among the first 10% and 20% of the articles presented to the evaluators when tested on the generalizability set. However, its use may be limited by the subjective definition of useful articles. For the specific automated system, it was found that only 20 articles were required to develop a specific automated system with a prediction performance (AUC 0.748) that was better than that of general automated system. Conclusions Specific automated systems can be developed rapidly and avoid problems caused by subjective definition of useful articles. Thus the efficiency of

Skeletal Muscle Insulin Resistance in Endocrine Disease

Directory of Open Access Journals (Sweden)

Melpomeni Peppa

2010-01-01

Full Text Available We summarize the existing literature data concerning the involvement of skeletal muscle (SM in whole body glucose homeostasis and the contribution of SM insulin resistance (IR to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS, adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism.

Improved insulin loading in poly (lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids

DEFF Research Database (Denmark)

Garcia Diaz, Maria; Foged, Camilla; Nielsen, Hanne Mørck

2015-01-01

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading...... of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique...... efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid–insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer...

Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

Science.gov (United States)

2012-05-16

This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

Biomek Cell Workstation: A Variable System for Automated Cell Cultivation.

Science.gov (United States)

Lehmann, R; Severitt, J C; Roddelkopf, T; Junginger, S; Thurow, K

2016-06-01

Automated cell cultivation is an important tool for simplifying routine laboratory work. Automated methods are independent of skill levels and daily constitution of laboratory staff in combination with a constant quality and performance of the methods. The Biomek Cell Workstation was configured as a flexible and compatible system. The modified Biomek Cell Workstation enables the cultivation of adherent and suspension cells. Until now, no commercially available systems enabled the automated handling of both types of cells in one system. In particular, the automated cultivation of suspension cells in this form has not been published. The cell counts and viabilities were nonsignificantly decreased for cells cultivated in AutoFlasks in automated handling. The proliferation of manual and automated bioscreening by the WST-1 assay showed a nonsignificant lower proliferation of automatically disseminated cells associated with a mostly lower standard error. The disseminated suspension cell lines showed different pronounced proliferations in descending order, starting with Jurkat cells followed by SEM, Molt4, and RS4 cells having the lowest proliferation. In this respect, we successfully disseminated and screened suspension cells in an automated way. The automated cultivation and dissemination of a variety of suspension cells can replace the manual method. © 2015 Society for Laboratory Automation and Screening.

Progress of artificial pancreas devices towards clinical use: the first outpatient studies.

Science.gov (United States)

Russell, Steven J

2015-04-01

This article describes recent progress in the automated control of glycemia in type 1 diabetes with artificial pancreas devices that combine continuous glucose monitoring with automated decision-making and insulin delivery. After a gestation period of closely supervised feasibility studies in research centers, the last 2 years have seen publication of studies testing these devices in outpatient environments, and many more such studies are ongoing. The most basic form of automation, suspension of insulin delivery for actual or predicted hypoglycemia, has been shown to be effective and well tolerated, and a first-generation device has actually reached the market. Artificial pancreas devices that actively dose insulin fall into two categories, those that dose insulin alone and those that also use glucagon to prevent and treat hypoglycemia (bihormonal artificial pancreas). Initial outpatient clinical trials have shown that both strategies can improve glycemic management in comparison with patient-controlled insulin pump therapy, but only the bihormonal strategy has been tested without restrictions on exercise. Artificial pancreas technology has the potential to reduce acute and chronic complications of diabetes and mitigate the burden of diabetes self-management. Successful outpatient studies bring these technologies one step closer to availability for patients.

The regulatory system for diabetes mellitus: Modeling rates of glucose infusions and insulin injections

Science.gov (United States)

Yang, Jin; Tang, Sanyi; Cheke, Robert A.

2016-08-01

Novel mathematical models with open and closed-loop control for type 1 or type 2 diabetes mellitus were developed to improve understanding of the glucose-insulin regulatory system. A hybrid impulsive glucose-insulin model with different frequencies of glucose infusions and insulin injections was analyzed, and the existence and uniqueness of the positive periodic solution for type 1 diabetes, which is globally asymptotically stable, was studied analytically. Moreover, permanence of the system for type 2 diabetes was demonstrated which showed that the glucose concentration level is uniformly bounded above and below. To investigate how to prevent hyperinsulinemia and hyperglycemia being caused by this system, we developed a model involving periodic intakes of glucose with insulin injections applied only when the blood glucose level reached a given critical glucose threshold. In addition, our numerical analysis revealed that the period, the frequency and the dose of glucose infusions and insulin injections are crucial for insulin therapies, and the results provide clinical strategies for insulin-administration practices.

Automating large-scale reactor systems

International Nuclear Information System (INIS)

Kisner, R.A.

1985-01-01

This paper conveys a philosophy for developing automated large-scale control systems that behave in an integrated, intelligent, flexible manner. Methods for operating large-scale systems under varying degrees of equipment degradation are discussed, and a design approach that separates the effort into phases is suggested. 5 refs., 1 fig

Levodopa delivery systems: advancements in delivery of the gold standard.

