The course of diabetic retinopathy during treatment with continuous subcutaneous insulin infusion

NARCIS (Netherlands)

Hooymans, Johanna Martina Maria

1986-01-01

The aim of this prospective study was to investigate the effect of normalization of blood sugar regulation by continuous subcutaneous insulin infusion (CSII) on the course of diabetic retinopathy in insulin-dependent (type I) diabetic patients. Zie: Summary

Effect of subcutaneous injection of insulin on 18F-FDG myocardial imaging in diabetics

International Nuclear Information System (INIS)

Tian Yueqin; Shi Rongfang; Guo Feng; Wei Hongxing; Wu Qingwen; Liu Xiujie

2001-01-01

Objective: To evaluate the effect of subcutaneous injection of insulin on 18 F-fluorodeoxyglucose (FDG) myocardial imaging in patients with diabetes mellitus. Methods: Fifty-seven patients with coronary artery disease complicated with diabetes mellitus [mean age (60 +- 8) years] underwent 18 F-FDG PET and dual isotope simultaneous acquisition SPECT with 99 Tc m -MIBI/ 18 F-FDG. Thirty minutes before FDG injection, blood glucose was measured with an automatic glucose analyzer and insulin was subcutaneously used, the dose was adjusted according to the level of blood glucose. Results: Regression analysis showed that the insulin was positively associated with blood glucose. The linear regression analysis showed that the correlation between dose of insulin (y) and blood glucose (x) was good, r 0.8172; the linear regression equation was y = -5.4 + 1.2x. 52 of 57 images were of good quality with 91% success rate. Conclusion: Subcutaneous injection of insulin is an effective and simple method for obtaining cardiac FDG images of good quality in patients with diabetes mellitus

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.

Continuous subcutaneous insulin infusion versus multiple daily injections: the impact of baseline A1c

NARCIS (Netherlands)

Retnakaran, Ravi; Hochman, Jackie; DeVries, J. Hans; Hanaire-Broutin, Helene; Heine, Robert J.; Melki, Vincent; Zinman, Bernard

2004-01-01

Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be

Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin in liposomes

International Nuclear Information System (INIS)

Stevenson, R.W.; Patel, H.M.; Parsons, J.A.; Ryman, B.E.

1982-01-01

The biologic action of insulin entrapped in liposomes (phospholipid vesicles) has been investigated following subcutaneous injection to dogs made diabetic with a combination of alloxan and streptozotocin. The fate of the liposomally entrapped material was determined by injecting rats subcutaneously with either 125 I-insulin or the labeled polysaccharide 14 C-inulin, incorporated in liposomes labeled with 3 H-cholesterol. Injection of liposome insulin (0.75 U/kg) to five diabetic dogs resulted in a mean (+/- SEM) blood glucose fall from 16.4 +/- 0.8 to 2.9 +/- 0.4 mmol/L. The glucose level had still not returned to baseline after 24 h and, correspondingly, immunoreactive insulin (IRI) could still be detected in frozen and thawed plasma 24 h after injection. In contrast, the hypoglycemic effect of the same dose of free insulin with or without empty liposomes virtually ended within 8 h and IRI levels returned to baseline by 3 h after injection. In experiments on rats with liposomally entrapped 125 I-insulin or 14 C-inulin the proportion of the injected dose of tracer recoverable by excision of the injection site remained constant after about 1 h and 70% of the dose was still fixed in subcutaneous tissue for at least 5 h thereafter. When the plasma collected 3 h after subcutaneous injection of labeled liposomes containing 125 I-insulin was passed through a column of Sepharose 6B, 50-75% of the 125 I-activity was found in the fractions associated with intact liposomes. One possibility for the persistence of the hypoglycemic effect and of measurable IRI following injection of liposome insulin could be the presence of intact liposomes in the circulation for many hours after adsorption had ceased

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

Science.gov (United States)

Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

2016-01-27

The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose

Imaging characteristics of subcutaneous amyloid deposits in diabetic patients: the ''insulin ball''

Energy Technology Data Exchange (ETDEWEB)

Tanio, Noriko; Nozaki, Taiki; Matsusako, Masaki; Starkey, Jay [St. Luke' s International Hospital, Department of Radiology, Tokyo (Japan); Suzuki, Koyu [St. Luke' s International Hospital, Department of Pathology, Tokyo (Japan)

2018-01-15

The purpose of this study was to describe the imaging characteristics of subcutaneous amyloid deposits occurring at sites of insulin injection, commonly known as ''insulin balls,'' in diabetic patients on ultrasound, CT, and MRI with pathologic correlation. We retrospectively reviewed the radiographic findings of 14 lesions in 9 patients diagnosed with subcutaneous amyloid deposits at our institution between 2005-2015. Three board-certified radiologists analyzed the following: (1) the shape, size, margin, morphologic characteristics, and blood flow on US using the color Doppler signal, (2) shape, size, margin, attenuation, and presence or absence of contrast enhancement on CT, and (3) shape, size, margin, signal intensity, and presence or absence of contrast enhancement on MRI. All lesions showed ill-defined hypovascular subcutaneous nodules with irregular margins. The median diameter of lesions was 50.4 mm on US, 46.8 mm on CT, and 51.4 mm on MRI. The internal echogenicity of subcutaneous amyloid deposits was hypoechoic and heterogeneous on US. All lesions showed isodensity compared to muscle with irregular margins and minimal contrast enhancement on CT. Both T1- and T2-weighted MR images showed low signal intensity compared with subcutaneous fat. Normal diffusion and minimal contrast enhancement were seen. Subcutaneous amyloid deposits which cause insulin resistance are typically ill-defined and heterogeneous hypovascular subcutaneous nodules with irregular margins on imaging that correspond to insulin injection sites. It is also characteristic that T2WI shows low intensity compared with fat on MRI, reflective of the amyloid content. (orig.)

Imaging characteristics of subcutaneous amyloid deposits in diabetic patients: the ''insulin ball''

International Nuclear Information System (INIS)

Tanio, Noriko; Nozaki, Taiki; Matsusako, Masaki; Starkey, Jay; Suzuki, Koyu

2018-01-01

The purpose of this study was to describe the imaging characteristics of subcutaneous amyloid deposits occurring at sites of insulin injection, commonly known as ''insulin balls,'' in diabetic patients on ultrasound, CT, and MRI with pathologic correlation. We retrospectively reviewed the radiographic findings of 14 lesions in 9 patients diagnosed with subcutaneous amyloid deposits at our institution between 2005-2015. Three board-certified radiologists analyzed the following: (1) the shape, size, margin, morphologic characteristics, and blood flow on US using the color Doppler signal, (2) shape, size, margin, attenuation, and presence or absence of contrast enhancement on CT, and (3) shape, size, margin, signal intensity, and presence or absence of contrast enhancement on MRI. All lesions showed ill-defined hypovascular subcutaneous nodules with irregular margins. The median diameter of lesions was 50.4 mm on US, 46.8 mm on CT, and 51.4 mm on MRI. The internal echogenicity of subcutaneous amyloid deposits was hypoechoic and heterogeneous on US. All lesions showed isodensity compared to muscle with irregular margins and minimal contrast enhancement on CT. Both T1- and T2-weighted MR images showed low signal intensity compared with subcutaneous fat. Normal diffusion and minimal contrast enhancement were seen. Subcutaneous amyloid deposits which cause insulin resistance are typically ill-defined and heterogeneous hypovascular subcutaneous nodules with irregular margins on imaging that correspond to insulin injection sites. It is also characteristic that T2WI shows low intensity compared with fat on MRI, reflective of the amyloid content. (orig.)

Insulin resistance in multiple tissues in patients with type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion therapy

NARCIS (Netherlands)

Donga, Esther; van Dijk, Marieke [Leiden Univ., LUMC; Hoogma, Roel P. L. M.; Corssmit, Eleonora P. M.; Romijn, Johannes A.

2013-01-01

The aim of this study was to determine whether insulin resistance is present in lean patients with uncomplicated type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion (CSII), compared with matched healthy controls. We studied eight patients (four men and four women) with

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

Science.gov (United States)

Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

1991-07-01

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Continuous subcutaneous insulin infusion preserves axonal function in type 1 diabetes mellitus.

Science.gov (United States)

Kwai, Natalie; Arnold, Ria; Poynten, Ann M; Lin, Cindy S-Y; Kiernan, Matthew C; Krishnan, Arun V

2015-02-01

Diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. Although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown. In the present study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical neurological assessment. Subsequently, 41 non-neuropathic patients, 24 of whom were receiving multiple daily insulin injections (MDII) and 17 receiving continuous subcutaneous insulin infusion (CSII), underwent nerve excitability testing, a technique that assesses axonal ion channel function and membrane potential in human nerves. Treatment groups were matched for glycaemic control, body mass index, disease duration and gender. Neurophysiological parameters were compared between treatment groups and those taken from age and sex-matched normal controls. Prominent differences in axonal function were noted between MDII-treated and CSII-treated patients. Specifically, MDII patients manifested prominent abnormalities when compared with normal controls in threshold electrotonus (TE) parameters including depolarizing TE(10-20ms), undershoot and hyperpolarizing TE (90-100 ms) (P type 1 diabetes is maintained within normal limits in patients treated with continuous subcutaneous insulin infusion and not with multiple daily insulin injections. This raises the possibility that CSII therapy may have neuroprotective potential in patients with type 1 diabetes. Copyright © 2014 John Wiley & Sons, Ltd.

Implementation of subcutaneous insulin protocol for non-critically ill hospitalized patients in andalusian tertiary care hospitals.

Science.gov (United States)

Martínez-Brocca, María Asunción; Morales, Cristóbal; Rodríguez-Ortega, Pilar; González-Aguilera, Beatriz; Montes, Cristina; Colomo, Natalia; Piédrola, Gonzalo; Méndez-Muros, Mariola; Serrano, Isabel; Ruiz de Adana, Maria Soledad; Moreno, Alberto; Fernández, Ignacio; Aguilar, Manuel; Acosta, Domingo; Palomares, Rafael

2015-02-01

In 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). To analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. A descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n=306) hospitalized for ≥48 hours in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. 288 patients were included for analysis (62.5% males; 70.3±10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5-61.2%) of patients, 63.1% SM vs. 37.8% SQ (P<.05). Alternatives to insulin regimen based on basal-bolus-correction included sliding scale insulin (43.7%), diet (31.3%), oral antidiabetic drugs (17.2%), premixed insulin (1.6%), and others (6.2%). For patients previously on oral antidiabetic drugs, in-hospital insulin dose was 0.32±0.1 IU/kg/day. In patients previously on insulin, in-hospital insulin dose was increased by 17% [-13-53], and in those on insulin plus oral antidiabetic drugs, in-hospital insulin dose was increased by 26.4% [-6-100]. Supplemental insulin doses used for<40 IU/day and 40-80 IU/day were 72.2% and 56.7% respectively. HbA1c was measured in 23.6% of patients (95CI%: 18.8-28.8); 27.7% SM vs. 13.3% SQ (P<.05). Strategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Biotelemetric detection of the disappearance of subcutaneously injected /sup 125/I-NPH insulin

Energy Technology Data Exchange (ETDEWEB)

Kolendorf, K; Bojsen, J

1982-02-01

A biotelemetric method with Geiger-Mueller (GM) detectors fixed to the skin surface was used for continuous registration of the disappearance rate of subcutaneously injected /sup 125/I-NPH insulin. Methodological problems concerning counting geometry were investigated by comparing the disappearance of radioactivity, measured the GM- and NaI-detectors, respectively, and by scanning of the radioactive source. The size and position of the subcutaneous depot was unchanged throughout the study. Movement artifacts could be avoided. The coefficient of variation for distribution of ratios between count rates for GM- and NaI-detectors was 3.0% +/- 1.1 (SD) (range 0.9-4.0%) over periods of 24 h. It is concluded that the biotelemetry technique proved to be a clinically useful procedure for insulin absorption studies.

Effect of continuous subcutaneous insulin pump infusion on glucolipid metabolism as well as inflammation and oxidative stress in placenta of patients with GDM

Directory of Open Access Journals (Sweden)

Liu Jie

2017-05-01

Full Text Available Objective: To study the effect of continuous subcutaneous insulin pump infusion on glucolipid metabolism as well as inflammation and oxidative stress in placenta of patients with gestational diabetes mellitus (GDM. Methods: Patients with GDM who received insulin therapy between March 2013 and May 2016 were selected as the research subjects and randomly divided into multiple subcutaneous insulin injection (MSII group and continuous subcutaneous insulin pump infusion (CSII group. Before and after treatment, serum glucolipid metabolism as well as inflammation and oxidative stress inexes in placenta were determined respectively. Results: 2 weeks and 4 weeks after treatment, FBG, 1hPBG, 2hPBG, Chemerin, Vaspin and Visfatin levels of both groups of patients were significantly lower than those before treatment and FBG, 1hPBG, 2hPBG, Chemerin, Vaspin and Visfatin levels of CSII group were significantly lower than those of MSII group; after delivery, TNF-α, IL-6, ROS and AGEs levels in placenta of CSII group were significantly lower than those of MSII group. Conclusion: Continuous subcutaneous insulin infusion can more effectively improve the glucolipid metabolism and inhibit the inflammation and oxidative stress in placenta of patients with GDM than multiple subcutaneous insulin injection.

Continuous intraperitoneal insulin infusion in the treatment of type 1 diabetes mellitus: Glycaemia and beyond

OpenAIRE

van Dijk, Peter R.

2015-01-01

Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a last-resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As compared to the most commonly used forms of insulin administration -injections and an externally placed pump- which deliver insulin in the subcutaneous (SC) tissue, CIPII delivers the insulin in the intraperitoneal space. CIPII using an implantable pump is an unique treatment which has been available for more than 30 year...

Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

Science.gov (United States)

Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

2009-01-01

Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as

Sustained Treatment with Insulin Detemir in Mice Alters Brain Activity and Locomotion.

Directory of Open Access Journals (Sweden)

Tina Sartorius

Full Text Available Recent studies have identified unique brain effects of insulin detemir (Levemir®. Due to its pharmacologic properties, insulin detemir may reach higher concentrations in the brain than regular insulin. This might explain the observed increased brain stimulation after acute insulin detemir application but it remained unclear whether chronic insulin detemir treatment causes alterations in brain activity as a consequence of overstimulation.In mice, we examined insulin detemir's prolonged brain exposure by continuous subcutaneous (s.c. application using either micro-osmotic pumps or daily s.c. injections and performed continuous radiotelemetric electrocorticography and locomotion recordings.Acute intracerebroventricular injection of insulin detemir activated cortical and locomotor activity significantly more than regular insulin in equimolar doses (0.94 and 5.63 mU in total, suggesting an enhanced acute impact on brain networks. However, given continuously s.c., insulin detemir significantly reduced cortical activity (theta: 21.3±6.1% vs. 73.0±8.1%, P<0.001 and failed to maintain locomotion, while regular insulin resulted in an increase of both parameters.The data suggest that permanently-increased insulin detemir levels in the brain convert its hyperstimulatory effects and finally mediate impairments in brain activity and locomotion. This observation might be considered when human studies with insulin detemir are designed to target the brain in order to optimize treatment regimens.

[The use of continuous subcutaneous insulin infusion (CSII) with personal insulin pumps in the treatment of children and adolescents with diabetes type 1].

Science.gov (United States)

Jarosz-Chobot, Przemysława

2004-01-01

This paper sums up recently published researches on the continuous subcutaneous insulin infusion (CSII) with the use of insulin pump in children and adolescents with diabetes type 1. Obtaining a balance in the organism metabolism in childhood and adolescence diabetology is nowadays one of the most important rules of the diabetes management in children. One of the modern ways to achieve that goal is the intensive insulin therapy model with use of the insulin pump. In this paper the advantages and disadvantages as well as the indications and contraindications for the CSII in children and adolescents with diabetes are widely discussed.

Effect of strict metabolic control on regulation of subcutaneous blood flow in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Kastrup, J; Mathiesen, E R; Saurbrey, Nina

1987-01-01

washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevated to a maximum of 65 mmHg by head-up tilt; in the latter position venous pressure was kept constantly low by activation of the leg muscle vein pump (heel raising......The effect of 10 weeks of improved metabolic control on the impaired autoregulation of the subcutaneous blood flow was studied at the level of the lateral malleolus in eight long-term insulin-dependent diabetic patients with clinical microangiopathy. Blood flow was measured by the local 133-Xenon......). Improved metabolic control was achieved using either continuous subcutaneous insulin infusion or multiple insulin injections. The blood glucose concentration declined from (median) 12.7 to 6.8 mmol/l and the HbA1C level from 10.1 to 7.5% during strict metabolic control (p less than 0.01 and p less than 0...

Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

International Nuclear Information System (INIS)

Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

1986-01-01

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting

Subcutaneous Injections

DEFF Research Database (Denmark)

Thomsen, Maria

This thesis is about visualization and characterization of the tissue-device interaction during subcutaneous injection. The tissue pressure build-up during subcutaneous injections was measured in humans. The insulin pen FlexTouchr (Novo Nordisk A/S) was used for the measurements and the pressure ...

Estimation of glucose rate of appearance from cgs and subcutaneous insulin delivery in type 1 diabetes

KAUST Repository

Laleg-Kirati, Taous-Meriem; Al-Matouq, Ali Ahmed

2017-01-01

Method and System for providing estimates of Glucose Rate of Appearance from the intestine (GRA) using continuous glucose sensor measurements (CGS) taken from the subcutaneous of a diabetes patient and the amount of insulin administered

Estimation of glucose rate of appearance from cgs and subcutaneous insulin delivery in type 1 diabetes

KAUST Repository

Laleg-Kirati, Taous-Meriem

2017-08-31

Method and System for providing estimates of Glucose Rate of Appearance from the intestine (GRA) using continuous glucose sensor measurements (CGS) taken from the subcutaneous of a diabetes patient and the amount of insulin administered to the patient.

Continuous subcutaneous insulin infusion therapy for Type 1 diabetes mellitus in children.

Science.gov (United States)

Mavinkurve, M; Quinn, A; O'Gorman, C S

2016-05-01

Continuous subcutaneous insulin pump therapy (CSII or pump therapy) is a well-recognised treatment option for Type 1 diabetes mellitus (T1DM) in paediatrics. It is especially suited to children because it optimises control by improving flexibility across age-specific lifestyles. The NICE guidelines (2008) recognise that pump therapy is advantageous and that it should be utilised to deliver best practice. In Ireland, the National Clinical Program for Diabetes will increase the availability and uptake of CSII in children and thus more clinicians are likely to encounter children using CSII therapy. This is a narrative review which discusses the basic principles of pump therapy and focuses on aspects of practical management. Insulin pump management involves some basic yet important principles which optimise the care of diabetes in children. This review addresses the principles of insulin pump management in children which all health care professionals involved in caring for the child with diabetes, shoud be familiar with.

Health-Related Quality of Life, Treatment Satisfaction, and Costs Associated With Intraperitoneal Versus Subcutaneous Insulin Administration in Type 1 Diabetes

NARCIS (Netherlands)

Logtenberg, Susan J.; Kleefstra, Nanne; Houweling, Sebastiaan T.; Groenier, Klaas H.; Gans, Reinold O.; Bilo, Henk J.

OBJECTIVE - To investigate the effects of continuous intraperitoneal insulin infusion (CIPII) compared with subcutaneous insulin on health-related quality of life (HRQOL) and treatment satisfaction, and to perform a cost analysis in type 1 diabetes. RESEARCH DESIGN AND METHODS - We used an

An observational study comparing continuous subcutaneous insulin infusion (CSII) and insulin glargine in children with type 1 diabetes.

Science.gov (United States)

Schiaffini, Riccardo; Ciampalini, Paolo; Spera, Sabrina; Cappa, Marco; Crinó, Antonino

2005-01-01

The advantages of continuous subcutaneous insulin infusion (CSII) or insulin glargine have been demonstrated both in adult and paediatric diabetic patients; however, as no data comparing these two approaches during childhood are available, we have examined the efficacy of these two intensive approaches. We retrospectively evaluated data from 36 diabetic children, who had changed their previous insulin regimen [with isophane insulin (NPH) at bedtime] because of HbA1c levels >8.0%. Twenty patients underwent CSII, while the other 16 (significantly younger for age) started insulin glargine at bedtime. At 6 and 12 months, CSII-treated patients showed a significant reduction in HbA1c values from 8.5 +/- 1.8 to 7.4 +/- 1.1% and to 7.6 +/- 1.2%, respectively. The insulin requirement significantly decreased from 0.93 +/- 0.2 IU/kg to 0.73 +/- 0.2 IU/kg of body weight and to 0.74 +/- 0.15 IU/kg of body weight, respectively, while no significant differences were observed for BMI SDS, fructosamine and severe hypoglycaemic events. The patients treated with glargine showed a small decline in HbA1c values from 8.9 +/- 1.7 to 8.3 +/- 0.9% (not significant) in the first 6 months of treatment and to 8.2 +/- 0.9% after 12 months. The basal insulin supplementation can be supplied effectively in children with type 1 diabetes by either CSII or insulin glargine. As previously reported for adults, it is confirmed that CSII is the best current intensive approach aimed to the improvement of glycaemic control.

Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes

DEFF Research Database (Denmark)

Roze, S.; Smith-Palmer, J.; Valentine, W.

2015-01-01

Aim: Continuous subcutaneous insulin infusion (CSII) is increasingly used in clinical practice for the management of selected patients with Type 1 diabetes. Several cost-effectiveness studies comparing CSII vs. multiple insulin injections (MDI) have been reported. The aim was systematically...... to review these analyses and test the hypothesis that CSII is a cost-effective use of healthcare resources across settings. Methods: A literature review was performed using MEDLINE, Cochrane Library and other databases. No time limit or language restrictions were applied. After two rounds of screening, 11...... cost-effectiveness analyses were included in the final review, of which nine used the CORE Diabetes Model. A narrative synthesis was conducted and mean cost effectiveness calculated. Results: CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11 studies in 8 countries, with a mean (95...

Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

Science.gov (United States)

Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

2012-12-01

Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats.

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Oliveira, Ariclecio Cunha de; Andreotti, Sandra; Sertie, Rogério António Laurato; Campana, Amanda Baron; de Proença, André Ricardo Gomes; Vasconcelos, Renata Prado; Oliveira, Keciany Alves de; Coelho-de-Souza, Andrelina Noronha; Donato-Junior, José; Lima, Fábio Bessa

2018-04-15

Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function. Copyright © 2017. Published by Elsevier Inc.

Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes.

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Farrar, Diane; Tuffnell, Derek J; West, Jane; West, Helen M

2016-06-07

Diabetes results in a rise in blood glucose above normal physiological levels; if untreated this may cause damage to many systems including the cardiovascular and renal systems. Pregnancy increases resistance to insulin action; for those women who have pre-gestational diabetes, this results in an increasing insulin requirement. There are several methods of administering insulin. Conventionally, insulin has been administered subcutaneously, formally referred to as intensive conventional treatment, but now more usually referred to as multiple daily injections (MDI). An alternative method of insulin administration is the continuous subcutaneous insulin infusion pump (CSII). To compare CSII with MDI of insulin for pregnant women with pre-existing and gestational diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016) and reference lists of retrieved studies. Randomised trials comparing CSII with MDI for pregnant women with diabetes. Three review authors independently assessed studies and two review authors extracted data. Disagreements were resolved through discussion with the third author. We assessed the quality of the evidence using the GRADE approach. We included five single-centre trials (undertaken in Italy) with 153 women and 154 pregnancies in this review.There were no clear differences in the primary outcomes reported between CSII and MDI in the included trials: caesarean section (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.66 to 1.77; three trials, 71 women, evidence graded very low), large-for-gestational age (RR 4.15, 95% CI 0.49 to 34.95; three trials, 73 infants; evidence graded very low), and perinatal mortality (RR 2.33, 95% CI 0.38 to 14.32; four trials, 83 infants, evidence graded very low). Other primary outcomes were not reported in these trials (hypertensive disorders of pregnancy, development of type 2 diabetes, composite outcome of serious neonatal outcomes, and neurosensory disability

Subcutaneous blood flow during insulin-induced hypoglycaemia: studies in juvenile diabetics with and without autonomic neuropathy and in normal subjects

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Hilsted, J; Madsbad, S; Sestoft, L

1982-08-01

Subcutaneous blood flow was measured preceding insulin-induced hypoglycaemia, at the onset of hypoglycaemic symptoms and 2 h later in juvenile diabetics with and without autonomic neuropathy and in normal males. In all groups subcutaneous blood flow decreased at the onset of hypoglycaemic symptoms compared with pre-hypoglycaemic flow. Two hours after onset of hypoglycaemic symptoms, subcutaneous blood flow was still significantly decreased compared with pre-hypoglycaemic flow. In normal subjects local nerve blockade had no effect on blood flow changes during hypoglycaemia, whereas local alpha-receptor blockade abolished the vasoconstrictor response. We suggest that circulating catecholamines stimulating vascular alpha-receptors are probably responsible for flow reduction in the subcutaneous tissue during hypoglycaemia.

Improved Insulin Pharmacokinetics Using a Novel Microneedle Device for Intradermal Delivery in Patients with Type 2 Diabetes.

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Kochba, Efrat; Levin, Yotam; Raz, Itamar; Cahn, Avivit

2016-09-01

Currently available short-acting insulin analogs have slower absorption compared with endogenous insulin occasionally resulting in immediate postprandial hyperglycemia. Intradermal (ID) injection facilitates faster drug absorption and may result in improved insulin pharmacokinetics. Seventeen patients with type 2 diabetes were included in this single-center, pilot, open-label crossover study. Patients received 0.2 U/kg Insulin aspart ID injections using a MicronJet (MJ) needle and subcutaneous (SC) injections, using a conventional needle in a crossover design. Thirteen patients were studied under fasting conditions and four before a standard meal test. The pharmacokinetic/pharmacodynamic (PK/PD) profile, as well as the safety and tolerability of injections, was compared. Fourteen patients completed the study per-protocol. ID versus SC injection demonstrated significantly shorter Tmax (median 35 vs. 87.5 min [P < 0.001]), while the Cmax did not significantly differ (median 80 vs. 55 μU/mL [P = 0.085]). Median insulin area under the curve (AUC; 360 min) did not differ between the groups (9914 vs. 10,936 μU/mL/min [p = 0.077]), yet 0-60 min insulin AUC was higher with ID versus SC injection (mean ± SD 3821 ± 1429 vs. 2534 ± 737 μU/mL/min [p = 0.01]) and 4-6 h AUC was lower with ID versus SC injection (mean ± SD 2054 ± 858 vs. 2929 ± 1412 μU/mL/min [p = 0.02]). The relative bioavailability of the ID versus the SC insulin (AUCID/AUCSC) was similar (median 0.91 [95% confidence interval 0.73-1.27]). ID insulin injection delivered through an MJ needle demonstrated superior PK profile compared with conventional SC administration, including shorter Tmax and higher early and lower late exposure in patients with type 2 diabetes. This may help achieve better insulin coverage of meals and lower postprandial glucose excursions.

Insulin Plays a Permissive Role for the Vasoactive Effect of GIP Regulating Adipose Tissue Metabolism in Humans

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Asmar, Meena; Simonsen, Lene; Asmar, Ali

2016-01-01

CONTEXT AND OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increases blood flow and triglyceride (TAG) clearance in subcutaneous (sc) abdominal adipose tissue in lean humans. The present experiments were performed to further investigate the role...... of insulin for the vasoactive effect of GIP in adipose tissue metabolism and whether the vasodilatory effect of GIP is dependent on C-peptide. METHODS: Six lean healthy subjects were studied. The sc abdominal adipose tissue metabolism was assessed by Fick's principle during GIP infusion (1.5 pmol...

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

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Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Bioavailability and variability of biphasic insulin mixtures

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Søeborg, Tue; Rasmussen, Christian Hove; Mosekilde, Erik

2012-01-01

Absorption of subcutaneously administered insulin is associated with considerable variability. Some of this variability was quantitatively explained for both soluble insulin and insulin suspensions in a recent contribution to this journal (Søeborg et al., 2009). In the present article......, the absorption kinetics for mixtures of insulins is described. This requires that the bioavailability of the different insulins is considered. A short review of insulin bioavailability and a description of the subcutaneous depot thus precede the presentation of possible mechanisms associated with subcutaneous...... insulin degradation. Soluble insulins are assumed to be degraded enzymatically in the subcutaneous tissue. Suspended insulin crystals form condensed heaps that are assumed to be degraded from their surface by invading macrophages. It is demonstrated how the shape of the heaps affects the absorption...

Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model

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A. Schaschkow

2016-01-01

Full Text Available Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC injection in a basal and bolus scheme using insulin pens (injection or pumps (preimplanted SC catheter. Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin at the same dosage (4 IU/200 g/day on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed.

Improvement of continuous subcutaneous insulin infusion on patients with type 2 diabetes mellitus by 3-dimensional speckle tracking echocardiography.

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Luo, Hong-Xia; Zhou, Xiao-Ling; Kou, Hong-Ju; Ni, Xian-Wei; Wu, Qing; Zou, Chun-Peng; Wu, Dao-Zhu; Liu, Yong-Fang

2018-03-01

Three-dimensional speckle tracking echocardiography (3D-STE) was used to evaluate the improvement of continuous subcutaneous insulin infusion on the left ventricular (LV) systolic function of patients with type 2 diabetes mellitu (T2DM). We recruited T2DM patients (38 cases, diabetic group) and healthy volunteers (35 cases, control group) to collect LV full volume imaging. TomTec software was used for calculating LV global longitudinal strain (LVGLS), global circumferential strain (LVGCS), peak twist (LVTW), peak apical rotation (LVPAR), ejection fraction (LVEF), and torsion (LVT). All indices were re-tested 2 weeks later after intensive treatment of insulin pump. LVGLS, LVGCS, LVTW and LVPAR in diabetic group were significantly decreased than control group. LVGLS and LVGCS in pre-treatment diabetic group were significantly increased than post-treatment. LVGLS, LVGCS, LVTW and LVPAR had correlations among control, pre-treatment and post-treatment diabetic groups. There were no significant differences in LVEDV, LVESV, LVEF, LVT and R-R. LV systolic function of patients with T2DM complicated with microangiopathy was improved after treatment of continuous subcutaneous insulin infusion. In addition, therapeutic effect could be accurately evaluated by 3D-STE which had vital clinical application.

The comparison of the intestinal adaptation effects of subcutaneous ...

African Journals Online (AJOL)

Aim: Insulin has been reported to have positive effects on intestinal adaptation after short bowel syndrome when applicated oral or subcutaneously. The purpose of this study is to compare the intestinal adaptation effects of subcutaneous and oral routes of insulin in rats with short bowel syndrome. Materials and Methods: ...

Treatment with continuous subcutaneous insulin infusion is associated with lower arterial stiffness

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Vestergaard Rosenlund, Signe; Theilade, Simone; Hansen, Tine Willum

2014-01-01

AIMS: To investigate the relationship between arterial stiffness and insulin treatment mode [continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI)] in type 1 diabetes patients. METHODS: Cross-sectional study, from 2009 to 2011, including 601 Caucasian type 1...... diabetes patients, 58 and 543 treated with CSII and MDI, respectively. Arterial stiffness was measured as pulse wave velocity (PWV) (SphygmoCor, AtCor Medical). Adjustment included gender, age, diabetes duration, HbA1c, heart rate, mean arterial pressure, P-creatinine, urinary albumin excretion rate (UAER......-treated patients were 48 versus 57 % men, 51 ± 11 versus 54 ± 13 years old (mean ± SD), had 33 ± 12 versus 32 ± 16 years diabetes duration and HbA1c 7.8 ± 0.9 % (62 ± 10 mmol/mol) versus 8.0 ± 1.2 % (64 ± 13 mmol/mol) (P ≥ 0.08 for all). PWV was lower in CSII- versus MDI-treated patients (9.3 ± 2.8 vs. 10.4 ± 3...

Subcutaneous NPH Insulin for Severe Hypertriglyceridemia in a Pregnant Patient with Type V Hyperlipoproteinemia: a Case Report

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Mustafa Kemal Balcı

2012-06-01

Full Text Available An increase in triglyceride levels in familial hyperlipidemia during pregnancy has been reported. Severe hypertriglyceridemia can lead to complications such as acute pancreatitis, preeclampsia, maternal and fetal complications. Because of the teratogenic effects associated with fibrate therapy in pregnancy, alternative treatment strategies such as insulin as a rapid and potent activator of lipoprotein lipase are required during pregnancy. We report a case of hypertriglyceridemia in a 33-year-old pregnant woman in whom treatment with merely single one time administration of Neutral Protamine Hagedorn insulin was accompanied by a reduction in the serum triglyceride level; to the best of our knowledge, this has never been reported in the literature. Her triglyceride level was 3616 mg/dL before insulin treatment and 1246 mg/dL after insulin treatment. Although this regimen was used safely and effectively in our patient, comprehensive studies are required to evaluate the effectiveness and safety of subcutaneously intermediate-acting Neutral Protamine Hagedorn insulin for the treatment of severe hypertriglyceridemia in non-diabetic pregnant women.

Successful treatment of young infants presenting neonatal diabetes mellitus with continuous subcutaneous insulin infusion before genetic diagnosis.

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Rabbone, Ivana; Barbetti, Fabrizio; Marigliano, Marco; Bonfanti, Riccardo; Piccinno, Elvira; Ortolani, Federica; Ignaccolo, Giovanna; Maffeis, Claudio; Confetto, Santino; Cerutti, Franco; Zanfardino, Angela; Iafusco, Dario

2016-08-01

Neonatal diabetes mellitus (NDM) is defined as hyperglycemia and impaired insulin secretion with onset within 6 months of birth. While rare, NDM presents complex challenges regarding the management of glycemic control. The availability of continuous subcutaneous insulin infusion pumps (CSII) in combination with continuous glucose monitoring systems (CGM) provides an opportunity to monitor glucose levels more closely and deliver insulin more safely. We report four cases of young infants with NDM successfully treated with CSII and CGM. Moreover, in two cases with Kir 6.2 mutation, we describe the use of CSII in switching therapy from insulin to sulfonylurea treatment. Insulin pump requirement for the 4 neonatal diabetes cases was the same regardless of disease pathogenesis and c-peptide levels. No dilution of insulin was needed. The use of an integrated CGM system helped in a more precise control of BG levels with the possibility of several modifications of insulin basal rates. Moreover, as showed in the first two case-reports, when the treatment was switched from insulin to glibenclamide, according to identification of Kir 6.2 mutation and diagnosis of NPDM, the CSII therapy demonstrated to be helpful in allowing gradual insulin suspension and progressive introduction of sulfonylurea. During the neonatal period, the use of CSII therapy is safe, more physiological, accurate and easier for the insulin administration management. Furthermore, CSII therapy is safe during the switch of therapy from insulin to glibenclamide for infants with permanent neonatal diabetes mellitus.

Intranasal insulin therapy: the clinical realities

DEFF Research Database (Denmark)

Hilsted, J; Madsbad, Sten; Hvidberg, A

1995-01-01

To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

NEUROPROTECTIVE EFFICACY OF SUBCUTANEOUS INSULIN-LIKE GROWTH FACTOR-I ADMINISTRATION IN NORMOTENSIVE AND HYPERTENSIVE RATS WITH AN ISCHEMIC STROKE

NARCIS (Netherlands)

de Geyter, D.; Stoop, W.; Sarre, S.; de Keyser, J.; Kooijman, R.

2013-01-01

The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a neuroprotective agent in a rat model for ischemic stroke and to compare its neuroprotective effects in conscious normotensive and spontaneously hypertensive rats. The effects of subcutaneous IGF-I injection were

Designing a global monitoring system for pilot introduction of a new contraceptive technology, subcutaneous DMPA (DMPA-SC).

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Stout, Anna; Wood, Siri; Namagembe, Allen; Kaboré, Alain; Siddo, Daouda; Ndione, Ida

2018-06-01

In collaboration with ministries of health, PATH and key partners launched the first pilot introductions of subcutaneous depot medroxyprogesterone acetate (DMPA-SC, brand name Sayana ® Press) in Burkina Faso, Niger, Senegal, and Uganda from July 2014 through June 2016. While each country implemented a unique introduction strategy, all agreed to track a set of uniform indicators to chart the effect of introducing this new method across settings. Existing national health information systems (HIS) were unable to track new methods or delivery channels introduced for a pilot, thus were not a feasible source for project data. We successfully monitored the four-country pilot introductions by implementing a four-phase approach: 1) developing and defining global indicators, 2) integrating indicators into existing country data collection tools, 3) facilitating consistent reporting and data management, and 4) analyzing and interpreting data and sharing results. Project partners leveraged existing family planning registers to the extent possible, and introduced new or modified data collection and reporting tools to generate project-specific data where necessary. We routinely shared monitoring results with global and national stakeholders, informing decisions about future investments in the product and scale up of DMPA-SC nationwide. Our process and lessons learned may provide insights for countries planning to introduce DMPA-SC or other new contraceptive methods in settings where stakeholder expectations for measureable results for decision-making are high. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Appropriateness of the Length of Insulin Needles Based on Determination of Skin and Subcutaneous Fat Thickness in the Abdomen and Upper Arm in Patients with Type 2 Diabetes

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Kang Hee Sim

2014-04-01

Full Text Available BackgroundLonger needle and complicated insulin injection technique such as injecting at a 45-degree angle and making skinfolds may decrease patient compliance to insulin injection therapy. In this light, shorter insulin needles have been recently developed. However, it is necessary to ascertain that such shorter needles are appropriate for Korean patients with diabetes as well.MethodsFirst, the diverse demographic and diabetic features of 156 Korean adults with diabetes were collected by a questionnaire and a device unit of body fat measurement. The skin and subcutaneous fat thicknesses of each subject were measured by Ultrasound device with a 7- to 12-MHz probe. Data were analyzed using analysis of variance and multiple linear regression.ResultsThe mean skin thickness was 2.29±0.37 mm in the abdomen and 2.00±0.34 mm in the upper arms, and the mean subcutaneous fat thickness was to 10.15±6.54 mm in the abdomen and 5.50±2.68 mm in the upper arms. Our analysis showed that the factors affecting the skin thickness of the abdomen and upper arms were gender and body mass index (BMI, whereas the factors influencing the subcutaneous fat thickness in the abdomen were gender and BMI, and the factors influencing the subcutaneous fat thickness in the upper arms were gender, BMI, and age. Insulin fluids may not appear to be intradermally injected into the abdomen and upper arms at any needle lengths. The risk of intramuscular injection is likely to increase with longer insulin needles and lower BMI.ConclusionIt is recommended to fully inform the patients about the lengths of needles for insulin injections. As for the recommended needle length, the findings of this study indicate that needles as short as 4 mm are sufficient to deliver insulin for Korean patients with diabetes.

Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.

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Laura L Gathercole

Full Text Available Patients with glucocorticoid (GC excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc and omental (om adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.

Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague-Dawley rats.

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Rojas, J M; Printz, R L; Niswender, K D

2011-07-04

Initiation and intensification of insulin therapy commonly causes weight gain, a barrier to therapy. A contrasting body of evidence indicates that insulin functions as an adiposity negative feedback signal and reduces food intake, weight gain and adiposity via action in the central nervous system. Basal insulin analogs, detemir (Det) and glargine (Glar), have been associated with less hypoglycemia compared with neutral protamine hagedorn insulin, and Det with less weight gain, especially in patients with higher body mass index (BMI). We sought to determine whether insulin therapy per se causes body weight and fat mass gain when delivered via a clinically relevant subcutaneous (SC) route in the absence of hypoglycemia and glycosuria in non-diabetic lean and diet-induced obese rats. Rats were exposed to either a low-fat diet (LFD; 13.5% fat) or high-fat diet (HFD; 60% fat), and received Det (0.5 U kg(-1)), Glar (0.2 U kg(-1)) or vehicle (Veh) SC once daily for 4 weeks. These dosages of insulin were equipotent in rats with respect to blood-glucose concentration and did not induce hypoglycemia. As predicted by current models of energy homeostasis, neither insulin Det nor Glar therapy affected food intake and weight gain in LFD rats. Det treatment significantly attenuated food intake, body weight gain and fat mass gain relative to the Glar and Veh in high-fat fed animals, mirroring observations in humans. That neither insulin group gained excess weight, suggests weight gain with SC basal insulin therapy may not be inevitable. Our data further suggest that Det possesses a unique property to attenuate the development of obesity associated with a HFD.

Position Statement on the management of continuous subcutaneous insulin infusion (CSII): The Italian Lazio experience.

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Maurizi, Anna R; Suraci, Concetta; Pitocco, Dario; Schiaffini, Riccardo; Tubili, Claudio; Morviducci, Lelio; Giordano, Renato; Manfrini, Silvia; Lauro, Davide; Frontoni, Simona; Pozzilli, Paolo; Buzzetti, Raffaella

2016-01-01

This document has been developed by a group of Italian diabetologists with extensive experience in continuous subcutaneous insulin infusion (CSII) therapy to provide indications for the clinical management of CSII in diabetic patients (both type 1 and type 2) based on delivery mode operating in Italy. Although the potential benefits of pump therapy in achieving glycemic goals is now accepted, such results cannot be obtained without specific knowledge and skills being conveyed to patients during ad hoc educational training. To ensure that these new technologies reach their full effectiveness, as demonstrated theoretically and clinically, a careful assessment of the overall therapeutic and educational process is required, in both qualitative and quantitative terms. Therefore, to ensure the cost-effectiveness of insulin pump therapy and to justify reimbursement of therapy costs by the National Health System in Italy, in this article we present a model for diabetes and healthcare centers to follow that provides for different levels of expertise in the field of CSII therapy. This model will guarantee the provision of excellent care during insulin pump therapies, thus representing the basis for a successful outcome and expansion of this form of insulin treatment in patients with diabetes while also keeping costs under control. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

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

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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.

Qualitative analysis of subcutaneous Lispro and regular insulin injections for stress hyperglycemia: a pilot numerical study.

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Strilka, Richard J; Armen, Scott B; Indeck, Matthew C

2014-09-07

Increased glucose variability (GV) is an independent risk factor for mortality in the critically ill; unfortunately, the optimal insulin therapy that minimizes GV is not known. We simulate the glucose-insulin feedback system to study how stress hyperglycemia (SH) states, taken to be a non-uniform group of physiologic disorders with varying insulin resistance (IR) and similar levels of hyperglycemia, respond to the type and dose of subcutaneous (SQ) insulin. Two groups of 100 virtual patients are studied: those receiving and those not receiving continuous enteral feeds. Stress hyperglycemia was facilitated by doubling the gluconeogenesis rate and IR was stepwise varied from a borderline to a high value. Lispro and regular insulin were simulated with dosages that ranged from 0 to 6 units; the resulting GV was analyzed after each insulin injection. The numerical model used consists of a set of non-linear differential equations with two time delays and five adjustable parameters. The results show that regular insulin decreased GV in both patient groups and rarely caused hypoglycemia. With continuous enteral feeds and borderline to mild IR, Lispro showed minimal effect on GV; however, rebound hyperglycemia that increased GV occurred when the IR was moderate to high. Without a nutritional source, Lispro worsened GV through frequent hypoglycemia episodes as the injection dose increased. The inferior performance of Lispro is a result of its rapid absorption profile; half of its duration of action is similar to the glucose ultradian period. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units, and if such dynamics are present, their clinical effects should be evaluated. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients.

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Jansen, Henry J; Vervoort, Gerald M; van der Graaf, Marinette; Stienstra, Rinke; Tack, Cees J

2013-11-01

Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an association between inflammatory features of the adipose tissue and liver fat content. To analyse associations between inflammatory features of the adipose tissue and liver fat content. A cross-sectional study. Twenty-seven obese patients with insulin-treated T2DM were studied. LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown-like structures (CLSs) within sc fat were assessed by CD68-immunohistochemical staining. Mean LFAT percentage was 11·1 ± 1·7% (range: 0·75-32·9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal ≤5·5%). Whereas adipocyte size did not correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and the percentage of macrophages present in sc adipose tissue was positively associated with LFAT. Protein concentrations of adiponectin within adipose tissue negatively correlated with LFAT. Adipose tissue protein levels of the key inflammatory adipokine plasminogen activator inhibitor-1 (PAI-1) were positively associated with LFAT. Several pro-inflammatory changes in sc adipose tissue associate with increased LFAT content in obese insulin-treated patients with T2DM. These findings suggest that inflammatory changes at the level of the adipose tissue may drive liver fat accumulation. © 2012 John Wiley & Sons Ltd.

High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling.

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Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

2011-04-13

The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days. Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test. High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet. Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet

A cross-sectional international survey of continuous subcutaneous insulin infusion in 377 children and adolescents with type 1 diabetes mellitus from 10 countries

NARCIS (Netherlands)

Danne, T; Battelino, T; Kordonouri, O; Hanas, R; Klinkert, C; Ludvigsson, J; Barrio, R; Aebi, C; Gschwend, S; Mullis, PE; Schumacher, U; Zumsteg, U; Morandi, A; Rabbone, [No Value; Cherubini, [No Value; Toni, S; de Beaufort, C; Hindmarsh, P; Sumner, A; van Waarde, WM; van den Berg, N; Phillip, M

2005-01-01

Objective: To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90-d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel.

Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes.

Science.gov (United States)

Lucidi, P; Porcellati, F; Marinelli Andreoli, A; Candeloro, P; Cioli, P; Bolli, G B; Fanelli, C G

2017-06-06

This study measured the insulin concentration (Ins [C] ) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). Measurements included Ins [C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. In vials of NPH(R+) (assumed to be 100%), Ins [C] in the clear phase of NPH(R-) wasEli Lilly NPH, respectively. Likewise, in pen cartridges, Ins [C] in the clear phase of NPH(R-) wasLilly and Sanofi NPH. Time needed to resuspend NPH (spent in tipping) in vials was brief with both Novo (5±1s) and Lilly NPH (6±1s), but longer with all pen cartridges (50±8s, 40±6s and 30±4s from Novo, Lilly and Sanofi, respectively; P=0.022). Time required for 50% separation into cloudy and clear parts of NPH was longer with Novo (60±7min) vs. Lilly (18±3min) in vials (P=0.021), and affected by temperature, but not by the different diameter sizes of the vials. With pen cartridges, separation into clear and cloudy parts was significantly faster than in vials (P<0.01). Ins [C] in NPH preparations varies depending on their resuspension or not. Thus, subcutaneous injection of the same number of units of NPH in patients with diabetes may deliver different amounts of insulin depending on its prior NPH resuspension. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sodium retention and insulin treatment in insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Nørgaard, K; Feldt-Rasmussen, B

1994-01-01

subcutaneously, contributes to the increased ENa. Three studies were performed. Study 1 was a cross-sectional study comprising 28 type 1 diabetic men (aged 18-35 years) with short-duration diabetes (diabetic complications, and 22 control subjects. Study 2 was a prospective study of 17...... subcutaneous insulin infusion for improvement of glycaemic control or to remain on conventional insulin treatment. In study 1, ENa was higher in short-duration type 1 diabetic men than in controls (3003 +/- 325 vs 2849 +/- 207 mEq/1.73 m2, P ...The hypothesis that total body exchangeable sodium (ENa) is elevated in type 1 (insulin-dependent) diabetic patients with short-duration diabetes and no signs of microangiopathy was tested. Also tested was whether peripheral hyperinsulinaemia, in terms of the amounts of insulin injected...

Comparison of the relative contributions of intra-abdominal and liver fat to components of the metabolic syndrome

DEFF Research Database (Denmark)

Kotronen, Anna; Yki-Järvinen, Hannele; Sevastianova, Ksenia

2011-01-01

insulin sensitivity independent of age, gender, subcutaneous (SC) fat, and/or lean body mass (LBM). Including both liver and IA fat, liver and IA fat both explained variation in TG, HDL cholesterol, insulin and hepatic insulin sensitivity independent of each other and of age, gender, SC fat, and LBM....... Liver fat independently predicted glucose and liver enzymes. SC fat and age explained variation in blood pressure. In conclusion, both IA and liver fat independently of each other explain variation in serum TG, HDL cholesterol, insulin concentrations and hepatic insulin sensitivity, thus supporting...

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

Science.gov (United States)

Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

1988-11-12

To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients.

Science.gov (United States)

Waldhäusl, W K; Bratusch-Marrain, P R; Francesconi, M; Nowotny, P; Kiss, A

1982-01-01

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.

Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation.

Science.gov (United States)

Granata, Riccarda; Gallo, Davide; Luque, Raul M; Baragli, Alessandra; Scarlatti, Francesca; Grande, Cristina; Gesmundo, Iacopo; Córdoba-Chacón, Jose; Bergandi, Loredana; Settanni, Fabio; Togliatto, Gabriele; Volante, Marco; Garetto, Stefano; Annunziata, Marta; Chanclón, Belén; Gargantini, Eleonora; Rocchietto, Stefano; Matera, Lina; Datta, Giacomo; Morino, Mario; Brizzi, Maria Felice; Ong, Huy; Camussi, Giovanni; Castaño, Justo P; Papotti, Mauro; Ghigo, Ezio

2012-08-01

The metabolic actions of the ghrelin gene-derived peptide obestatin are still unclear. We investigated obestatin effects in vitro, on adipocyte function, and in vivo, on insulin resistance and inflammation in mice fed a high-fat diet (HFD). Obestatin effects on apoptosis, differentiation, lipolysis, and glucose uptake were determined in vitro in mouse 3T3-L1 and in human subcutaneous (hSC) and omental (hOM) adipocytes. In vivo, the influence of obestatin on glucose metabolism was assessed in mice fed an HFD for 8 wk. 3T3-L1, hSC, and hOM preadipocytes and adipocytes secreted obestatin and showed specific binding for the hormone. Obestatin prevented apoptosis in 3T3-L1 preadipocytes by increasing phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. In both mice and human adipocytes, obestatin inhibited isoproterenol-induced lipolysis, promoted AMP-activated protein kinase phosphorylation, induced adiponectin, and reduced leptin secretion. Obestatin also enhanced glucose uptake in either the absence or presence of insulin, promoted GLUT4 translocation, and increased Akt phosphorylation and sirtuin 1 (SIRT1) protein expression. Inhibition of SIRT1 by small interfering RNA reduced obestatin-induced glucose uptake. In HFD-fed mice, obestatin reduced insulin resistance, increased insulin secretion from pancreatic islets, and reduced adipocyte apoptosis and inflammation in metabolic tissues. These results provide evidence of a novel role for obestatin in adipocyte function and glucose metabolism and suggest potential therapeutic perspectives in insulin resistance and metabolic dysfunctions.

Islet Transplantation Provides Superior Glycemic Control With Less Hypoglycemia Compared With Continuous Subcutaneous Insulin Infusion or Multiple Daily Insulin Injections.

Science.gov (United States)

Holmes-Walker, Deborah Jane; Gunton, Jenny E; Hawthorne, Wayne; Payk, Marlene; Anderson, Patricia; Donath, Susan; Loudovaris, Tom; Ward, Glenn M; Kay, Thomas Wh; OʼConnell, Philip J

2017-06-01

The aim was to compare efficacy of multiple daily injections (MDI), continuous subcutaneous insulin infusion (CSII) and islet transplantation to reduce hypoglycemia and glycemic variability in type 1 diabetes subjects with severe hypoglycemia. This was a within-subject, paired comparison of MDI and CSII and CSII with 12 months postislet transplantation in 10 type 1 diabetes subjects referred with severe hypoglycemia, suitable for islet transplantation. Individuals were assessed with HbA1c, Edmonton Hypoglycemia Score (HYPOscore), continuous glucose monitoring (CGM) and in 8 subjects measurements of glucose variability using standard deviation of glucose (SD glucose) from CGM and continuous overlapping net glycemic action using a 4 hour interval (CONGA4). After changing from MDI to CSII before transplantation, 10 subjects reduced median HYPOscore from 2028 to 1085 (P transplantation, there were significant reductions in all baseline parameters versus CSII, respectively, HbA1c (6.4% cf 8.2%), median HYPOscore (0 cf 1085), mean glucose (7.1 cf 8.6 mmol L), SD glucose (1.7 cf 3.2 mmol/L), and CONGA4 (1.6 cf 3.0). In subjects with severe hypoglycemia suitable for islet transplantation, CSII decreased hypoglycemia frequency and glycemic variability compared with MDI whereas islet transplantation resolved hypoglycemia and further improved glycemic variability regardless of insulin independence.

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.

Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline.

Science.gov (United States)

Peters, Anne L; Ahmann, Andrew J; Battelino, Tadej; Evert, Alison; Hirsch, Irl B; Murad, M Hassan; Winter, William E; Wolpert, Howard

2016-11-01

To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes. The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.

Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine

NARCIS (Netherlands)

Birkeland, Kåre I.; Home, Philip D.; Wendisch, Ulrich; Ratner, Robert E.; Johansen, Thue; Endahl, Lars A.; Lyby, Karsten; Jendle, Johan H.; Roberts, Anthony P.; DeVries, J. Hans; Meneghini, Luigi F.

2011-01-01

Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1

Psychopathology and Continuous Subcutaneous Insulin Infusion in Type 1 Diabetes

Directory of Open Access Journals (Sweden)

Francesco Rotella

2013-01-01

Full Text Available Aim. Continuous subcutaneous insulin infusion (CSII is used as an option in patients with diabetes failing to multiple daily injections (MDI. Psychological factors may play a relevant role in the failure to attain therapeutic goals in patients on MDI. This could lead to an overrepresentation of psychopathology in patients treated with CSII. Methods. A consecutive series of 100 patients with type 1 diabetes was studied, collecting main clinical parameters and assessing psychopathology with the self-reported questionnaire Symptom Checklist 90-revised. Patients on CSII were then compared with those on MDI. Results. Of the 100 enrolled patients, 44 and 56 were on CSII and MDI, respectively. Among men, those on CSII were younger than those on MDI; conversely, no difference in age was observed in women. Women on CSII showed higher scores on most Symptom Checklist 90 subscales than those on MDI, whereas no differences were observed in men. Conclusion. Women with type 1 diabetes treated with CSII display higher levels of psychopathology than those on MDI. This is probably the consequence of the fact that patients selected for CSII are those failing to MDI. Higher levels of psychopathology could represent a limit for the attainment and maintenance of therapeutic goals with CSII.

Model Study of the Pressure Build-Up during Subcutaneous Injection

DEFF Research Database (Denmark)

Thomsen, Maria; Hernandez Garcia, Anier; Mathiesen, Joachim

2014-01-01

In this study we estimate the subcutaneous tissue counter pressure during drug infusion from a series of injections of insulin in type 2 diabetic patients using a non-invasive method. We construct a model for the pressure evolution in subcutaneous tissue based on mass continuity and the flow laws...

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

NARCIS (Netherlands)

Mihajlović, J.; Bax, P.; Van Breugel, E.; Blommestein, H.M.; Hoogendoorn, M.; Hospes, W.; Postma, M.J.

2015-01-01

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will

Insulin delivery systems combined with microneedle technology.

Science.gov (United States)

Jin, Xuan; Zhu, Dan Dan; Chen, Bo Zhi; Ashfaq, Mohammad; Guo, Xin Dong

2018-03-29

Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs ("poke and patch"), hollow MNs ("poke and flow") and reservoir-based swelling MNs ("poke and swell R-type"), and drug loaded MNs include coated MNs ("coat and poke"), dissolving MNs ("poke and release") and insulin incorporated swelling MNs ("poke and swell I-type"). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. "Poke and patch" approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. "Poke and flow" approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. "Poke and release" approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. "Poke and swell R-type" can be seen as a combination of "poke and flow" and "poke and patch" approach, while "poke and swell I-type" is an approach between "coat and

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

Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH-deficient patients

DEFF Research Database (Denmark)

Laursen, Torben; Møller, Jens; Ørskov, Hans

1996-01-01

Abstract OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the pr......Abstract OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim...... = 0.09) were observed on the two occasions. CONCLUSIONS: A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity....

Continuous subcutaneous insulin infusion (CSII) therapy at Derby Teaching Hospitals: sustained benefits in glucose control.

Science.gov (United States)

Anyanwagu, U; Olaoye, H; Jennings, P; Ashton-Cleary, S; Sugunendran, S; Hughes, D; Idris, I; Wilmot, E G

2017-08-01

In the short term, continuous subcutaneous insulin infusion (CSII) has been associated with improved glycaemic control, reduced hypoglycaemia and improved quality of life (QOL). However, limited data are available on its long-term benefits, particularly in the UK. We aimed to assess the impact of CSII on longer term outcomes. Patient-level data were obtained for CSII users at Derby Teaching Hospitals, UK. Patient confidence and satisfaction questionnaires using the Likert scale were used to assess confidence in self-management. Comparative statistics were conducted using Pearson's chi-square and Student's t-tests. Some 258 CSII users were identified (60.1% female, mean age 43.9 ± 13.4 years). Overall, there was significant decrease in HbA 1c from 78 mmol/mol (9.3 ± 2.0%) at baseline, to 69 mmol/mol (8.5 ± 1.3%) at 6 months [mean difference (md): -0.64; 95% confidence interval (95% CI): -0.91 to -0.37; P quality of care received in the insulin pump service. CSII therapy led to a sustained long-term improvement in glycaemic control in addition to a reduction in self-reported hypoglycaemia. © 2017 Diabetes UK.

miRNAs in Human Subcutaneous Adipose Tissue

DEFF Research Database (Denmark)

Kristensen, Malene M.; Davidsen, Peter K.; Vigelso, Andreas

2017-01-01

Objective Obesity is central in the development of insulin resistance. However, the underlying mechanisms still need elucidation. Dysregulated microRNAs (miRNAs; post-transcriptional regulators) in adipose tissue may present an important link. Methods The miRNA expression in subcutaneous adipose ...

Comparison of treatment with continuous subcutaneous insulin infusion versus multiple daily insulin injections with bolus calculator in patients with type 1 diabetes.

Science.gov (United States)

Pérez-García, L; Goñi-Iriarte, M J; García-Mouriz, M

2015-01-01

A study of the glycemic control, quality of life, and fear and perception of hypoglycemia by comparing continuous subcutaneous insulin infusion (CSII) group with multiple daily inyections (MDI) with bolus calculator group. This is a retrospective cohort study with following up during the first 12 months that CSII group (n=30) begins the use of "bolus wizard" and the MDI-calculator (n=30) group begins the use of the bolus calculator (Accu-Chek(®) Aviva Expert). HbA1c (3, 6 and 12 months). Questionnaires used: EsDQOL (quality of life), FH-15 (fear of hypoglycemia), and Clarke (perception of hypoglycemia). T Student and nonparametric tests. The average reduction in HbA1c during the study was significantly higher in CSII group (-0.56±0.84%) compared with the MDI group (0.097±0.94%), P=.028. The average basal insulin dose was significantly higher in the MDI group (at baseline, 6 and 12 months). No significant differences were found between the 2 treatment groups after analyzing the EsDQOL, FH-15 and Clarke questionnaires. In the CSII group, perceived quality of life assessed by the EsDQOL questionnaire was found to be better at the end of the study than at the beginning of using the insulin pump. The average reduction in HbA1c was significantly higher in the CSII group. In the CSII group, perceived quality of life was better at the end of the study than at the beginning. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

New ways of insulin delivery.

Science.gov (United States)

Heinemann, L

2011-02-01

The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

Use and Effectiveness of Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily Insulin Injection Therapy (MIT) in Children, Adolescents and Young Adults with Type 1 Diabetes Mellitus.

Science.gov (United States)

Schiel, R; Burgard, D; Perenthaler, T; Stein, G; Kramer, G; Steveling, A

2016-02-01

Today continuous subcutaneous insulin infusion (CSII) is frequently used in children and adolescents with type 1 diabetes mellitus. The present cross-sectional trial aimed to document current practice, quality of diabetes control and incidence of acute complications in different age-groups under CSII vs. multiple daily insulin injection therapy (MIT). Moreover the survey analyzed socio-demographic backgrounds of the patients. A total of 901 patients (age 11.5±4.0, diabetes duration 4.0±3.6 years) was entered in the database. Clinical data, laboratory parameters and, using a standardized questionnaire, socio-demographic data were assessed. For age-related analyses patients were allocated to 4 groups: pre-school children (MIT. Patients with CSII vs. MIT had a longer diabetes duration, they used more frequently insulin analogues, performed more frequently blood-glucose self-tests and had a lower insulin dosage per kilogram body weight. In respect of HbA1c, the mean amplitude of blood-glucose excursions, but also of lipids, creatinine, microalbuminuria and blood pressure, there were no differences in neither age-group between patients with CSII and MIT. In patients with CSII and MIT, there was a tendency (pMIT there is an increase of HbA1c towards adolescence. It must also highlighted that CSII seems to be expansive and that CSII is more frequently used in patients with better educational levels and deriving from higher social classes. © Georg Thieme Verlag KG Stuttgart · New York.

Subcutaneous rather than visceral adipose tissue is associated with adiponectin levels and insulin resistance in young men

DEFF Research Database (Denmark)

Frederiksen, L; Nielsen, T L; Wraae, K

2009-01-01

INTRODUCTION: Studies on the association between adiponectin, body composition, and insulin resistance (IR) have been conflicting. AIM: Our aim was to evaluate the impact of body composition on adiponectin and IR determined by homeostasis model assessment (HOMA) in a population-based study......, and IR was determined using HOMA. Central fat mass (CFM) and lower extremity fat mass (LEFM) was measured by dual-energy x-ray absorptiometry, and visceral adipose tissue (VAT), sc adipose tissue (SAT), and thigh fat area (TFA) were assessed by magnetic resonance imaging. RESULTS: Using multiple linear...... regression analysis, adiponectin correlated negatively with CFM (r = -0.27; P HOMA-IR (dependent variable...

Pharmacokinetics of a new subcutaneous diclofenac formulation administered to three body sites: quadriceps, gluteus, and abdomen.

Science.gov (United States)

Salomone, Salvatore; Piazza, Cateno; Vitale, Daniela Cristina; Cardì, Francesco; Gugliotta, Barbara; Drago, Filippo

2014-02-01

To assess the relative bioavailability of a new subcutaneous (SC) diclofenac hydroxypropyl b-cyclodextrin (HPbCD) formulation administered to three body sites: quadriceps, gluteus, and abdomen. This was a pilot, single-dose, randomized, three-way crossover relative bioavailability study. A total of 12 healthy subjects received a single SC injection of diclofenac HPbCD 50 mg/1 mL in the quadriceps, gluteus, or abdomen. The AUC was comparable after SC diclofenac HPbCD in the quadriceps, gluteus, and abdomen. The Cmax was comparable after SC administration in the quadriceps or abdomen, and ~ 17% higher in the gluteus. The absorption was rapid (30 minutes) after administration of the treatment at any site. The treatment was well tolerated. The relative bioavailability of SC diclofenac HPbCD was comparable when administered to the quadriceps, gluteus, and abdomen. The new diclofenac formulation can therefore be administered subcutaneously to any of these sites without clinically significant differences. A further adequately powered study would be necessary to reveal any differences among injection sites in terms of peak plasma concentration.

An observational 7-year study of continuous subcutaneous insulin infusion for the treatment of type 1 diabetes mellitus.

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Papargyri, Panagiota; Ojeda Rodríguez, Sylvie; Corrales Hernández, Juan José; Mories Álvarez, María Teresa; Recio Córdova, José María; Delgado Gómez, Manuel; Sánchez Marcos, Ana Isabel; Iglesias López, Rosa Ana; Herrero Ruiz, Ana; Beaulieu Oriol, Myriam; Miralles García, José Manuel

2014-03-01

This work reports the experience with use of continuous subcutaneous insulin infusion (CSII) in 112 type 1 diabetic patients followed up for 7 years and previously treated with multiple daily insulin injections (MDII). A retrospective, observational study in 112 patients with diabetes mellitus treated with CSII from 2005 to 2012, previously treated with MDII and receiving individualized diabetic education with a specific protocol. Variables analyzed included: prevalence of the different indications of pump treatment; mean annual HbA1c and fructosamine values before and after CSII treatment; and hypoglycemia frequency and symptoms. The most common reason for pump treatment was brittle diabetes (74.1%), followed by frequent or severe hypoglycemia or hypoglycemia unawareness (44.6%). Other indications were irregular food intake times for professional reasons (20.2%), dawn phenomenon (15.7%), pregnancy (12.3%), requirement of very low insulin doses (8.9%), and gestational diabetes (0.9%). HbA1c decreased by between 0.6% and 0.9%, and fructosamine by between 5.1% and 12.26%. Nine percent of patients experienced hypoglycemia weekly, 24% every two weeks, and 48% monthly. No hypoglycemia occurred in 19% of patients. Only 10% had neuroglycopenic symptoms. Hypoglycemia unawareness was found in 21%. Hypoglycemia was more common at treatment start, and its frequency rapidly decreased thereafter. CSII therapy provides a better glycemic control than MDII treatment. Specific patient training and fine adjustment of insulin infusion doses are required to prevent hypoglycemic episodes, which are the most common complications, mainly at the start of treatment. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Relationships among Body Condition, Insulin Resistance and Subcutaneous Adipose Tissue Gene Expression during the Grazing Season in Mares.

Directory of Open Access Journals (Sweden)

Shaimaa Selim

Full Text Available Obesity and insulin resistance have been shown to be risk factors for laminitis in horses. The objective of the study was to determine the effect of changes in body condition during the grazing season on insulin resistance and the expression of genes associated with obesity and insulin resistance in subcutaneous adipose tissue (SAT. Sixteen Finnhorse mares were grazing either on cultivated high-yielding pasture (CG or semi-natural grassland (NG from the end of May to the beginning of September. Body measurements, intravenous glucose tolerance test (IVGTT, and neck and tailhead SAT gene expressions were measured in May and September. At the end of grazing, CG had higher median body condition score (7 vs. 5.4, interquartile range 0.25 vs. 0.43; P=0.05 and body weight (618 kg vs. 572 kg ± 10.21 (mean ± SEM; P=0.02, and larger waist circumference (P=0.03 than NG. Neck fat thickness was not different between treatments. However, tailhead fat thickness was smaller in CG compared to NG in May (P=0.04, but this difference disappeared in September. Greater basal and peak insulin concentrations, and faster glucose clearance rate (P=0.03 during IVGTT were observed in CG compared to NG in September. A greater decrease in plasma non-esterified fatty acids during IVGTT (P<0.05 was noticed in CG compared to NG after grazing. There was down-regulation of insulin receptor, retinol binding protein 4, leptin, and monocyte chemoattractant protein-1, and up-regulation of adiponectin (ADIPOQ, adiponectin receptor 1 and stearoyl-CoA desaturase (SCD gene expressions in SAT of both groups during the grazing season (P<0.05. Positive correlations were observed between ADIPOQ and its receptors and between SCD and ADIPOQ in SAT (P<0.01. In conclusion, grazing on CG had a moderate effect on responses during IVGTT, but did not trigger insulin resistance. Significant temporal differences in gene expression profiles were observed during the grazing season.

Arteriolar hyalinosis does not interfere with the local veno-arteriolar reflex regulation of subcutaneous blood flow in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Kastrup, J; Nørgaard, T; Parving, H H

1987-01-01

The function of the local nervous veno-arteriolar reflex regulation of blood flow in subcutaneous tissue of the lower leg was studied in diabetic patients. The material comprised 11 long-term insulin-dependent diabetic (IDDM) patients with retinopathy and nephropathy and eight short-term IDDM...... patients without retinopathy or nephropathy and 11 non-diabetic subjects. The diabetic patients had no or a slight to moderate degree of peripheral autonomic and sensoric neuropathy. Blood flow was measured by the local 133Xe wash-out technique. Blood flow was determined before, during and after...

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

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Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

[Continuous subcutaneous insulin infusion in children less than 6 years-old: long-term progress].

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Colino, Esmeralda; Martín Frías, María; Roldán, Belén; Álvarez, María Ángeles; Yelmo, Rosa; Barrio, Raquel

2017-11-01

The aims of the study are to evaluate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) treatment in pre-school children with type I diabetes, and to assess whether the criteria of good metabolic control are achieved. A review was performed on the medical charts of patient's180mg/dl), and hypoglycaemia (<70mg/dl), mean blood glucose, standard deviation and coefficient of variation (SD/mean glucose ×100). Statistical analysis was performed using SPSS. HbA1c decreased from 6.9% (6.7-7.5) to 6.8% (6.4-7.1) after one year of CSII. Afterwards, it remained under 6.8% during the follow-up (median 5 years [3-6]). Prior to CSII, 74% of children had HbA1c levels < 7.5%. It increased to 96% after one year of CSII. Median blood glucose measurements /day was 10 (9-11). Total insulin dose did not change significantly. During the follow-up, there was one episode of DKA and one episode of HS. I/HC at breakfast were higher than at other meals (0.92 vs. 0.55, 0.6 and 0.5, respectively). CSII is effective and safe in pre-school children. It allows good metabolic control (based on Society for Paediatric and Adolescent Diabetes / American Diabetes Association criteria) to be achieved and maintained for long periods of time without an increase in adverse events. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Continuous subcutaneous use of levetiracetam: a retrospective review of tolerability and clinical effects.

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Rémi, Constanze; Lorenzl, Stefan; Vyhnalek, Birgit; Rastorfer, Karin; Feddersen, Berend

2014-12-01

To evaluate the tolerability and clinical effects of subcutaneous (SC) levetiracetam for the treatment of epileptic seizures in a palliative care setting, we conducted a retrospective chart review of patients treated with subcutaneous levetiracetam in the Department of Palliative Medicine at the University Munich, between September 2006 and March 2013. The following parameters were extracted from the charts: reason for antiepileptic drug treatment, daily dose, concentration, infusion rate, co-administration of other drugs, and clinical effects. Furthermore, the charts were screened for signs of adverse drug reactions, e.g., irritation or pain at the infusion site. We identified 20 patients that were treated with levetiracetam SC in the inpatient (n = 7) and outpatient (n = 13) settings. Most patients (n = 17) tolerated the subcutaneous infusion well. Nineteen patients (95%) received levetiracetam in combination with other drugs. These were mainly metamizol (80%), midazolam (75%), and morphine (45%). The median dose of levetiracetam was 95.8 mg/h (SD 37 mg/h), median osmolarity of the infusion solution 2203 mOsmol/L (SD 717 mOsmol/L), and infusion rate 2 mL/h (SD 2.4 ml/h). In 16 patients (80%), seizures were controlled and status epilepticus were interrupted, respectively. We conclude that SC levetiracetam is an effective treatment and well tolerated in the palliative care setting.

Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

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Russell, Steven J; El-Khatib, Firas H; Nathan, David M; Damiano, Edward R

2010-11-01

During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BGMicrodose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today. © 2010 Diabetes Technology Society.

Switching between intravenous and subcutaneous trastuzumab

DEFF Research Database (Denmark)

Gligorov, Joseph; Curigliano, Giuseppe; Müller, Volkmar

2017-01-01

AIM: To assess the safety and tolerability of switching between subcutaneous (SC) and intravenous (IV) trastuzumab in the PrefHer study (NCT01401166). PATIENTS AND METHODS: Patients with HER2-positive early breast cancer completed (neo)adjuvant chemotherapy and were randomised to receive four...... cycles of SC trastuzumab, via single-use injection device (SID; Cohort 1) or hand-held syringe (Cohort 2), followed by four cycles of IV, or vice versa (the crossover period presented here) as part of their 18 standard cycles of adjuvant trastuzumab treatment. Adverse events (AEs) were reported using....... Rates of clinically important events, including grade ≥3 AEs, serious AEs, AEs leading to study drug discontinuation and cardiac AEs, were low and similar between treatment arms (trastuzumab were observed. CONCLUSIONS: PrefHer revealed...

Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats.

Science.gov (United States)

Fernández-Varón, Emilio; Cárceles-García, Carlos; Serrano-Rodríguez, Juan Manuel; Cárceles-Rodríguez, Carlos M

2016-10-13

Bacterial pneumonia in goats is usually caused by Mannheimia haemolytica and Pasteurella multocida. Another important infection disease in lactating goats is intramammary infection producing mastitis, usually associated with coagulase-negative Staphylococcus spp. However, treatment of bacterial pneumonia in goats not affected by mastitis problems should be restricted to antimicrobials with scant penetration to milk in order to avoid long withdrawal times. Ceftiofur is a third-generation cephalosporin antimicrobial with activity against various gram-positive and gram-negative, aerobic and anaerobic bacteria encountered by domestic animals. The objectives of the present study were to establish the serum concentration-time profile for ceftiofur in lactating goats after intravenous, subcutaneous and a SC-long-acting ceftiofur formulation; to determine ceftiofur penetration into milk; to determine in vitro and ex vivo activity of ceftiofur establishing MIC, MBC, MPC and time-kill profiles against field strains of M. haemolytica and finally to calculate the main surrogate markers of efficacy. The pharmacokinetics studies revealed an optimal PK properties for the SC-LA formulation tested. Ceftiofur was well absorbed following SC and SC-LA administration, with absolute bioavailabilities (F) of 85.16 and 84.43 %, respectively. After ceftiofur analysis from milk samples, no concentrations were found at any sampling time. The MIC, MBC and MPC data of ceftiofur against five M. haemolytica strains isolated from goats affected by pneumonia were tested showing excelent sensitivity of ceftiofur against this pathogen. For PK-PD analysis, ratios were calculated suggesting a high level of bacterial kill against the five strains of M. haemolytica tested. The systemic ceftiofur exposure achieved in lactating goats following IV, SC and especially with the SC-LA administration is consistent with the predicted PK-PD ratios needed for a positive therapeutic outcome for M. haemolytica

LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol

DEFF Research Database (Denmark)

Nøhr, Mark K; Dudele, Anete; Poulsen, Morten M

2016-01-01

we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered...... through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b......, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during...

Quality of life in Danish children and adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections

DEFF Research Database (Denmark)

Birkebæk, Niels; Kristensen, Lene Juel; Mose, Anne

2014-01-01

), and to investigate whether HRQoL assessments were influenced by treatment duration. METHODS: Participants were recruited through the Danish Registry for Diabetes in Childhood and Adolescence. A total of 700 children and adolescents (360 girls), 8-17 years, were included. Of these, 295 were treated with CSII (160......AIMS: The aims of the study were to compare health-related quality of life (HRQoL) in a National Danish population of children and adolescents with type 1 diabetes (T1D) treated with either continuous subcutaneous insulin injection (CSII) or multiple daily insulin injections (MDI...... for more than one year) and 405 with MDI (238 for more than one year). Participants and their parents completed the Pediatric Quality of Life Inventory Diabetes and Generic Module. HbA1c was analyzed centrally. RESULTS: Parents reported children and adolescents on CSII for more than one year to have less...

UK service level audit of insulin pump therapy in paediatrics.

Science.gov (United States)

Ghatak, A; Paul, P; Hawcutt, D B; White, H D; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Weston, P J

2015-12-01

To conduct an audit of insulin pump therapy in the UK after the issue of guidelines for the use of continuous subcutaneous insulin infusion by NICE in 2008 (Technology Appraisal 151). All centres in the UK, providing pump services to children and young people were invited to participate in an online audit. Audit metrics were aligned to NICE Technology Appraisal 151 and an electronic data collection tool was used. Of the 176 UK centres identified as providing pump services, 166 (94.3%) participated in the study. A total of 5094 children and young people were identified as using continuous subcutaneous insulin infusion (19% of all paediatric patients with Type 1 diabetes), with a median (range) of 16.9 (0.67-69.4)% per centre. Units had a median of 0.58 consultant sessions, 0.43 full-time equivalent diabetic specialist nurses, and 0.1 full-time equivalent dieticians delivering the pump service. The majority of this time was not formally funded. Families could access 24-h clinical and technical support (83% units), although the delivery varied between consultant, diabetic specialist nurse and company representatives. Only 53% of units ran, or accessed, structured education programmes for continuous subcutaneous insulin infusion use. Most units (86%) allowed continuous subcutaneous insulin infusion use for paediatric inpatients, but only 56% had written guidelines for this scenario. Nine percent of units had encountered funding refusal for a patient fulfilling NICE (Technology Appraisal 151) criteria. The number of children and young people on continuous subcutaneous insulin infusion therapy is consistent with numbers estimated by NICE. There is a worrying lack of funded healthcare professional time. The audit also identified gaps in the provision of structured education and absence of written inpatient guidelines. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Young people with type 1 diabetes mellitus: Attitudes, perceptions, and experiences of diabetes management and continuous subcutaneous insulin infusion therapy.

Science.gov (United States)

Perry, Lin; James, Steven; Steinbeck, Katharine; Dunbabin, Janet; Lowe, Julia

2017-06-01

Continuous subcutaneous insulin infusion (CSII; insulin pump) use is increasing. However, there is little information about how this technology is used compared with other insulin delivery methods (ie, injections) by young people with type 1 diabetes mellitus in Australia. This study explored young people's attitudes, perceptions, and experiences with diabetes management comparing those using with those not using CSII, and proportions likely to transition to adult services requiring initiation and/or support for CSII use. A survey was undertaken of young people (aged 12 to 18 years) with type 1 diabetes mellitus and their parents/guardians living in Hunter New England, Australia, using a questionnaire designed to collect quantitative, descriptive, and demographic data. Most questions were based on previously developed and validated instruments. In total, 107 respondents returned partially or fully completed questionnaires. Respondents had positive attitudes and perceptions of their self-efficacy and diabetes management, but were moderately disturbed by their diabetes and reported experiencing suboptimal management outcomes. Patterns of associations were demonstrated between knowledge, attitudes, and experiences of diabetes modeled by regression analysis. There were no statistically significant differences in responses between users and nonusers of CSII. Over 40% indicated their intention to use the technology as adults. Opportunities for enhanced diabetes service support were clear, and CSII did not appear to be used to its full potential. Service redesign could enhance support for this young population using all preferred insulin delivery methods and should align to patients' goals and preferences to maximize service and patient gain. © 2017 John Wiley & Sons, Ltd.

Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow and insulin absorption in humans

DEFF Research Database (Denmark)

Clausen, Trine Schnedler; Kaastrup, Peter; Stallknecht, Bente

2009-01-01

blood flow (ATBF) and absorption of the rapid-acting insulin analog insulin aspart over a period of 4 days. METHODS: Teflon insulin catheters (Medtronic, Minneapolis, MN) were inserted into the abdominal SAT of 10 healthy men without diabetes (mean +/- SEM age, 23.0 +/- 1.1 years; body mass index, 22...... +/- 3 min on day 0 to 45 +/- 4 min on day 4 (P = 0.019). Neither peak plasma concentration nor area under the curve of insulin aspart changed significantly. CONCLUSIONS: Insertion of a Teflon insulin catheter into the SAT results in increased ATBF and faster absorption of insulin aspart in a period of 4...

Continue subcutane insuline-infusie : Een klinisch onderzoek

NARCIS (Netherlands)

Ballegooie, Evert van

1984-01-01

In dit proefschrift worden de resultaten beschreven van een onderzoek naar: (1) de rol van bloedsuikerstrips en insuline-infusiepompjes bij de behandeling van diabetes mellitus; (2) de invloed van een verbetering van de diabetesregulatie op het verloop van de nefro-, neuro- en retinopathie en (3) de

Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows.

Science.gov (United States)

Sadri, H; Bruckmaier, R M; Rahmani, H R; Ghorbani, G R; Morel, I; van Dorland, H A

2010-10-01

Gene expression of adipose factors, which may be part of the mechanisms that underlie insulin sensitivity, were studied in dairy cows around parturition. Subcutaneous fat biopsies and blood samples were taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.) and in week 5 p.p. In the adipose tissue samples, mRNA was quantified by real-time reverse transcription polymerase chain reaction for tumour necrosis factor alpha (TNFα), insulin-independent glucose transporter (GLUT1), insulin-responsive glucose transporter (GLUT4), insulin receptor, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), regulatory subunit of phosphatidylinositol-3 kinase (p85) and catalytic subunit of phosphatidylinositol-3 kinase. Blood plasma was assayed for concentrations of glucose, β-hydroxybutyric acid, non-esterified fatty acids (NEFA) and insulin. Plasma parameters followed a pattern typically observed in dairy cows. Gene expression changes were observed, but there were no changes in TNFα concentrations, which may indicate its local involvement in catabolic adaptation of adipose tissue. Changes in GLUT4 and GLUT1 mRNA abundance may reflect their involvement in reduced insulin sensitivity and in sparing glucose for milk synthesis in early lactation. Unchanged gene expression of IRS1, IRS2 and p85 over time may imply a lack of their involvement in terms of insulin sensitivity dynamics. Alternatively, it may indicate that post-transcriptional modifications of these factors came into play and may have concealed an involvement. © 2010 Blackwell Verlag GmbH.

Optimal dose and timing of insulin Aspart to mimic first phase insulin response in patients with recently onset type 2 diabetes

DEFF Research Database (Denmark)

Gredal, C.; Rosenfalck, A.; Dejgaard, A.

2008-01-01

OBJECTIVE: To assess the optimal dose and timing of subcutaneous injection of insulin Aspart (IAsp) in relation to meal to mimic first phase insulin response in patients with recently diagnosed type 2 diabetes. DESIGN AND METHODS: Twenty patients were randomised in a double blind, double dummy...... design to four standard meal tests with pre-meal injection of insulin Aspart 0.08 IU/kg BW 30 min before the meal, insulin Aspart 0.04 IU/kg BW 30 or 15 min before the meal and placebo. RESULTS: All three insulin regimes significantly reduced postprandial glucose increment (area under the curve AUC(-30...... injection of IAsp 0.08 IU/kg BW. No difference in postprandial glucose profile was demonstrated whether IAsp 0.04 IU/kg BW was administrated 15 or 30 min before mealtime. CONCLUSIONS: IAsp 0.04IU/kg BW injected subcutaneously 15 or 30 min before meal reduced the postprandial blood glucose increment without...

Impaired autoregulation of blood flow in skeletal muscle and subcutaneous tissue in long-term Type 1 (insulin-dependent) diabetic patients with microangiopathy

DEFF Research Database (Denmark)

Faris, I; Vagn Nielsen, H; Henriksen, O

1983-01-01

Autoregulation of blood flow was studied in skeletal muscle and subcutaneous tissue in seven Type 1 (insulin-dependent) diabetic patients (median age: 36 years) with nephropathy and retinopathy and in eight normal subjects of the same age. Blood flow was measured by the local 133Xe washout...... technique. Reduction in arterial perfusion pressure was produced by elevating the limb 20 and 40 cm above heart level. Blood flow remained within 10% of control values when the limb was elevated in normal subjects. In five of the seven diabetic subjects blood flow fell significantly in both tissues when...