Science.gov (United States)

Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

2010-02-01

Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the

Towards a characterization of information automation systems on the flight deck

Science.gov (United States)

Dudley, Rachel Feddersen

This thesis summarizes research to investigate the characteristics that define information automation systems used on aircraft flight decks and the significant impacts that these characteristics have on pilot performance. Major accomplishments of the work include the development of a set of characteristics that describe information automation systems on the flight deck and an experiment designed to study a subset of these characteristics. Information automation systems on the flight deck are responsible for the collection, processing, analysis, and presentation of data to the flightcrew. These systems pose human factors issues and challenges that must be considered by designers of these systems. Based on a previously developed formal definition of information automation for aircraft flight deck systems, an analysis process was developed and conducted to reach a refined set of information automation characteristics. In this work, characteristics are defined as a set of properties or attributes that describe an information automation system's operation or behavior, which can be used to identify and assess potential human factors issues. Hypotheses were formed for a subset of the characteristics: Automation Visibility, Information Quality, and Display Complexity. An experimental investigation was developed to measure performance impacts related to these characteristics, which showed mixed results of expected and surprising findings, with many interactions. A set of recommendations were then developed based on the experimental observations. Ensuring that the right information is presented to pilots at the right time and in the appropriate manner is the job of flight deck system designers. This work provides a foundation for developing recommendations and guidelines specific to information automation on the flight deck with the goal of improving the design and evaluation of information automation systems before they are implemented.

Automated discovery systems and the inductivist controversy

Science.gov (United States)

Giza, Piotr

2017-09-01

The paper explores possible influences that some developments in the field of branches of AI, called automated discovery and machine learning systems, might have upon some aspects of the old debate between Francis Bacon's inductivism and Karl Popper's falsificationism. Donald Gillies facetiously calls this controversy 'the duel of two English knights', and claims, after some analysis of historical cases of discovery, that Baconian induction had been used in science very rarely, or not at all, although he argues that the situation has changed with the advent of machine learning systems. (Some clarification of terms machine learning and automated discovery is required here. The key idea of machine learning is that, given data with associated outcomes, software can be trained to make those associations in future cases which typically amounts to inducing some rules from individual cases classified by the experts. Automated discovery (also called machine discovery) deals with uncovering new knowledge that is valuable for human beings, and its key idea is that discovery is like other intellectual tasks and that the general idea of heuristic search in problem spaces applies also to discovery tasks. However, since machine learning systems discover (very low-level) regularities in data, throughout this paper I use the generic term automated discovery for both kinds of systems. I will elaborate on this later on). Gillies's line of argument can be generalised: thanks to automated discovery systems, philosophers of science have at their disposal a new tool for empirically testing their philosophical hypotheses. Accordingly, in the paper, I will address the question, which of the two philosophical conceptions of scientific method is better vindicated in view of the successes and failures of systems developed within three major research programmes in the field: machine learning systems in the Turing tradition, normative theory of scientific discovery formulated by Herbert Simon

Impact of lipid-based drug delivery systems on the transport and uptake of insulin across Caco-2 Cell monolayers

DEFF Research Database (Denmark)

Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

2016-01-01

Self-(nano)-emulsifying drug delivery systems (SNEDDSs) used to deliver peptides and proteins across biological barriers, such as the small intestinal membrane, represents an increasingly interesting field in nanomedicine. Hence, the present study was designed to evaluate the impact of SNEDDS...

Computer automation of a dilution cryogenic system

International Nuclear Information System (INIS)

Nogues, C.

1992-09-01

This study has been realized in the framework of studies on developing new technic for low temperature detectors for neutrinos and dark matter. The principles of low temperature physics and helium 4 and dilution cryostats, are first reviewed. The cryogenic system used and the technic for low temperature thermometry and regulation systems are then described. The computer automation of the dilution cryogenic system involves: numerical measurement of the parameter set (pressure, temperature, flow rate); computer assisted operating of the cryostat and the pump bench; numerical regulation of pressure and temperature; operation sequence full automation allowing the system to evolve from a state to another (temperature descent for example)

A closed-loop anesthetic delivery system for real-time control of burst suppression

Science.gov (United States)

Liberman, Max Y.; Ching, ShiNung; Chemali, Jessica; Brown, Emery N.

2013-08-01

Objective. There is growing interest in using closed-loop anesthetic delivery (CLAD) systems to automate control of brain states (sedation, unconsciousness and antinociception) in patients receiving anesthesia care. The accuracy and reliability of these systems can be improved by using as control signals electroencephalogram (EEG) markers for which the neurophysiological links to the anesthetic-induced brain states are well established. Burst suppression, in which bursts of electrical activity alternate with periods of quiescence or suppression, is a well-known, readily discernible EEG marker of profound brain inactivation and unconsciousness. This pattern is commonly maintained when anesthetics are administered to produce a medically-induced coma for cerebral protection in patients suffering from brain injuries or to arrest brain activity in patients having uncontrollable seizures. Although the coma may be required for several hours or days, drug infusion rates are managed inefficiently by manual adjustment. Our objective is to design a CLAD system for burst suppression control to automate management of medically-induced coma. Approach. We establish a CLAD system to control burst suppression consisting of: a two-dimensional linear system model relating the anesthetic brain level to the EEG dynamics; a new control signal, the burst suppression probability (BSP) defining the instantaneous probability of suppression; the BSP filter, a state-space algorithm to estimate the BSP from EEG recordings; a proportional-integral controller; and a system identification procedure to estimate the model and controller parameters. Main results. We demonstrate reliable performance of our system in simulation studies of burst suppression control using both propofol and etomidate in rodent experiments based on Vijn and Sneyd, and in human experiments based on the Schnider pharmacokinetic model for propofol. Using propofol, we further demonstrate that our control system reliably