Ivermectin disposition kinetics after subcutaneous and intramuscular administration of an oil-based formulation to cattle.

Science.gov (United States)

Lifschitz, A; Virkel, G; Pis, A; Imperiale, F; Sanchez, S; Alvarez, L; Kujanek, R; Lanusse, C

1999-10-01

Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.

Switching between intravenous and subcutaneous trastuzumab: safety results from the PrefHer trial

OpenAIRE

Gligorov, Joseph; Curigliano, Giuseppe; Müller, Volkmar; Knoop, Ann; Jenkins, Valerie; Verma, Sunil; Osborne, Stuart; Lauer, Sabine; Machackova, Zuzana; Fallowfield, Lesley; Pivot, Xavier

2017-01-01

Aim: To assess the safety and tolerability of switching between subcutaneous (SC) and intravenous (IV) trastuzumab in the PrefHer study (NCT01401166).\\ud \\ud Patients and methods: Patients with HER2-positive early breast cancer completed (neo)adjuvant chemotherapy and were randomised to receive four cycles of SC trastuzumab, via single-use injection device (SID; Cohort 1) or hand-held syringe (Cohort 2), followed by four cycles of IV, or vice versa (the crossover period presented here) as par...

Insulin aspart pharmacokinetics

DEFF Research Database (Denmark)

Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

2014-01-01

Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

Monomeric insulins and their experimental and clinical implications.

Science.gov (United States)

Brange, J; Owens, D R; Kang, S; Vølund, A

1990-09-01

Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier

Pharmacokinetics of imipenem after intravenous, intramuscular and subcutaneous administration to cats.

Science.gov (United States)

Albarellos, Gabriela A; Denamiel, Graciela A; Montoya, Laura; Quaine, Pamela C; Lupi, Martín P; Landoni, María F

2013-06-01

The study describes the pharmacokinetics and predicted efficacy of imipenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to five adult cats at a dose of 5 mg/kg. Susceptibility to imipenem [minimum inhibitory concentration (MIC)] was determined for antimicrobial resistant Escherichia coli (n = 13) and staphylococci (n = 3) isolated from domestic cat infections (urinary system, skin and conjunctiva). Maximum plasma concentrations of imipenem were 13.45 µg/ml (IV), 6.47 µg/ml (IM) and 3.83 µg/ml (SC). Bioavailability was 93.18% (IM) and 107.90% (SC). Elimination half-lives for IV, IM and SC administration were 1.17, 1.44 and 1.55 h, respectively. All tested bacteria were susceptible to imipenem; MIC values were 0.03 µg/ml for Staphylococcus species and imipenem concentrations remained above a MIC of 0.5 µg/ml for approximately 4 h (IV and IM) and 9 h (SC). Imipenem would be predicted to be effective for the treatment of antimicrobial resistant bacterial infections in cats at a dosage of 5 mg/kg every 6-8 h (IV, IM), or longer for the SC route. However, clinical trials are mandatory to establish its efficacy and proper dosing.

Costs of subcutaneous and intravenous administration of trastuzumab for patients with HER2-positive breast cancer

DEFF Research Database (Denmark)

Olsen, Jens; Jensen, Kenneth Forsstrøm; Olesen, Daniel Sloth

2018-01-01

AIM: Trastuzumab is available in an intravenous (iv.) and a subcutaneous (sc.) formulation. The objective of this study was to estimate the costs of administration of iv. and sc. trastuzumab treatment. MATERIALS & METHODS: Via interviews, we identified all the activities associated with iv. and sc....... administration. The outcome was time estimates. To estimate the administration costs, the time estimates were valued by average gross wages. RESULTS: The iv. administration takes longer time as infusion time is longer (25 or 85 min). The iv. administration is associated with higher cost for 17 cycles; €971...... (€1858 vs €887). CONCLUSION: sc. administration is associated with lower administration costs. Switching patients from iv. to sc. would make it possible to treat more patients without increasing the personnel resources....

Effectiveness of Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for Children with Type 1 Diabetes Mellitus in Clinical Practice

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Chun-xiu Gong

2014-01-01

Full Text Available Aims. To determine whether multiple daily injections (MDIs or continuous subcutaneous insulin infusion (CSII contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (≤1 year after disease onset; 1A or late (1–3 years after onset; 2A MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2: 7.37% versus 8.21%; 12 months (T3: 7.61% versus 8.41%; 24/36 months (T4/T5: 7.61% versus 8.72%; all P<0.05, but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; P=0.04. Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; P<0.05. Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management.

Monomeric insulins obtained by protein engineering and their medical implications.

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Brange, J; Ribel, U; Hansen, J F; Dodson, G; Hansen, M T; Havelund, S; Melberg, S G; Norris, F; Norris, K; Snel, L

1988-06-16

The use of insulin as an injected therapeutic agent for the treatment of diabetes has been one of the outstanding successes of modern medicine. The therapy has, however, had its associated problems, not least because injection of insulin does not lead to normal diurnal concentrations of insulin in the blood. This is especially true at meal times when absorption from subcutaneous tissue is too slow to mimic the normal rapid increments of insulin in the blood. In the neutral solutions used for therapy, insulin is mostly assembled as zinc-containing hexamers and this self-association, which under normal physiological circumstances functions to facilitate proinsulin transport, conversion and intracellular storage, may limit the rate of absorption. We now report that it is possible, by single amino-acid substitutions, to make insulins which are essentially monomeric at pharmaceutical concentrations (0.6 mM) and which have largely preserved their biological activity. These monomeric insulins are absorbed two to three times faster after subcutaneous injection than the present rapid-acting insulins. They are therefore capable of giving diabetic patients a more physiological plasma insulin profile at the time of meal consumption.

Radionuclide venography of lower limbs by subcutaneous injection; A clinical evaluation

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Wu, Chung-Chieng; Jong, Shiang-Bin (Kaohsiung Medical Coll., Taiwan (China))

1993-02-01

SC-RNV, radionuclide venography by subcutaneous injection of Tc-99m pertechnetate at acupuncture points K-3, a new alternative of lower limb venography, was recently developed in our clinical laboratory. In some of the previous studies, we have proved its superiority to radionuclide venography by intravenous injection. The current investigation was conducted to understand the reliability of SC-RNV in the diagnosis of deep vein thrombosis (DVT). Fifty-seven cases with lower leg edema, from November 1989 through October 1990, received both SC-RNV and duplex US for causative evaluation. As a result of duplex US, 26 were considered normal (non-DVT), 19 were classified as unilateral DVT, and 12 as bilateral DVT. In nineteen cases (61%, 19/31) with DVT also a XCT and/or a CV (contrast venography) was taken, that showed compatible results. All of the non-DVT had a normal pattern of SC-RNV, all of the unilateral DVT had unilateral impairment of deep vein drainage in SC-RNV, and all of the bilateral DVT had impaired deep venous drainage bilaterally in SC-RNV. It is therefore, concluded that SC-RNV is one of the best choices among available non-invasive lower-limb venographic methods. (author).

Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children

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Grohmann, Malcolm; Stewart, Claire; Welsh, Gavin; Hunt, Linda; Tavare, Jeremy; Holly, Jeff; Shield, Julian; Sabin, Matt; Crowne, Elizabeth

2005-01-01

Body fat distribution determines obesity-related morbidity in adults but little is known of the aetiology or pathophysiology in children. This study investigates differences in insulin-mediated metabolism in primary cell cultures of subcutaneous and visceral preadipocytes derived from prepubertal children. The impact of differentiation and responses to TNFα exposure was also investigated. Proliferation rates were greater in subcutaneous versus visceral preadipocytes (41 h(3) versus 69 h(4); P = 0.008). Insulin caused a dose-dependent increase in GSK-3 phosphorylation and an increase in MAPK phosphorylation over time, with increased sensitivity in subcutaneous preadipocytes. Post-differentiation, dose-dependent increases in GSK-3 phosphorylation were maintained, while MAPK phosphorylation was identical in both subtypes. No changes were observed in insulin receptor abundance pre-/post-differentiation. GLUT4 abundance was significantly increased in visceral versus subcutaneous adipocytes by 76(4)%; P = 0.03), coincidental with increased insulin-stimulated 2-deoxy-glucose transport (+150(26)% versus +79(10)%; P = 0.014) and further elevated by acute exposure to TNFα (+230(52)%; P = 0.019 versus +123(24)%; P = 0.025, respectively). TNFα also significantly increased basal glucose transport rates (+44(14)%; P = 0.006 versus +34(11)%; P = 0.007) and GLUT1 localisation to the plasma membrane. These data establish site-specific differences in subcutaneous and visceral fat cells from children. Responses to insulin varied with differentiation and TNFα exposure in the two depots, consistent with parallel changes in GLUT1/4 abundance and localisation

[News and perspectives in insulin treatment].

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Haluzík, Martin

2014-09-01

Insulin therapy is a therapeutic cornerstone in patients with type 1 diabetes and also in numerous patients with type 2 diabetes especially with longer history of diabetes. The initiation of insulin therapy in type 2 diabetes patients is often delayed which is at least partially due to suboptimal pharmacokinetic characteristics of available insulins. The development of novel insulins with more favorable characteristics than those of current insulins is therefore still ongoing. The aim of this paper is to review current knowledge of novel insulins that have been recently introduced to the market or are getting close to routine clinical use. We will also focus on the perspectives of insulin therapy in the long-term run including the alternative routes of insulin administration beyond its classical subcutaneous injection treatment.Key words: alternative routes of insulin administration - diabetes mellitus - hypoglycemia - insulin - insulin analogues.

Insulin appearance of subcutaneously infused insulin: influence of the basal rate pulse interval of the infusion pump.

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Birch, K; Hildebrandt, P; Jensen, B M; Kühl, C; Brange, J

1985-05-01

To compare the metabolic control and the pharmacokinetics of infused insulin using an insulin pump (Auto-Syringe AS 6C) which provides the basal rate in pulses every 2-10 min with a pump (Medix Syringe Driver 209) providing the basal rate in pulses every 15-60 min, 6 C-peptide negative diabetic patients received, in random order, identical, but individual, insulin treatment during one 4-day period using the Auto-Syringe pump and another 4-day period using the Medix pump. On the fourth day of each period, blood glucose and plasma-free insulin were estimated every 30 min for 7 hr and every 5 min for the next hour. Plasma-free insulin was significantly higher on 3 time points out of the 26 possible when using the Medix pump, but this was not reflected in the blood glucose concentrations which were similar in the 2 periods. The results indicate that, from a metabolic and pharmacokinetic point of view, insulin pumps working with larger intervals between the basal rate pulses are just as good as the more technically advanced and hence often more expensive pumps which provide the basal rate in more and smaller pulses.

The relationship between regional abdominal fat distribution and both insulin resistance and subclinical chronic inflammation in non-diabetic adults

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2014-01-01

Objective Obesity is associated with a high risk of insulin resistance (IR) and its metabolic complications. It is still debated that distributions of adipose tissue relate to an excess risk of IR and chronic inflammation in different race. This study was designed to examine the relation between insulin sensitivity, chronic inflammation and central fat distribution in non-diabetic volunteers in Taiwanese. Methods There were 328 volunteers without family history of diabetes mellitus and with normal oral glucose tolerance test enrolled. Total body fat and abdominal fat were measured. Abdominal fat was categorized into intraperitoneal (IP), retroperitoneal (RP) and subcutaneous (SC) fat. The IR index was estimated by homeostatic model assessment. Five inflammatory markers: adiponectin, leptin, tumor necrosing factor-α (TNF-α), resistin and high sensitive CRP (hs-CRP) were measured. Results IR was related to IP fat (r = 0.23, p fat, SC fat or total body fat. After correcting for age and sex, IP fat was the only significant predictor of IR (r2 = 58%, p = 0.001). Leptin showed the strongest relationship with all fat compartments (IP fat: r = 0.44, p = 0.001; RP fat: r = 0.36, p = 0.005, SC fat: r = 0.54, p fat: r = 0.61, p fat (r = 0.29, p = 0.004; r = -0.29, p = 0.005, respectively), but not RP, or SC fat. TNF-α and resistin were not correlated to any fat compartment. After correcting for age and sex, leptin variance was mostly explained by SC fat (41.3%), followed by IP fat (33.6%) and RP fat (25.3%). The hs-CRP and adiponectin variance were mostly explained by IP fat (40% and 49% respectively). Conclusions IP fat is better predictors of IR and subclinical chronic inflammation in Taiwanese adults. A disproportionate accumulation of abdominal fat is associated with increased risk of cardiovascular diseases. PMID:24684833

Lipid mobilization in subcutaneous adipose tissue during exercise in lean and obese humans. Roles of insulin and natriuretic peptides

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Koppo, Katrien; Larrouy, Dominique; Marques, Marie A

2010-01-01

The aim of this study was to evaluate the relative contributions of various hormones involved in the regulation of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise and to assess the impact of obesity on this regulation. Eight lean and eight obese men performed a 60-min cycle...... phentolamine and propranolol while another probe was perfused with the phosphodiesterase and adenosine receptor inhibitor aminophylline. Compared with the control condition, infusion of octreotide reduced plasma insulin levels in lean (from approximately 3.5 to 0.5 microU/ml) and in obese (from approximately 9...... to 2 microU/ml), blunted the exercise-induced rise in plasma GH and epinephrine levels in both groups, and enhanced the exercise-induced natriuretic peptide (NP) levels in lean but not in obese subjects. In both groups, octreotide infusion resulted in higher exercise-induced increases in dialysate...

Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus

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Bolinder, J.; Ostman, J.; Arner, P.

1982-01-01

The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono- 125 I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis

A time and motion study of subcutaneous versus intravenous trastuzumab in patients with HER2-positive early breast cancer

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De Cock, Erwin; Pivot, Xavier; Hauser, Nik

2016-01-01

Within PrefHer (NCT01401166), patients and healthcare professionals (HCPs) preferred subcutaneous (SC) over intravenous (IV) trastuzumab. We undertook a prospective, observational time and motion study to quantify patients' time in infusion chairs and active HCP time in PrefHer. Patients with HER2......-positive early breast cancer received four adjuvant cycles of SC trastuzumab (600 mg fixed dose via SC single-use injection device [SID, Cohort 1] or SC handheld syringe [HHS, Cohort 2]) then four cycles of standard IV trastuzumab or the reverse sequence. Generic case report forms for IV and SC management...... (range across countries: 4-16; P trastuzumab, delivered via SID or HHS, saved patient chair and active HCP times versus IV infusion, supporting a transition to either SC method....

Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

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Lu HuiLing

2010-01-01

Full Text Available Abstract Background Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP and Triglyceride (TG (LAT vs High ASP and TG (HAT. Subcutaneous (SC and omental (OM adipose tissues (n = 21 were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. Methods LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1. ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p Results HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL, lipolysis (HSL, CES1, perilipin, fatty acid binding proteins (FABP1, FABP3 and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ. By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7. HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p Conclusion Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.

Hyperglycemia in critical patients: Determinants of insulin dose choice

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Aline Klitzke Paliosa

Full Text Available Summary Objective: To identify factors that can determine the choice of intermittent subcutaneous regular insulin dose in critically ill patients with hyperglycemia. Method: Cross-sectional study in a general adult ICU with 26 beds, data collected between September and October 2014. The variables analyzed were: sex, age, previous diagnosis of diabetes mellitus, use of corticosteroids, use of lactulose, sepsis, fasting, enteral nutrition, use of dextrose 5% in water, NPH insulin prescription and blood glucose level. Patients with one or more episodes of hyperglycemia (blood glucose greater than 180 mg/dL were included as a convenience sample, not consecutively. Those with continuous insulin prescription were excluded from analysis. Results: We included 64 records of hyperglycemia observed in 22 patients who had at least one episode of hyperglycemia. The median administered subcutaneous regular human insulin was 6 IU and among the factors evaluated only blood glucose levels were associated with the choice of insulin dose administered. Conclusion: Clinical characteristics such as diet, medications and diagnosis of diabetes mellitus are clearly ignored in the decision-making regarding insulin dose to be administered for glucose control in critically ill patients with hyperglycemia.

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

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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.

Insulin signaling, inflammation, and lipolysis in subcutaneous adipose tissue of transition dairy cows either overfed energy during the prepartum period or fed a controlled-energy diet.

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Mann, S; Nydam, D V; Abuelo, A; Leal Yepes, F A; Overton, T R; Wakshlag, J J

2016-08-01

Adipose tissue mobilization is a hallmark of the transition period in dairy cows. Cows overfed energy during the dry period have higher concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) compared with cows fed a controlled-energy diet prepartum. The reason for an increase in blood NEFA concentrations at the level of adipose tissue in cows overfed energy has not been fully elucidated. One hypothesis is that cows with high BHB concentrations suffer from adipose tissue-specific insulin resistance, leading to higher rates of adipose tissue mobilization in the postpartum period. To test this hypothesis, subcutaneous adipose tissue biopsies of cows overfed energy in excess of predicted requirements by 50% in the dry period, and that had high concentrations of blood BHB postpartum (group H; n=12), were used. Findings were compared with results of biopsies from cows fed a controlled-energy diet and with low BHB concentrations postpartum (group C; n=12) to create the biggest contrast in BHB concentrations. Subcutaneous adipose tissue biopsies were obtained before and 60 min after an intravenous glucose challenge (0.25 g/kg of glucose) at 28 and 10 d before expected calving as well as on d 4 and 21 postpartum. Phosphorylation of protein kinase B, extracellular signal-regulated kinase, and hormone-sensitive lipase was determined before and after glucose infusion by Western blot. Western blot was also used to assess the baseline protein abundance of peroxisome proliferator-activated receptor gamma and insulin receptor β-subunit. In addition, gene expression of fatty acid synthase, adiponectin, monocyte chemoattractant protein 1, and tumor necrosis factor α was determined by real-time quantitative reverse-transcription PCR. Backfat thickness was determined in the thurl area by ultrasonography. Cows in group H showed a greater degree of lipogenesis prepartum, but no differences were found in lipolytic enzyme activity postpartum compared with cows

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs.

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Laber, G

1988-03-01

Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax = 0.61 +/- 0.15 micrograms/ml, a Tmax = 6 h and a t1/2 = 4.7 +/- 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax = 1.55 +/- 0.11 micrograms/ml, Tmax = 8 h and t1/2 = 4.28 +/- 0.18 h were obtained. For the higher dose Cmax = 3.14 +/- 0.04 micrograms/ml, Tmax = 8 h and t1/2 = 12.4 +/- 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.

Comparison of insulin analogue B9AspB27Glu and soluble human insulin in insulin-treated diabetes.

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Kang, S; Owens, D R; Vora, J P; Brange, J

1990-02-10

Postprandial plasma glucose excursions and plasma levels of free insulin after subcutaneous bolus injection of a rapidly absorbed monomeric insulin analogue (B9AspB27Glu) or soluble human insulin ('Actrapid HM' U100) were studied in six insulin-treated diabetic subjects. 10 U actrapid or an equimolar amount of the analogue were injected, in random order with an interval of 1 week, immediately before a 500 kcal test meal. Basal insulin levels were similar on the 2 study days (mean 74.1 [SE 5.1] pmol/l, actrapid; 79.7 [13.0] pmol/l, analogue). After injection of actrapid plasma free insulin levels rose slowly, reaching a plateau by 105 min at 222 (19) pmol/l. Injection of the analogue resulted in a rapid early peak at 30 min (798 [112] pmol/l), and levels were significantly higher than those after actrapid between 15 and 210 min. The more physiological plasma insulin levels achieved with the analogue were accompanied by a substantial reduction in postprandial plasma glucose excursions; the integrated area under the incremental plasma glucose curve was 45% lower after the analogue than after actrapid.

The effectiveness of continuous subcutaneous insulin pumps with continuous glucose monitoring in outpatient adolescents with type 1 diabetes: A systematic review.

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Matsuda, Erin; Brennan, Patricia

2012-01-01

The review question is: Are metabolic outcomes improved in outpatient adolescents (aged 13 to 19 years) with type 1 diabetes on a Continuous Subcutaneous Insulin Infusion (CSII) when continuous glucose monitoring is used, compared to self-glucose monitoring alone? Type 1 diabetes is the most common childhood paediatric disease, characterised by impairment of insulin producing βeta-cells in the pancreas. Internationally, there is variation in the incidence of type 1 diabetes in paediatric patients. According to the Center for Disease Control and Prevention (CDC) and the SEARCH for Diabetes in Youth Study Group, the overall incidence rate of this autoimmune disease is 24.3/100,000 in those 19 years of age . Annually, more than 15,000 children and adolescents are diagnosed in the United States (US) . From 1990 to 1999, the World Health Organization (WHO) launched the Multinational Project for Childhood Diabetes (DIAMOND), which was tasked with assessing type 1 diabetes in those 14 years or younger worldwide . Finland was discovered to have the highest age-adjusted incidence at 40.9 cases per 100,000/year. The lowest age-adjusted incidence is in China and Venezuela at 0.1 cases per 100,000/year. Globally, the largest increase in incidence is in those aged 10 to 14 years . This systematic review will focus on adolescent patients with type 1 diabetes, aged 13 to 19 years who manage their diabetes with an insulin pump.Patients with type 1 diabetes mellitus typically present with a history of polydipsia, polyuria, polyphagia, and weight loss . Initial findings include hyperglycemia, glycosuria, and ketones in the blood or urine . In 2009, the International Expert Committee deemed a haemoglobin A1C (glycosylated haemoglobin) of 6.5% or higher to be the standard for diagnosis . The American Diabetes Association (ADA) as well as the International Diabetes Federation and the European Association Study of Diabetes (EASD) accept this measure as the diagnostic tool for diabetes

Drug delivery options to increase patient adherence and satisfaction in the management of rheumatoid arthritis – focus on subcutaneous tocilizumab

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Nakashima Y

2014-07-01

Full Text Available Yasuharu Nakashima,1 Masakazu Kondo,2 Hisaaki Miyahara,3 Yukihide Iwamoto11Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan; 2Kondo Clinic of Rheumatology and Orthopaedic Surgery, Fukuoka, Japan; 3Department of Orthopaedic Surgery and Rheumatology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanAbstract: Rheumatoid arthritis (RA is a chronic, progressive, inflammatory disease associated with joint destruction. Tocilizumab (TCZ is a humanized monoclonal anti-interleukin-6 receptor antibody that was initially developed for use as an intravenous (IV infusion. Previous studies have shown that TCZ-IV is an important treatment option in patients with moderate-to-severe RA. A subcutaneous (SC formulation of 162 mg TCZ that was recently developed and approved provides an additional treatment option for RA patients. In the present review, we provide an update on the efficacy and safety of TCZ-SC, compared with TCZ-IV. The TCZ-SC doses of 162 mg every 2 weeks (q2w or weekly (qw were selected based on pharmacokinetic and pharmacodynamic studies. Both TCZ-SC q2w and qw regimens showed equivalent effects to TCZ-IV in most patients; however, the TCZ-SC qw regimen consistently showed a more rapid effect in terms of C-reactive protein normalization. Randomized controlled studies showed that TCZ-SC monotherapy or combined with disease-modifying antirheumatic drugs demonstrated comparable efficacy to TCZ-IV in patients who were both biologic-naïve and refractory to tumor necrosis factor inhibitors. TCZ-SC at both qw and q2w were generally well-tolerated for up to 24 weeks. There was a low rate of withdrawal due to adverse events, and their incidence was comparable with that seen with TCZ-IV. An injection site reaction was seen in approximately 10% of patients who received the subcutaneous formulation. In conclusion, although clinical results are still limited, the currently available evidence

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis

DEFF Research Database (Denmark)

Sørensen, P S; Sellebjerg, F; Lycke, J

2016-01-01

BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. METHODS: This was a double......-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying...... were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence...

Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV-infected women123

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Albu, Jeanine B; Kenya, Sonjia; He, Qing; Wainwright, Marsha; Berk, Evan S; Heshka, Stanley; Kotler, Donald P; Engelson, Ellen S

2009-01-01

Background Obesity and insulin resistance are growing problems in HIV-positive (HIV+) women receiving highly active antiretroviral therapy (HAART). Objective The objective was to determine the contribution of adipose tissue (AT) enlargement and distribution to the presence of insulin resistance in obese HIV+ women. Design Whole-body intermuscular AT (IMAT), visceral AT (VAT), subcutaneous AT (SAT), and SAT distribution (leg versus upper body) were measured by whole-body magnetic resonance imaging. Insulin sensitivity (SI) was measured with an intravenous glucose tolerance test in obese HIV+ women recruited because of their desire to lose weight (n = 17) and in obese healthy controls (n = 32). Results The HIV+ women had relatively less whole-body SAT and more VAT and IMAT than did the controls (P < 0.05 for all). A significant interaction by HIV status was observed for the relation of total SAT with SI (P < 0.001 for the regression’s slope interactions after adjustment for age, height, and weight). However, relations of IMAT, VAT, and SAT distribution (leg SAT as a percentage of total SAT; leg SAT%) with SI did not differ significantly between groups. For both groups combined, the best model predicting a low SI included significant contributions by both high IMAT and low leg SAT%, independent of age, height, and weight, and no interaction between groups was observed (overall r2 = 0.44, P = 0.0003). Conclusion In obese HIV+ women, high whole-body IMAT and low leg SAT% distribution are independently associated with insulin resistance. PMID:17616768

Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

DEFF Research Database (Denmark)

Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

2007-01-01

in lipodystrophic patients compared to nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating hormone and prolactin were similar and normal in both study groups. Ratio of subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity, which were all decreased in lipodystrophic...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression......OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose...

Will availability of inhaled human insulin (Exubera® improve management of type 2 diabetes? The design of the Real World trial

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Freemantle Nick

2006-08-01

Full Text Available Abstract Background Common deterrents to insulin therapy for both physicians and patients are the complexity and burden of daily injections. In January 2006, the first inhaled human insulin (INH, Exubera® (insulinhuman [rDNA origin]InhalationPowder was approved for use in adult patients with type 1 diabetes mellitus (T1DM or type 2 diabetes mellitus (T2DM in the United States and European Union. Results from the INH clinical trial program have shown comparable efficacy of INH to subcutaneous (SC insulin and superior efficacy versus oral antidiabetic agents; thus providing effective glycemic control in adult patients with T2DM without the requirement for preprandial injections. However, because subjects in those trials were randomized to either INH or an alternative, the studies could not estimate the effect of INH on patient acceptance of insulin therapy. Therefore, traditional study designs cannot provide answers to important and practical questions regarding real world effectiveness, which is influenced by psychological and other access barriers. Methods To overcome these limitations, the Real World Trial was designed to estimate the effect of the availability of INH as a treatment option for glycemic control. A total of approximately 700 patients from Canada, France, Germany, Italy, Spain, United Kingdom, and the United States with T2DM poorly controlled by oral agent therapy will be randomized to two different treatment settings. Patients and clinicians in both groups (A & B may choose from all licensed therapies for diabetes including SC insulin delivered by pens; INH will be an additional treatment option only available in Group A. The Real World Trial (Protocol A2171018 has been registered with ClincalTrials.gov, registration id NCT00134147. Results The primary outcome for the trial will be the difference in mean glycosylated hemoglobin (HbA1c at 6 months between groups. The design was based on a preceding feasibility study examining the

Visceral fat dominant distribution in male type 2 diabetic patients is closely related to hepatic insulin resistance, irrespective of body type

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Miyazaki Yoshinori

2009-08-01

Full Text Available Abstract Background All previous studies that investigated the association between abdominal fat distribution and insulin resistance evaluated subcutaneous and visceral fat area and/or volume, but these values were not related to the body type of each subject. In the present study we have examined the association between abdominal fat distribution and peripheral (muscle/hepatic sensitivity to insulin using the visceral to abdominal subcutaneous fat area ratio (VF/SF ratio in male patients with type 2 diabetes mellitus. This ratio defines the predominancy of visceral or subcutaneous abdominal adiposity, independent of the body type of each individual. Methods Thirty-six type 2 diabetic male patients underwent a euglycemic insulin clamp (insulin infusion rate = 40 mU/m2·min with 3-3H-glucose to measure insulin-mediated total body (primarily reflects muscle glucose disposal (TGD and suppression of endogenous (primarily reflects liver glucose production (EGP in response to a physiologic increase in plasma insulin concentration. Abdominal subcutaneous (SF and intraabdominal visceral fat (VF areas were quantitated with magnetic resonance imaging (MRI at the level of L4–5. Results TGD and TGD divided by steady state plasma insulin concentration during the insulin clamp (TGD/SSPI correlated inversely with body mass index (BMI, total fat mass (FM measured by 3H2O, SF and VF areas, while VF/SF ratio displayed no significant relationship with TGD or TGD/SSPI. In contrast, EGP and the product of EGP and SSPI during the insulin clamp (an index hepatic insulin resistance correlated positively with VF/SF ratio, but not with BMI, FM, VF or SF. Conclusion We conclude that, independent of the individual's body type, visceral fat dominant accumulation as opposed to subcutaneous fat accumulation is associated with hepatic insulin resistance, whereas peripheral (muscle insulin resistance is more closely related to general obesity (i.e. higher BMI and total FM

[Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid].

Science.gov (United States)

Arranz Martín, Alfonso; Calle Pascual, Alfonso; Del Cañizo Gómez, Francisco Javier; González Albarrán, Olga; Lisbona Gil, Arturo; Botella Serrano, Marta; Pallardo Sánchez, Luis Felipe

2015-04-01

To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Effect of insulin pump and continuous intravenous insulin on ketone body metabolism, blood gas indexes and stress state in patients with diabetic ketoacidosis

Directory of Open Access Journals (Sweden)

Hui-Jin Shi

2017-09-01

Full Text Available Objective: To study the effect of insulin pump and continuous intravenous insulin on ketone body metabolism, blood gas indexes and stress state in patients with diabetic ketoacidosis. Methods: Patients with diabetic ketoacidosis who were treated in Meizhou Maternal and Child Heath Hospital between May 2014 and March 2017 were selected as the research subjects and randomly divided into the group A who received subcutaneous insulin infusion by insulin pump and the group B who received intravenous small-dose insulin injection by micropump. The indexes of ketone body, blood gas and stress were measured before and after treatment. Results: 12 h and 24 h after treatment, serum β-hydroxybutyrate, MDA, NE, ACTH and Cor contents of both groups of patients were significantly lower than those before treatment while pH, HCO3 - and base excess levels as well as serum SOD, GSH-Px, CAT and TAC contents were significantly higher than those before treatment, and serum β-hydroxybutyrate, MDA, NE, ACTH and Cor contents of group A were significantly lower than those of group B while pH, HCO3 - and base excess levels as well as serum SOD, GSH-Px, CAT and TAC contents were significantly higher than those of group B. Conclusion: Subcutaneous insulin infusion by insulin pump can improve ketone body metabolism, acidosis status and stress state in patients with diabetic ketoacidosis.

Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

Science.gov (United States)

Morçöl, T; Nagappan, P; Nerenbaum, L; Mitchell, A; Bell, S J D

2004-06-11

An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.

21 CFR 522.1160 - Insulin.

Science.gov (United States)

2010-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a... IU per kilogram of body weight by subcutaneous injection concurrently with or right after a meal...

Browning of Subcutaneous White Adipose Tissue in Humans

OpenAIRE

Sidossis, Labros S.; Porter, Craig; Saraf, Manish K.; Børsheim, Elisabet; Radhakrishnan, Ravi S.; Chao, Tony; Ali, Arham; Chondronikola, Maria; Mlcak, Ronald; Finnerty, Celeste C.; Hawkins, Hal K.; Toliver-Kinsky, Tracy; Herndon, David N.

2015-01-01

Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT w...

Lymphatic uptake and biodistribution of liposomes after subcutaneous injection - IV. Fate of liposomes in regional lymph nodes

NARCIS (Netherlands)

Oussoren, C; Scherphof, G; van der Want, JJ; van Rooijen, N; Storm, G

1998-01-01

The ability of clodronate-containing liposomes to deplete lymph nodes of macrophages was used as a tool to investigate the fate of liposomes in regional lymph nodes after subcutaneous (s.c.) administration. Reduced lymph node localization of liposomes in macrophage-depleted lymph nodes confirmed

Radionuclide venography of lower limbs by subcutaneous injection

International Nuclear Information System (INIS)

Wu, Chung-Chieng; Jong, Shiang-Bin

1989-01-01

We have proved that subcutaneous injection (SC) of a small dose of Tc-99m pertechnetate (1 to 2 mCi: 37 to 74 MBq) at acupuncture points (K-3 and B-60) may offer an alternative method of radionuclide venography (RNV) of the lower limbs. In this study, we compared intravenous (IV) RNV and SC-RNV in 22 consecutive cases with typical signs and symptoms suggesting venous abnormality of the lower limb(s) from March to May 1988. They are 11 male and 11 female, aged 47.7±15.7 years. Among the 44 limbs of the 22 cases, 4 were normal, 12 (27.3%) were found to have varicose veins in the legs only, 18 (40.9%) had partial stenosis of the deep veins (14 poplito-tibial and 4 superficial femoral), and 13 (29.6%) had complete stenosis of the deep veins (4 poplito-tibial, 1 superficial femoral and 8 ilio-femoral. SC-RNV showed almost the same results as IV-RNV in 21 (47.7%), superior to IV-RNV in 22 (50%) (including 4.6% failure of IV-RNV), and inferior to IV-RNV in 1 (2.3%). We conclude that SC-RNV is definitely an alternative method of lower-limb venography. Since it is in most cases superior to IV-RNV, we suggest that it can take the place of IV-RNV in routine work. (author) 62 refs

Pre-exercise blood glucose affects glycemic variation of aerobic exercise in patients with type 2 diabetes treated with continuous subcutaneous insulin infusion.

Science.gov (United States)

Hu, Yun; Zhang, Dan-Feng; Dai, Lu; Li, Zheng; Li, Hui-Qin; Li, Feng-Fei; Liu, Bing-Li; Sun, Xiao-Juan; Ye, Lei; He, Ke; Ma, Jian-Hua

2018-05-03

Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC 0-60 min ). The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC 0-60 min (standardized β = -0.386, P AUC of blood glucose ≤ 4.4 mmol/L (standardized β = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P AUC 0-60 min during post-dinner was significantly higher than that during pre-lunch, post-lunch and pre-dinner (P  16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. ChiCTR-ONC-17010400, www.chictr.org.cn. Copyright © 2018 Elsevier B.V. All rights reserved.

Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs.

Science.gov (United States)

Cai, Chunbo; Qian, Lili; Jiang, Shengwang; Sun, Youde; Wang, Qingqing; Ma, Dezun; Xiao, Gaojun; Li, Biao; Xie, Shanshan; Gao, Ting; Chen, Yaoxing; Liu, Jie; An, Xiaorong; Cui, Wentao; Li, Kui

2017-05-23

Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation (Mstn -/- ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn -/- pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue. Additionally, the serum insulin level decreased and the insulin sensitivity increased significantly in Mstn -/- pigs. Moreover, we found a significant increase in levels of insulin receptor and insulin receptor substrate proteins in skeletal muscle of Mstn -/- pigs, which then activating the insulin signaling pathway. Irisin-mediated regulation is not the only pathway for the activation of insulin signal in Mstn -/- skeletal muscle. This study provides valuable insight for the treatment of human obesity and diabetes mellitus.

Pharmacokinetics of chloramphenicol following administration of intravenous and subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol, to koalas (Phascolarctos cinereus).

Science.gov (United States)

Black, L A; McLachlan, A J; Griffith, J E; Higgins, D P; Gillett, A; Krockenberger, M B; Govendir, M

2013-10-01

Clinically normal koalas (n = 19) received a single dose of intravenous (i.v.) chloramphenicol sodium succinate (SS) (25 mg/kg; n = 6), subcutaneous (s.c.) chloramphenicol SS (60 mg/kg; n = 7) or s.c. chloramphenicol base (60 mg/kg; n = 6). Serial plasma samples were collected over 24-48 h, and chloramphenicol concentrations were determined using a validated high-performance liquid chromatography assay. The median (range) apparent clearance (CL/F) and elimination half-life (t(1/2)) of chloramphenicol after i.v. chloramphenicol SS administration were 0.52 (0.35-0.99) L/h/kg and 1.13 (0.76-1.40) h, respectively. Although the area under the concentration-time curve was comparable for the two s.c. formulations, the absorption rate-limited disposition of chloramphenicol base resulted in a lower median C(max) (2.52; range 0.75-6.80 μg/mL) and longer median tmax (8.00; range 4.00-12.00 h) than chloramphenicol SS (C(max) 20.37, range 13.88-25.15 μg/mL; t(max) 1.25, range 1.00-2.00 h). When these results were compared with susceptibility data for human Chlamydia isolates, the expected efficacy of the current chloramphenicol dosing regimen used in koalas to treat chlamydiosis remains uncertain and at odds with clinical observations. © 2012 John Wiley & Sons Ltd.

Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats.

Science.gov (United States)

Albarellos, Gabriela A; Montoya, Laura; Passini, Sabrina M; Lupi, Martín P; Lorenzini, Paula M; Landoni, María F

2016-12-01

The aim of the study was to describe the pharmacokinetics and predicted efficacy of meropenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to cats at a single dose of 10 mg/kg. Five adult healthy cats were used. Blood samples were withdrawn at predetermined times over a 12 h period. Meropenem concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed with computer software. Initial estimates were determined using the residual method and refitted by non-linear regression. The time that plasma concentrations were greater than the minimum inhibitory concentration (T >MIC) was estimated by applying bibliographic MIC values and meropenem MIC breakpoint. Maximum plasma concentrations of meropenem were 101.02 µg/ml (C p(0) , IV), 27.21 µg/ml (C max , IM) and 15.57 µg/ml (C max , SC). Bioavailability was 99.69% (IM) and 96.52 % (SC). Elimination half-lives for the IV, IM and SC administration were 1.35, 2.10 and 2.26 h, respectively. Meropenem, when administered to cats at a dose of 10 mg/kg q12h,, is effective against bacteria with MIC values of 6 μg/ml, 7 μg/ml and 10 μg/ml for IV, IM and SC administration, respectively. However, clinical trials are necessary to confirm clinical efficacy of the proposed dosage regimen. © The Author(s) 2015.

Biopharmaceutical characterisation of insulin and recombinant human growth hormone loaded lipid submicron particles produced by supercritical gas micro-atomisation.

Science.gov (United States)

Salmaso, Stefano; Bersani, Sara; Elvassore, Nicola; Bertucco, Alberto; Caliceti, Paolo

2009-09-08

Homogeneous dispersions of insulin and recombinant human growth hormone (rh-GH) in tristearin/phosphatidylcholine/PEG mixtures (1.3:1.3:0.25:0.15 w/w ratio) were processed by supercritical carbon dioxide gas micro-atomisation to produce protein-loaded lipid particles. The process yielded spherical particles, with a 197+/-94 nm mean diameter, and the insulin and rh-GH recovery in the final product was 57+/-8% and 48+/-5%, respectively. In vitro, the proteins were slowly released for about 70-80 h according to a diffusive mechanism. In vivo, the insulin and glucose profiles in plasma obtained by subcutaneous administration of a dose of particles containing 2 microg insulin to diabetic mice overlapped that obtained with 2 microg of insulin in solution. Administration of a dose of particles containing 5 microg insulin resulted in faster and longer glycaemia reduction. Oral administration of 20 and 50 microg insulin equivalent particles produced a significant hypoglycaemic effect. The glucose levels decreased since 2h after administration, reaching about 50% and 70% glucose reduction in 1-2h with the lower and higher dose, respectively. As compared to subcutaneous administration, the relative pharmacological bioavailability obtained with 20 and 50 microg equivalent insulin particles was 7.7% and 6.7%, respectively. Daily subcutaneous administration of 40 microg of rh-GH-loaded particles to hypophysectomised rats induced similar body weight increase as 40 microg rh-GH in solution. The daily oral administration of 400 microg rh-GH equivalent particles elicited a slight body weight increase, which corresponded to a relative pharmacological bioavailability of 3.4% compared to subcutaneous administration.

A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

International Nuclear Information System (INIS)

Anne, Pramila Rani; Machtay, Mitchell; Rosenthal, David I.; Brizel, David M.; Morrison, William H.; Irwin, David H.; Chougule, Prakash B.; Estopinal, Noel C.; Berson, Anthony; Curran, Walter J.

2007-01-01

Purpose: Intravenous amifostine 200 mg/m 2 reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. Patients and Methods: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of ≥Grade 2 acute xerostomia. Results: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of ≥Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of ≥Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. Conclusions: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients

Efficacy of nanogold-insulin as a hypoglycemic agent

International Nuclear Information System (INIS)

Ehsan, O.; Qadir, M.I.; Malik, A.A.; Abbasi, W.S.; Ahmad, B.

2012-01-01

Nano materials have gained tremendous importance in biology and medicine, because they can be used as carriers for delivering small molecules such as drugs, proteins and genes. We have reported the binding of insulin to gold nanoparticles and its application or efficiency in subcutaneous delivery for the therapeutic treatment of diabetes mellitus. The inert gas condensation (IGC) process was used in the synthesis of gold nanoparticles. A total of hundred rabbits were used in this study. Twenty rabbits were normal designated as Group A. The remaining eighty rabbits were divided into 4 groups. In Groups B, C and D diabetes was induced by giving streptozotocin and named Diabetic control, Diabetic insulin treated and Diabetic nG-I conjugate treated respectively. It was concluded from the study that there is a significant reduction of blood glucose levels when insulin is delivered using gold nanoparticles as carriers by the subcutaneous route in diabetic rabbits and this reduction in the blood glucose level was sustained for a significantly longer period. (author)

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.

The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

Directory of Open Access Journals (Sweden)

Jin JF

2015-07-01

Full Text Available Jing-fen Jin,1 Ling-ling Zhu,2 Meng Chen,3 Hui-min Xu,3 Hua-fen Wang,1 Xiu-qin Feng,1 Xiu-ping Zhu,3 Quan Zhou31Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaBackground: Intravenous (IV, intramuscular (IM, and subcutaneous (SC are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods.Methods: A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies.Results: “SC better than IV” involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. “IV better than SC” involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. “IM better than IV” involves epinephrine, hepatitis B immunoglobulin, pegaspargase, and some antibiotics. “IV better than IM” involves ketamine, morphine, and antivenom. “IM better than SC” involves epinephrine. “SC better than IM” involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles

Rapid alleviation of signs and symptoms of rheumatoid arthritis with intravenous or subcutaneous administration of adalimumab in combination with methotrexate.

NARCIS (Netherlands)

Rau, R.; Simianer, S.; Riel, P.L.C.M. van; Putte, L.B.A. van de; Kruger, K.; Schattenkirchner, M.; Allaart, C.F.; Breedveld, F.C.; Kempeni, J.; Beck, K.; Kupper, H.

2004-01-01

OBJECTIVE: This randomized, placebo-controlled, double-blind, Phase 1 study assessed the magnitude, onset, and duration of response with intravenous (i.v.) and subcutaneous (s.c.) adalimumab (Humira, Abbott Laboratories) combined with methotrexate (MTX) in patients with active rheumatoid arthritis

A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance

Science.gov (United States)

Newgard, Christopher B; An, Jie; Bain, James R; Muehlbauer, Michael J; Stevens, Robert D; Lien, Lillian F; Haqq, Andrea M; Shah, Svati H.; Arlotto, Michelle; Slentz, Cris A; Rochon, James; Gallup, Dianne; Ilkayeva, Olga; Wenner, Brett R; Yancy, William E; Eisenson, Howard; Musante, Gerald; Surwit, Richard; Millington, David S; Butler, Mark D; Svetkey, Laura P

2009-01-01

Summary Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA) or standard chow (SC) diets. Despite having reduced food intake and weight gain equivalent to the SC group, HF/BCAA rats were equally insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1(ser307), accumulation of multiple acylcarnitines in muscle, and was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a poor dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance. PMID:19356713

The effects of increasing doses of 2 preparations of long-acting insulin on short-term plasma profiles of glucose and insulin in lactating dairy cows.

Science.gov (United States)

Winkelman, L A; Overton, T R

2012-12-01

Two experiments were conducted to investigate effects of administering increasing doses of 2 different preparations of long-acting insulin on the 24-h profiles of plasma glucose and insulin concentrations in mid lactation dairy cows. The 2 separately analyzed experiments investigated the effects administering either Humulin N (H), a neutral protamine Hagedorn insulin, or insulin glargine (Lantus, L), an insulin analog, at doses of 0 (control), 0.1, 0.2, and 0.4 IU/kg of body weight in a randomized complete block design. Sixteen cows (237±11 d in milk for H; 213±10 d in milk for L; mean ± SD) were used for each insulin preparation, resulting in n=4 for each dose within insulin preparation. Cows were fitted with a single jugular catheter on the day before the study. On the day of the study, cows were given treatments by subcutaneous injection of either sterile water or the designated insulin type and dose. Blood samples were taken hourly from the jugular catheter. Subcutaneous injection of both H and L resulted in linear decreases in plasma glucose concentrations, increased area under the curve, and decreased nadir for plasma glucose following administration of the insulin preparations. Plasma insulin concentration linearly increased with increasing dose of H. Though elevated concentrations of insulin were measurable in cows treated with H, they were not measurable in cows treated with L. Attempts to measure overall insulin concentrations and metabolites of L by a commercially available ELISA and a commercially available RIA kit were not successful and did not retrieve values that we felt truly represented the amount of insulin activity exhibited during this treatment. Both long-acting insulin preparations elicited insulin-like activity in lactating dairy cows, as evidenced by reduced plasma glucose concentrations. Given these results, the potential exists to use both H and L to study the effects of insulin in mid lactation dairy cows without the confounding

Subcutaneous white adipocytes express a light sensitive signaling pathway mediated via a melanopsin/TRPC channel axis.

Science.gov (United States)

Ondrusova, Katarina; Fatehi, Mohammad; Barr, Amy; Czarnecka, Zofia; Long, Wentong; Suzuki, Kunimasa; Campbell, Scott; Philippaert, Koenraad; Hubert, Matthew; Tredget, Edward; Kwan, Peter; Touret, Nicolas; Wabitsch, Martin; Lee, Kevin Y; Light, Peter E

2017-11-27

Subcutaneous white adipose tissue (scWAT) is the major fat depot in humans and is a central player in regulating whole body metabolism. Skin exposure to UV wavelengths from sunlight is required for Vitamin D synthesis and pigmentation, although it is plausible that longer visible wavelengths that penetrate the skin may regulate scWAT function. In this regard, we discovered a novel blue light-sensitive current in human scWAT that is mediated by melanopsin coupled to transient receptor potential canonical cation channels. This pathway is activated at physiological intensities of light that penetrate the skin on a sunny day. Daily exposure of differentiated adipocytes to blue light resulted in decreased lipid droplet size, increased basal lipolytic rate and alterations in adiponectin and leptin secretion. Our results suggest that scWAT function may be directly under the influence of ambient sunlight exposure and may have important implications for our current understanding of adipocyte biology. (150 words).

Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

DEFF Research Database (Denmark)

Vestergaard, H; Andersen, P H; Lund, S

1994-01-01

The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle...... glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin...... were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis of muscle biopsies from...

Subcutaneous injection of thallium-201 chloride and gallium-67 citrate at acupuncture point K-3

International Nuclear Information System (INIS)

Johg, Shiang-Bin; Wu, Chung-Chieng; Chen, Ming-Feng; Wu, Sheng-Nan

1992-01-01

Subcutaneous (SC) injection of 99m Tc pertechnetate ( 99m Tc) at acupuncture points K-3 is a new method of lower-limb radionuclide venography. To investigate the mechanism of absorption of 99m Tc from SC injected sites into vascular system, various radioisotopes such as 201 Tl chloride ( 201 Tl) and 67 Ga citrate ( 67 Ga) were SC injected at K-3 points in animal and human-beings experiments. It was found that 99m Tc and 201 Tl were absorbed rapidly from K-3 points through venous system and into whole body soft tissue. However, 67 Ga with a larger effective ionic radius than 201 Tl was not absorbed throughout the observation of 5 minutes. Furthermore, intravenous administration of digitalis, a Na + -K + pump blocker, did not inhibit the absorption of 99m Tc and 201 Tl after SC injection at K-3 points. These results suggest that absorption of radionuclides on SC injection at K-3 points is mainly through the passive pathway of diffusion rather than the active transport, and the effective ionic radius may be a major factor influencing the absorption rate of the radionuclides. (author)

Insulin aspart pharmacokinetics: an assessment of its variability and underlying mechanisms.

Science.gov (United States)

Rasmussen, Christian Hove; Røge, Rikke Meldgaard; Ma, Zhulin; Thomsen, Maria; Thorisdottir, Rannveig Linda; Chen, Jian-Wen; Mosekilde, Erik; Colding-Jørgensen, Morten

2014-10-01

Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control post-prandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between and within individuals. The present article identifies the main physiological mechanisms that govern the PK of IAsp following subcutaneous administration and quantifies them in terms of their contribution to the overall variability. CT scanning data from Thomsen et al. (2012) are used to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic distribution and elimination (Pørksen et al., 1997; Sjöstrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b) are analyzed in the nonlinear mixed effects software Monolix® to determine the presence and effects of the mechanisms described in this article. The distribution of IAsp in the subcutaneous depot show an initial dilution of approximately a factor of two in a single experiment. Injected insulin hexamers exist in a chemical equilibrium with monomers and dimers, which depends strongly on the degree of dilution in subcutis, the presence of auxiliary substances, and a variety of other factors. Sensitivity to the initial dilution in subcutis can thus be a cause of some of the variability. Temporal variations in the PK are explained by variations in the subcutaneous blood flow. IAsp antibodies are found to be a large contributor to the variability of total insulin PK in a study by Chen et al. (2005), since only

Addition of 20-kDa PEG to Insulin Lispro Alters Absorption and Decreases Clearance in Animals.

Science.gov (United States)

Knadler, Mary Pat; Nguyen, Tri-Hung; Campanale, Kristina; De Veer, Michael J; Beals, John M; Li, Shun; Hansen, Ryan; Siesky, Angela; Michael, M Dodson; Porter, Christopher J H

2016-12-01

Determine the pharmacokinetics of insulin peglispro (BIL) in 5/6-nephrectomized rats and study the absorption in lymph duct cannulated (LDC) sheep. BIL is insulin lispro modified with 20-kDa linear PEG at lysine B28 increasing the hydrodynamic size to 4-fold larger than insulin lispro. Pharmacokinetics of BIL and insulin lispro after IV administration were compared in 5/6-nephrectomized and sham rats. BIL was administered IV or SC into the interdigital space of the hind leg, and peripheral lymph and/or serum samples were collected from both LDC and non-LDC sheep to determine pharmacokinetics and absorption route of BIL. The clearance of BIL was similar in 5/6-nephrectomized and sham rats, while the clearance of insulin lispro was 3.3-fold slower in 5/6-nephrectomized rats than in the sham rats. In non-LDC sheep, the terminal half-life after SC was about twice as long vs IV suggesting flip-flop pharmacokinetics. In LDC sheep, bioavailability decreased to <2%; most of the dose was absorbed via the lymphatic system, with 88% ± 19% of the dose collected in the lymph after SC administration. This work demonstrates that increasing the hydrodynamic size of insulin lispro through PEGylation can impact both absorption and clearance to prolong drug action.

EFFECT OF INSULIN ON ENDOCRINE PANCREAS FUNCTION DURING LATE PREGNANCY IN THE RAT

NARCIS (Netherlands)

WIJKSTRA, S; MOES, H; SCHUILING, GA; KOITER, TR

To partly or completely satisfy the increasing demand for insulin, pregnant rats were infused SC with human insulin (2.4 or 4.8 IU/day) from day 14 to day 20 of gestation. Cyclic control rats underwent the same procedure of 6 days of insulin-treatment. During the treatment all,stoups of rats were

Subcutaneously administered antibiotics: a national survey of current practice from the French Infectious Diseases (SPILF) and Geriatric Medicine (SFGG) society networks.

Science.gov (United States)

Forestier, E; Paccalin, M; Roubaud-Baudron, C; Fraisse, T; Gavazzi, G; Gaillat, J

2015-04-01

A national survey was performed to explore antibiotic prescription by the subcutaneous (sc) route among French infectious diseases and geriatric practitioners. Among the participating physicians, 367 (96.1%) declared administering sc antibiotics at some point. Ceftriaxone was prescribed sc by all but one, and ertapenem, teicoplanin, aminoglycosides and amoxicillin by 33.2%, 39.2%, 35.1% and 15.3%, respectively. The sc route was resorted to mainly in case of unavailable oral, intravenous or intramuscular routes, especially during palliative care. Pain, skin necrosis and lack of efficacy were the main adverse effects, reported by 70.8%, 12.8% and 19.9% of practitioners, respectively. Further studies are needed to precise the indications, modalities and tolerance of sc antibiotic use. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Determination of 24-hour insulin infusion pattern by an artificial endocrine pancreas for intravenous insulin infusion with a miniature pump

DEFF Research Database (Denmark)

Kølendorf, K; Christiansen, J S; Bojsen, J

1981-01-01

UNLABELLED: Intravenous insulin infusion with a glucose controlled insulin infusion system (GCIIS) is known to restore glucose homeostasis. A simpler approach to improve blood glucose regulation is preprogrammed intravenous insulin infusion with portable pumps without sensor-mediated feedback. We...... report a study designed to evaluate whether the preprogrammed insulin infusion pattern to be used in the miniature insulin infusion pump (MIIP) could be optimized by concomitant employment of the GCIIS for blood glucose control. Six juvenile-onset insulin-dependent diabetics (mean age 31 yrs) were...... studied. Mean blood glucose (MBG) was 6.2 mmol/l +/- 0.5 (SD) during glucose controlled infusion and 5.3 +/- 0.6 during the combined MIIP + GCIIS-day. The insulin requirements calculated from the s.c. regimen (56 U +/- 10 SD) were identical to the GCIIS-measured (51 U +/- 14) and to the amounts delivered...

Relationship between Optimum Mini-doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes - A Simulation Study

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Wendt, Sabrina Lyngbye; Schmidt, Signe

2017-01-01

-treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba-insulin), insulin on board...... (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre-defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin...... levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin...

Health-Related Quality of Life with Subcutaneous C1-Inhibitor for Prevention of Attacks of Hereditary Angioedema.

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Lumry, William R; Craig, Timothy; Zuraw, Bruce; Longhurst, Hilary; Baker, James; Li, H Henry; Bernstein, Jonathan A; Anderson, John; Riedl, Marc A; Manning, Michael E; Keith, Paul K; Levy, Donald S; Caballero, Teresa; Banerji, Aleena; Gower, Richard G; Farkas, Henriette; Lawo, John-Philip; Pragst, Ingo; Machnig, Thomas; Watson, Douglas J

2018-01-31

Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on

Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

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Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

2017-05-01

In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

Budget impact of continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes who experience severe recurrent hypoglycemic episodes in Spain.

Science.gov (United States)

Giménez, Marga; Elías, Isabel; Álvarez, María; Quirós, Carmen; Conget, Ignacio

Hypoglycemia is one of the most common complications to achieve a good metabolic control, and has been listed by several scientific associations as a common indication to start treatment with continuous subcutaneous insulin infusion (CSII). Use of CSII is still residual in Spain as compared to neighbouring countries, and cost of acquisition cost is one of the main reasons. This study estimates the budget impact of treatment with CSII, as compared to multiple daily insulin injections, of patients with type 1 diabetes mellitus who experience recurrent severe hypoglycemia episodes from the National Healthcare System perspective. Budget impact was based on a retrospective, observational study evaluating the efficacy of CSII in patients with type 1 diabetes mellitus conducted at Hospital Clínic i Universitari in Barcelona, where one of the main indications for switching to CSII were recurrent severe hypoglycemia episodes. The mean number of annual episodes was 1.33 in the two years prior to CSII start and 0.08 in the last two years of follow up (p=0.003). Costs of treatment and major hypoglycemic events over a four-year period were considered. Costs were taken from different Spanish data sources and expressed in € of 2016. Treatment with CSII increased costs by €9,509 per patient as compared to multiple daily insulin injections (€11,902-€2,393). Cost associated to severe hypoglycemic events decreased by €19,330 per patient treated with CSIII (€1,371-€20,701). Results suggest mean total savings of €9,821 per patient during the four-year study period. The higher costs associated to CSII therapy may be totally offset by the severe hypoglycemic events prevented. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Short-and long-term glucocorticoid treatment enhances insulin signalling in human subcutaneous adipose tissue

OpenAIRE

Gathercole, LL; Morgan, SA; Bujalska, IJ; Stewart, PM; Tomlinson, JW

2011-01-01

Background: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's syndrome) is characterized by increased adiposity and insulin resistance. Although GCs cause global insulin resistance in vivo, we have previously shown that GCs are able to augment insulin action in human adipose tissue, contrasting with their action in skeletal muscle. Cushing's syndrome develops following chronic GC exposure and, in addition, is a state of hyperinsulinemia. Objectives: We have therefore compared the ...

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.

Testosterone therapy decreases subcutaneous fat and adiponectin in aging men

DEFF Research Database (Denmark)

Frederiksen, L.; Højlund, K.; Hougaard, D. M.

2012-01-01

OBJECTIVE: Testosterone therapy increases lean body mass and decreases total fat mass in aging men with low normal testosterone levels. The major challenge is, however, to determine whether the metabolic consequences of testosterone therapy are overall positive. We have previously reported that 6......-month testosterone therapy did not improve insulin sensitivity. We investigated the effect of testosterone therapy on regional body fat distribution and on the levels of the insulin-sensitizing adipokine, adiponectin, in aging men with low normal bioavailable testosterone levels. DESIGN: A randomized......, double-blinded, placebo-controlled study on 6-month testosterone treatment (gel) in 38 men, aged 60–78 years, with bioavailable testosterone 94 cm. METHODS: Central fat mass (CFM) and lower extremity fat mass (LEFM) were measured by dual X-ray absorptiometry. Subcutaneous abdominal adipose tissue (SAT...

Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy.

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Belen Sadaba

Full Text Available Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV or oral routes, but subcutaneous (SC administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA.From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p=0.160. Bioavalability of SC palonosetron was 118% (95% IC: 69-168. Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration.Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy.ClinicalTrials.gov NCT01046240.

Peripheral Insulin Doesn’t Alter Appetite of Broiler Chicks

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Lei Liu

2016-09-01

Full Text Available An experiment was conducted to investigate the effect of peripheral insulin treatment on appetite in chicks. Six-d-age chicks with ad libitum feeding or fasting for 3 h before injection received a subcutaneous injection of 0, 1, 3, 5, 10, or 20 IU of insulin or vehicle (saline. The results showed peripheral insulin treatment (1 to 20 IU did not alter significantly the feed intake in chicks under either ad libitum feeding or fasting conditions within 4 h (p>0.05. Compared with the control, plasma glucose concentration was significantly decreased after insulin treatment of 3, 5, 10, and 20 IU for 4 h in chicks with ad libitum feeding (p0.05. All results suggest peripheral administration of insulin has no effect on appetite in chicks.

The use of Continuous Subcutaneous Insulin Infusion (CSII): parental and professional perceptions of self-care mastery and autonomy in children and adolescents.

Science.gov (United States)

Weissberg-Benchell, Jill; Goodman, Shirley S; Antisdel Lomaglio, Jeanne; Zebracki, Kathy

2007-01-01

To describe parent-perceived mastery of Continuous Subcutaneous Insulin Infusion (CSII) specific skills and level of autonomy for these tasks among youth with type 1 diabetes. One hundred and sixty-three parents of youth using CSII and 142 diabetes clinicians participated. Parents reported their child's mastery and autonomy of CSII-specific skills. Clinicians indicated the age at which 50% of their patients mastered these skills. Parents report CSII skill mastery between 10.9 and 12.8 years. Very few achieved skill mastery on all CSII-related tasks. Parent- and clinician-expectations for age of skill acquisition were consistent with one another. Parents shared CSII task responsibility with their children even after their children have attained skill mastery. The recent emphasis on maintaining parental involvement in diabetes care seems to have been translated into clinical practice. Parents remain involved in their child's CSII care even after they believe their child has mastered these skills.

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

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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.

WNT5A-JNK regulation of vascular insulin resistance in human obesity.

Science.gov (United States)

Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

2016-12-01

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese (BMI 26±2 kg/m 2 ) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

Neutral insulin solutions physically stabilized by addition of Zn2+.

Science.gov (United States)

Brange, J; Havelund, S; Hommel, E; Sørensen, E; Kühl, C

1986-01-01

Commercial neutral insulin solutions, all of which contain 2-3 zinc atoms per hexameric unit of insulin, have a relatively limited physical stability when exposed to heat and movement, as for example in insulin infusion pumps. Physical stabilization of neutral insulin solutions has been obtained by addition of two extra Zn2+ per hexamer of insulin. This addition stabilizes porcine and human neutral solutions equally well and does not affect the chemical stability of the insulin. The stabilization is probably obtained by a further strengthening of the hexameric structure of insulin, so that the formation of insoluble insulin fibrils (via the dissociation into the insulin monomer or dimer) is impeded or prevented. The addition of an extra 2 Zn2+ has been shown to be without influence on the insulin immunogenicity in rabbits or on the rate of absorption after subcutaneous injection in diabetic patients. It is concluded that neutral insulin solution can be physically stabilized by addition of extra Zn2+ without affecting other qualities of the insulin preparation including chemical stability, immunogenicity, and duration of action after injection.

Assessment of use of specific features of subcutaneous insulin infusion systems and their relationship to metabolic control in patients with type 1 diabetes.

Science.gov (United States)

Quirós, Carmen; Patrascioiu, Ioana; Giménez, Marga; Vinagre, Irene; Vidal, Mercè; Jansà, Margarita; Conget, Ignacio

2014-01-01

Patients with type 1 diabetes (T1DM) treated with continuous subcutaneous insulin infusion (CSII) have available several specific features of these devices. The aim of this study was to evaluate the relationship between real use of them and the degree of glycemic control in patients using this therapy. Forty-four T1DM patients on CSII therapy with or without real-time continuous glucose monitoring (CGM) were included. Data from 14 consecutive days were retrospectively collected using the therapy management software CareLink Personal/Pro(®) and HbA1c measurement performed at that period. The relationship between the frequency of usie of specific features of insulin pumps (non-sensor augmented or sensor-augmented) and glycemic control was analyzed. Mean HbA1c in the group was 7.5 ± .8%. Mean daily number of boluses administered was 5.1 ± 1.8, with 75.4% of them being bolus wizards (BW). Daily number of boluses was significantly greater in patients with HbA1c 7.5% (5.3 ± 1.6 vs. 4.3 ± 1.6, P=.056). There was a trend to greater use of BW in patients with better control (82.8 ± 21.4% vs. 69.9 ± 29.1%, P=.106). HbA1c was lower in patients using CGM (n=8) as compared to those not using sensor-augmented pumps (7.6 ± .8 vs 7.1 ± .7, P=.067), but the difference was not statistically significant. More frequent use of BW appears to be associated to better metabolic control in patients with T1DM using pump therapy. In standard clinical practice, augmentation of insulin pump with CGM may be associated to improved glycemic control. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

The brain response to peripheral insulin declines with age: a contribution of the blood-brain barrier?

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Sartorius, Tina; Peter, Andreas; Heni, Martin; Maetzler, Walter; Fritsche, Andreas; Häring, Hans-Ulrich; Hennige, Anita M

2015-01-01

It is a matter of debate whether impaired insulin action originates from a defect at the neural level or impaired transport of the hormone into the brain. In this study, we aimed to investigate the effect of aging on insulin concentrations in the periphery and the central nervous system as well as its impact on insulin-dependent brain activity. Insulin, glucose and albumin concentrations were determined in 160 paired human serum and cerebrospinal fluid (CSF) samples. Additionally, insulin was applied in young and aged mice by subcutaneous injection or intracerebroventricularly to circumvent the blood-brain barrier. Insulin action and cortical activity were assessed by Western blotting and electrocorticography radiotelemetric measurements. In humans, CSF glucose and insulin concentrations were tightly correlated with the respective serum/plasma concentrations. The CSF/serum ratio for insulin was reduced in older subjects while the CSF/serum ratio for albumin increased with age like for most other proteins. Western blot analysis in murine whole brain lysates revealed impaired phosphorylation of AKT (P-AKT) in aged mice following peripheral insulin stimulation whereas P-AKT was comparable to levels in young mice after intracerebroventricular insulin application. As readout for insulin action in the brain, insulin-mediated cortical brain activity instantly increased in young mice subcutaneously injected with insulin but was significantly reduced and delayed in aged mice during the treatment period. When insulin was applied intracerebroventricularly into aged animals, brain activity was readily improved. This study discloses age-dependent changes in insulin CSF/serum ratios in humans. In the elderly, cerebral insulin resistance might be partially attributed to an impaired transport of insulin into the central nervous system.

Effect of increasing body condition on key regulators of fat metabolism in subcutaneous adipose tissue depot and circulation of nonlactating dairy cows.

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Locher, L; Häussler, S; Laubenthal, L; Singh, S P; Winkler, J; Kinoshita, A; Kenéz, Á; Rehage, J; Huber, K; Sauerwein, H; Dänicke, S

2015-02-01

In response to negative energy balance, overconditioned cows mobilize more body fat than thin cows and subsequently are prone to develop metabolic disorders. Changes in adipose tissue (AT) metabolism are barely investigated in overconditioned cows. Therefore, the objective was to investigate the effect of increasing body condition on key regulator proteins of fat metabolism in subcutaneous AT and circulation of dairy cows. Nonlactating, nonpregnant dairy cows (n=8) investigated in the current study served as a model to elucidate the changes in the course of overcondition independent from physiological changes related to gestation, parturition, and lactation. Cows were fed diets with increasing portions of concentrate during the first 6wk of the experiment until 60% were reached, which was maintained for 9wk. Biopsy samples from AT of the subcutaneous tailhead region were collected every 8wk, whereas blood was sampled monthly. Within the experimental period cows had an average BW gain of 243±33.3 kg. Leptin and insulin concentrations were increased until wk 12. Based on serum concentrations of glucose, insulin, and nonesterified fatty acids, the surrogate indices for insulin sensitivity were calculated. High-concentrate feeding led to decreased quantitative insulin sensitivity check index and homeostasis model assessment due to high insulin and glucose concentrations indicating decreased insulin sensitivity. Adiponectin, an adipokine-promoting insulin sensitivity, decreased in subcutaneous AT, but remained unchanged in the circulation. The high-concentrate diet affected key enzymes reflecting AT metabolism such as AMP-activated protein kinase and hormone-sensitive lipase, both represented as the proportion of the phosphorylated protein to total protein, as well as fatty acid synthase. The extent of phosphorylation of AMP-activated protein kinase and the protein expression of fatty acid synthase were inversely regulated throughout the experimental period, whereas

PPARβ expression in rectus abdominis and abdominal subcutaneous fat of patients with gestational diabetes mellitus and its relationship with glucolipid metabolism

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Xiao-Yan Zhang

2017-01-01

Full Text Available Objective: To study the relationship between peroxisome proliferator-activated receptor β (PPARβ expression in rectus abdominis as well as abdominal subcutaneous fat of patients with gestational diabetes mellitus (GDM and glucolipid metabolism. Methods: The pregnant women who received routine antenatal care and planned to receive selective caesarean section in Obstetrics Department of our hospital between May 2012 and March 2016 were retrospectively analyzed, and 74 healthy pregnant women and 58 pregnant women with GDM were screened and included in the control group and gestational diabetes mellitus group (GDM group respectively. Rectus abdominis and abdominal subcutaneous fat were collected during Cesarean section to determine the expression of PPARβ was measured; peripheral blood was collected at middle-late pregnancy to determine the content of blood glucose metabolism and lipid metabolism indexes as well as adipocytokines. Results: PARβ mRNA expression and protein expression in rectus abdominis and abdominal subcutaneous fat of GDM group were significantly lower than those of control group (P＜0.05; homeostasis model assessment insulin secretion index (HOMA-β, homeostasis model assessment insulin resistance (HOMA-IR and OGTT glucose curve (AUCG levels as well as serum low-density lipoprotein cholesterol (LDL-C, triglyceride (TG, cholesterol (TC, Leptin, Resistin and Chemerin content of GDM group were significantly higher than those of control group (P＜0.05 while early insulin secretion index (ΔI30/ΔG30 and insulin sensitive index composite (ISIcomp levels as well as serum high-density lipoprotein cholesterol (HDL-C, Omentin-1 and Omentin-1 and adiponectin (ADPN content were significantly lower than those of control group (P＜0.05; PARβ mRNA expression and protein expression were negatively correlated with HOMA-β, HOMA IR, area under the AUCG, LDL-C, TG, TC, Leptin, Resistin and Chemerin, and positively correlated with ΔI30/�

Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients.

Science.gov (United States)

Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

2015-05-01

Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

Meal fat storage in subcutaneous adipose tissue: comparison of pioglitazone and glipizide treatment of type 2 diabetes.

Science.gov (United States)

Basu, Ananda; Basu, Rita; Pattan, Vishwanath; Rizza, Robert A; Jensen, Michael D

2010-10-01

Treatment of type 2 diabetes (T2DM) with pioglitazone changes abdominal fat in the opposite direction as treatment with glipizide. To determine whether these two medications affect adipose tissue meal fatty acid storage differently we studied 19 T2DM treated with either pioglitazone (n = 8) or glipizide (n = 11) and 11 non-DM control subjects matched for age, BMI, abdominal and leg fat. A breakfast mixed meal containing [1-(14)C]triolein was given and abdominal and femoral subcutaneous (sc) adipose tissue biopsies were collected 6 and 24 h later to measure meal fatty acid storage. The portion of meal fatty acids stored in upper body sc and lower body sc adipose tissue did not differ between non-DM and T2DM subjects either at 6 or 24 h. Likewise, meal fatty acid storage did not differ between the T2DM participants treated with pioglitazone or glipizide. We conclude that meal fatty acid storage in upper body and lower body sc adipose tissue is not abnormal in T2DM patients treated with pioglitazone or glipizide.

Using Glucose Tolerance Tests to Model Insulin Secretion and Clearance

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Anthony Shannon

2005-04-01

Full Text Available The purpose of the studies described in this paper is to develop theoretically and to validate experimentally mathematical compartment models which can be used to predict plasma insulin levels in patients with diabetes mellitus (DM. In the case of Type 2 Diabetes Mellitus (T2DM, the C-peptide levels in the plasma were measured as part of routine glucose tolerance tests in order to estimate the prehepatic insulin secretion rates. In the case of Type 1 Diabetes Mellitus (T1DM, a radioactive labelled insulin was used to measure the absorption rate of insulin after a subcutaneous injection of insulin. Both models gave close fits between theoretical estimates and experimental data, and, unlike other models, it is not necessary to seed these models with initial estimates.

Effect of continuous subcutaneous insulin infusion on kidney function and size in IDDM patients

DEFF Research Database (Denmark)

Christensen, C K; Christiansen, J S; Schmitz, A

1987-01-01

insulin infusion (CSII) (n = 12) or unchanged conventional insulin treatment (CIT) (n = 12). GFR, RPF, and kidney volume were identical but significantly increased above normal values in the two groups at the start of the study. After 24 months of CSII treatment, significant reduction in GFR was seen...

A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the Management of Diabetes Mellitus.

Science.gov (United States)

Candido, Riccardo; Wyne, Kathleen; Romoli, Ester

2018-04-13

Basal-bolus therapy (BBT) refers to the combination of a long-acting basal insulin with a rapid-acting insulin at mealtimes. Basal insulin glargine 100 U/mL and prandial insulin lispro have been available for many years and there is a substantial evidence base to support the efficacy and safety of these agents when they are used in BBT or basal-plus therapy for patients with type 1 or type 2 diabetes mellitus (T1DM, T2DM). With the growing availability of alternative insulins for use in such regimens, it seems timely to review the data regarding BBT with insulin glargine 100 U/mL and insulin lispro. In patients with T1DM, BBT with insulin glargine plus insulin lispro provides similar or better glycemic control and leads to less nocturnal hypoglycemia compared to BBT using human insulin as the basal and/or prandial component, and generally provides similar glycemic control and rates of severe hypoglycemia to those achieved with insulin lispro administered by continuous subcutaneous insulin infusion (CSII). Studies evaluating BBT with insulin glargine plus insulin lispro in patients with T2DM also demonstrate the efficacy and safety of these insulins. Available data suggest that BBT with insulin glargine and insulin lispro provides similar levels of efficacy and safety in pediatric and adult populations with T1DM and in adult patients and those aged more than 65 years with T2DM. These insulin preparations also appear to be safe and effective for controlling T2DM in people of different ethnicities and in patients with T1DM or T2DM and comorbidities. Eli Lilly and Company.

Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats

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Xin-Yu Huang

2016-01-01

Full Text Available To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6, Zusanli (ST36, and Sanyinjiao (SP6; in contrast, acupuncture to Shenshu (BL23 was administered perpendicularly. For Neiguan (PC6 and Zusanli (ST36, needles were connected to an electroacupuncture (EA apparatus. Fasting blood glucose (FPG was measured by glucose oxidase method. Plasma fasting insulin (FINS and serum C peptide (C-P were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR, which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

Pharmacokinetics of a new diclofenac sodium formulation developed for subcutaneous and intramuscular administration.

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Zeitlinger, Markus; Rusca, Antonio; Oraha, Alhan Z; Gugliotta, Barbara; Müller, Markus; Ducharme, Murray P

2012-06-01

To assess the relative bioavailability of diclofenac sodium hydroxypropyl β-cyclodextrin (HPβCD) administered via the subcutaneous (s.c.) and intramuscular (i.m.) route versus Voltaren® i.m. and to evaluate the dose linearity and pharmacokinetics of the s.c. formulation at three dose levels. Safety and local tolerability were also assessed. One single-dose, randomized, three-way, crossover relative bioavailability study and one linearity single escalating dose, randomized, three-way cross-over pharmacokinetic study were conducted at two different clinical sites. A total of 42 healthy male and female subjects participated in both studies. Subjects received 75 mg/ml diclofenac sodium HPβCD (i.m. and s.c.) and Voltaren® 75 mg/3 ml (i.m.) in Study 1 and 25, 50, or 75 mg/ml diclofenac sodium HPβCD (s.c.) in Study 2. Study 1 demonstrated bioequivalence of the s.c. test formulation with Voltaren® i.m. with respect to Cmax and AUC. Bioequivalence of the test i.m. with Voltaren® i.m. was also demonstrated (except the upper limit of the 90% confidence interval (CI) for Cmax which marginally exceeded the 80 - 125% range (125.78%)). Study 2 demonstrated that after s.c. administration of the test formulation, both Cmax and AUC are linearly related to the tested diclofenac doses. All tested doses were safe and locally well-tolerated with no serious adverse events reported. Bioequivalence of diclofenac HPβCD 75 mg/ml after s.c. and i.m. administration with Voltaren® i.m. was demonstrated, except for the marginal deviation in Cmax when comparing the i.m. test and Voltaren®. Linearity was also demonstrated for the three doses intended for marketing.

Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

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Tinahones Francisco

2012-04-01

Full Text Available Abstract Background The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR. Results Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC and omentum (OM adipose tissues from morbidly obese patients (n = 26 with low (OB/L-IR (healthy obese and high (OB/H-IR degrees of IR, and lean controls (n = 17. Another objective was to examine angiogenic factor correlations with obesity and IR. Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. Conclusion We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology.

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

International Nuclear Information System (INIS)

Fujii, Masakazu; Inoguchi, Toyoshi; Batchuluun, Battsetseg; Sugiyama, Naonobu; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

2013-01-01

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

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Fujii, Masakazu, E-mail: masakazu731079@yahoo.co.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inoguchi, Toyoshi, E-mail: toyoshi@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Batchuluun, Battsetseg, E-mail: battsetseg.batchuluun@gmail.com [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sugiyama, Naonobu, E-mail: nao1@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Kobayashi, Kunihisa, E-mail: nihisak@fukuoka-u.ac.jp [Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin, Chikushino, Fukuoka 818-8502 (Japan); Sonoda, Noriyuki, E-mail: noriyuki@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Takayanagi, Ryoichi, E-mail: takayana@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2013-08-16

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.

Effects of Preceding Ethanol Intake on Glucose Response to Low-Dose Glucagon in Individuals With Type 1 Diabetes

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Nørgaard, Kirsten; Tetzschner, Rikke

2018-01-01

OBJECTIVE: This study investigated whether preceding ethanol intake impairs glucose response to low-dose glucagon in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a randomized, crossover, placebo-controlled study in 12 insulin pump-treated individuals (median...... ethanol compared with placebo. The second glucagon bolus had similar responses between visits, but PG remained 1.8 ± 0.7 mmol/L lower after ethanol compared with placebo. CONCLUSIONS: The ability of low-dose glucagon to treat mild hypoglycemia persisted with preceding ethanol intake, although it tended...... to be metabolized, and a subcutaneous (s.c.) insulin bolus was given to induce mild hypoglycemia. When plasma glucose (PG) was ≤3.9 mmol/L, 100 µg glucagon was given s.c., followed by another s.c. 100 µg glucagon 2 h later. Primary end point was incremental peak PG induced by the first glucagon bolus. RESULTS...

An overview of natural polymers for oral insulin delivery.

Science.gov (United States)

Sonia, T A; Sharma, Chandra P

2012-07-01

Current therapy for diabetes mellitus through oral anti-diabetic drugs and subcutaneous administration of insulin suffers from serious disadvantages, such as patient noncompliance and occasional hypoglycemia. Moreover, these approaches doesn't mimic the normal physiological pattern of insulin release. Oral route would be the most convenient and preferred route if it is available. Polymeric nano and/or microparticles, either natural or synthetic have been used as matrices for oral insulin delivery. Natural polymers are of particular interest due to their nontoxic, biocompatible, biodegradable and hydrophilic nature. Among the natural polymers used for oral insulin delivery, chitosan (CS) is widely explored owing to its ease of chemical modification and favorable biological properties. In addition, many advantages such as safety, biodegradability, widespread availability and low cost justify the continuing development of promising insulin delivery system based on CS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patient safety and minimizing risk with insulin administration - role of insulin degludec.

Science.gov (United States)

Aye, Myint M; Atkin, Stephen L

2014-01-01

Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long

Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers

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Cecile Berteau

2010-09-01

Full Text Available Cecile Berteau1, Florence Schwarzenbach1, Yves Donazzolo2, Mathilde Latreille2, Julie Berube3, Herve Abry1, Joël Cotten1, Celine Feger1, Philippe E Laurent11BD Medical Pharmaceutical Systems, Le-Pont-de-Claix, 2Eurofins Optimed Clinical Research, Gières, France; 3Statistics, BD Corporate, Franklin Lakes, NJ, USAObjective: A disposable autoinjector was developed for subcutaneous (SC self-injection by patients with chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections performed by nurses using a syringe.Methods: This was a randomized, single-center, crossover study comparing SC self-injection using an autoinjector with SC nurse-administered injection using a syringe. Two volumes (0.2 mL and 1 mL were injected into healthy volunteers. Study objectives included assessment of the accuracy and consistency of the volume injected by the injection systems, and skin reaction and pain associated with the injection. The fluid depot in the SC tissue layer was evaluated by ultrasound. Subject acceptance was evaluated using questionnaires on attitudes and emotions towards the injection technique, and challenged by seeking the subjects’ preferred system for a final study injection or future treatment.Results: A total of 960 injections (480 with autoinjector, 480 with syringe were performed in 40 subjects. There were no significant differences in mean fluid leakage and injected volumes between the systems. Pain associated with the injection was significantly lower with the autoinjector than with the syringe. Local skin reaction at the injection site was overall satisfactory. Injections were appropriately performed by all subjects. At study end, all 40 subjects preferred the autoinjector for a final study injection and for future treatment.Conclusion: This study indicated that the autoinjector used by

Investigating high-concentration monoclonal antibody powder suspension in nonaqueous suspension vehicles for subcutaneous injection.

Science.gov (United States)

Bowen, Mayumi; Armstrong, Nick; Maa, Yuh-Fun

2012-12-01

Developing high-concentration monoclonal antibody (mAb) liquid formulations for subcutaneous (s.c.) administration is challenging because increased viscosity makes injection difficult. To overcome this obstacle, we investigated a nonaqueous powder suspension approach. Three IgG1 mAbs were spray dried and suspended at different concentrations in Miglyol® 840, benzyl benzoate, or ethyl lactate. Suspensions were characterized for viscosity, particle size, and syringeability; physical stability was visually inspected. Suspensions generally outperformed liquid solutions for injectability despite higher viscosity at the same mAb concentrations. Powder formulations and properties had little effect on viscosity or injectability. Ethyl lactate suspensions had lowest viscosity (Miglyol® 840 improved overall performance in high mAb concentration suspensions. This study demonstrated the viability of high mAb concentration (>300 mg/mL) in suspension formulations for s.c. administration. Copyright © 2012 Wiley Periodicals, Inc.

Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity.

Science.gov (United States)

Barquissau, Valentin; Léger, Benjamin; Beuzelin, Diane; Martins, Frédéric; Amri, Ez-Zoubir; Pisani, Didier F; Saris, Wim H M; Astrup, Arne; Maoret, Jean-José; Iacovoni, Jason; Déjean, Sébastien; Moro, Cédric; Viguerie, Nathalie; Langin, Dominique

2018-01-23

Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT). Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity

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Valentin Barquissau

2018-01-01

Full Text Available Caloric restriction (CR is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT. Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity.

In vivo studies on insulin permeability of an immunoisolation device intended for islet transplantation using the microdialysis technique.