Pathways for insulin access to the brain: the role of the microvascular endothelial cell

OpenAIRE

Meijer, Rick I.; Gray, Sarah M.; Aylor, Kevin W.; Barrett, Eugene J.

2016-01-01

New understanding of the directional flow of subarachnoid cerebrospinal fluid (CSF) through the Virchow-Robin space (VRS) to brain parenchyma, coupled with the demonstration here of rapid, insulin receptor-dependent trapping of plasma insulin by the brain microvasculature, underscores the direct role of insulin's blood-brain barrier transit to insulin delivery to the brain.

Automated Podcasting System for Universities

Directory of Open Access Journals (Sweden)

Ypatios Grigoriadis

2013-03-01

Full Text Available This paper presents the results achieved at Graz University of Technology (TU Graz in the field of automating the process of recording and publishing university lectures in a very new way. It outlines cornerstones of the development and integration of an automated recording system such as the lecture hall setup, the recording hardware and software architecture as well as the development of a text-based search for the final product by method of indexing video podcasts. Furthermore, the paper takes a look at didactical aspects, evaluations done in this context and future outlook.

Insulin-loaded polymeric mucoadhesive nanoparticles: development, characterization and cytotoxicity evaluation

Directory of Open Access Journals (Sweden)

Tiago Henrique Honorato Gatti

2018-06-01

Full Text Available Abstract Mucoadhesive nanoparticles are particularly interesting for delivery through nasal or pulmonary routes, as an approach to overcome the mucociliary clearance. Moreover, these nanoparticles are attractive for peptide and protein delivery, particularly for insulin to treat diabetes, as an alternative to conventional parenteral administration. Thus, chitosan, a cationic mucoadhesive polysaccharide found in shells of crustaceans, and the negatively-charged dextran sulfate are able to form nanoparticles through ionic condensation, representing a potential insulin carrier. Herein, chitosan/dextran sulfate nanoparticles at various ratios were prepared for insulin loading. Formulations were characterized for particle size, zeta potential, encapsulation efficiency, scanning electron microscopy, differential scanning calorimetry, and in vitro drug release. Moreover, the interaction with mucin and the cytotoxicity against a lung cell line were studied, which altogether have not been addressed before. Results evidenced that a proper selection of polyelectrolytes is necessary for smaller particle size formation and also the composition and zeta potential impact encapsulation efficiency, which is benefited by the positive charge of chitosan. Insulin remained stable after encapsulation as evidenced by calorimetric assays, and was released in a sustained manner in the first 10 h. Positively-charged nanoparticles based on chitosan/dextran-sulfate at the ratio of 6:4 successfully interacted with mucin, which is a prerequisite for delivery to mucus-containing tissues. Finally, insulin-loaded nanoparticles displayed no cytotoxicity effect against lung cells at tested concentrations, suggesting the potential for further in vivo studies.

Mucosal delivery of liposome-chitosan nanoparticle complexes.

Science.gov (United States)

Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

2009-01-01

Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

Ion-Responsive Drug Delivery Systems.

Science.gov (United States)

Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

2018-02-08

Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Software complex AS (automation of spectrometry). User interface of experiment automation system implementation

International Nuclear Information System (INIS)

Astakhova, N.V.; Beskrovnyj, A.I.; Bogdzel', A.A.; Butorin, P.E.; Vasilovskij, S.G.; Gundorin, N.A.; Zlokazov, V.B.; Kutuzov, S.A.; Salamatin, I.M.; Shvetsov, V.N.

2003-01-01

An instrumental software complex for automation of spectrometry (AS) that enables prompt realization of experiment automation systems for spectrometers, which use data buferisation, has been developed. In the development new methods of programming and building of automation systems together with novel net technologies were employed. It is suggested that programs to schedule and conduct experiments should be based on the parametric model of the spectrometer, the approach that will make it possible to write programs suitable for any FLNP (Frank Laboratory of Neutron Physics) spectrometer and experimental technique applied and use different hardware interfaces for introducing the spectrometric data into the data acquisition system. The article describes the possibilities provided to the user in the field of scheduling and control of the experiment, data viewing, and control of the spectrometer parameters. The possibility of presenting the current spectrometer state, programs and the experimental data in the Internet in the form of dynamically formed protocols and graphs, as well as of the experiment control via the Internet is realized. To use the means of the Internet on the side of the client, applied programs are not needed. It suffices to know how to use the two programs to carry out experiments in the automated mode. The package is designed for experiments in condensed matter and nuclear physics and is ready for using. (author)