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Rafael, E; Wernerson, A; Arner, P; Tibell, A

1999-01-01

In this study, insulin was injected into Theracyte immunoisolation devices to analyze changes in the permeability of the device over time after implantation. The recovery of insulin was studied after subcutaneous implantation of the devices in rats, using the microdialysis technique. The area under the insulin concentration vs. time curves (AUC) after insulin injection in devices implanted 1 day previously did not differ significantly from the AUC after subcutaneous injection. At 1, 2 and 4 weeks after implantation, the recovery of insulin was significantly reduced, but at 3 months, the AUC was not significantly different from that in the control group. Histological examination showed that the number of vascular profiles within 15 microm of the device were significantly higher at 2, 4 weeks and 3 months after transplantation when compared to numbers at 1 week. The design of the device allows transplantation of cells at a chosen time point after its implantation. Delayed filling of the device would allow neovascularization of the device surface before graft implantation and we suggest that such a schedule might improve function of the encapsulated graft.

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

Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.

Science.gov (United States)

Warnken, Tobias; Brehm, Ralph; Feige, Karsten; Huber, Korinna

2017-10-01

The aim of the study was to analyze key proteins of the equine insulin signaling cascade and their extent of phosphorylation in biopsies from muscle tissue (MT), liver tissue (LT), and nuchal AT, subcutaneous AT, and retroperitoneal adipose tissues. This was investigated under unstimulated (B1) and intravenously insulin stimulated (B2) conditions, which were achieved by injection of insulin (0.1 IU/kg bodyweight) and glucose (150 mg/kg bodyweight). Twelve warmblood horses aged 15 ± 6.8 yr (yr), weighing 559 ± 79 kg, and with a mean body condition score of 4.7 ± 1.5 were included in the study. Key proteins of the insulin signaling cascade were semiquantitatively determined using Western blotting. Furthermore, modulation of the cascade was assessed. The basal expression of the proteins was only slightly influenced during the experimental period. Insulin induced a high extent of phosphorylation of insulin receptor in LT (P < 0.01) but not in MT. Protein kinase B and mechanistic target of rapamycin expressed a higher extent of phosphorylation in all tissues in B2 biopsies. Adenosine monophosphate protein kinase, as a component related to insulin signaling, expressed enhanced phosphorylation in MT (P < 0.05) and adipose tissues (nuchal AT P < 0.05; SCAT P < 0.01; retroperitoneal adipose tissue P < 0.05), but not in LT at B2. Tissue-specific variations in the acute response of insulin signaling to intravenously injected insulin were observed. In conclusion, insulin sensitivity in healthy horses is based on a complex concerted action of different tissues by their variations in the molecular response to insulin. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of AIDA v4.3b Diabetes Simulator: Technical Upgrade to Support Incorporation of Lispro, Aspart, and Glargine Insulin Analogues

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Eldon D. Lehmann

2011-01-01

Full Text Available Introduction. AIDA is an interactive educational diabetes simulator available on the Internet without charge since 1996 (accessible at: http://www.2aida.org/. Since the program’s original release, users have developed new requirements, with new operating systems coming into use and more complex insulin management regimens being adopted. The current work has aimed to design a comprehensive diabetes simulation system from both a clinical and information technology perspective. Methods. A collaborative development is taking place with a new generic model of subcutaneous insulin absorption, permitting the simulation of rapidly-acting and very long-acting insulin analogues, as well as insulin injections larger than 40 units. This novel, physiological insulin absorption model has been incorporated into AIDA v4. Technical work has also been undertaken to install and operate the AIDA software within a DOSBox emulator, to ensure compatibility with Windows XP, Vista and 7 operating systems as well as Apple Macintosh computers running Parallels PC emulation software. Results. Plasma insulin simulations are demonstrated following subcutaneous injections of a rapidly-acting insulin analogue, a short-acting insulin preparation, intermediate-acting insulin, and a very long-acting insulin analogue for injected insulin doses up to 60 units of insulin. Discussion. The current work extends the useful life of the existing AIDA v4 program.

A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

Science.gov (United States)

Zhang, Liang; Navaratna, Tejas; Thurber, Greg M.

2016-01-01

Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (SC) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. The ease and efficiency of double-click helix stabilization chemistries is a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control SC absorption and clearance rates to customize plasma pharmacokinetics. PMID:27327034

Longitudinal profiling of the tissue-specific expression of genes related with insulin sensitivity in dairy cows during lactation focusing on different fat depots.

Directory of Open Access Journals (Sweden)

Behnam Saremi

Full Text Available In dairy cows the milk associated energy output in early lactation exceeds the input via voluntary feed intake. To spare glucose for mammary lactose synthesis, peripheral insulin sensitivity (IS is reduced and fat mobilization is stimulated. For these processes a link between IS and the endocrine functions of adipose tissue (AT is likely; we thus aimed to characterise the mRNA expression from bovine AT derived proteins and receptors that are related to IS according to the literature in metabolically active tissues plus systemic IS throughout lactation. Conjugated linoleic acids (CLA reduce milk fat thus decreasing the milk drain of energy and potentially dampening lipolysis, but may also affect IS. Subcutaneous (s.c. AT and liver from pluriparous cows receiving either control fat or CLA supplement (100 g/day from 1 to 182 days in milk each were biopsied covering week -3 to 36 relative to parturition. In an additional trial with primiparous cows treated analogously and slaughtered on days in milk 1, 42 or 105, samples from liver, udder, skeletal muscle and 3 visceral and 3 s.c. AT were obtained and assayed for mRNA abundance of adiponectin, its receptors, leptin, leptin receptor, PPARγ, PPARγ2, IL-6, and TNF-α. In pluriparous animals, the mRNA abundance of most of the target genes decreased after parturition in s.c. AT but increased in liver. In primiparous cows, AT depot specific differences were mostly related to retroperitoneal AT; adiponectin receptor 1 and TNF-α were affected predominantly. CLA effects in primiparous cows were largely limited to decreased PPARγ2 mRNA abundance in udder tissue. In pluriparous cows, insulin secretion was increased by CLA resulting in decreased systemic IS but without consistent changes in tissue target mRNA abundance. The temporal gene expression profiles from the adipokines and related receptors support their coactive function in adapting to the needs of lactation.

Longitudinal Profiling of the Tissue-Specific Expression of Genes Related with Insulin Sensitivity in Dairy Cows during Lactation Focusing on Different Fat Depots

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Saremi, Behnam; Winand, Sarah; Friedrichs, Paula; Kinoshita, Asako; Rehage, Jürgen; Dänicke, Sven; Häussler, Susanne; Breves, Gerhard; Mielenz, Manfred; Sauerwein, Helga

2014-01-01

In dairy cows the milk associated energy output in early lactation exceeds the input via voluntary feed intake. To spare glucose for mammary lactose synthesis, peripheral insulin sensitivity (IS) is reduced and fat mobilization is stimulated. For these processes a link between IS and the endocrine functions of adipose tissue (AT) is likely; we thus aimed to characterise the mRNA expression from bovine AT derived proteins and receptors that are related to IS according to the literature in metabolically active tissues plus systemic IS throughout lactation. Conjugated linoleic acids (CLA) reduce milk fat thus decreasing the milk drain of energy and potentially dampening lipolysis, but may also affect IS. Subcutaneous (s.c.) AT and liver from pluriparous cows receiving either control fat or CLA supplement (100 g/day from 1 to 182 days in milk each) were biopsied covering week −3 to 36 relative to parturition. In an additional trial with primiparous cows treated analogously and slaughtered on days in milk 1, 42 or 105, samples from liver, udder, skeletal muscle and 3 visceral and 3 s.c. AT were obtained and assayed for mRNA abundance of adiponectin, its receptors, leptin, leptin receptor, PPARγ, PPARγ2, IL-6, and TNF-α. In pluriparous animals, the mRNA abundance of most of the target genes decreased after parturition in s.c. AT but increased in liver. In primiparous cows, AT depot specific differences were mostly related to retroperitoneal AT; adiponectin receptor 1 and TNF-α were affected predominantly. CLA effects in primiparous cows were largely limited to decreased PPARγ2 mRNA abundance in udder tissue. In pluriparous cows, insulin secretion was increased by CLA resulting in decreased systemic IS but without consistent changes in tissue target mRNA abundance. The temporal gene expression profiles from the adipokines and related receptors support their coactive function in adapting to the needs of lactation. PMID:24465964

Patient subgroup analyses of the treatment effect of subcutaneous interferon beta-1a on development of multiple sclerosis in the randomized controlled REFLEX study

NARCIS (Netherlands)

Freedman, M.S.; De Stefano, N.; Barkhof, F.; Polman, C.H.; Comi, G.; Uitdehaag, B.M.J.; Casset-Semanaz, F.; Hennessy, B.; Lehr, L.; Stubinski, B.; Jack, D.L.; Kappos, L.

2014-01-01

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to

Insulin-like plant proteins as potential innovative drugs to treat diabetes-The Moringa oleifera case study.

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Paula, P C; Oliveira, J T A; Sousa, D O B; Alves, B G T; Carvalho, A F U; Franco, O L; Vasconcelos, I M

2017-10-25

Various plant species have long been used in traditional medicine worldwide to treat diabetes. Among the plant-based compounds with hypoglycemic properties, studies on insulin-like proteins isolated from leaves, fruits and seeds are rarely reported in the relevant literature. Our research group has been investigating the presence of insulin-like proteins in Moringa oleifera, a plant species native to India, and we have obtained a leaf protein isolate and semi-purified derived fractions, as well as a seed coat protein fraction (Mo-SC), with hypoglycemic activity in chemically induced diabetic mice that have increased tolerance to orally administered glucose. Equally importantly, Mo-SC possesses insulin-like antigenic epitopes. In this context, the present review aims to highlight that prospection of insulin-like proteins in plants is of the utmost importance both for finding new drugs for the treatment of diabetes and for shedding light on the mechanisms involved in diabetes. Copyright © 2016 Elsevier B.V. All rights reserved.

Implantable batteryless device for on-demand and pulsatile insulin administration

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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.

Changes in HbA1c and Weight Following Transition to Continuous Subcutaneous Insulin Infusion Therapy in Adults With Type 1 Diabetes.

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Mehta, Sanjeev N; Andersen, Henrik Ullits; Abrahamson, Martin J; Wolpert, Howard A; Hommel, Eva E; McMullen, William; Ridderstråle, Martin

2017-01-01

Historically, intensive insulin therapy for type 1 diabetes (T1D) has improved glycemic control at the risk of adverse weight gain. The impact of continuous subcutaneous insulin infusion therapy (CSII) on weight in the current era remains unknown. We assessed changes in hemoglobin A1c (HbA1c) and weight in adults with T1D transitioning to CSII at 2 diabetes centers in Denmark and the United States. Patients with T1D, aged ≥18 years, managed with multiple daily injections (MDI) who transitioned to CSII between 2002 and 2013 were identified using electronic health record data from the Steno Diabetes Center (n = 600) and Joslin Diabetes Center (n = 658). Changes in HbA1c and weight after 1 year was assessed overall and by baseline HbA1c cut points. Multivariate regression assessed correlates of HbA1c reduction. In adults with T1D transitioning to CSII, clinically significant HbA1c reductions were found in patients with baseline HbA1c 8.0-8.9% (Steno, -0.7%; Joslin, -0.4%) and baseline HbA1c ≥9.0% (Steno, -1.1%; Joslin, -0.9%) ( P HbA1c ≥9% at Steno (1.1 ± 0.3 kg, P HbA1c reduction was associated with higher HbA1c, older age, female sex at Steno ( R 2 = .28, P HbA1c at Joslin ( R 2 = .19, P HbA1c without a negative impact on weight 1 year after transitioning from MDI to CSII.

Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM

DEFF Research Database (Denmark)

Nauck, M A; Wollschläger, D; Werner, J

1996-01-01

with the indicator-dilution method and phenol red. Repeated measures ANOVA was used for statistical analysis. GLP-1 injection led to a short-lived increment in GLP-1 concentrations (peak at 30-60 min, then return to basal levels after 90-120 min). Each GLP-1 injection stimulated insulin (insulin, C-peptide, p ....0001, respectively) and inhibited glucagon secretion (p ... emptying for 30-45 min (p statistically different from placebo) followed by emptying at a normal rate. As a consequence, integrated incremental glucose responses were reduced by 40% (p = 0.051). In conclusion, subcutaneous GLP-1 [7-36 amide] has similar effects in NIDDM patients as an intravenous...

Design of insulin analogues for meal-related therapy.

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Brange, J

1993-01-01

The human insulin in replacement therapy has a hexameric structure. Hexamerization of the insulin molecule facilitates biosynthesis and beta-cell storage of insulin, but is unnecessary for biologic activity and appears to contribute to delayed absorption of exogenous insulin from the subcutis. Insulin analogues with reduced self-association that are produced through recombinant DNA techniques have been shown to have in vivo activity comparable to that of human insulin and absorption kinetics characterized by higher and more constant rates of disappearance from the subcutaneous injection site. In preliminary studies in patients receiving insulin therapy, monomeric insulin analogues have been found to provide glycemic control in the postprandial period that is at least equivalent to that of human insulin. Findings in these studies suggest that the use of such analogues may provide meal-related insulin effects closer to those observed in the physiologic state by limiting excessive postprandial glucose excursions and decreasing the risk of late hypoglycemia. Banting and Best revolutionized diabetes therapy 70 years ago with the extraction of insulin from animal pancreas glands (J Lab Clin Med 7:464-472, 1922). Since that time, many refinements of the therapeutic properties of pharmaceutical preparations of the hormone have been introduced. Until recently, however, such advances have been limited to improvements in insulin purity, insulin species, and adjustment of the composition of the vehicle with respect to auxiliary substances and other additives. With the advent of recombinant DNA techniques, it has become possible to optimize the insulin molecule itself for purposes of replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of life and impact of continuous subcutaneous insulin infusion for children and their parents

DEFF Research Database (Denmark)

Barnard, Katharine D.; Speight, Jane; Skinner, T. Chas

2008-01-01

This study aimed to identify key components of quality of life (QoL) and assess the impact of insulin pump therapy on children/adolescents with type 1 diabetes and their parents. The Schedule for the Evaluation of Individualised Quality of Life (SEIQoL) interview was adapted to be (1) insulin pum...

A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.

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Nelson, K A; Glare, P A; Walsh, D; Groh, E S

1997-05-01

The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was

Modelling the Effect of Exercise on Insulin Pharmacokinetics in "Continuous Subcutaneous Insulin Infusion" Treated Type 1 Diabetes Patients

DEFF Research Database (Denmark)

Duun-Henriksen, Anne Katrine; Juhl, Rune; Schmidt, Signe

Introduction: The artificial pancreas is believed to ease the burden of constant management of type 1 diabetes for the patients substantially. An important aspect of the artificial pancreas development is the mathematical models used for control, prediction or simulation. A major challenge...... infusion (CSII) treated patients by modelling the absorption rate as a function of exercise. Methods: Three models are estimated from 17 data sequences. All of them are based on a linear three-compartment base model. The models are based on stochastic differential equations to allow noise to enter...... of the measurement variance. Conclusion: A model to predict the insulin appearance in plasma during exercise in CSII treated patients is identified. Further clinical studies are needed to confirm the increase in insulin plasma concentration during exercise in type 1 diabetes patients. These studies should include...

Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study.

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Branco, Jaime C; Barcelos, Anabela; de Araújo, Filipe Pombo; Sequeira, Graça; Cunha, Inês; Patto, José Vaz; Oliveira, Margarida; Mateus, Margarida Pratas; Couto, Maura; Nero, Patrícia; Pinto, Patrícia; Monteiro, Paulo; Castelão, Walter; Félix, Jorge; Ferreira, Diana; Almeida, João; Silva, Maria João

2016-01-01

Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA. Utilization of Metoject(®) in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient's clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration. Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three. The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

SC*994C>T causes the Sc(null) phenotype in Pacific Islanders and successful transfusion of Sc3+ blood to a patient with anti-Sc3.

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Reid, Marion E; Hue-Roye, Kim; Velliquette, Randall W; Larimore, Kathleen; Moscarelli, Sue; Ohswaldt, Nicolas; Lomas-Francis, Christine

2013-01-01

Antigens in the SC blood group system are expressed by the human erythrocyte membrane-associated protein (ERMAP).Two molecular bases have been reported for the Sc,un phenotype:SC*307del2 and SC*994C>T. We report our investigation of the molecular background of five Sc,n1 individuals from the Pacific Islands and describe the successful transfusion of Sc3+ blood to a patient with anti-Sc3 in her plasma. SC (ERMAP) exons 2,3, and 12 and their flanking intronic regions were analyzed. TheSC*994C>T change introduces a restriction enzyme cleavage site for Tsp45I, and polymerase chain reaction (PCR) products from exon 12 were subjected to this PCR-restriction fragment length polymorphism (RFLP) assay. The five samples had the variant SC*994T/T. One sample, from a first cousin of one Marshallese proband, was heterozygous for SC*1514C/T (in the 3' untranslated region); the other four samples were SC*1514C/C(consensus sequence). Samples from white donors (n = 100) and African American donors (n = 99) were tested using the Tsp45IPCR-RFLP assay; all gave a banding pattern that was consistent with the SC*994C/C consensus sequence. In all five samples,our analyses showed homozygosity for the nonsense nucleotide change SC*994C>Tin an allele carrying the nucleotide associated with SLd. Further investigation determined that one of the probands reported previously with the SC*994C>T change was from the Marshall Islands (which form part of the Micronesian Pacific Islands) and the other was from an unspecified location within the large collection of Pacific Islands. Taken together, the five known probands with the SC*994C>T silencing nucleotide change were from the Pacific Islands.

Insulin resistance in tetraplegia but not in mid-thoracic paraplegia: is the mid-thoracic spinal cord involved in glucose regulation?

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Bluvshtein, V; Korczyn, A D; Pinhas, I; Vered, Y; Gelernter, I; Catz, A

2011-05-01

Controlled experimental human study. To assess insulin resistance (IR) in tetraplegia and paraplegia, and the role of the spinal cord (SC) in glucose regulation. Laboratory of Spinal Research, Loewenstein Rehabilitation Hospital. Glucose and insulin levels and the heart rate variation spectral components LF (low frequency), HF (high frequency) and LF/HF were studied at supine rest, head-up tilt and after a standard meal in three groups: 13 healthy subjects, 7 patients with T(4)-T(6) paraplegia and 11 patients with C(4)-C(7) tetraplegia. Glucose and insulin increased significantly after the meal in all groups (Pinsulin level tended to accompany increases in LF/HF after the meal in the tetraplegia and control groups but not in the paraplegia group. Post-prandial IR appears in C(4)-C(7) but not in T(4)-T(6) SC injury. The results of the study, combined with previously published findings, are consistent with the hypotheses that IR is related to activation of the sympathetic nervous system, and that below T(4) the mid-thoracic SC is involved in the regulation of glucose and insulin levels.

Sc-W-Si and Sc-W-Ge ternary systems

International Nuclear Information System (INIS)

Kotur, B.Ya.; Voznyak, O.M.; Bodak, O.I.

1989-01-01

Phase equilibria in Sc-W-Si and Sc-W-Ge ternary systems are investigated at 1070 K. Sc 2+x W 3-x Si 4 ternary compound (0≤x≤1) is determined, its crystal structure (Ce 2 Sc 3 Si 4 structural type), as well as, change of elementary cell parameters and microhardness within homogeneity range are determined. Regularities of component interaction within Sc-M-Si(Ge) (M-Cr, Mo, W) ternary system are determined. Ternary systems with Mo and W are more closer to each other according to the phase equilibria character, than to ternary systems with Cr

Diabetes Is Reversed in a Murine Model by Marginal Mass Syngeneic Islet Transplantation Using a Subcutaneous Cell Pouch Device.

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Pepper, Andrew R; Pawlick, Rena; Gala-Lopez, Boris; MacGillivary, Amanda; Mazzuca, Delfina M; White, David J G; Toleikis, Philip M; Shapiro, A M James

2015-11-01

Islet transplantation is a successful β-cell replacement therapy for selected patients with type 1 diabetes mellitus. Although high rates of early insulin independence are achieved routinely, long-term function wanes over time. Intraportal transplantation is associated with procedural risks, requires multiple donors, and does not afford routine biopsy. Stem cell technologies may require potential for retrievability, and graft removal by hepatectomy is impractical. There is a clear clinical need for an alternative, optimized transplantation site. The subcutaneous space is a potential substitute, but transplantation of islets into this site has routinely failed to reverse diabetes. However, an implanted device, which becomes prevascularized before transplantation, may alter this equation. Syngeneic mouse islets were transplanted subcutaneously within Sernova Corp's Cell Pouch (CP). All recipients were preimplanted with CPs 4 weeks before diabetes induction and transplantation. After transplantation, recipients were monitored for glycemic control and glucose tolerance. Mouse islets transplanted into the CP routinely restored glycemic control with modest delay and responded well to glucose challenge, comparable to renal subcapsular islet grafts, despite a marginal islet dose, and normoglycemia was maintained until graft explantation. In contrast, islets transplanted subcutaneously alone failed to engraft. Islets within CPs stained positively for insulin, glucagon, and microvessels. The CP is biocompatible, forms an environment suitable for islet engraftment, and offers a potential alternative to the intraportal site for islet and future stem cell therapies.

11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance

DEFF Research Database (Denmark)

Koska, Juraj; de Courten, Barbora; Wake, Deborah J

2006-01-01

Increased mRNA and activity levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non-diab......-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)]....

Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.

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Condorelli, R A; Calogero, A E; Di Mauro, M; Mongioi', L M; Cannarella, R; Rosta, G; La Vignera, S

2018-04-01

Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic β-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. A comprehensive MEDLINE ® search was performed using relevant key terms for PCOS and DM II. Insulin-induced hyperandrogenism could impair pancreatic β-cell function, the SC abdominal adipocytes' lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome.

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Svendsen, P F; Madsbad, S; Nilas, L; Paulsen, S K; Pedersen, S B

2009-11-01

To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity. Cross-sectional study. A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR. Polycystic ovary syndrome (PPCOS or obesity on11beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH. Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.

Self-Tuning Insulin Adjustment Algorithm for Type 1 Diabetic Patients based on Multi-Doses Regime

Directory of Open Access Journals (Sweden)

D. U. Campos-Delgado

2005-01-01

Full Text Available A self-tuning algorithm is presented for on-line insulin dosage adjustment in type 1 diabetic patients (chronic stage. The algorithm suggested does not need information of the patient insulin–glucose dynamics (model-free. Three doses are programmed daily, where a combination of two types of insulin: rapid/short and intermediate/long acting is injected into the patient through a subcutaneous route. The doses adaptation is performed by reducing the error in the blood glucose level from euglycemics. In this way, a total of five doses are tuned per day: three rapid/short and two intermediate/long, where there is large penalty to avoid hypoglycemic scenarios. Closed-loop simulation results are illustrated using a detailed nonlinear model of the subcutaneous insulin–glucose dynamics in a type 1 diabetic patient with meal intake.

Subcutaneous adipose tissue macropage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kB stress pathway

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The goal was to examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), Beta-cell function, and SAT gene expression. SAT biopsies were obtained from...

Investigation of the mechanisms that influence the accretion of bovine intramuscular and subcutaneous adipose tissue

International Nuclear Information System (INIS)

Miller, M.F.

1987-01-01

The understanding of the mechanisms that differ between breeds of cattle and their ability to deposit intramuscular adipose tissue is imperative to profitable beef production. Thus, the interactions among breeds, metabolic substrates and specific hormones in bovine intramuscular and subcutaneous adipose tissue were investigated. Subcutaneous and intramuscular adipose tissues were obtained from 10 Angus and 9 Santa Gertrudis steers immediately postmortem. The adipose tissues were incubated for 2 h and 48 h with and without 1 mU/ml insulin and 30 mg/ml bovine serum albumin (BSA) to measure the incorporation of 14 C-labeled acetate and glucose into lipid fractions. At the same chronological age, Angus steers had a more youthful lean maturity score, higher USDA marbling scores and higher USDA quality grades than carcasses from Santa Gertrudis steers

Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

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Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

2014-01-01

Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

Insulin action in adipose tissue and muscle in hypothyroidism.

Science.gov (United States)

Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia; Boutati, Eleni; Maratou, Eirini; Panagiotakos, Demosthenes B; Koukkou, Efi; Tzanela, Marinela; Thalassinos, Nikos; Raptis, Sotirios A

2006-12-01

Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited. To investigate this, a meal was given to 11 hypothyroid (HO; aged 45 +/- 3 yr) and 10 euthyroid subjects (EU; aged 42 +/- 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V)glucose(BF), lipoprotein lipase as (A-V)Triglycerides(BF), and lipolysis as [(V-A)glycerol(BF)]-lipoprotein lipase. The HO group had higher glucose and insulin levels than the EU group (P hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.

Metabolic syndrome and insulin resistance in obese adolescents

Directory of Open Access Journals (Sweden)

Amanda Oliva Gobato

2014-03-01

Full Text Available Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI, body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032 and with metabolic syndrome (p=0.006. All body composition indicators were correlated with insulin resistance (p<0.01. In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

Radionuclide venography of lower limbs by subcutaneous injection; Comparison with venography by intravenous injection

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Wu, Chung-Chieng; Jong, Shiang-Bin (Kaohsiung Medical College, Kaohsiung (Taiwan))

1989-11-01

We have proved that subcutaneous injection (SC) of a small dose of Tc-99m pertechnetate (1 to 2 mCi: 37 to 74 MBq) at acupuncture points (K-3 and B-60) may offer an alternative method of radionuclide venography (RNV) of the lower limbs. In this study, we compared intravenous (IV) RNV and SC-RNV in 22 consecutive cases with typical signs and symptoms suggesting venous abnormality of the lower limb(s) from March to May 1988. They are 11 male and 11 female, aged 47.7{plus minus}15.7 years. Among the 44 limbs of the 22 cases, 4 were normal, 12 (27.3%) were found to have varicose veins in the legs only, 18 (40.9%) had partial stenosis of the deep veins (14 poplito-tibial and 4 superficial femoral), and 13 (29.6%) had complete stenosis of the deep veins (4 poplito-tibial, 1 superficial femoral and 8 ilio-femoral). SC-RNV showed almost the same results as IV-RNV in 21 (47.7%), superior to IV-RNV in 22 (50%) (including 4.6% failure of IV-RNV), and inferior to IV-RNV in 1 (2.3%). We conclude that SC-RNV is definitely an alternative method of lower-limb venography. Since it is in most cases superior to IV-RNV, we suggest that it can take the place of IV-RNV in routine work. (author) 62 refs.

The activity of the endocannabinoid metabolising enzyme fatty acid amide hydrolase in subcutaneous adipocytes correlates with BMI in metabolically healthy humans

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Alexander Stephen PH

2011-08-01

Full Text Available Abstract Background The endocannabinoid system (ECS is a ubiquitously expressed signalling system, with involvement in lipid metabolism and obesity. There are reported changes in obesity of blood concentrations of the endocannabinoids anandamide (AEA and 2-arachidonoylglcyerol (2-AG, and of adipose tissue expression levels of the two key catabolic enzymes of the ECS, fatty acid amide hydrolase (FAAH and monoacylglycerol lipase (MGL. Surprisingly, however, the activities of these enzymes have not been assayed in conditions of increasing adiposity. The aim of the current study was to investigate whether FAAH and MGL activities in human subcutaneous adipocytes are affected by body mass index (BMI, or other markers of adiposity and metabolism. Methods Subcutaneous abdominal mature adipocytes, fasting blood samples and anthropometric measurements were obtained from 28 metabolically healthy subjects representing a range of BMIs. FAAH and MGL activities were assayed in mature adipocytes using radiolabelled substrates. Serum glucose, insulin and adipokines were determined using ELISAs. Results MGL activity showed no relationship with BMI or other adiposity indices, metabolic markers (fasting serum insulin or glucose or serum adipokine levels (adiponectin, leptin or resistin. In contrast, FAAH activity in subcutaneous adipocytes correlated positively with BMI and waist circumference, but not with skinfold thickness, metabolic markers or serum adipokine levels. Conclusions In this study, novel evidence is provided that FAAH activity in subcutaneous mature adipocytes increases with BMI, whereas MGL activity does not. These findings support the hypothesis that some components of the ECS are upregulated with increasing adiposity in humans, and that AEA and 2-AG may be regulated differently.

Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets.

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Vlahos, Alexander E; Cober, Nicholas; Sefton, Michael V

2017-08-29

The transplantation of pancreatic islets, following the Edmonton Protocol, is a promising treatment for type I diabetics. However, the need for multiple donors to achieve insulin independence reflects the large loss of islets that occurs when islets are infused into the portal vein. Finding a less hostile transplantation site that is both minimally invasive and able to support a large transplant volume is necessary to advance this approach. Although the s.c. site satisfies both these criteria, the site is poorly vascularized, precluding its utility. To address this problem, we demonstrate that modular tissue engineering results in an s.c. vascularized bed that enables the transplantation of pancreatic islets. In streptozotocin-induced diabetic SCID/beige mice, the injection of 750 rat islet equivalents embedded in endothelialized collagen modules was sufficient to restore and maintain normoglycemia for 21 days; the same number of free islets was unable to affect glucose levels. Furthermore, using CLARITY, we showed that embedded islets became revascularized and integrated with the host's vasculature, a feature not seen in other s.c. Collagen-embedded islets drove a small (albeit not significant) shift toward a proangiogenic CD206 + MHCII - (M2-like) macrophage response, which was a feature of module-associated vascularization. While these results open the potential for using s.c. islet delivery as a treatment option for type I diabetes, the more immediate benefit may be for the exploration of revascularized islet biology.

Comparison of rechargeable versus battery-operated insulin pumps: temperature fluctuations.

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Vereshchetin, Paul; McCann, Thomas W; Ojha, Navdeep; Venugopalan, Ramakrishna; Levy, Brian L

2016-01-01

The role of continuous subcutaneous insulin infusion (insulin pumps) has become increasingly important in diabetes management, and many different types of these systems are currently available. This exploratory study focused on the reported heating issues that lithium-ion battery-powered pumps may have during charging compared with battery-operated pumps. It was found that pump temperature increased by 6.4°C during a long charging cycle of a lithiumion battery-operated pump under ambient temperatures. In an environmental-chamber kept at 35°C, the pump temperature increased by 4.4°C, which indicates that the pump temperature was above that of the recommended safety limit for insulin storage of 37°C. When designing new pumps, and when using currently available rechargeable pumps in warmer climates, the implications of these temperature increases should be taken into consideration. Future studies should also further examine insulin quality after charging.

Posttransplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: A promising clinical alternative to the conventional intrahepatic site.

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Komatsu, H; Rawson, J; Barriga, A; Gonzalez, N; Mendez, D; Li, J; Omori, K; Kandeel, F; Mullen, Y

2018-04-01

Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-basic fibroblast growth factor. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mm Hg, compared to 45 mm Hg under ambient air. In vitro, islets cultured under 140 mm Hg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mm Hg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with postoperative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Randomized, double-blind, crossover study comparing DFN-11 injection (3 mg subcutaneous sumatriptan) with 6 mg subcutaneous sumatriptan for the treatment of rapidly-escalating attacks of episodic migraine.

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Cady, Roger K; Munjal, Sagar; Cady, Ryan J; Manley, Heather R; Brand-Schieber, Elimor

2017-12-01

A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy. This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg). The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P  =  .87). The proportions of subjects experiencing pain relief (P  ≥  .48); reductions in migraine pain intensity (P  ≥  .78); and relief from nausea, photophobia, or phonophobia (P  ≥  .88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M  =  2.6 vs M  =  2.4, P  =  .81) and the mean number of rescue medications used (M  =  .11 vs M  =  .26, P  =  .32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n  =  14 [44%]; 6 mg, n  =  18 [56%], P  =  .60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events. The 3-mg SC dose

Combining insulins for optimal blood glucose control in type 1 and 2 diabetes: focus on insulin glulisine

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Heather Ulrich

2007-07-01

lispro or RHI in type 1 or 2 DM and it has been shown to be as safe and effective when used in a continuous subcutaneous insulin infusion (CSII. In summary, insulin glulisine is a safe, effective, and well tolerated rapid-acting insulin analogue across all BMIs and a worthy option for prandial glucose control in type 1 or 2 DM.Keywords: glycemic control, glycosylated hemoglobin A1c (HbA1c, rapid-acting insulin analogues, type 1 diabetes mellitus, type 2 diabetes mellitus, insulin glulisine, body mass index (BMI

Effect of insulin on the mitotic activity of bone marrow cells after irradiation. [Gamma radiation, rats

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Barkalaya, A I

1976-02-01

A total of 236 white rats were given a whole-body gamma dose of 750 R. Part of the rats were given a subcutaneous insulin injection of 0.2 units/kg. After 10, 20, 30 min, 1, 2, 3, 5, 8, 10 and 12 hours the mitotic index was determined in both groups of rats in the bone marrow of the femur. The content of glucose and insulin in the blood was determined. The mitotic index was found to be higher on administering insulin. The use of insulin in radiation sickness intensifies the mitotic activity of bone marrow cells and stimulates the recovery of bone marrow hematopoiesis. 5 references.

Do very small adipocytes in subcutaneous adipose tissue (a proposed risk factor for insulin insensitivity have a fetal origin?

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Mette Olaf Nielsen

2016-08-01

Conclusions: The present study showed that greater preponderance of very small adipocytes, increased collagen infiltration and reduced subcutaneous lipid accumulation ability, as well as altered perirenal fat preferences for accumulation of C14:0 can have a fetal origin. Disturbance of normal (subcutaneous adipose tissue development may play a key role in linking fetal malnutrition to disease risk later in life.

Insulin pump therapy in children with type 1 diabetes

DEFF Research Database (Denmark)

Szypowska, Agnieszka; Schwandt, Anke; Svensson, Jannet

2016-01-01

BACKGROUND: Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control. OBJECTIVE: To examine the frequency of pump usage in T1D children treated...... in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI. METHODS: This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized...... is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age....

Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study.

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van Dijkhuizen, E H Pieter; Pouw, Juliëtte N; Scheuern, Andrea; Hügle, Boris; Hardt, Sven; Ganser, Gerd; Kümmerle-Deschner, Jasmin Beate; Horneff, Gerd; Holzinger, Dirk; Bulatović Ćalasan, Maja; Wulffraat, Nico M

2016-01-01

Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients. A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO). Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056). The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials.

Migration of iron-labeled KHYG-1 natural killer cells to subcutaneous tumors in nude mice, as detected by magnetic resonance imaging.

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Mallett, Christiane L; McFadden, Catherine; Chen, Yuhua; Foster, Paula J

2012-07-01

A novel cell line of cytotoxic natural killer (NK) cells, KHYG-1, was examined in vivo for immunotherapy against prostate cancer. The feasibility of using magnetic resonance imaging (MRI) tracking to monitor the fate of injected NK cells following intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c.) administration was assessed. PC-3M human prostate cancer cells were injected s.c. into the flank of nude mice (day 0). KHYG-1 NK cells were labeled with an iron oxide contrast agent and injected s.c., i.v. or i.p. on day 8. Mice were imaged by MRI on days 7, 9 and 12. Tumor sections were examined with fluorescence microscopy and immunohistologic staining for NK cells. NK cells were detected in the tumors by histology after all three administration routes. NK cells and fluorescence from the iron label were co-localized. Signal loss was seen in the areas around the tumors and between the tumor lobes in the s.c. group. We are the first to label this cell line of NK cells with an iron oxide contrast agent. Accumulation of NK cells was visualized by MRI after s.c. injection but not after i.v. and i.p. injection.

Subcutaneous granuloma annulare

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Dhar Sandipan

1993-01-01

Full Text Available Two cases of subcutaneous granuloma annulare are reported. Clinical presentation was in the form of hard subcutaneous nodules, histopathology confirmed the clinical diagnosis. The cases were unique because of onset in adult age, occurrence over unusual sites and absence of classical lesions of granuloma annulare elsewhere.

Design of ultra-stable insulin analogues for the developing world

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Michael A Weiss

2013-01-01

Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

DEFF Research Database (Denmark)

Frydelund-Larsen, Lone; Åkerström, Thorbjörn; Nielsen, Søren

2006-01-01

in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4......Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression.......5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied...

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

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Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

2016-01-01

A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

Longterm Safety and Efficacy of Subcutaneous Tocilizumab Monotherapy: Results from the 2-year Open-label Extension of the MUSASHI Study.

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Ogata, Atsushi; Amano, Koichi; Dobashi, Hiroaki; Inoo, Masayuki; Ishii, Tomonori; Kasama, Tsuyoshi; Kawai, Shinichi; Kawakami, Atsushi; Koike, Tatsuya; Miyahara, Hisaaki; Miyamoto, Toshiaki; Munakata, Yasuhiko; Murasawa, Akira; Nishimoto, Norihiro; Ogawa, Noriyoshi; Ojima, Tomohiro; Sano, Hajime; Shi, Kenrin; Shono, Eisuke; Suematsu, Eiichi; Takahashi, Hiroki; Tanaka, Yoshiya; Tsukamoto, Hiroshi; Nomura, Akira

2015-05-01

To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA). Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks. The proportions of patients who achieved American College of Rheumatology 20/50/70 responses, low disease activity [28-joint Disease Activity Score (DAS28) ≤ 3.2], or remission (DAS28 < 2.6) at Week 24 were maintained until Week 108. The incidences of adverse events and serious adverse events were 498.3 and 16.9 per 100 patient-years (PY), respectively. The overall safety of TCZ-SC monotherapy was similar to that of TCZ-IV monotherapy. Rates of injection site reactions (ISR) through 108 weeks remained similar to rates through 24 weeks. ISR were mild and did not cause any patient withdrawals. No serious hypersensitivity events (including anaphylactic reactions) occurred. Anti-TCZ antibodies were present in 2.1% of patients treated with TCZ-SC monotherapy. TCZ-SC monotherapy maintained a favorable safety profile and consistent efficacy throughout the 108-week study. Like TCZ-IV, TCZ-SC could provide an additional treatment option for patients with RA.

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study.

Science.gov (United States)

Sørensen, P S; Sellebjerg, F; Lycke, J; Färkkilä, M; Créange, A; Lund, C G; Schluep, M; Frederiksen, J L; Stenager, E; Pfleger, C; Garde, E; Kinnunen, E; Marhardt, K

2016-05-01

Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy. © 2016 EAN.

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

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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.

Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

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Lackey, Denise E.; Lynch, Christopher J.; Olson, Kristine C.; Mostaedi, Rouzbeh; Ali, Mohamed; Smith, William H.; Karpe, Fredrik; Humphreys, Sandy; Bedinger, Daniel H.; Dunn, Tamara N.; Thomas, Anthony P.; Oort, Pieter J.; Kieffer, Dorothy A.; Amin, Rajesh; Bettaieb, Ahmed; Haj, Fawaz G.; Permana, Paska; Anthony, Tracy G.

2013-01-01

Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35–50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals. PMID:23512805

Structure and bonding of ScCN and ScNC: Ground and low-lying states

International Nuclear Information System (INIS)

Kalemos, Apostolos; Metropoulos, Aristophanes; Mavridis, Aristides

2012-01-01

Graphical abstract: The experimentally unknown systems ScCN and ScNC have been studied through single reference CISD and CCSD(T) methods. A total of 20 = 10 (ScCN) + 10 (ScNC) states were examined. All states are quite ionic whereas ScNC(X ∼3 Δ) is stabler than ScCN(X ∼3 Δ) by ∼5 kcal/mol. Display Omitted Highlights: ► We have studied through ab initio methods the polytopic system Sc[CN]. ► A series of low lying states for both isomeric forms have been examined. ► Around equilibrium the system displays a pronounced Sc + [CN] − ionic character. - Abstract: We have studied the experimentally unknown Sc[CN] molecular system in both its isomeric forms, scandium cyanide (ScCN) and isocyanide (ScNC), through ab initio computations. We report energetics, geometries, harmonic frequencies, and dipole moments for the first 20 Sc[CN] states correlating diabatically to Sc + ( 3 D, 1 D, 3 F) + CN − (X 1 Σ + ). Both isomers have a pronounced ionic character around equilibrium due to the high electron affinity of the CN group and the low ionization energy of the Sc atom. According to our calculations the ScNC isomer (X ∼3 Δ) is stabler than the ScCN(X ∼3 Δ) by ∼5 kcal/mol.

Subcutaneously administered Menopur(R, a new highly purified human menopausal gonadotropin, causes significantly fewer injection site reactions than Repronex(R in subjects undergoing in vitro fertilization

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Somkuti Stephen

2005-11-01

Full Text Available Abstract Background The safety and tolerability of a new highly purified, urine-derived human menopausal gonadotropin (hMG preparation [Menopur(R] was compared with a currently available hMG [Repronex (R] in women undergoing in vitro fertilization (IVF. Methods This was a randomized, open-label, parallel-group, multicenter study conducted in subjects undergoing IVF. Women (N = 125, 18–39 years of age, underwent pituitary down-regulation with leuprolide acetate beginning 7 days prior to onset of menses and continuing up to the day before hCG administration. Subjects were randomized to receive subcutaneous (SC Menopur (R (n = 61 or Repronex (R SC (n = 64 for a maximum of 12 days. All adverse events (AEs were recorded and subject self-assessments of injection site reactions were recorded in a daily diary. Results Significantly fewer subjects in the Menopur (R group reported injection site reactions (P Conclusion Menopur (R SC offers a greater safety and tolerability profile compared to Repronex (R SC.

Influence of adipocyte size and adipose depot on the in vitro lipolytic activity and insulin sensitivity of adipose tissue in dairy cows at the end of the dry period.

Science.gov (United States)

De Koster, J; Van den Broeck, W; Hulpio, L; Claeys, E; Van Eetvelde, M; Hermans, K; Hostens, M; Fievez, V; Opsomer, G

2016-03-01

The aim of the present research was to describe characteristics of adipose tissue lipolysis in dairy cows with a variable body condition score (BCS). Ten clinically healthy Holstein Friesian cows were selected based on BCS and euthanized 10 to 13 d before the expected parturition date. Immediately after euthanasia, adipose tissue samples were collected from subcutaneous and omental fat depots. In both depots, we observed an increase in adipocyte size with increasing BCS. Using an in vitro explant culture of subcutaneous and omental adipose tissue, we aimed to determine the influence of adipocyte size and localization of adipose depot on the lipolytic activity in basal conditions and after addition of isoproterenol (nonselective β-agonist) and insulin in different concentrations. Glycerol release in the medium was used as a measure for lipolytic activity. We observed that the basal lipolytic activity of subcutaneous and omental adipose tissue increased with adipocyte volume, meaning that larger fat cells have higher basal lipolytic activity independent of the location of the adipose depot. Dose-response curves were created between the concentration of isoproterenol or insulin and the amount of glycerol released. The shape of the dose-response curves is determined by the concentration of isoproterenol and insulin needed to elicit the half-maximal effect and the maximal amount of stimulated glycerol release or the maximal inhibitory effect of insulin. We observed that larger fat cells released more glycerol upon maximal stimulation with isoproterenol and this was more pronounced in subcutaneous adipose tissue. Additionally, larger fat cells had a higher sensitivity toward lipolytic signals. We observed a trend for larger adipocytes to be more resistant to the maximal antilipolytic effect of insulin. The insulin concentration needed to elicit the half-maximal inhibitory effect of insulin was within the physiological range of insulin and was not influenced by adipocyte

Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.

Science.gov (United States)

Leonetti, D L; Bergstrom, R W; Shuman, W P; Wahl, P W; Jenner, D A; Harrison, G A; Fujimoto, W Y

1991-05-01

The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus

Skeletal Muscle Sorbitol Levels in Diabetic Rats with and without Insulin Therapy and Endurance Exercise Training

Science.gov (United States)

Sánchez, O. A.; Walseth, T. F.; Snow, L. M.; Serfass, R. C.; Thompson, L. V.

2009-01-01

Sorbitol accumulation is postulated to play a role in skeletal muscle dysfunction associated with diabetes. The purpose of this study was to determine the effects of insulin and of endurance exercise on skeletal muscle sorbitol levels in streptozotocin-induced diabetic rats. Rats were assigned to one experimental group (control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary no-insulin). Diabetic rats received daily subcutaneous insulin. The exercise-trained rats ran on a treadmill (1 hour, 5X/wk, for 12 weeks). Skeletal muscle sorbitol levels were the highest in the diabetic sedentary no-insulin group. Diabetic sedentary rats receiving insulin had similar sorbitol levels to control sedentary rats. Endurance exercise did not significantly affect sorbitol levels. These results indicate that insulin treatment lowers sorbitol in skeletal muscle; therefore sorbitol accumulation is probably not related to muscle dysfunction in insulin-treated diabetic individuals. Endurance exercise did not influence intramuscular sorbitol values as strongly as insulin. PMID:20016800

Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Myrup, B; Hansen, P M; Jensen, T

1995-01-01

We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU...

Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

NARCIS (Netherlands)

Myrup, B.; Hansen, P.M.; Jensen, T.; Kofoed-Enevoldsen, A.; Feldt-Rasmussen, B.; Gram, J.; Kluft, C.; Jespersen, J.; Deckert, T.

1995-01-01

We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU

Beneficial effects of exercise training (treadmill on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice

Directory of Open Access Journals (Sweden)

C.M.M. Marques

2010-05-01

Full Text Available C57BL/6 mice develop signs and symptoms comparable, in part, to the human metabolic syndrome. The objective of the present study was to evaluate the effects of exercise training on carbohydrate metabolism, lipid profile, visceral adiposity, pancreatic islet alterations, and nonalcoholic fatty liver disease in C57BL/6 mice. Animals were fed one of two diets during an 8-week period: standard (SC, N = 12 or very high-fat (HF, N = 24 chow. An exercise training protocol (treadmill was then established and mice were divided into SC and HF sedentary (SC-Sed, HF-Sed, exercised groups (SC-Ex, HF-Ex, or switched from HF to SC (HF/SC-Sed and HF/SC-Ex. HF/HF-Sed mice had the greatest body mass (65% more than SC/SC-Sed; P < 0.0001, and exercise reduced it by 23% (P < 0.0001. Hepatic enzymes ALP (+80%, ALT (+100% and AST (+70% were higher in HF/HF mice than in matched SC/SC. Plasma insulin was higher in both the HF/HF-Sed and HF/SC-Sed groups than in the matched exercised groups (+85%; P < 0.001. Pancreatic islets, adipocytes and liver structure were greatly affected by HF, ultimately resulting in islet β-cell hypertrophy and severe liver steatosis. The HF group had larger islets than the SC/SC group (+220%; P < 0.0001, and exercise significantly reduced liver steatosis and islet size in HF. Exercise attenuated all the changes due to HF, and the effects were more pronounced in exercised mice switched from an HF to an SC diet. Exercise improved the lipid profile by reducing body weight gain, visceral adiposity, insulin resistance, islet alterations, and fatty liver, contributing to obesity and steatohepatitis control.

Subcutaneous injection of thallium-201 chloride and gallium-67 citrate at acupuncture point K-3; An animal experiment and human-being study

Energy Technology Data Exchange (ETDEWEB)

Johg, Shiang-Bin; Wu, Chung-Chieng; Chen, Ming-Feng; Wu, Sheng-Nan (Kaohsiung Medical Coll., Taiwan (China))

1992-09-01

Subcutaneous (SC) injection of [sup 99m]Tc pertechnetate ([sup 99m]Tc) at acupuncture points K-3 is a new method of lower-limb radionuclide venography. To investigate the mechanism of absorption of [sup 99m]Tc from SC injected sites into vascular system, various radioisotopes such as [sup 201]Tl chloride ([sup 201]Tl) and [sup 67]Ga citrate ([sup 67]Ga) were SC injected at K-3 points in animal and human-beings experiments. It was found that [sup 99m]Tc and [sup 201]Tl were absorbed rapidly from K-3 points through venous system and into whole body soft tissue. However, [sup 67]Ga with a larger effective ionic radius than [sup 201]Tl was not absorbed throughout the observation of 5 minutes. Furthermore, intravenous administration of digitalis, a Na[sup +]-K[sup +] pump blocker, did not inhibit the absorption of [sup 99m]Tc and [sup 201]Tl after SC injection at K-3 points. These results suggest that absorption of radionuclides on SC injection at K-3 points is mainly through the passive pathway of diffusion rather than the active transport, and the effective ionic radius may be a major factor influencing the absorption rate of the radionuclides. (author).

Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation.

Science.gov (United States)

Melo, Arine M; Benatti, Rafaela O; Ignacio-Souza, Leticia M; Okino, Caroline; Torsoni, Adriana S; Milanski, Marciane; Velloso, Licio A; Torsoni, Marcio Alberto

2014-05-01

The goal of this study was to determine the presence early of markers of endoplasmic reticulum stress (ERS) and insulin resistance in the offspring from dams fed HFD (HFD-O) or standard chow diet (SC-O) during pregnancy and lactation. To address this question, we evaluated the hypothalamic and hepatic tissues in recently weaned mice (d28) and the hypothalamus of newborn mice (d0) from dams fed HFD or SC during pregnancy and lactation. Body weight, adipose tissue mass, and food intake were more accentuated in HFD-O mice than in SC-O mice. In addition, intolerance to glucose and insulin was higher in HFD-O mice than in SC-O mice. Compared with SC-O mice, levels of hypothalamic IL1-β mRNA, NFκB protein, and p-JNK were increased in HFD-O mice. Furthermore, compared with SC-O mice, hypothalamic AKT phosphorylation after insulin challenge was reduced, while markers of ERS (p-PERK, p-eIF2α, XBP1s, GRP78, and GRP94) and p-AMPK were increased in the hypothalamic tissue of HFD-O at d28 but not at d0. These damages to hypothalamic signaling were accompanied by increased triglyceride deposits, activation of NFκB, p-JNK, p-PERK and p-eIF2α. These point out lactation period as maternal trigger for metabolic changes in the offspring. These changes may occur early and quietly contribute to obesity and associated pathologies in adulthood. Although in rodents the establishment of ARC neuronal projections occurs during the lactation period, in humans it occurs during the third trimester. Gestational diabetes and obesity in this period may contribute to impairment of energy homeostasis. Copyright © 2014 Elsevier Inc. All rights reserved.

Sc-45 nuclear magnetic resonance analysis of precipitation in dilute Al-Sc alloys

NARCIS (Netherlands)

Celotto, S; Bastow, TJ

Nuclear magnetic resonance (NMR) with Sc-45 is used to determine the solid solubility of scandium in aluminium and to follow the precipitation of Al3Sc during the ageing of an Al-0.06 at.% Sc alloy via the two fully resolved peaks, corresponding to Sc in the solid solution Al matrix and to Sc in the

Short communication : Supplementation of fructo-oligosaccharides does not improve insulin sensitivity in heavy veal calves fed different sources of carbohydrates

NARCIS (Netherlands)

Pantophlet, A. J.; Gilbert, M. S.; Gerrits, W. J. J.; Vonk, R. J.

Heavy veal calves (4–6 mo old) often develop problems with insulin sensitivity. This could lead to metabolic disorders and impaired animal growth performance. Studies in various animal species have shown that the supplementation of short-chain fructo-oligosaccharides (scFOS) can improve insulin

Intravenous and Subcutaneous Toxicity and Absorption Kinetics in Mice and Dogs of the Antileishmanial Triterpene Saponin PX-6518

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Louis Maes

2013-04-01

Full Text Available The intravenous (IV and subcutaneous (SC toxicity and absorption kinetics of the antileishmanial triterpene saponin PX-6518 and its active constituents maesabalide-III and -IV were studied in mice and dogs. A high-dose wash-out study of PX-6518 at 20 mg/kg SC for 5 days and a single low-dose wash-out study at 1, 2.5 or 5 mg/kg SC and IV with follow-up until day 35 after treatment were performed in mice. Beagle dogs received three escalating doses of maesabalide-III and -IV at weekly intervals (0.01, 0.1 and 0.5 mg/kg IV and maesabalide-III was also dosed SC at 0.1, 0.2 and 0.4 mg/kg. Endpoint measurements included clinical, hematological and serum biochemical parameters. Pathology and toxicokinetic studies were performed on the dogs. Whereas the neutrophils and aspartate aminotransferase and alanine aminotransferase levels were increased in the high-dose wash-out mouse study, these parameters did not change in the low-dose wash-out study. The dogs were far more susceptible than mice to liver toxicity (hepatocellular necrosis and elevated liver enzymes and developed a painful inflammatory reaction at the SC injection site. Toxicokinetic analysis revealed a non dose-linear systemic availability with plasma concentrations above the antileishmanial IC50 after only a single dose at 0.01 mg/kg IV or 0.1 mg/kg SC. Related to the long half-life (T1/2 71–91 h after SC dosing, repeated dosing at weekly intervals may result in drug accumulation and enhanced toxicity. It was decided not to pursue further drug development for PX-6518 because of the hepatotoxic risk.

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.

Fat distribution and insulin resistance in young adult nonobese Asian Indian women.

Science.gov (United States)

Szuszkiewicz-Garcia, Magdalene; Li, Rong; Grundy, Scott M; Abate, Nicola; Chandalia, Manisha

2012-10-01

Although Asian Indian (people of Indian subcontinent descent) men are shown to have higher total and truncal body fat as well as greater insulin resistance compared to white men matched for total body fat and age, data in women are not conclusive. The objective of this study was to compare total and regional fat distribution and insulin sensitivity between healthy young premenopausal Asian Indian and white women of similar body mass index (BMI). Twenty Asian Indian women (65% immigrants and 35% first generation living in Dallas) and 31 white women of similar age and BMI [age 24±3 vs. 25±4; BMI 22±4 vs. 23±5; mean±standard deviation (SD) in Asian Indian and white, respectively] without diabetes were evaluated with anthropometric measurements, underwater weighing for percentage of total body fat mass, magnetic resonance imaging of whole abdomen for measurement of abdominal subcutaneous and intraperitoneal fat mass, and euglycemic-hyperinsulinemic clamp study for measurement of insulin sensitivity. There were no differences in waist or hip circumference, total body subcutaneous abdominal or intraperitoneal fat mass, fasting plasma glucose, and insulin levels between Asian Indian women and white women. The peripheral glucose disposal rate (Rd) during hyperinsulinemic-euglycemic clamp was found to be almost identical in the two study groups (median value of 6.9 and 6.8 mg/min per kg of body weight, for Asian Indians and whites, respectively). For similar total or regional fat content, the glucose disposal rate was comparable in the two study groups. In conclusion, we demonstrate that young Asian Indian women do not have excess abdominal or intraperitoneal fat or insulin resistance for similar BMI compared to white women of European descent.

FOXC2 mRNA Expression and a 5' untranslated region polymorphism of the gene are associated with insulin resistance

DEFF Research Database (Denmark)

Ridderstråle, Martin; Carlsson, Emma; Klannemark, Mia

2002-01-01

with subcutaneous fat from obese subjects (12 +/- 4-fold; P = 0.0001), and there was a correlation between whole-body insulin sensitivity and FOXC2 mRNA levels in visceral fat (fS-insulin R = -0.64, P = 0.01, and homeostasis model assessment of insulin resistance [HOMA-IR] R = -0.68, P = 0.007) and skeletal muscle...... (fS-insulin R = -0.57, P = 0.03, and HOMA-IR R = -0.55, P = 0.04). Mutation screening of the FOXC2 gene identified a common polymorphism in the 5' untranslated region (C-512T). The T allele was associated with enhanced insulin sensitivity (HOMA-IR P = 0.007) and lower plasma triglyceride levels...

Crystal structure and phase stability of AlSc in the near-equiatomic Al–Sc alloy

Energy Technology Data Exchange (ETDEWEB)

Li, Juan; Huang, Li; Liang, Yongfeng [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, 30 Xueyuan Road, Beijing 100083 (China); Ye, Feng, E-mail: yefeng@skl.ustb.edu.cn [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, 30 Xueyuan Road, Beijing 100083 (China); Lin, Junpin [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, 30 Xueyuan Road, Beijing 100083 (China); Shang, Shunli; Liu, Zikui [Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA 16802 (United States)

2015-01-05

Highlights: • Two lattice structures of equiatomic Al–Sc compounds are confirmed. • Al–Sc phase at Sc 50 at.% has a space group of Pbam. • Al–Sc phase at Sc 55 at.% has a space group of B2. • B2 AlSc is a metastable phase with Sc 50 at.%. • Lattice transition between two compounds is proposed under local thermal stress. - Abstract: Intermetallic compound AlSc is found in the equiatomic Al–Sc binary alloy. The present work indicates that the orthorhombic AlSc with the Au{sub 2}CuZn-type structure can be formed at 50 at.% Sc, while the CsCl-type (B2) AlSc will be formed at 55 at.% Sc. After annealing at 1100 °C, some orthorhombic AlSc grains transit to the B2 structure, and the annealing at lower temperatures leads to the disappearance of B2 phase, indicating that the B2 AlSc is also a metastable phase in the alloy at lower Sc content (<50 at.%). First-principle calculations at 0 K reveal that the orthorhombic AlSc is more stable than the B2 AlSc with the energy difference between them being 5.4 meV/atom. The fast transition between these two phases, which cannot be interpreted by the mechanism of atomic diffusion, was tentatively analyzed by the volume change based on the calculated atomic positions of these two phases.

Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers.

Science.gov (United States)

Berteau, Cecile; Schwarzenbach, Florence; Donazzolo, Yves; Latreille, Mathilde; Berube, Julie; Abry, Herve; Cotten, Joël; Feger, Celine; Laurent, Philippe E

2010-10-05

A disposable autoinjector was developed for subcutaneous (SC) self-injection by patients with chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections performed by nurses using a syringe. This was a randomized, single-center, crossover study comparing SC self-injection using an autoinjector with SC nurse-administered injection using a syringe. Two volumes (0.2 mL and 1 mL) were injected into healthy volunteers. Study objectives included assessment of the accuracy and consistency of the volume injected by the injection systems, and skin reaction and pain associated with the injection. The fluid depot in the SC tissue layer was evaluated by ultrasound. Subject acceptance was evaluated using questionnaires on attitudes and emotions towards the injection technique, and challenged by seeking the subjects' preferred system for a final study injection or future treatment. A total of 960 injections (480 with autoinjector, 480 with syringe) were performed in 40 subjects. There were no significant differences in mean fluid leakage and injected volumes between the systems. Pain associated with the injection was significantly lower with the auto-injector than with the syringe. Local skin reaction at the injection site was overall satisfactory. Injections were appropriately performed by all subjects. At study end, all 40 subjects preferred the autoinjector for a final study injection and for future treatment. This study indicated that the autoinjector used by the subject was similar to a syringe used by a nurse in terms of performance and safety in administering the injections, and better in terms of pain, overall acceptance, and preference.

Efficacy and Safety of Rapid-Acting Insulin Analogs in Special Populations with Type 1 Diabetes or Gestational Diabetes

DEFF Research Database (Denmark)

Nørgaard, Kirsten; Sukumar, Nithya; Rafnsson, Snorri B

2018-01-01

Med, EMBASE and Cochrane Reviews were searched electronically, and their bibliographies examined to identify suitable studies for review and inclusion in a meta-analysis. Eligible studies were randomized controlled trials that reported data on relevant clinical outcomes. A different reviewer abstracted data...... concerns. Meta-analysis indicated severe hypoglycemic events were comparable for rapid-acting insulin analogs versus RHI (risk difference: 0.00 [95% confidence interval - 0.01; 0.01]). In the pregnancy group, insulin lispro and insulin aspart were safe and effective for both mother and fetus, with glycemic......INTRODUCTION: To assess the efficacy and safety of three available rapid-acting insulin analogs (insulins lispro, aspart and glulisine, respectively) in pregnant women, children/adolescents and people using continuous subcutaneous insulin infusion (CSII) with type 1 diabetes. METHODS: Pub...

Relative Bioavailability of a Single 4-mg Dose of Somatropin Administered by Subcutaneous Injection or by Needle-free Device and Coadministered With the Growth Hormone Inhibitor Octreotide Acetate in Healthy Adult Subjects.

Science.gov (United States)

Brimhall, Darin B; Petri, Niclas; D'Angelo, Pina

2018-05-01

Somatropin, used to treat growth hormone deficiency, has been traditionally administered by subcutaneous (SC) injection with needle and syringe. Needle-free devices offer ease of administration and may improve adherence and outcomes. This study evaluated the relative bioavailability of somatropin delivered with a needle-free device compared with traditional SC injection. In this randomized, single-dose, crossover study, healthy adults aged 18 to 35 years received single 4-mg doses of somatropin via a needle-free device or SC injection, along with octreotide to suppress endogenous growth hormone production. Blood samples were analyzed for serum somatropin and insulin-like growth factor-1 (IGF-1) concentrations over 24 hours after somatropin dosing. Pharmacokinetic and pharmacodynamic parameters were evaluated by using noncompartmental methods, and bioequivalence was determined based on ln transformation of the AUC 0-24 , AUC 0-∞ , C max , area under the effect-time curve from time 0 to 24 hours (AUEC 0-24 ), and maximum effect concentration (E max ). Bioequivalence was concluded if the 90% CIs of the needle-free device compared with the SC injection, constructed by using the two 1-sided hypotheses at the α = 0.05 level, for these pharmacokinetic/pharmacodynamic parameters fell within the 80.00% to125.00% regulatory acceptance range. A total of 57 subjects completed both study periods and were included in the pharmacokinetic analyses. Point estimates (90% CIs) of the geometric mean ratio (needle-free device/SC injection) based on serum somatropin were 1.013 (0.987-1.040) for AUC 0-24 , 1.012 (0.986-1.038) for AUC 0-∞ , and 1.200 (1.137-1.267) for C max . For IGF-1, baseline-corrected point estimates (90% CIs) were 0.901 (0.818-0.993) for AUEC 0-24 and 0.867 (0.795-0.946) for E max . Non-baseline-corrected values were 0.978 (0.953-1.004) for AUEC 0-24 and 0.953 (0.923-0.984) for E max . Both treatments were well tolerated; blood glucose levels increased in nearly

The effects of early insulin treatment combined with thrombolysis in rat embolic stroke

DEFF Research Database (Denmark)

Meden, Per; Andersen, Martin; Overgaard, Karsten

2002-01-01

in % of the affected hemisphere. Mortality was calculated as the number of animals dying spontaneously before the scheduled euthanasia. The median infarct volume in control animals (n = 12) was 24%. Insulin (3 IU kg(-1)) was given subcutaneously 15 min, 3 h, and 24 h after embolization (n = 12) and reduced median...

46 CFR 7.70 - Folly Island, SC to Hilton Head Island, SC.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Folly Island, SC to Hilton Head Island, SC. 7.70 Section... BOUNDARY LINES Atlantic Coast § 7.70 Folly Island, SC to Hilton Head Island, SC. (a) A line drawn from the...′ W. (Port Royal Sound Lighted Whistle Buoy “2PR”); thence to the easternmost extremity of Hilton Head...

Long-term effects of continuous subcutaneous infusion versus daily subcutaneous injections of growth hormone (GH) on the insulin-like growth factor system, insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH-deficient adults

DEFF Research Database (Denmark)

Laursen, Torben; Gravholt, Claus Højbjerg; Heickendorff, Lene

2001-01-01

injections (inj) in the evening as usual, and 7 received a continuous infusion (inf) of GH by means of a portable pump. The GH dose was kept unchanged before and during the study. Serum levels of insulin-like growth factor I (IGF-I) tended to increase in the patients switched to constant infusion (from 175...... for 6 months are comparable with respect to the IGF-IGFBP axis, whereas intermittent exposure may be of importance for the lipolytic effect of GH. The data on insulin sensitivity and lipoproteins suggest that constant GH exposure is as safe as intermittent GH administration....

Evaluation of subcutaneous infiltration of autologous platelet-rich plasma on skin-wound healing in dogs.

Science.gov (United States)

Farghali, Haithem A; AbdElKader, Naglaa A; Khattab, Marwa S; AbuBakr, Huda O

2017-04-28

Platelet-rich plasma (PRP) is known to be rich in growth factors and cytokines, which are crucial to the healing process. This study investigate the effect of subcutaneous (S/C) infiltration of autologous PRP at the wound boundaries on wound epithelization and contraction. Five adult male mongrel dogs were used. Bilateral acute full thickness skin wounds (3 cm diameter) were created on the thorax symmetrically. Right side wounds were subcutaneously infiltrated with activated PRP at day 0 and then every week for three consecutive weeks. The left wound was left as control. Wound contraction and epithelization were clinically evaluated. Expression of collagen type I (COLI) A2, (COLIA2),histopathology and immunohistochemical (IHC) staining of COLI α1 (COLIA1) were performed on skin biopsies at first, second and third weeks. The catalase activity, malondialdehyde (MDA) concentration and matrix metalloproteinase (MMP) 9 (MMP-9) activity were assessed in wound fluid samples. All data were analysed statistically. The epithelization percent significantly increased in the PRP-treated wound at week 3. Collagen was well organized in the PRP-treated wounds compared with control wounds at week 3. The COLIA2 expression and intensity of COLIA1 significantly increased in PRP-treated wounds. MDA concentration was significantly decreased in PRP-treated wound at week 3. The catalase activity exhibited no difference between PRP treated and untreated wounds. The activity of MMP-9 reached its peak at the second week and was significantly high in the PRP-treated group. S/C infiltration of autologous PRP at the wound margins enhances the wound epithelization and reduces the scar tissue formation. © 2017 The Author(s).

Frontal subcutaneous blood flow, and epi- and subcutaneous temperatures during scalp cooling in normal man

DEFF Research Database (Denmark)

Bülow, J; Friberg, L; Gaardsting, O

1985-01-01

Cooling of the scalp has been found to prevent hair loss following cytostatic treatment, but in order to obtain the hair preserving effect the subcutaneous temperature has to be reduced below 22 degrees C. In order to establish the relationship between epicutaneous and subcutaneous temperatures...... epicutaneous and subcutaneous temperatures could be demonstrated with the regression equation: s = 0.9 c + 4.9 (r = 0.99). In eight of the 10 subjects the subcutaneous temperature could be reduced below 22 degrees C with the applied technique. It is concluded that the hair preserving effect of scalp cooling...

High-resolution clean-sc

NARCIS (Netherlands)

Sijtsma, P.; Snellen, M.

2016-01-01

In this paper a high-resolution extension of CLEAN-SC is proposed: HR-CLEAN-SC. Where CLEAN-SC uses peak sources in “dirty maps” to define so-called source components, HR-CLEAN-SC takes advantage of the fact that source components can likewise be derived from points at some distance from the peak,

Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle.

Science.gov (United States)

Tran, Ha T; Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

2017-01-01

Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

DEFF Research Database (Denmark)

Stallknecht, B; Larsen, J J; Mikines, K J

2000-01-01

Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration......-time: T, 44 +/- 9 min (n = 7); S, 102 +/- 23 min (n = 5); P training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis...

Comparison of Insulin Detemir and Insulin Glargine for Hospitalized Patients on a Basal-Bolus Protocol

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Sondra Davis

2017-04-01

Full Text Available BACKGROUND: The primary purpose of this study is to determine whether insulin detemir is equivalent to insulin glargine in controlling hyperglycemia for the adult hospitalized patient on a basal-bolus treatment regimen. METHODS: A retrospective study was conducted at two acute care hospitals within the same health system. Patients from both facilities who were initiated on a basal-bolus subcutaneous insulin regimen were included in the study. The basal-bolus regimen consisted of three components: basal, bolus, and corrective insulin with only the data from the first seven days analyzed. Once the basal-bolus protocol was initiated, all previous glycemic agents were discontinued. The target glycemic goal of the study was 100–180 mg/dL. RESULTS: In both groups, 50% of the patients had achieved the target glycemic control goal (100–180 mg/dL by day 2 (p = 0.3. However, on the seventh or last day of basal-bolus treatment, whichever came first, 36.36% of patients receiving insulin detemir (n = 88 achieved the blood glucose reading goal compared to 52.00% in patients receiving insulin glargine (n = 100 (p = 0.03. This corresponded to an adjusted odds ratio of 2.12 (1.08 to 4.15, p = 0.03. The adjusting variables were provider type, whether the patient was hospitalized within 30 days prior and diagnosis of stroke. The mean blood glucose readings for the insulin glargine and the insulin detemir groups while on basal-bolus therapy were 200 mg/dL and 215 mg/dL, respectively (p = 0.05. The total number of blood glucose readings less than 70 mg/dL and less than 45 mg/dL was very low and there were no differences in number of episodes with hypoglycemia between the two groups. CONCLUSION: There was not a statistical difference between the two groups at 2 days, however there was on the seventh day or the last day of basal-bolus treatment. There were nonsignificant hypoglycemia events between basal insulin groups and the results for the last or seventh day

Clinical value of Flash glucose monitoring in patients with type 1 diabetes treated with continuous subcutaneous insulin infusion.

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Moreno-Fernandez, Jesus; Pazos-Couselo, Marcos; González-Rodriguez, Maria; Rozas, Pedro; Delgado, Manuel; Aguirre, Miguel; Garcia-Lopez, Jose Manuel

2018-06-12

To analyze the clinical impact of the Flash glucose monitoring system in patients with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). A 24-week retrospective cohort study in CSII-treated T1DM patients exposed (1:1) to the Flash glucose monitoring system vs. self-monitoring of capillary blood glucose (SMBG). The primary outcome was the difference in hemoglobin A1c (HbA1c) levels between both groups at the end of the study. Thirty-six patients with a mean age of 38.2 years (range 22-55) and a mean T1DM duration of 20.9±7.8 years, treated with CSII for 7.1±5.4 years, were enrolled into the study. At the end of the study, mean HbA1c levels improved in patients in the Flash group (7.1±0.7 vs. 7.8±1.0, p=0.04). Only the Flash group showed a significant decrease in HbA1c levels of -0.4% (95% CI, -0.6, -0.2; p=0.004) during follow-up. Flash patients captured 93.9% of data through 17.8±9.9 scans daily. In fact, the Flash cohort showed a three-fold increase in daily self-monitoring of glucose, while daily frequency of SMBG decreased during the study (-1.8 tests/24h (95% CI -3, -0.7; p=0.01). No safety issues related to Flash use were recorded. The Flash glucose monitoring system is a novel approach to improve blood glucose control in CSII-treated T1DM patients. Randomized controlled trials are needed to assess the effectiveness of this system in CSII-treated T1DM patients. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men. The Ohtori study

International Nuclear Information System (INIS)

Koh, Hideo; Hayashi, Tomoshige; Kogawa Sato, Kyoko

2011-01-01

Visceral adiposity is considered to have a key role in cardiometabolic diseases. The purpose of this study is to investigate cross-sectionally the association between intra-abdominal fat area (IAFA) measured by computed tomography (CT) and high blood pressure independent of abdominal subcutaneous fat area (ASFA) and insulin resistance. Study participants included 624 Japanese men not taking oral hypoglycemic medications or insulin. Abdominal, thoracic and thigh fat areas were measured by CT. Total fat area (TFA) was calculated as the sum of abdominal, thoracic and thigh fat area. Total subcutaneous fat area (TSFA) was defined as TFA minus IAFA. Hypertension and high normal blood pressure were defined using the 1999 criteria of the World Health Organization. Multiple-adjusted odds ratios of hypertension for tertiles of IAFA were 2.64 (95% confidence interval, 1.35-5.16) for tertile 2, and 5.08 (2.48-10.39) for tertile 3, compared with tertile 1 after adjusting for age, fasting immunoreactive insulin, diabetes status, ASFA, alcohol consumption, regular physical exercise and smoking habit. IAFA remained significantly associated with hypertension even after adjustment for ASFA, TSFA, TFA, body mass index or waist circumference, and no other measure of regional or total adiposity was associated with the odds of hypertension in models, which included IAFA. Similar results were obtained for the association between IAFA and the prevalence of high normal blood pressure or hypertension. In conclusion, greater visceral adiposity was associated with a higher odds of high blood pressure in Japanese men. (author)

Fear of needles in children with type 1 diabetes mellitus on multiple daily injections and continuous subcutaneous insulin infusion.

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Cemeroglu, Ayse Pinar; Can, Argun; Davis, Alan T; Cemeroglu, Ozlem; Kleis, Lora; Daniel, Maala S; Bustraan, Jessica; Koehler, Tracy J

2015-01-01

To assess the prevalence of fear of needles and its effect on glycemic control in children with type 1 diabetes mellitus (T1DM) on multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Patients aged 6 to 17 years with T1DM on MDI or CSII (n = 150) were enrolled. All caregivers and patients aged ≥11 years completed a "Diabetes Fear of Injecting and Self-testing Questionnaire" (D-FISQ). Needle phobia was defined as a score ≥6 for fear of self-testing (FST), fear of injections (FI), and fear of infusion-site changes (FISC). Positive FST scores were noted in 10.0% and positive FI or FISC scores in 32.7% (caregivers' responses). Patients aged 6 to 10 years on CSII had greater fear (FISC) than those on MDI (FI) (P = .010). FST was inversely related to the number of daily blood sugar checks (P = .003). Patients with positive scores for FI/FISC or FST had significantly higher glycated hemoglobin (HbA1c) levels than those without. An inverse association was noted between positive FI/FISC scores and age of the patient (P = .029). Based on patient responses, FST severity was directly related to the age of the patient (P = .013). Needle phobia is common in children with T1DM. Although FI/FISC are more common in younger children, especially in those on CSII, FST is more often encountered in older patients. Patients with a more intense fear of needles have higher HbA1c levels and less frequent blood sugar monitoring. Identifying these patients may help improve glycemic control.

Evaluation of current trends and recent development in insulin therapy for management of diabetes mellitus.

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Nawaz, Muhammad Sarfraz; Shah, Kifayat Ullah; Khan, Tahir Mehmood; Rehman, Asim Ur; Rashid, Haroon Ur; Mahmood, Sajid; Khan, Shahzeb; Farrukh, Muhammad Junaid

2017-12-01

Diabetes mellitus is a major health problem in developing countries. There are various insulin therapies to manage diabetes mellitus. This systematic review evaluates various insulin therapies for management of diabetes mellitus worldwide. This review also focuses on recent developments being explored for better management of diabetes mellitus. We reviewed a number of published articles from 2002 to 2016 to find out the appropriate management of diabetes mellitus. The paramount parameters of the selected studies include the insulin type & its dose, type of diabetes, duration and comparison of different insulin protocols. In addition, various newly developed approaches for insulin delivery with potential output have also been evaluated. A great variability was observed in managing diabetes mellitus through insulin therapy and the important controlling factors found for this therapy include; dose titration, duration of insulin use, type of insulin used and combination therapy of different insulin. A range of research articles on current trends and recent advances in insulin has been summarized, which led us to the conclusion that multiple daily insulin injections or continuous subcutaneous insulin infusion (insulin pump) is the best method to manage diabetes mellitus. In future perspectives, development of the oral and inhalant insulin would be a tremendous breakthrough in Insulin therapy. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Exercise Protects Against Defective Insulin Signaling and Insulin Resistance of Glucose Transport in Skeletal Muscle of Angiotensin II-Infused Rat

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Juthamard Surapongchai

2018-04-01

Full Text Available Objectives: The present study investigated the impact of voluntary exercise on insulin-stimulated glucose transport and the protein expression and phosphorylation status of the signaling molecules known to be involved in the glucose transport process in the soleus muscle as well as other cardiometabolic risks in a rat model with insulin resistance syndrome induced by chronic angiotensin II (ANGII infusion.Materials and Methods: Male Sprague-Dawley rats were assigned to sedentary or voluntary wheel running (VWR groups. Following a 6-week period, rats in each group were subdivided and subcutaneously administered either normal saline or ANGII at 100 ng/kg/min for 14 days. Blood pressure, glucose tolerance, insulin-stimulated glucose transport and signaling proteins, including insulin receptor (IR, insulin receptor substrate 1 (IRS-1, Akt, Akt substrate of 160 kDa (AS160, AMPKα, c-Jun NH2-terminal kinase (JNK, p38 MAPK, angiotensin converting enzyme (ACE, ANGII type 1 receptor (AT1R, ACE2, Mas receptor (MasR and oxidative stress marker in the soleus muscle, were evaluated.Results: Exercise protected against the insulin resistance of glucose transport and defective insulin signaling molecules in the soleus muscle; this effect was associated with a significant increase in AMPK Thr172 (43% and decreases in oxidative stress marker (31% and insulin-induced p38 MAPK Thr180/Tyr182 (45% and SAPK/JNK Thr183/Tyr185 (25%, without significant changes in expression of AT1R, AT2R, ACE, ACE2, and MasR when compared to the sedentary rats given ANGII infusion. At the systemic level, VWR significantly decreased body weight, fat weight, and systolic blood pressure as well as improved serum lipid profiles.Conclusion: Voluntary exercise can alleviate insulin resistance of glucose transport and impaired insulin signaling molecules in the soleus muscle and improve whole-body insulin sensitivity in rats chronically administered with ANGII.

Reversal of the toxic effects of cachectin by concurrent insulin administration.

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Fraker, D L; Merino, M J; Norton, J A

1989-06-01

Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

The role of insulin glulisine to improve glycemic control in children with diabetes mellitus

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Carter J

2010-11-01

Full Text Available Anna Lih, Emily Hibbert, Tang Wong, Christian M Girgis, Nidhi Garg, John N CarterDepartment of Endocrinology and Metabolism, Concord Hospital, NSW, Australia; University of Sydney, Camperdown, NSW, AustraliaAbstract: Glulisine (Apidra® is a rapid-acting human insulin analog approved for use in children with diabetes mellitus ≥4 years of age. Management of children with type 1 diabetes has seen a shift in favor of mimicking normal physiological insulin responses with multiple daily injections or continuous subcutaneous insulin infusions (CSII. Few studies have compared the rapid-acting insulin analogs in this population but limited data indicate that glulisine is as effective as lispro when used in a basal–bolus regimen. This review appraises the current available studies and reviews on insulin glulisine in children. An extensive keyword search of ‘insulin glulisine’, ‘insulin analogs’, and ‘Apidra’ in the pediatric population was performed. These studies have suggested that glulisine is safe, well tolerated, and is an effective option in the diabetes armamentarium. Further studies are needed to determine its safety for use in CSII pumps in the pediatric population.Keywords: glulisine, pediatrics, type 1 diabetes mellitus

Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.

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Agné Kulyté

Full Text Available Although the mechanisms linking obesity to insulin resistance (IR and type 2 diabetes (T2D are not entirely understood, it is likely that alterations of adipose tissue function are involved. The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin resistant (OIR or sensitive (OIS adipocytes. Insulin sensitivity was first determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT in a large observational study. Lipogenesis was measured under conditions where glucose transport was the rate limiting step and reflects in vivo insulin sensitivity. We then performed microarray-based transcriptome profiling on subcutaneous WAT specimen from a subgroup of 9 lean, 21 OIS and 18 obese OIR women. We could identify 432 genes that were differentially expressed between the OIR and OIS group (FDR ≤5%. These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include genes such as SLC2A4, AKT2, as well as genes coding for enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 encoding a transcription factor and SLC25A10 encoding a dicarboxylate carrier, were selected for functional evaluation in adipocytes differentiated in vitro. Knockdown of KLF15 and SLC25A10 using siRNA inhibited insulin-stimulated lipogenesis in adipocytes. Transcriptome profiling of siRNA-treated cells suggested that KLF15 might control insulin sensitivity by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had only modest impact on the transcriptome, suggesting that it might directly influence insulin sensitivity in adipocytes independently of transcription due to its important role in fatty acid synthesis. In summary, this study identifies novel genes associated with insulin sensitivity in

Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration.

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Fathallah, Anas M; Turner, Michael R; Mager, Donald E; Balu-Iyer, Sathy V

2015-03-01

The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability. Copyright © 2014 John Wiley & Sons, Ltd.

Determination of Sc and Th in ScI3-NaI-ThI4 sample

International Nuclear Information System (INIS)

Yuan Hui; Yang Zhihong

1999-01-01

Determination of Sc and Th in ScI 3 -NaI-ThI 4 sample is studied by X-ray fluorescence and complexometry. The effect of working condition of Sc on X-ray fluorescence spectrometer and different sample-making method on the determination of Sc and Th are studied experimentally. The X-ray fluorescence analysis of determination of Sc and Th is developed by polyester film sample-making technique, the measuring precision of Sc and Th is better than 4%. The effect of acidity and temperature on the determining end point of titration is obvious. The results of different complexometric methods are compared. The precision of Sc and Th is less than 2% by comlexometry, it is fit for the routine analysis of ScI 3 -NaI-ThI 4 sample

Subcutaneous granuloma annulare: radiologic appearance

International Nuclear Information System (INIS)

Kransdorf, M.J.; Murphey, M.D.; Temple, H.T.

1998-01-01

Objective. Granuloma annulare is an uncommon benign inflammatory dermatosis characterized by the formation of dermal papules with a tendency to form rings. There are several clinically distinct forms. The subcutaneous form is the most frequently encountered by radiologists, with the lesion presenting as a superficial mass. There are only a few scattered reports of the imaging appearance of this entity in the literature. We report the radiologic appearance of five cases of subcutaneous granuloma annulare. Design and patients. The radiologic images of five patients (three male, two female) with subcutaneous granuloma annulare were retrospectively studied. Mean patient age was 6.4 years (range, 2-13 years). The lesions occurred in the lower leg (two), foot, forearm, and hand. MR images were available for all lesions, gadolinium-enhanced imaging in three cases, radiographs in four, and bone scintigraphy in one. Results. Radiographs showed unmineralized nodular masses localized to the subcutaneous adipose tissue. The size range, in greatest dimension on imaging studies, was 1-4 cm. MR images show a mass with relatively decreased signal intensity on all pulse sequences, with variable but generally relatively well defined margins. There was extensive diffuse enhancement following gadolinium administration. Conclusion. The radiologic appearance of subcutaneous granuloma annulare is characteristic, typically demonstrating a nodular soft-tissue mass involving the subcutaneous adipose tissue. MR images show a mass with relatively decreased signal intensity on all pulse sequences and variable but generally well defined margins. There is extensive diffuse enhancement following gadolinium administration. Radiographs show a soft-tissue mass or soft-tissue swelling without evidence of bone involvement or mineralization. This radiologic appearance in a young individual is highly suggestive of subcutaneous granuloma annulare. (orig.)

Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents.

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Liu, Y-L; Ford, H E; Druce, M R; Minnion, J S; Field, B C T; Shillito, J C; Baxter, J; Murphy, K G; Ghatei, M A; Bloom, S R

2010-12-01

To determine the efficacy of a long-acting oxyntomodulin (OXM) analogue, OXM6421, in inhibiting food intake and decreasing body weight in lean and diet-induced obese (DIO) rodents. The glucagon-like peptide-1 (GLP-1) receptor binding affinity and efficacy, sensitivity to enzymatic degradation in vitro and persistence in the circulation after peripheral administration were investigated for OXM6421 and compared with native OXM. The chronic effect of OXM6421 on food intake, body weight and energy expenditure was examined in lean rats, and its anti-obesity potential was evaluated in DIO mice. OXM6421 showed enhanced GLP-1 receptor binding affinity and cyclic adenosine monophosphate (cAMP) stimulation, and higher resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase (NEP) compared with native OXM. OXM6421 persisted longer in the circulation than OXM after peripheral administration. Acute administration of OXM6421 potently inhibited food intake in lean rodents, with cumulative effects lasting up to 24 h. In lean rats, daily subcutaneous (s.c.) administration of OXM6421 caused greater weight loss than the pair-fed animals, and a higher rate of oxygen consumption than both the pair-fed and the saline controls. In DIO mice, continuous s.c. infusion of OXM6421 resulted in a significant weight loss, accompanied by an improvement in glucose homeostasis and an increase in circulating adiponectin levels. Once-daily s.c. administration of OXM6421 for 21 days caused sustained weight loss in DIO mice. OXM6421 induces negative energy balance in both lean and obese rodents, suggesting that long-acting OXM analogues may represent a potential therapy for obesity.

Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries

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De Cock, Erwin; Kritikou, Persefoni; Sandoval, Mariana; Tao, Sunning; Wiesner, Christof; Carella, Angelo Michele; Ngoh, Charles; Waterboer, Tim

2016-01-01

Background Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. Methods This non-interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient’s first year of treatment (11 rituximab sessions). Results Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p time was 27–58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1–5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p time for the first year of treatment was 3.1–5.5 eight-hour days. Conclusions Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. Trial Registration ClinicalTrials.gov NCT01200758 PMID:27362533

The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

DEFF Research Database (Denmark)

Henstridge, Darren C; Forbes, Josephine M; Penfold, Sally A

2010-01-01

Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans. We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young...... healthy human population free of hyperglycemia. Healthy participants (N = 17; age, 30 ± 3 years) underwent measurement of body composition (dual-energy x-ray absorptiometry), a maximum aerobic capacity test (VO(2max)), an oral glucose tolerance test, and a hyperinsulinemic-euglycemic clamp (M) to access...... insulin sensitivity. Skeletal muscle and subcutaneous adipose tissue biopsies were obtained by percutaneous needle biopsy. HSP72 protein expression in skeletal muscle was inversely related to percentage body fat (r = -0.54, P

Subcutaneous sarcoidosis associated with sarcoid tenosynovitis.

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Enzenauer, R J; Waterhouse, W J; West, S G

1996-10-01

Subcutaneous sarcoidosis and sarcoid tenosynovitis are unusual manifestations of systemic sarcoidosis. We report two Japanese women with disseminated sarcoidosis presenting with subcutaneous and tenosynovial involvement demonstrated by computed tomography and magnetic resonance imaging. Sarcoidosis must be considered in the differential diagnosis of unexplained subcutaneous nodulosis or tenosynovitis in patients with or without a previous diagnosis of sarcoidosis.

Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37

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Wolf-Georg Forssmann

2016-08-01

Full Text Available Background/Aims: Parathyroid hormone (PTH derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median tmax of 30 minutes for 20 and 40 µg of PTH-1-37. tmax was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD, and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34 increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.

Effects of Weight Loss and Exercise on Apelin Serum Concentrations and Adipose Tissue Expression in Human Obesity

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Joanna Krist

2013-02-01

Full Text Available Objective: Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases. Here we investigate the role of omental and subcutaneous (SC adipose tissue apelin and its receptor APJ mRNA expression in human obesity and test the hypothesis that changes in circulating apelin are associated with reduced fat mass in three weight loss intervention studies. Methods: Apelin serum concentration was measured in 740 individuals in a cross-sectional (n = 629 study including a subgroup (n = 161 for which omental and SC apelin mRNA expression has been analyzed and in three interventions: 12 weeks exercise (n = 60, 6 months calorie-restricted diet (n = 19, 12 months after bariatric surgery (n = 32. Results: Apelin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes and correlates with circulating apelin, BMI, body fat, C-reactive protein, and insulin sensitivity. Obesity surgery-induced weight loss causes a significant reduction in omental and SC apelin expression. All interventions led to significantly reduced apelin serum concentrations which significantly correlate with improved insulin sensitivity, independently of changes in BMI. Conclusions: Reduced apelin expression and serum concentration may contribute to improved insulin sensitivity beyond significant weight loss.

The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity.

LENUS (Irish Health Repository)

O'Connell, Jean

2012-02-01

OBJECTIVE: Several studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity. SUBJECTS: Thirty-five patients undergoing bariatric surgery were classified as MHO (n = 15) or metabolically unhealthy obese (MUO, n = 20) according to cut-off points adapted from the International Diabetes Federation definition of the metabolic syndrome. Median body mass index (BMI) was 48 (range 40-71). RESULTS: There was a moderate correlation between omental adipocyte size and subcutaneous adipocyte size (r = 0.59, p<0.05). The MHO group had significantly lower mean omental adipocyte size (80.9+\\/-10.9 microm) when compared with metabolically unhealthy patients (100.0+\\/-7.6 microm, p<0.0001). Mean subcutaneous adipocyte size was similar between the two groups (104.1+\\/-8.5 microm versus 107.9+\\/-7.1 microm). Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r = 0.73, p<0.0005), as well as other metabolic parameters including triglyceride\\/HDL-cholesterol ratio and HbA1c. Twenty-eight patients consented to liver biopsy. Of these, 46% had steatohepatitis and fibrosis. Fifty percent (including all the MHO patients) had steatosis only. Both omental and subcutaneous adipocyte size were significantly associated with the degree of steatosis (r = 0.66, p<0.0001 and r = 0.63, p<0.005 respectively). However, only omental adipocyte size was an independent predictor of the presence or absence of fibrosis. CONCLUSION: Metabolically healthy individuals are a distinct subgroup of the severely obese. Both subcutaneous and omental adipocyte size correlated positively with the degree of fatty liver, but only omental adipocyte size was related to metabolic health

Effects of Everyday Life Events on Glucose, Insulin, and Glucagon Dynamics in Continuous Subcutaneous Insulin Infusion–Treated Type 1 Diabetes: Collection of Clinical Data for Glucose Modeling

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Schmidt, Signe; Finan, Daniel Aaron; Duun-Henriksen, Anne Katrine

2012-01-01

metabolism, we designed and conducted a clinical study.Methods: Patients with insulin pump–treated T1D were recruited to perform everyday life events on two separate days. During the study, patients wore their insulin pumps and, in addition, a continuous glucose monitor and an activity monitor to estimate...

Subcutaneous Fentanyl Administration: A Novel Approach for Pain Management in a Rural and Suburban Prehospital Setting.

Science.gov (United States)

Lebon, Johann; Fournier, Francis; Bégin, François; Hebert, Denise; Fleet, Richard; Foldes-Busque, Guilaume; Tanguay, Alain

2016-01-01

To determine the feasibility, safety, and effectiveness of the subcutaneous route of fentanyl administration by Basic Life Support-Emergency Medical Technicians (BLS-EMT) in a rural and suburban region, with the support of an online pain management medical control center. Retrospective study of patients who received subcutaneous fentanyl and were transported by BLS-EMT to the emergency department (ED) of an academic hospital between July 1, 2013 and January 1, 2014, inclusively. Fentanyl orders were obtained from emergency physicians via an online medical control (OLMC) center. Effectiveness was defined by changes in pain scores 15 minutes, 30 minutes, and 45+ minutes after initial fentanyl administration. Safety was evaluated by measuring vital signs, Ramsay sedation scores, and adverse events subsequent to fentanyl administration. Feasibility was defined as successful fentanyl administration by BLS-EMT. SPSS-20 was used for descriptive statistics, and independent t-tests and Mann-Whitney U tests were used to determine inter- and intra-group differences based on transport time. Two hundred and eighty-eight patients (288; 14 to 93 years old) with pain scores ≥7 were eligible for the study. Of the 284 (98.6%) who successfully received subcutaneous fentanyl, 35 had missing records or data, and 249 (86.5%) were included in analyses. Average pain score pre-fentanyl was 8.9 ± 1.1. Patients fentanyl than those ≥70 years old (1.4 ± 0.3 vs, 0.8 ± 0.2 mcg/kg, p fentanyl administration and the proportion of patients achieving pain relief increased significantly (p 3 (n = 1; 0.4%). Prehospital subcutaneous fentanyl administration by BLS-EMT with the support of an OLMC center is a safe and feasible approach to pain relief in prehospital settings, and is not associated with major adverse events. Effectiveness, subsequent to subcutaneous fentanyl administration is characterized by a decrease in pain over the course of transport to ED. Further studies are needed to

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

Directory of Open Access Journals (Sweden)

Andrew R. Pepper

2017-06-01

Full Text Available Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of “healthy” human donor pancreata restricts the broader application of this effective curative therapy. “β-Like” cells derived from human embryonic stem cells (hESC, with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.

Recombinant human hyaluronidase-enabled subcutaneous pediatric rehydration.

Science.gov (United States)

Allen, Coburn H; Etzwiler, Lisa S; Miller, Melissa K; Maher, George; Mace, Sharon; Hostetler, Mark A; Smith, Sharon R; Reinhardt, Neil; Hahn, Barry; Harb, George

2009-11-01

The Increased Flow Utilizing Subcutaneously-Enabled (INFUSE)-Pediatric Rehydration Study was designed to assess efficacy, safety, and clinical utility of recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous rehydration in children 2 months to 10 years of age. Patients with mild/moderate dehydration requiring parenteral treatment in US emergency departments were eligible for this phase IV, multicenter, single-arm study. They received subcutaneous injection of 1 mL rHuPH20 (150 U), followed by subcutaneous infusion of 20 mL/kg isotonic fluid over the first hour. Subcutaneous rehydration was continued as needed for up to 72 hours. Rehydration was deemed successful if it was attributed by the investigator primarily to subcutaneous fluid infusion and the child was discharged without requiring an alternative method of rehydration. Efficacy was evaluated in 51 patients (mean age: 1.9 years; mean weight: 11.2 kg). Initial subcutaneous catheter placement was achieved with 1 attempt for 46/51 (90.2%) of patients. Rehydration was successful for 43/51 (84.3%) of patients. Five patients (9.8%) were hospitalized but deemed to be rehydrated primarily through subcutaneous therapy, for a total of 48/51 (94.1%) of patients. No treatment-related systemic adverse events were reported, but 1 serious adverse event occurred (cellulitis at infusion site). Investigators found the procedure easy to perform for 96% of patients (49/51 patients), and 90% of parents (43/48 parents) were satisfied or very satisfied. rHuPH20-facilitated subcutaneous hydration seems to be safe and effective for young children with mild/moderate dehydration. Subcutaneous access is achieved easily, and the procedure is well accepted by clinicians and parents.

33 CFR 80.712 - Morris Island, SC to Hilton Head Island, SC.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Morris Island, SC to Hilton Head..., SC to Hilton Head Island, SC. (a) A line drawn from the easternmost tip of Folley Island to the... easternmost extremity of Hilton Head at latitude 32°13.0′ N. longitude 80°40.1′ W. [CGD 77-118a, 42 FR 35784...

An iterative learning strategy for the auto-tuning of the feedforward and feedback controller in type-1 diabetes.

Science.gov (United States)

Fravolini, M L; Fabietti, P G

2014-01-01

This paper proposes a scheme for the control of the blood glucose in subjects with type-1 diabetes mellitus based on the subcutaneous (s.c.) glucose measurement and s.c. insulin administration. The tuning of the controller is based on an iterative learning strategy that exploits the repetitiveness of the daily feeding habit of a patient. The control consists of a mixed feedback and feedforward contribution whose parameters are tuned through an iterative learning process that is based on the day-by-day automated analysis of the glucose response to the infusion of exogenous insulin. The scheme does not require any a priori information on the patient insulin/glucose response, on the meal times and on the amount of ingested carbohydrates (CHOs). Thanks to the learning mechanism the scheme is able to improve its performance over time. A specific logic is also introduced for the detection and prevention of possible hypoglycaemia events. The effectiveness of the methodology has been validated using long-term simulation studies applied to a set of nine in silico patients considering realistic uncertainties on the meal times and on the quantities of ingested CHOs.

Insulin-coated gold nanoparticles as a new concept for personalized and adjustable glucose regulation

Science.gov (United States)

Shilo, Malka; Berenstein, Peter; Dreifuss, Tamar; Nash, Yuval; Goldsmith, Guy; Kazimirsky, Gila; Motiei, Menachem; Frenkel, Dan; Brodie, Chaya; Popovtzer, Rachela

2015-12-01

Diabetes mellitus is a chronic metabolic disease, characterized by high blood glucose levels, affecting millions of people around the world. Currently, the main treatment for diabetes requires multiple daily injections of insulin and self-monitoring of blood glucose levels, which markedly affect patients' quality of life. In this study we present a novel strategy for controlled and prolonged glucose regulation, based on the administration of insulin-coated gold nanoparticles (INS-GNPs). We show that both intravenous and subcutaneous injection of INS-GNPs into a mouse model of type 1 diabetes decreases blood glucose levels for periods over 3 times longer than free insulin. We further showed that conjugation of insulin to GNPs prevented its rapid degradation by the insulin-degrading-enzyme, and thus allows controlled and adjustable bio-activity. Moreover, we assessed different sizes and concentrations of INS-GNPs, and found that both parameters have a critical effect in vivo, enabling specific adjustment of blood glucose levels. These findings have the potential to improve patient compliance in diabetes mellitus.

stausartikel: behandling af subcutane abscesser

DEFF Research Database (Denmark)

Hardgrib, Nina; Petersen, Klaus Kjær

2017-01-01

Simple subcutaneous abscesses are common, and we have examined the literature concerning the ideal treatment of subcutaneous abscesses. We recommend radical debridement with removal of all pus, the abscess wall and any necrosis. If primary suture is chosen, preoperative antibiotics should be admi...

Toxicity, tissue distribution and excretion of 46ScCl3 and 46Sc-EDTA in mice

International Nuclear Information System (INIS)

Lachine, E.E.; Noujaim, A.A.; Ediss, C.; Wiebe, L.I.

1976-01-01

The acute toxicity, differential distribution in tissue, and elimination of ScCl 3 , 46 ScCl 3 , Sc-EDTA and 46 Sc-EDTA, in mice, has been investigated. The LD 50 sup(24hr) doses for ScCl 3 were 440 and 24 mg kg -1 respectively after intraperitioneal and intravenous injection, and 720 and 108 mg kg -1 respectively for Sc-EDTA. 46 ScCl 3 was extensively deposited in the liver and the spleen. 46 Sc-EDTA was rapidly taken up by the kidney with subsequent elimation via the urine. While-body desaturation kinetics for 46 Sc-EDTA were found to fit a three compartmental model. The fast elimination phase (T1/2 = 12.75 min; K = 0.05540 min -1 ) accounted for 74.6% of the dose; the intermediate phase (T1/2 = 40.2 min; K = 0.01722 min -1 ) for 21.8%, and the slow (T1/2 = 5351 min; K = 0.00013 min -1 ) for 3.6% of the dose. (author)

Subcutaneous versus subcutaneous and intraperitoneal local anaesthetic in the management of post appendicectomy pain

International Nuclear Information System (INIS)

Qureshi, K.Z.; Gondal, Z.I.; Raza, A.

2014-01-01

To compare the efficacy of subcutaneous only and combined subcutaneous and peritoneal infiltration of 0.5% bupivacaine during appendicectomy for the management of early post operative pain. Study Design: Randomized controlled study. Place and Duration of Study: Department of Surgery, CMH Kohat from 13th December 2007 to 20th December 2008. Patients and Methods: Sixty patients of a cute appendicitis, divided into two groups of 30 each, were included in the study. Group A was given 0.5% bupivacaine subcutaneously, whereas group B was given the anaesthetic subcutaneously as well as intraperitoneally during appendectomy. Results: In group A, 24 (80%) were VAS (visual analoguescoring) 3 (uncomfortable) and 6 (20%) were VAS 2 (mild pain) whereas in study group B, 11 (36.6%) were VAS 3, 19 (63.3%) were VAS 2 and 19 (63.3%) were VAS 2 during 1st 12 hrs postoperatively (p=0.001). In 12-24 hrs post operatively, 15 (50%) patients were VAS 3 in group A and same number was VAS 2 and in group B, only 3 (10%) were in VAS 3 and 27 (90%) were VAS 2 (p=0.001). Conclusion: A combination of subcutaneous and peritoneal infiltration with bupivacaine is superior in relieving post appendectomy pain so patients require less dosage of analgesics in early post operative period along with early mobilization. (author)

In vitro and in vivo evaluation of silicated hydroxyapatite and impact of insulin adsorption.

Science.gov (United States)

Lasgorceix, M; Costa, A M; Mavropoulos, E; Sader, M; Calasans, M; Tanaka, M N; Rossi, A; Damia, C; Chotard-Ghodsnia, R; Champion, E

2014-10-01

This study evaluates the biological behaviour, in vitro and in vivo, of silicated hydroxyapatite with and without insulin adsorbed on the material surface. Insulin was successfully adsorbed on hydroxyapatite and silicated hydroxyapatite bioceramics. The modification of the protein secondary structure after the adsorption was investigated by means of infrared and circular dichroism spectroscopic methods. Both results were in agreement and indicated that the adsorption process was likely to change the secondary structure of the insulin from a majority of α-helix to a β-sheet form. The biocompatibility of both materials, with and without adsorbed insulin on their surface, was demonstrated in vitro by indirect and direct assays. A good viability of the cells was found and no proliferation effect was observed regardless of the material composition and of the presence or absence of insulin. Dense granules of each material were implanted subcutaneously in mice for 1, 3 and 9 weeks. At 9 weeks of implantation, a higher inflammatory response was observed for silicated hydroxyapatite than for pure hydroxyapatite but no significant effect of adsorbed insulin was detected. Though the presence of silicon in hydroxyapatite did not improve the biological behaviour, the silicon substituted hydroxyapatite remained highly viable.

Magnetic moment of {sup 48}Sc

Energy Technology Data Exchange (ETDEWEB)

Ohtsubo, T., E-mail: tohtsubo@np.gs.niigata-u.ac.jp; Kawamura, Y.; Ohya, S. [Niigata University, Department of Physics (Japan); Izumikawa, T. [Niigata University, Radioisotope Center (Japan); Nishimura, K. [Toyama University, Faculty of Engineering (Japan); Muto, S. [Neutron Science Laboratory, KEK (Japan); Shinozuka, T. [Tohoku University, Cyclotron and Radioisotope Center (Japan)

2007-11-15

Nuclear magnetic resonances were measured for {sup 48}Sc and {sup 44m}Sc oriented at 8 mK in an Fe host metal. The magnetic hyperfine splitting frequencies at an external magnetic field of 0.2 T were determined to be 63.22(11) MHz and 64.81(1) MHz for {sup 48}Sc and {sup 44m}Sc, respectively. With the known magnetic moment of {mu}({sup 44m}Sc)=+3.88 (1) {mu}{sub N}, the magnetic moment of {sup 48}Sc is deduced as {mu}({sup 44}Sc)=+3.785(12) {mu}{sub N}. The measured magnetic moment of {sup 48}Sc is discussed in terms of the shell model using the effective interactions.

Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration

International Nuclear Information System (INIS)

Draganov, Dragomir I.; Markham, Dan A.; Beyer, Dieter; Waechter, John M.; Dimond, Stephen S.; Budinsky, Robert A.; Shiotsuka, Ronald N.; Snyder, Stephanie A.; Ehman, Kimberly D.; Hentges, Steven G.

2015-01-01

Orally administered bisphenol A (BPA) undergoes efficient first-pass metabolism to produce the inactive conjugates BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). This study was conducted to evaluate the pharmacokinetics of BPA, BPA-G and BPA-S in neonatal mice following the administration of a single oral or subcutaneous (SC) dose. This study consisted of 3 phases: (1) mass-balance phase in which effective dose delivery procedures for oral or SC administration of 3 H-BPA to postnatal day three (PND3) mice were developed; (2) pharmacokinetic phase during which systemic exposure to total 3 H-BPA-derived radioactivity in female PND3 mice was established; and (3) metabolite profiling phase in which 50 female PND3 pups received either a single oral or SC dose of 3 H-BPA. Blood was collected from 5 pups/route/time-point at various times post-dosing, the blood plasma samples were pooled by group, and time-point and samples were profiled by HPLC with fraction collection. Fractions were analyzed for total radioactivity and data used to reconstruct radiochromatograms and to integrate individual peaks. The identity of the BPA, BPA-G, and BPA-S peaks was confirmed using authentic standards and LC–MS/MS analysis. The result of this study revealed that female PND3 mice have the capacity to metabolize BPA to BPA-G, BPA-S and other metabolites after both routes of administration. Systemic exposure to free BPA is route-dependent as the plasma concentrations were lower following oral administration compared to SC injection

Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Schmidt, Signe; Damm-Frydenberg, Camilla

2017-01-01

OBJECTIVE: This study compared the ability of glucagon to restore plasma glucose (PG) after mild hypoglycemia in patients with type 1 diabetes on an isocaloric high-carbohydrate diet (HCD) versus a low-carbohydrate diet (LCD). RESEARCH DESIGN AND METHODS: Ten patients with insulin pump-treated type...... 1 diabetes randomly completed 1 week of the HCD (≥250 g/day) and 1 week of the LCD (≤50 g/day). After each week, mild hypoglycemia was induced by a subcutaneous insulin bolus in the fasting state. When PG reached 3.9 mmol/L, 100 µg glucagon was given subcutaneously, followed by 500 µg glucagon 2 h...... later. RESULTS: Compared with the HCD, the LCD resulted in lower incremental rises in PG after the first (mean ± SEM: 1.3 ± 0.3 vs. 2.7 ± 0.4 mmol/L, P = 0.002) and second glucagon bolus (4.1 ± 0.2 vs. 5.6 ± 0.5 mmol/L, P = 0.002). No differences were observed between the diets regarding concentrations...

Topotactic oxidation pathway of ScTiO3 and high-temperature structure evolution of ScTiO3.5 and Sc4Ti3O12-type phases.

Science.gov (United States)

Shafi, Shahid P; Hernden, Bradley C; Cranswick, Lachlan M D; Hansen, Thomas C; Bieringer, Mario

2012-02-06

The novel oxide defect fluorite phase ScTiO(3.5) is formed during the topotactic oxidation of ScTiO(3) bixbyite. We report the oxidation pathway of ScTiO(3) and structure evolution of ScTiO(3.5), Sc(4)Ti(3)O(12), and related scandium-deficient phases as well as high-temperature phase transitions between room temperature and 1300 °Cusing in-situ X-ray diffraction. We provide the first detailed powder neutron diffraction study for ScTiO(3). ScTiO(3) crystallizes in the cubic bixbyite structure in space group Ia3 (206) with a = 9.7099(4) Å. The topotactic oxidation product ScTiO(3.5) crystallizes in an oxide defect fluorite structure in space group Fm3m (225) with a = 4.89199(5) Å. Thermogravimetric and differential thermal analysis experiments combined with in-situ X-ray powder diffraction studies illustrate a complex sequence of a topotactic oxidation pathway, phase segregation, and ion ordering at high temperatures. The optimized bulk synthesis for phase pure ScTiO(3.5) is presented. In contrast to the vanadium-based defect fluorite phases AVO(3.5+x) (A = Sc, In) the novel titanium analogue ScTiO(3.5) is stable over a wide temperature range. Above 950 °C ScTiO(3.5) undergoes decomposition with the final products being Sc(4)Ti(3)O(12) and TiO(2). Simultaneous Rietveld refinements against powder X-ray and neutron diffraction data showed that Sc(4)Ti(3)O(12) also exists in the defect fluorite structure in space group Fm3m (225) with a = 4.90077(4) Å. Sc(4)Ti(3)O(12) undergoes partial reduction in CO/Ar atmosphere to form Sc(4)Ti(3)O(11.69(2)).

CERN: SC-33

Energy Technology Data Exchange (ETDEWEB)

Anon.

1991-06-15

On 22 April a forward-looking CERN also looked back for a day, when the 'SC-33' event reviewed the achievements of CERN's first machine, the 600 MeV SynchroCyclotron (SC), which closed down on 17 December after 33 years of valiant service.

Comparison of the Effects of Continuous Subcutaneous Insulin Infusion and Add-On Therapy with Sitagliptin in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Heng Wan

2016-01-01

Full Text Available To identify a new regimen to optimize treatment for patients with newly diagnosed type 2 diabetes (T2DM by short-term continuous subcutaneous insulin infusion (CSII alone. Methods. 60 patients with newly diagnosed T2DM were randomized into two groups (n=30 each and treated for 2 weeks with CSII alone (CSII group or with CSII plus sitagliptin (CSII + Sig group. The glycemic variability of the patients was measured using a continuous glucose monitoring system (CGMS for the last 72 hours. A standard meal test was performed before and after the interventions, and the levels of glycated albumin, fasting glucose, fasting C-peptide, postprandial 2 h blood glucose, and postprandial 2 h C-peptide were examined. Results. Compared with the CSII group, the indicators of glycemic variability, such as the mean amplitude of glycemic excursion (MAGE and the standard deviation of blood glucose (SDBG, were decreased significantly in the CSII + Sig group. The changes before and after treatment in the C-peptide reactivity index (ΔCPI and the secretory unit of islet in transplantation index (ΔSUIT indicated a significant improvement in the CSII + Sig group. Conclusions. Add-on therapy with sitagliptin may be an optimized treatment for patients with newly diagnosed T2DM compared with short-term CSII alone.

The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology.

Science.gov (United States)

Pastina, B; Early, P J; Bergman, R L; Nettifee, J; Maller, A; Bray, K Y; Waldron, R J; Castel, A M; Munana, K R; Papich, M G; Messenger, K M

2018-05-15

The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m 2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg -1 day -1 ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 μg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 μg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m 2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs. © 2018 John Wiley & Sons Ltd.

Adipokines mediate inflammation and insulin resistance

Directory of Open Access Journals (Sweden)

Jeffrey E. Pessin

2013-06-01

Full Text Available For many years, adipose tissue was considered as an inert energy storage organ that accumulates and stores triacylglycerols during energy excess and releases fatty acids in times of systemic energy need. However, over the last two decades adipose tissue depots have been established as highly active endocrine and metabolically important organs that modulate energy expenditure and glucose homeostasis. In rodents, brown adipose tissue plays an essential role in non-shivering thermogenesis and in energy dissipation that can serve to protect against diet-induced obesity. White adipose tissue collectively referred too as either subcutaneous or visceral adipose tissue is responsible for the secretion of an array of signaling molecules, termed adipokines. These adipokines function as classic circulating hormones to communicate with other organs including brain, liver, muscle, the immune system and adipose tissue itself. The dysregulation of adipokines has been implicated in obesity, type 2 diabetes and cardiovascular disease. Recently, inflammatory responses in adipose tissue have been shown as a major mechanism to induce peripheral tissue insulin resistance. Although leptin and adiponectin regulate feeding behavior and energy expenditure, these adipokines are also involved in the regulation of inflammatory responses. Adipose tissue secrete various pro- and anti-inflammatory adipokines to modulate inflammation and insulin resistance. In obese humans and rodent models, the expression of pro-inflammatory adipokines is enhanced to induce insulin resistance. Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines. Thus we will review the recent progress regarding the physiological and molecular functions of adipokines in the obesity-induced inflammation and insulin resistance with perspectives on future directions.

Model of the Glucose-Insulin-Glucagon Dynamics after Subcutaneous Administration of a Glucagon Rescue Bolus in Healthy Humans

OpenAIRE

Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Haidar, Ahmad; Bysted, Britta V.; Knudsen, Carsten B.; Madsen, Henrik; Jørgensen, John Bagterp

2016-01-01

In healthy individuals, insulin and glucagon work in a complex fashion to maintain blood glucose levels within a narrow range. This regulation is distorted in patients with diabetes. The hepatic glucose response due to an elevated glucagon level depends on the current insulin concentration and thus endogenous glucose production (EGP) can not be modelled without knowledge of the concentration of both hormones in plasma. Furthermore, literature suggests an upper limit to EGP irrespective of glu...

Retinal characteristics during 1 year of insulin pump therapy in type 1 diabetes

DEFF Research Database (Denmark)

Klefter, Oliver Niels; Hommel, Eva; Munch, Inger Christine

2016-01-01

of CSII led to an HbA1c reduction relative to continued MDI and a small increase in retinal thickness but not to early retinopathy worsening or to changes in retinal vascular, structural or functional characteristics. Longer duration of type 1 diabetes appears to be associated with lower macular venous......PURPOSE: To investigate changes in retinal metabolism, function, structure and morphology in relation to initiation of insulin pump therapy (continuous subcutaneous insulin infusion, CSII). METHODS: Visual acuity, retinopathy level, dark adaptation kinetics, retinal and subfoveal choroidal...... thickness, macular perfusion velocities, retinal vessel diameters and blood oxygen saturations were measured at baseline and after 1, 4, 16, 32 and 52 weeks in 31 patients with type 1 diabetes who started CSII and 20 patients who continued multiple daily insulin injections (MDI). RESULTS: One year of CSII...

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab

Directory of Open Access Journals (Sweden)

Theodore-Oklota C

2016-09-01

Full Text Available Christina Theodore-Oklota,1 Louise Humphrey,2 Christof Wiesner,1 Gabriel Schnetzler,3 Stacie Hudgens,4 Alicyn Campbell1 1Genentech, South San Francisco, CA, USA; 2Adelphi Values, Macclesfield, Cheshire, UK; 3F. Hoffmann La-Roche Ltd, Basel, Switzerland; 4Clinical Outcomes Solutions, Tucson, AZ, USA Background: A subcutaneous (SC formulation of rituximab (MabThera®/Rituxan® has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ was created to assess patients’ perceptions and satisfaction with rituximab SC (RASQ-SC or rituximab intravenous (RASQ-IV. We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma.Methods: Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ, using questionnaire data from the PrefMab (NCT01724021 and MabCute (NCT01461928 clinical studies.Results: RASQ-IV demonstrated excellent coverage of concepts relevant to patients’ (n=10 own treatment experiences and no new concepts were identified. Patients’ expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as “RASQ: Physical Impacts” and “CTSQ: Feelings About Side Effects”, “RASQ: Physical Impacts” and “CTSQ: Satisfaction With Therapy”, and “RASQ: Satisfaction” and “CTSQ: Satisfaction With Therapy”, achieved moderate-to-high correlations (>0.4 for convergent domains and <0.3 for divergent domains.Conclusion: This study supports the qualitative face and

The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

International Nuclear Information System (INIS)

Siposova, Katarina; Pospiskova, Kristyna; Bednarikova, Zuzana; Safarik, Ivo; Safarikova, Mirka; Kubovcikova, Martina; Kopcansky, Peter; Gazova, Zuzana

2017-01-01

Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe 3 O 4 -based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15–20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15–20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran). - Highlights: • Interference of dextran- magnetite nanoparticles with insulin amyloid aggregation. • Nanoparticles inhibited insulin fibrillization and depolymerized insulin amyloid fibrils. • Size of nanoparticles significantly influences their anti-amyloid activities. • The most effective inhibition of insulin amyloid fibrillization was detected for the smallest nanoparticles. • Contrary, DC 50 values decreased with increasing size of nanoparticles.

CERN: SC-33

International Nuclear Information System (INIS)

Anon.

1991-01-01

On 22 April a forward-looking CERN also looked back for a day, when the 'SC-33' event reviewed the achievements of CERN's first machine, the 600 MeV SynchroCyclotron (SC), which closed down on 17 December after 33 years of valiant service

S-C Mylonites

NARCIS (Netherlands)

Lister, G.S.; Snoke, A.W.

1984-01-01

Two types of foliations are commonly developed in mylonites and mylonitic rocks: (a) S-surfaces related to the accumulation of finite strain and (b) C-surfaces related to displacement discontinuities or zones of relatively high shear strain. There are two types of S-C mylonites. Type I S-C

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.

Science.gov (United States)

Genovese, Mark C; Pacheco-Tena, César; Covarrubias, Arturo; Leon, Gustavo; Mysler, Eduardo; Keiserman, Mauro; Valente, Robert M; Nash, Peter; Simon-Campos, J Abraham; Box, Jane; Legerton, Clarence W; Nasonov, Evgeny; Durez, Patrick; Elegbe, Ayanbola; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

2018-04-15

To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

Habitual dietary intake of fatty acids are associated with leptin gene expression in subcutaneous and visceral adipose tissue of patients without diabetes.

Science.gov (United States)

Rostami, Hosein; Samadi, Mohammad; Yuzbashian, Emad; Zarkesh, Maryam; Asghari, Golaleh; Hedayati, Mehdi; Daneshafrooz, Afsoon; Mirmiran, Parvin; Khalaj, Alireza

2017-11-01

The purpose of the study was to investigate the association of leptin gene expression in visceral and subcutaneous adipose tissues with habitual fatty acid intake and its subtypes in adults. Visceral and subcutaneous adipose tissues were gathered from 97 participants aged ≥ 20, who had undergone elective abdominal surgery. Dietary fatty acid intakes including total fatty acids (TFA), saturated fatty acid (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-3, n-6, and n-9 fatty acids were collected using a valid and reliable food-frequency questionnaire (FFQ). The leptin gene expression in visceral and subcutaneous adipose tissues was measured by Real-Time PCR. After controlling for body mass index (BMI) and insulin, energy-adjusted dietary intake of SFA was positively and MUFA and n-3 fatty acids were negatively associated with subcutaneous and visceral adipose tissues leptin gene expression. Besides, a significant negative association of PUFA, n-6, and n-9 fatty acids with leptin mRNA from visceral adipose tissue were observed. In order to better interpretations of the results, the participants were allocated two groups including non-obese (BMI fatty acids had a negative association with visceral leptin gene expression. Habitual intake of SFA, MUFA, and n-3 fatty acids were associated with leptin gene expression in visceral and subcutaneous adipose tissues, suggesting an important role of quality and quantity of fatty acids intake in adipose tissue to regulate leptin expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of 46Sc in water

International Nuclear Information System (INIS)

Huo Bijun; Ji Zhaogang; Wang Juying

1985-01-01

Analytical procedures for the determination of 46 Sc in water is presented. 46 Sc in water is concentrated with Fe(OH) 3 ; Then 46 Sc is extracted with TBP and purified by precipitating it with Amygdalic Acid. Finally the precipitate is ignited into Sc 2 O 3 under 800 deg C and β-activity is counted. In this method chemical reeovery for Sc was (90.8 +- 2.8)% and radiochemical recovery for 46 Sc was (89.8 +- 3.8)%. Purification factors for some of the relevant Radionuclides ranged from 10 3 to 10 5

CYP19 gene expression in subcutaneous adipose tissue is associated with blood pressure in women with polycystic ovary syndrome.

Science.gov (United States)

Lecke, Sheila B; Morsch, Débora M; Spritzer, Poli M

2011-11-01

In polycystic ovary syndrome (PCOS), hypertension has been linked to androgen excess and insulin resistance. Aromatase, an enzyme encoded by the CYP19 gene, affects androgen metabolism and estrogen synthesis, influencing the androgen to estrogen balance. We characterized CYP19 gene expression in subcutaneous adipose tissue of women with PCOS and normal controls and evaluated the association between subcutaneous fat CYP19 mRNA, circulating hormone levels, and blood pressure. This case-control study was carried out with 31 PCOS patients and 27 BMI-matched normotensive non-hirsute women with regular cycles. Participants underwent anthropometric measurements, collection of blood samples, and adipose tissue biopsy (28 PCOS and 19 controls). Hypertension was defined as systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg. PCOS patients were divided into normotensive and hypertensive. Main outcome measures were serum estrogen and androgen levels, estrogen-to-androgen ratio, and CYP19 gene expression in subcutaneous fat. Subcutaneous CYP19 mRNA was higher in hypertensive PCOS than in control and normotensive PCOS women (p = 0.014). Estrogen-to-androgen ratio was lower in hypertensive PCOS than controls (p androgen ratio ≤ 0.06 (median for the three groups) was observed in 91% of hypertensive PCOS women, vs. 37% and 61% in the control and normotensive PCOS groups (p = 0.011). CYP19 gene expression in subcutaneous fat of PCOS patient correlated positively with systolic (p = 0.006) and diastolic blood pressure (p = 0.009). Androgen excess and hyperinsulinemia may play a role in the molecular mechanisms that activate aromatase mRNA transcription in abdominal fat tissue. Copyright © 2011 Elsevier Inc. All rights reserved.

Accuracy of a Fourth-Generation Subcutaneous Continuous Glucose Sensor.

Science.gov (United States)

Christiansen, Mark P; Garg, Satish K; Brazg, Ronald; Bode, Bruce W; Bailey, Timothy S; Slover, Robert H; Sullivan, Ashley; Huang, Suiying; Shin, John; Lee, Scott W; Kaufman, Francine R

2017-08-01

This study evaluated the accuracy and performance of a fourth-generation subcutaneous glucose sensor (Guardian ™ Sensor 3) in the abdomen and arm. Eighty-eight subjects (14-75 years of age, mean ± standard deviation [SD] of 42.0 ± 19.1 years) with type 1 or type 2 diabetes participated in the study. Subjects wore two sensors in the abdomen that were paired with either a MiniMed ™ 640G insulin pump, or an iPhone ® or iPod ® touch ® running a glucose monitoring mobile application (Guardian Connect system) and a third sensor in the arm, which was connected to a glucose sensor recorder (GSR). Subjects were also asked to undergo in-clinic visits of 12-14 h on study days 1, 3, and 7 for frequent blood glucose sample testing using a Yellow Springs Instrument (YSI) reference. The overall mean absolute relative difference (MARD ± SD) between abdomen sensor glucose (SG) and YSI reference values was 9.6% ± 9.0% and 9.4% ± 9.8% for the MiniMed 640G insulin pump and Guardian Connect system, respectively; and 8.7% ± 8.0% between arm SG and YSI reference values. The percentage of SG values within 20% agreement of the YSI reference value (for YSI >80 mg/dL) was 90.7% with the MiniMed 640G insulin pump, 91.8% with the Guardian Connect system, and 93.1% for GSR-connected arm sensors. Mean functional sensor life, when calibrating 3-4 times/day, was 145.9 ± 39.3 h for sensors paired with the MiniMed 640G insulin pump, 146.1 ± 41.6 h for sensors paired with the Guardian Connect system, and 147.6 ± 40.4 h for sensors connected to the GSR. Responses to survey questions regarding sensor comfort and ease of use were favorable. The Guardian Sensor 3 glucose sensor, whether located in abdomen or the arm, provided accurate glucose readings when compared with the YSI reference and demonstrated functional life commensurate with the intended 7-day use. ClinicalTrials.gov : NCT02246582.

The effect of Sc additions on the microstructure and age hardening behaviour of as cast Al–Sc alloys

International Nuclear Information System (INIS)

Costa, S.; Puga, H.; Barbosa, J.; Pinto, A.M.P.

2012-01-01

Highlights: ► The Sc effect on the microstructure and ageing behaviour of Al–Sc alloys is studied. ► Cast into copper mould allows the elimination of solution heat treatment. ► Directly aged as cast alloys exhibits higher hardness and precipitation kinetics. ► Sc addition and optimised ageing result in an increase in Al–Sc mechanical properties. -- Abstract: The grain refinement effect and the ageing behaviour of Al–0.5 wt.% Sc, Al–0.7 wt.% Sc, and Al–1 wt.% Sc alloys are studied on the basis of optic microscopy (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD) observations and hardness measurements. In Al–Sc alloys the higher grain refinement is observed for Sc contents greater than 0.5 wt.% accompanied by a notorious morphology modification, from coarse columnar grains to a fine perfect equiaxed structure. The as cast structures are characterised by a rich supersaturated solid solution in Sc, that promotes a great age hardening response at 250 °C and 300 °C. The age hardening curves also demonstrate a low overageing kinetics for all the alloys. Although the higher Sc content in solid solution for the alloys with 0.7 and 1 wt.% Sc, the age hardening response of all the Al–Sc alloys remains similar. The direct age hardening response of the as cast Al–0.5 wt.% Sc is shown to be greater than the solutionised and age hardened alloy.

Evaluation of Subcutaneous Phenobarbital Administration in Hospice Patients.

Science.gov (United States)

Hosgood, Jessica Richards; Kimbrel, Jason M; McCrate Protus, Bridget; Grauer, Phyllis A

2016-04-01

Phenobarbital is used in hospice and palliative care to treat refractory symptoms. In end-of-life care, Food and Drug Administration approved routes of administration may be unreasonable based on patients' status. In these cases, phenobarbital may be administered subcutaneously for symptom management. However, according to the American Hospital Formulary Service, subcutaneous administration of commercially available injectable phenobarbital is cautioned due to possible skin reactions. This study evaluates the tolerability of phenobarbital administered subcutaneously. Of 69 patients and 774 distinct subcutaneous phenobarbital injections, 2 site reactions were recorded (2.9% of patients; 0.3% of injections). Both were mild, grade 1 reactions. Each patient continued to receive subcutaneous phenobarbital via newly placed ports with no additional reactions. Based on these findings, phenobarbital appears to be well tolerated when administered subcutaneously. © The Author(s) 2014.

Hypertrophic remodeling of subcutaneous small resistance arteries in patients with Cushing's syndrome.

Science.gov (United States)

Rizzoni, Damiano; Porteri, Enzo; De Ciuceis, Carolina; Rodella, Luigi F; Paiardi, Silvia; Rizzardi, Nicola; Platto, Caterina; Boari, Gianluca E M; Pilu, Annamaria; Tiberio, Guido A M; Giulini, Stefano M; Favero, Gaia; Rezzani, Rita; Rosei, Claudia Agabiti; Bulgari, Giuseppe; Avanzi, Daniele; Rosei, Enrico Agabiti

2009-12-01

Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome. We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress. Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels. Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

NARCIS (Netherlands)

Robben, J.H.; Brom, W.E. van den; Mol, J.A.; Haeften, T.W. van; Rijnberk, A.

2006-01-01

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 lg

Subcutaneous Administration of Tramadol after Elective Surgery Is as Effective as Intravenous Administration in Relieving Acute Pain and Inflammation in Dogs

Science.gov (United States)

Buhari, Salisu; Hashim, Kalthum; Yong Meng, Goh; Mustapha, Noordin Mohamed; Gan, Siew Hua

2012-01-01

Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 ± 0.65 years), weighing between 10.5 and 17.1 kg (13.12 ± 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, β-endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and β-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE. PMID:22778699

Construction, expression, and function of 6B11ScFv-mIL-12, a fusion protein that attacks human ovarian carcinoma.

Science.gov (United States)

Cheng, Hongyan; Ye, Xue; Chang, Xiaohong; Ma, Ruiqiong; Cong, Xu; Niu, Yidong; Zhang, Menglei; Liu, Kai; Cui, Heng; Sang, Jianli

2015-04-01

We previously produced an anti-idiotypic monoclonal antibody, 6B11, which mimics ovarian cancer antigen CA166-9 and induces cellular and humoral immunity. Here, to enhance the immunogenicity of 6B11, we constructed the 6B11ScFv-mIL-12 fusion protein (FP), by fusing single-chain fragment of 6B11 variable region (6B11ScFv) with mouse interleukin-12 (mIL-12), which was expressed in eukaryotic 293EBNA cells transfected with pSBI vectors. A binding activity assay showed 6B11ScFv-mIL-12 to have activities of both 6B11 and mIL-12-it specifically bound both ovarian monoclonal antibody COC166-9 and rabbit anti-mouse IL-12 antibody. The immune activity assay showed 6B11ScFv-mIL-12 to promote proliferation of lymphocytes stimulated by phytohemagglutinin, increase the absolute numbers and percentages of CD3(-)/CD56(+) natural killer cells and CD3(+)/CD56(+) natural killer T cells among peripheral lymphocytes, and increase interferon-γ. The FP was specifically cytotoxic to the CA166-9(+) ovarian cancer cell lines HOC1A and SKOV3 and inhibited growth of ID8 subcutaneous tumors in C57BL/6J mice. This study provides an experimental basis for clinical use of 6B11ScFv-mIL-12 in ovarian cancer therapy. To our knowledge, this is the first report of a fusion protein from an anti-idiotypic antibody and IL-12.

Solid-State NMR Spectroscopy Proves the Presence of Penta-coordinated Sc Sites in MIL-100(Sc).

Science.gov (United States)

Giovine, Raynald; Volkringer, Christophe; Ashbrook, Sharon E; Trébosc, Julien; McKay, David; Loiseau, Thierry; Amoureux, Jean-Paul; Lafon, Olivier; Pourpoint, Frédérique

2017-07-18

Advanced solid-state NMR methods and first-principles calculations demonstrate for the first time the formation of penta-coordinated scandium sites. These coordinatively unsaturated sites were shown during the thermal activation of scandium-based metal-organic frameworks (MOFs). A 45 Sc NMR experiment allows their specific observation in activated Sc 3 BTB 2 (H 3 BTB=1,3,5-tris(4-carboxyphenyl)benzene) and MIL-100(Sc) MOFs. The assignment of the ScO 5 groups is supported by the DFT calculations of NMR parameters. The presence of ScO 5 Lewis acid sites in MIL-100(Sc) explains furthermore its catalytic activity. The first NMR experiment to probe 13 C- 45 Sc distances is also introduced. This advanced solid-state NMR pulse sequence allows the demonstration of the shrinkage of the MIL-100(Sc) network when the activation temperature is raised. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.

Science.gov (United States)

Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E

2015-01-01

To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

Antecedent caloric intake and glucose excursion following a subsequent meal in Type 1 diabetes.

Science.gov (United States)

Mehra, Rinku; Raman, Ramesh; Bayless, Margaret L; Sivitz, William I

2009-12-01

In the present study, we tested the hypothesis that calories consumed at a prior meal (lunch) may impair glycemic control after a subsequent meal (supper) even if the pre-supper glucose did not differ regardless of the size of the lunch meal. Nine subjects with Type 1 diabetes using continuous subcutaneous (s.c.) insulin infusion (CSII) therapy were studied on two separate days. Lunch (1200 h) was randomly assigned as 25% or 50% of the usual daily intake on alternate study days. The CSII was stopped at 1000 h on the day of the study and glucose was controlled until supper by adjusting the rate of intravenous (i.v.) insulin based on glucose measurements every 15 min. The CSII was restarted 1 h before supper and i.v. insulin discontinued 15 min before the first bite of supper. An identical supper meal and pre-supper s.c. bolus of short-acting insulin were administered on both visits. Pre-supper glycemia was nearly identical on each of the two study days. However, the post-supper glucose area under the curve was 27.5% greater on the day of the antecedent large lunch compared with the small lunch (P = 0.0039). For optimal postprandial glucose control, people with Type 1 diabetes may need to consider not only anticipated meal calories, but also prior food intake, a practice not commonly recommended based on currently used insulin dosing algorithms.

The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

Science.gov (United States)

Siposova, Katarina; Pospiskova, Kristyna; Bednarikova, Zuzana; Safarik, Ivo; Safarikova, Mirka; Kubovcikova, Martina; Kopcansky, Peter; Gazova, Zuzana

2017-04-01

Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe3O4-based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15-20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15-20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran).

Facilitated subcutaneous immunoglobulin administration (fSCIg)

DEFF Research Database (Denmark)

Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert

2016-01-01

and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...

Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging

DEFF Research Database (Denmark)

Reichkendler, M. H.; Auerbach, P.; Rosenkilde, M.

2013-01-01

abdominal SAT compared with CON but not in either intra- or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose...

Adipose Tissue Insulin Resistance in Gestational Diabetes.

Science.gov (United States)

Tumurbaatar, Batbayar; Poole, Aaron T; Olson, Gayle; Makhlouf, Michel; Sallam, Hanaa S; Thukuntla, Shwetha; Kankanala, Sucharitha; Ekhaese, Obos; Gomez, Guillermo; Chandalia, Manisha; Abate, Nicola

2017-03-01

Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC] glucose ). Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.

The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

Energy Technology Data Exchange (ETDEWEB)

Siposova, Katarina [Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia); Pospiskova, Kristyna [Regional Centre of Advanced Technologies and Materials, Palacky University, Olomouc (Czech Republic); Bednarikova, Zuzana [Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia); Department of Biochemistry, Faculty of Science, Safarik University, Kosice (Slovakia); Safarik, Ivo [Regional Centre of Advanced Technologies and Materials, Palacky University, Olomouc (Czech Republic); Department of Nanobiotechnology, Biology Centre, ISB, CAS, Ceske Budejovice (Czech Republic); Safarikova, Mirka [Department of Nanobiotechnology, Biology Centre, ISB, CAS, Ceske Budejovice (Czech Republic); Kubovcikova, Martina; Kopcansky, Peter [Department of Magnetism, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia); Gazova, Zuzana, E-mail: gazova@saske.sk [Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia)

2017-04-01

Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe{sub 3}O{sub 4}-based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15–20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15–20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran). - Highlights: • Interference of dextran- magnetite nanoparticles with insulin amyloid aggregation. • Nanoparticles inhibited insulin fibrillization and depolymerized insulin amyloid fibrils. • Size of nanoparticles significantly influences their anti-amyloid activities. • The most effective inhibition of insulin amyloid fibrillization was detected for the smallest nanoparticles. • Contrary, DC{sub 50} values decreased with increasing size of nanoparticles.

Infectivity-associated PrP(Sc) and disease duration-associated PrP(Sc) of mouse BSE prions.

Science.gov (United States)

Miyazawa, Kohtaro; Okada, Hiroyuki; Masujin, Kentaro; Iwamaru, Yoshifumi; Yokoyama, Takashi

2015-01-01

Disease-related prion protein (PrP(Sc)), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrP(Sc) in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrP(Sc) in the brain. Centrifugation (20,000 ×g) of the brain homogenate showed that most of the PrP(Sc) was precipitated into the pellet, and the supernatant contained only a slight amount of PrP(Sc). Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 d longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrP(Sc) may be responsible for prion infectivity and that large, aggregated PrP(Sc) may contribute to determining prion disease duration.

[Cellular subcutaneous tissue. Anatomic observations].

Science.gov (United States)

Marquart-Elbaz, C; Varnaison, E; Sick, H; Grosshans, E; Cribier, B

2001-11-01

We showed in a companion paper that the definition of the French "subcutaneous cellular tissue" considerably varied from the 18th to the end of the 20th centuries and has not yet reached a consensus. To address the anatomic reality of this "subcutaneous cellular tissue", we investigated the anatomic structures underlying the fat tissue in normal human skin. Sixty specimens were excised from the surface to the deep structures (bone, muscle, cartilage) on different body sites of 3 cadavers from the Institut d'Anatomie Normale de Strasbourg. Samples were paraffin-embedded, stained and analysed with a binocular microscope taking x 1 photographs. Specimens were also excised and fixed after subcutaneous injection of Indian ink, after mechanic tissue splitting and after performing artificial skin folds. The aspects of the deep parts of the skin greatly varied according to their anatomic localisation. Below the adipose tissue, we often found a lamellar fibrous layer which extended from the interlobular septa and contained horizontally distributed fat cells. No specific tissue below the hypodermis was observed. Artificial skin folds concerned either exclusively the dermis, when they were superficial or included the hypodermis, but no specific structure was apparent in the center of the fold. India ink diffused to the adipose tissue, mainly along the septa, but did not localise in a specific subcutaneous compartment. This study shows that the histologic aspects of the deep part of the skin depend mainly on the anatomic localisation. Skin is composed of epidermis, dermis and hypodermis and thus the hypodermis can not be considered as being "subcutaneous". A difficult to individualise, fibrous lamellar structure in continuity with the interlobular septa is often found under the fat lobules. This structure is a cleavage line, as is always the case with loose connective tissues, but belongs to the hypodermis (i.e. fat tissue). No specific tissue nor any virtual space was

SC tuning fork

CERN Document Server

The tuning fork used to modulate the radiofrequency system of the synchro cyclotron (SC) from 1957 to 1973. This piece is an unused spare part. The SC was the 1st accelerator built at CERN. It operated from August 1957 until it was closed down at the end of 1990. In the SC the magnetic field did not change with time, and the particles were accelerated in successive pulses by a radiofrequency voltage of some 20kV which varied in frequency as they spiraled outwards towards the extraction radius. The frequency varied from 30MHz to about 17Mz in each pulse. The tuning fork vibrated at 55MHz in vacuum in an enclosure which formed a variable capacitor in the tuning circuit of the RF system, allowing the RF to vary over the appropriate range to accelerate protons from the centre of the macine up to 600Mev at extraction radius. In operation the tips of the tuning fork blade had an amplitude of movement of over 1 cm. The SC accelerator underwent extensive improvements from 1973 to 1975, including the installation of a...

Measurement for commercial exposives with SC-DSC test. Sangyoyo bakuhayaku no SC-DSC sokutei

Energy Technology Data Exchange (ETDEWEB)

Yabashi, H.; Wada, Y.; Hwang, D.; Akutsu, Y.; Tamura, M.; Yoshida, T. (The University of Tokyo, Tokyo (Japan). Faculty of Engineering); Matsuzawa, T. (Nippon Kayaku Co. Ltd., Tokyo (Japan))

1991-08-30

The sealed cell differential scanning calorimetry (SC-DSC) was sintroduced of commercial blasting explosives. As a series of testing the commercial blasting explosives in performance, an SC-DSC test was made to compare the critical detonability line with that resulting therefrom. From the result of SC-DSC measurement, the critical dilution rate was estimated of commercial blasting explosives to become without detonating propagation. As a result, all the explosives with exception of ANFO one were assumed to have a possibility of detonating propagation so that the ANFO explosive was known to be material, unable to exactly evaluate the detonability by the SC-DSC test. The explosion heat, then calculated by the REITP2 in order to assume how the reaction proceeded in the DSC cell, was compared with the reaction heat measured by the SC-DSC test. As a result, the calculated value was known to be almost equal to or slightly larger than the measured one. 15 refs., 4 figs., 2 tabs.

Preclinical evaluation of melanocortin-1 receptor (MC1-R) specific 68Ga- and 44Sc-labeled DOTA-NAPamide in melanoma imaging.

Science.gov (United States)

Nagy, Gábor; Dénes, Noémi; Kis, Adrienn; Szabó, Judit P; Berényi, Ervin; Garai, Ildikó; Bai, Péter; Hajdu, István; Szikra, Dezső; Trencsényi, György

2017-08-30

Alpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET). In this present study the MC1-R selectivity of the newly developed Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using melanoma tumors. DOTA-NAPamide was labeled with Ga-68 and Sc-44 radionuclides. The MC1-R specificity of Ga-68- and Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using MC1-R positive (B16-F10) and negative (A375) melanoma cell lines. For in vivo imaging studies B16-F10 and A375 tumor-bearing mice were injected with 44 Sc/ 68 Ga-DOTA-NAPamide (in blocking studies with α-MSH) and whole body PET/MRI scans were acquired. Radiotracer uptake was expressed in terms of standardized uptake values (SUVs). 44 Sc/ 68 Ga-labeled DOTA-NAPamide were produced with high specific activity (approx. 19 GBq/μmol) and with excellent radiochemical purity (99%DOTA-NAPamide (SUVmean: 0.38±0.02), and Sc-44-DOTA-NAPamide (SUVmean: 0.52±0.13) uptake was observed in subcutaneously growing B16-F10 tumors, than in receptor negative A375 tumors, where the SUVmean values of Ga-68-DOTA-NAPamide and Sc-44-DOTA-NAPamide were 0.04±0.01 and 0.07±0.01, respectively. Tumor-to-muscle (T/M SUVmean) ratios were approximately 15-fold higher in B16-F10 tumor-bearing mice, than that of A375 tumors, and this difference was also significant (p≤0.01) using both radiotracers after 60 min incubation time. Our newly synthesized 44 Sc-labeled DOTA-NAPamide probe showed excellent binding properties to melanocortin-1 receptor (MC1-R) positive melanoma cell and tumors. Due to its high specificity and sensitivity 44 Sc-DOTA-NAPamide is a promising radiotracer in

α-ScVSe2O8, β-ScVSe2O8, and ScVTe2O8: new quaternary mixed metal oxides composed of only second-order Jahn-Teller distortive cations.

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Kim, Yeong Hun; Lee, Dong Woo; Ok, Kang Min

2013-10-07

Three new quaternary scandium vanadium selenium/tellurium oxides, α-ScVSe2O8, β-ScVSe2O8, and ScVTe2O8 have been synthesized through hydrothermal and standard solid-state reactions. Although all three reported materials are stoichiometrically similar, they exhibit different crystal structures: α-ScVSe2O8 has a three-dimensional framework structure consisting of ScO6, VO6, and SeO3 groups. β-ScVSe2O8 reveals another three-dimensional framework composed of ScO7, VO5, and SeO3 polyhedra. ScVTe2O8 shows a layered structure with ScO6, VO4, and TeO4 polyhedra. Interestingly, the constituent cations, that is, Sc(3+), V(5+), Se(4+), and Te(4+) are all in a distorted coordination environment attributable to second-order Jahn-Teller (SOJT) effects. Complete characterizations including infrared spectroscopy, elemental analyses, thermal analyses, dipole moment calculation, and the magnitudes of out-of-center distortions for the compounds are reported. Transformation reactions suggest that α-ScVSe2O8 may change to β-ScVSe2O8, and then to Sc2(SeO3)3·H2O under hydrothermal conditions.

Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial.

Science.gov (United States)

Gillet, Yves; Habermehl, Pirmin; Thomas, Stéphane; Eymin, Cécile; Fiquet, Anne

2009-04-14

When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) compared with the subcutaneous route. An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to 18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374) or subcutaneously (SC group, n = 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit. Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of >or= 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (vaccines was comparable regardless of administration route. Integration of both administration routes in the current European indications for the two vaccines will now allow physicians in Europe to choose their preferred administration route

Small angle X-ray scattering-based elucidation of the self-association mechanism of human insulin analogue lys(B29)(N(e)¿-carboxyheptadecanoyl) des(B30)

DEFF Research Database (Denmark)

Jensen, Malene Hillerup; Wahlund, Per-Olof; Toft, Katrine Nørgaard

2013-01-01

of biophysical and structural methods (field flow fractionation, dynamic and multiangle light scattering, circular dichroism, size exclusion chromatography, and crystallography), we propose a mechanism for the self-association expected to occur upon subcutaneous injection of this insulin analogue. SAXS data...... provide evidence of the in solution structure of the self-associated oligomer, which is a long straight rod composed of "tense" state insulin hexamers (T(6)-hexamers) as the smallest repeating unit. The smallest oligomer building block in the process is a T(6)T(6)-dihexamer. This tense dihexamer is formed...... by the allosteric change of the initial equilibrium between a proposed "relaxed" state R(6)-hexamer and an R(3)T(3)T(3)R(3)-dihexamer. The allosteric change from relaxed to tense is triggered by removal of phenol, mimicking subcutaneous injection. The data hence provide the first unequivocal evidence...

Metformin Mitigates Fibrosis and Glucose Intolerance Induced by Doxorubicin in Subcutaneous Adipose Tissue

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Luana A. Biondo

2018-05-01

Full Text Available Doxorubicin (DX is a chemotherapeutic drug that is used in clinical practice that promotes deleterious side effects in non-tumor tissues such as adipose tissue. We showed that DX leads to extensive damage in adipose tissue via a disruption in 5′-adenosine monophosphate-activated protein kinase (AMPK and PPAR-gamma signaling. Thus, we investigated whether co-treatment with the biguanide drug metformin (MET could prevent the side effects of DX through the activation of AMPK in adipose tissue. The goal of the present study was to verify the effects of DX and adjuvant MET treatment in subcutaneous adipose tissue (SAT and to determine whether MET could protect against chemotherapy-induced side effects. C57/BL6 mice received DX hydrochloride (2.5 mg/kg intraperitoneally 2 times per week for 2 weeks (DX, concomitantly or not, with MET administration (300 mg/kg oral daily (DX + MET. The control group (CTRL was pair-fed according to the food consumption of the DX group. After euthanasia, adipose tissue fat pads were collected, and SAT was extracted so that adipocytes could be isolated. Glucose uptake was then measured, and histological, gene, and protein analyses were performed. One-way analysis of variance was also performed, and significance was set to 5%. DX reduced retroperitoneal fat mass and epididymal pads and decreased glycemia. In cultured primary subcutaneous adipocytes, mice in the DX group had lower glucose uptake when stimulated with insulin compared with mice in the CTRL group. Adipocytes in the DX group exhibited a reduced area, perimeter, and diameter; decreased adiponectin secretion; and decreased fatty acid synthase gene expression. SAT from MET-treated mice also showed a reduction in collagen deposition. Treatment with MET prevented fibrosis and restored glucose uptake in SAT after insulin stimulation, yet the drug was unable to prevent other side effects of DX such as tissue loss and inflammatory response.

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

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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.

Subcutaneous phaeohyphomycosis caused by cladophialophora boppii

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Pereira Rickson

2010-01-01

Full Text Available Subcutaneous phaeohyphomycosis is an infection of the skin and subcutaneous tissue, caused by dematiaceous fungi. An adult male presented with a history of multiple reddish nodules over the face and hands. Histopathological examination of the skin biopsies showed a dense granulomatous infiltrate of macrophages, containing intracytoplasmic basophilic bodies throughout the dermis. Gomori methenamine-silver stained sections revealed yeast cells within macrophages. Multiple cultures on Sabouraud′s dextrose agar grew Cladophialophora boppii. The patient was treated with oral itraconazole for a year and the response monitored with dermal ultrasound. This is the first case report of subcutaneous phaeohyphomycosis caused by Cl. boppii in India.

Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK).

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Mueller, Ruediger B; Gengenbacher, Michael; Richter, Symi; Dudler, Jean; Möller, Burkhard; von Kempis, Johannes

2016-04-14

Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks. This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included. The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in

Rational Design of Glucose-Responsive Insulin Using Pharmacokinetic Modeling.

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Bakh, Naveed A; Bisker, Gili; Lee, Michael A; Gong, Xun; Strano, Michael S

2017-11-01

A glucose responsive insulin (GRI) is a therapeutic that modulates its potency, concentration, or dosing of insulin in relation to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. Current GRI design lacks a theoretical basis on which to base fundamental design parameters such as glucose reactivity, dissociation constant or potency, and in vivo efficacy. In this work, an approach to mathematically model the relevant parameter space for effective GRIs is induced, and design rules for linking GRI performance to therapeutic benefit are developed. Well-developed pharmacokinetic models of human glucose and insulin metabolism coupled to a kinetic model representation of a freely circulating GRI are used to determine the desired kinetic parameters and dosing for optimal glycemic control. The model examines a subcutaneous dose of GRI with kinetic parameters in an optimal range that results in successful glycemic control within prescribed constraints over a 24 h period. Additionally, it is demonstrated that the modeling approach can find GRI parameters that enable stable glucose levels that persist through a skipped meal. The results provide a framework for exploring the parameter space of GRIs, potentially without extensive, iterative in vivo animal testing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two anionically derivatized scandium oxoselenates(IV): ScF[SeO3] and Sc2O2[SeO3

Science.gov (United States)

Greiner, Stefan; Chou, Sheng-Chun; Schleid, Thomas

2017-02-01

Scandium fluoride oxoselenate(IV) ScF[SeO3] and scandium oxide oxoselenate(IV) Sc2O2[SeO3] could be synthesized through solid-state reactions. ScF[SeO3] was obtained phase-pure, by reacting mixtures of Sc2O3, ScF3 and SeO2 (molar ratio: 1:1:3) together with CsBr as fluxing agent in corundum crucibles embedded into evacuated glassy silica ampoules after firing at 700 °C for seven days. Sc2O2[SeO3] first emerged as by-product during the attempts to synthesize ScCl[SeO3] following aforementioned synthesis route and could later be reproduced from appropriate Sc2O3/SeO3 mixtures. ScF[SeO3] crystallizes monoclinically in space group P21/m with a=406.43(2), b =661.09(4), c=632.35(4) pm, β=93.298(3)° and Z=2. Sc2O2[SeO3] also crystallizes in the monoclinic system, but in space group P21/n with a=786.02(6), b=527.98(4), c=1086.11(8) pm, β=108.672(3)° for Z=4. The crystal structures of both compounds are strongly influenced by the stereochemically active lone pairs of the ψ1-tetrahedral [SeO3]2- anions. They also show partial structures, where the derivatizing F- or O2- anions play an important role. For ScF[SeO3] chains of the composition 2+∞ 1[FS c 2 / 2 ] form from connected [FSc2]5+ dumbbells, while [OSc3]7+ pyramids and [OSc4]10+ tetrahedra units are condensed to layers according to 2+ ∞ 2[O2Sc2 ] in Sc2O2[SeO3].

Intra-adrenal murine TH-MYCN neuroblastoma tumors grow more aggressive and exhibit a distinct tumor microenvironment relative to their subcutaneous equivalents.

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Kroesen, Michiel; Brok, Ingrid C; Reijnen, Daphne; van Hout-Kuijer, Maaike A; Zeelenberg, Ingrid S; Den Brok, Martijn H; Hoogerbrugge, Peter M; Adema, Gosse J

2015-05-01

In around half of the patients with neuroblastoma (NBL), the primary tumor is located in one of the adrenal glands. We have previously reported on a transplantable TH-MYCN model of subcutaneous (SC) growing NBL in C57Bl/6 mice for immunological studies. In this report, we describe an orthotopic TH-MYCN transplantable model where the tumor cells were injected intra-adrenally (IA) by microsurgery. Strikingly, 9464D cells grew out much faster in IA tumors compared to the subcutis. Tumors were infiltrated by equal numbers of lymphocytes and myeloid cells. Within the myeloid cell population, however, tumor-infiltrating macrophages were more abundant in IA tumors compared to SC tumors and expressed lower levels of MHC class II, indicative of a more immunosuppressive phenotype. Using 9464D cells stably expressing firefly luciferase, enhanced IA tumor growth could be confirmed using bioluminescence. Collectively, these data show that the orthotopic IA localization of TH-MYCN cells impacts the NBL tumor microenvironment, resulting in a more stringent NBL model to study novel immunotherapeutic approaches for NBL.

Compensation of native donor doping in ScN: Carrier concentration control and p-type ScN

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Saha, Bivas; Garbrecht, Magnus; Perez-Taborda, Jaime A.; Fawey, Mohammed H.; Koh, Yee Rui; Shakouri, Ali; Martin-Gonzalez, Marisol; Hultman, Lars; Sands, Timothy D.

2017-06-01

Scandium nitride (ScN) is an emerging indirect bandgap rocksalt semiconductor that has attracted significant attention in recent years for its potential applications in thermoelectric energy conversion devices, as a semiconducting component in epitaxial metal/semiconductor superlattices and as a substrate material for high quality GaN growth. Due to the presence of oxygen impurities and native defects such as nitrogen vacancies, sputter-deposited ScN thin-films are highly degenerate n-type semiconductors with carrier concentrations in the (1-6) × 1020 cm-3 range. In this letter, we show that magnesium nitride (MgxNy) acts as an efficient hole dopant in ScN and reduces the n-type carrier concentration, turning ScN into a p-type semiconductor at high doping levels. Employing a combination of high-resolution X-ray diffraction, transmission electron microscopy, and room temperature optical and temperature dependent electrical measurements, we demonstrate that p-type Sc1-xMgxN thin-film alloys (a) are substitutional solid solutions without MgxNy precipitation, phase segregation, or secondary phase formation within the studied compositional region, (b) exhibit a maximum hole-concentration of 2.2 × 1020 cm-3 and a hole mobility of 21 cm2/Vs, (c) do not show any defect states inside the direct gap of ScN, thus retaining their basic electronic structure, and (d) exhibit alloy scattering dominating hole conduction at high temperatures. These results demonstrate MgxNy doped p-type ScN and compare well with our previous reports on p-type ScN with manganese nitride (MnxNy) doping.

Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence.

Science.gov (United States)

Comisford, Ross; Lubbers, Ellen R; Householder, Lara A; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L; List, Edward O; Kopchick, John J; Berryman, Darlene E

2016-01-01

Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of

Efficacy and Safety of Subcutaneous Amifostine in Minimizing Radiation-Induced Toxicities in Patients Receiving Combined-Modality Treatment for Squamous Cell Carcinoma of the Head and Neck

International Nuclear Information System (INIS)

Law, Amy; Kennedy, Thomas; Pellitteri, Phillip; Wood, Craig; Christie, Douglas; Yumen, Omar

2007-01-01

Purpose: To report long-term data from a prospective trial of subcutaneous (s.c.) amifostine in patients who received chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: Patients ≥18 years of age with previously untreated Stage III/IV SCCHN received fractionated radiotherapy, 1.8-2.0 Gy/day, 5 days per week, to a total dose of 70-72 Gy, plus weekly paclitaxel (40 mg/m 2 ) and carboplatin (100 mg/m 2 ) administered intravenously (i.v.) for 6 weeks. All patients received 500 mg s.c. amifostine 30-60 min before radiotherapy with antihistamine and antiemetic prophylaxis. Results: Twenty patients were evaluable (median age, 55 years). The incidence of Grade 2 xerostomia was 42% and 29% at 12 and 18 months, respectively; there were no reports of Grade ≥3 xerostomia. Grade ≥3 mucositis occurred in 30% of patients, with median time to resolution of 12.5 weeks (range, 5-17 weeks). Survival estimates at 1 and 2 years were 95% and 71%, respectively. All patients experienced Grade 2 weight loss; 7 patients (35%) experienced Grade ≤2 nausea/vomiting. There were no reports of Grade ≥3 amifostine-related adverse events. Conclusions: Subcutaneous amifostine was well tolerated by patients receiving chemoradiotherapy for SCCHN, with lower rates of nausea/vomiting than reported in trials with i.v. amifostine. Xerostomia and mucositis rates were similar to those reported in trials with i.v. amifostine

Primary Kaposi sarcoma of the subcutaneous tissue

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Dezube Bruce J

2008-09-01

Full Text Available Abstract Background Involvement of the subcutis by Kaposi sarcoma (KS occurs primarily when cutaneous KS lesions evolve into deep penetrating nodular tumors. Primary KS of the subcutaneous tissue is an exceptional manifestation of this low-grade vascular neoplasm. Case presentation We present a unique case of acquired immune deficiency syndrome (AIDS-associated KS manifesting primarily in the subcutaneous tissue of the anterior thigh in a 43-year-old male, which occurred without overlying visible skin changes or concomitant KS disease elsewhere. Radiological imaging and tissue biopsy confirmed the diagnosis of KS. Conclusion This is the first documented case of primary subcutaneous KS occurring in the setting of AIDS. The differential diagnosis of an isolated subcutaneous lesion in an human immunodeficiency virus (HIV-infected individual is broad, and requires both imaging and a histopathological diagnosis to guide appropriate therapy.

Investigation of Sc(3) state in nonaqueous solutions by the 45Sc NMR method of high permission

International Nuclear Information System (INIS)

Buslaev, Yu.A.; Kirakosyan, G.A.; Tarasov, V.P.

1980-01-01

The ScCl 3 + CH 3 CN and ScCl 3 + KNCS + CH 3 CN solutions have been studied by a high-resolution NMR 45 Sc method. It has been estimated that in acetonitrile solutions, with competing ligands of Cl - and NCS - being available, hexacoordination Sc(3) complexes of various compositions are formed, and solvent molecules also take part in formation of the coordination sphere of scandium. Chemical shifts in NMR 45 Sc signals depend linearly on the number of chlor- or NCS - ions bound to scandium(3). This made it possible to determine the value of chemical shifts in signals of all 28 potential complexes formed in a system with three competing ligands

Massive Preperitoneal Hematoma after a Subcutaneous Injection

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Hideki Katagiri

2016-01-01

Full Text Available Preperitoneal hematomas are rare and can develop after surgery or trauma. A 74-year-old woman, receiving systemic anticoagulation, developed a massive preperitoneal hematoma after a subcutaneous injection of teriparatide using a 32-gauge, 4 mm needle. In this patient, there were two factors, the subcutaneous injection of teriparatide and systemic anticoagulation, associated with development of the hematoma. These two factors are especially significant, because they are widely used clinically. Although extremely rare, physicians must consider this potentially life-threatening complication after subcutaneous injections, especially in patients receiving anticoagulation.

In vitro and in vivo potency of insulin analogues designed for clinical use.

Science.gov (United States)

Vølund, A; Brange, J; Drejer, K; Jensen, I; Markussen, J; Ribel, U; Sørensen, A R; Schlichtkrull, J

1991-11-01

Analogues of human insulin designed to have improved absorption properties after subcutaneous injection have been prepared by recombinant DNA technology. Five rapidly absorbed analogues, being predominantly in mono- or di-meric states in the pharmaceutical preparation, and a hexameric analogue with very low solubility at neutral pH and slow absorption, were studied. Receptor binding assays with HEP-G2 cells showed overall agreement with mouse free adipocyte assays. Two analogues, B28Asp and A21Gly + B27Arg + B30Thr-NH2, had nearly the same molar in vitro potency as human insulin. Another two showed increased adipocyte potency and receptor binding, B10Asp 194% and 333% and A8His + B4His + B10Glu + B27His 575% and 511%, while B9Asp + B27Glu showed 29% and 18% and the B25Asp analogue only 0.12% and 0.05% potency. Bioassays in mice or rabbits of the analogues except B25Asp showed that they had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation in in vivo potency reflects the differences in receptor binding affinity. Relative to human insulin a low concentration is sufficient for a high affinity analogue to produce a given receptor complex formation and metabolic response. In conclusion, human insulin and analogues with markedly different in vitro potencies were equipotent in terms of hypoglycaemic effect. This is in agreement with the concept that elimination of insulin from blood and its subsequent degradation is mediated by insulin receptors.

Cross-sectional study into quality of life issues surrounding insulin pump use in type 1 diabetes

DEFF Research Database (Denmark)

Barnard, Katharine D.; Skinner, T. Chas

2008-01-01

This study aimed to determine whether continuous subcutaneous insulin infusion (CSII) is associated with improved quality of life (QoL) in routine care in the UK. We conducted a multiple cohort survey study of individuals with type 1 diabetes (matched for age, gender and frequency of blood glucose......-economic environment, individuals using CSII reported better QoL than a matched cohort of individuals managing their diabetes using MDI....

Learning From Past Failures of Oral Insulin Trials.

Science.gov (United States)

Michels, Aaron W; Gottlieb, Peter A

2018-07-01

Very recently one of the largest type 1 diabetes prevention trials using daily administration of oral insulin or placebo was completed. After 9 years of study enrollment and follow-up, the randomized controlled trial failed to delay the onset of clinical type 1 diabetes, which was the primary end point. The unfortunate outcome follows the previous large-scale trial, the Diabetes Prevention Trial-Type 1 (DPT-1), which again failed to delay diabetes onset with oral insulin or low-dose subcutaneous insulin injections in a randomized controlled trial with relatives at risk for type 1 diabetes. These sobering results raise the important question, "Where does the type 1 diabetes prevention field move next?" In this Perspective, we advocate for a paradigm shift in which smaller mechanistic trials are conducted to define immune mechanisms and potentially identify treatment responders. The stage is set for these interventions in individuals at risk for type 1 diabetes as Type 1 Diabetes TrialNet has identified thousands of relatives with islet autoantibodies and general population screening for type 1 diabetes risk is under way. Mechanistic trials will allow for better trial design and patient selection based upon molecular markers prior to large randomized controlled trials, moving toward a personalized medicine approach for the prevention of type 1 diabetes. © 2018 by the American Diabetes Association.

Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

DEFF Research Database (Denmark)

Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

2007-01-01

of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression...

Development of standardized radioactive 46Sc solution

International Nuclear Information System (INIS)

Du Hongshan; Jia Zhang; Yu Yiguang; Sun Naiyao

1988-01-01

A method of preparation of standardized radioactive 46 Sc solution is developed. The separation of 46 Sc, the composition of 46 Sc solution and its stability, and radioactivity measurement of 46 Sc are systematically studied. The results obtained in the study and in the applications in many laboratories have shown that our method is effective and reliable

Knowledge insufficient: the management of haemoglobin SC disease.

Science.gov (United States)

Pecker, Lydia H; Schaefer, Beverly A; Luchtman-Jones, Lori

2017-02-01

Although haemoglobin SC (HbSC) accounts for 30% of sickle cell disease (SCD) in the United States and United Kingdom, evidence-based guidelines for genotype specific management are lacking. The unique pathology of HbSC disease is complex, characterized by erythrocyte dehydration, intracellular sickling and increased blood viscosity. The evaluation and treatment of patients with HbSC is largely inferred from studies of SCD consisting mostly of haemoglobin SS (HbSS) patients. These studies are underpowered to allow definitive conclusions about HbSC. We review the pathophysiology of HbSC disease, including known and potential differences between HbSS and HbSC, and highlight knowledge gaps in HbSC disease management. Clinical and translational research is needed to develop targeted treatments and to validate management recommendations for efficacy, safety and impact on quality of life for people with HbSC. © 2016 John Wiley & Sons Ltd.

Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

DEFF Research Database (Denmark)

Hilsted, J C; Madsbad, S; Rasmussen, M H

1996-01-01

Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...... subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment...

Vascular infarction by subcutaneous application of tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity profile.

Science.gov (United States)

Dreischalück, Johannes; Schwöppe, Christian; Spieker, Tilmann; Kessler, Torsten; Tiemann, Klaus; Liersch, Ruediger; Schliemann, Christoph; Kreuter, Michael; Kolkmeyer, Astrid; Hintelmann, Heike; Mesters, Rolf M; Berdel, Wolfgang E

2010-12-01

tTF-NGR consists of the extracellular domain of the (truncated) tissue factor (tTF), a central molecule for coagulation in vivo, and the peptide GNGRAHA (NGR), a ligand of the surface protein aminopeptidase N (CD13). After deamidation of the NGR-peptide moiety, the fusion protein is also a ligand for integrin αvβ3 (CD51/CD61). Both surface proteins are upregulated on endothelial cells of tumor vessels. tTF-NGR showed binding to specific binding sites on endothelial cells in vitro as shown by flow cytometry. Subcutaneous injection of tTF-NGR into athymic mice bearing human HT1080 fibrosarcoma tumors induced tumor growth retardation and delay. Contrast enhanced ultrasound detected a decrease in tumor blood flow in vivo after application of tTF-NGR. Histological analysis of the tumors revealed vascular disruption due to blood pooling and thrombotic occlusion of tumor vessels. Furthermore, a lack of resistance was shown by re-exposure of tumor-bearing mice to tTF-NGR after regrowth following a first cycle of treatment. However, after subcutaneous (s.c.) push injection with therapeutic doses (1-5 mg/kg bw) side effects have been observed, such as skin bleeding and reduced performance. Since lethality started within the therapeutic dose range (LD10 approximately 2 mg/kg bw) no safe therapeutic window could be found. Limiting toxicity was represented by thrombo-embolic events in major organ systems as demonstrated by histology. Thus, subcutaneous injection of tTF-NGR represents an active, but toxic application procedure and compares unfavourably to intravenous infusion.

SC-FDMA for mobile communications

CERN Document Server

Abd El-Samie, Fathi E

2013-01-01

SC-FDMA for Mobile Communications examines Single-Carrier Frequency Division Multiple Access (SC-FDMA). Explaining this rapidly evolving system for mobile communications, it describes its advantages and limitations and outlines possible solutions for addressing its current limitations. The book explores the emerging trend of cooperative communication with SC-FDMA and how it can improve the physical layer security. It considers the design of distributed coding schemes and protocols for wireless relay networks where users cooperate to send their data to the destination. Supplying you with the re

EFFECTIVENESS OF SUBCUTANEOUS ALLERGEN-SPECIFIC IMMUNOTHERAPY WITH TREE POLLEN ALLERGEN EXTRACT ADSORBED ON CALCIUM PHOSPHATE IN CHILDREN WITH ALLERGIC RHINOCONJUNCTIVITIS: RESULTS OF A 2 YEAR-LONG OBSERVATION

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N. V. Shakhova

2014-01-01

Full Text Available The study was aimed at evaluating effectiveness and safety of subcutaneous allergen-specific immunotherapy (scASIT with tree pollen allergen extract adsorbed on calcium phosphate at allergic rhinoconjunctivitis in children. Patients and methods: open-label prospective study of 50 children and adolescents (5-17 years of age with allergic rhinoconjunctivitis caused by high sensitivity to tree pollen allergens. The first group involved the patients undergoing scASIT for 2 years 6 months (n = 23, the control group – the patients (n = 27 not undergoing any specific immunotherapy. Results: scASIT was accompanied by a statistically significant (in comparison with the control group reduction in intensity of rhinoconjunctivitis symptoms (6.1 ± 3.1; 11.8 ± 4.5; p = 0.00002, reduction in the use of symptomatic drugs (1.0 ± 0.4; 1.8 ± 0.3; p = 0.000004 and improvement of quality of all spheres of children’s life – physical (p = 0.001, social (p = 0.04, emotional (p = 0.001 and role functioning (p = 0.03. Systemic side reactions were not observed in the patients. Local reactions were observed in 23% of all allergen injections. Conclusions: the authors established high effectiveness and safety of scASIT with tree pollen allergen extract adsorbed on calcium phosphate suspension at allergic rhinoconjunctivitis in children. 

Precipitation in cold-rolled Al-Sc-Zr and Al-Mn-Sc-Zr alloys prepared by powder metallurgy

KAUST Repository

Vlach, Martin

2013-12-01

The effects of cold-rolling on thermal, mechanical and electrical properties, microstructure and recrystallization behaviour of the AlScZr and AlMnScZr alloys prepared by powder metallurgy were studied. The powder was produced by atomising in argon with 1% oxygen and then consolidated by hot extrusion at 350 C. The electrical resistometry and microhardness together with differential scanning calorimetry measurements were compared with microstructure development observed by transmission and scanning electron microscopy, X-ray diffraction and electron backscatter diffraction. Fine (sub)grain structure developed and fine coherent Al3Sc and/or Al3(Sc,Zr) particles precipitated during extrusion at 350 C in the alloys studied. Additional precipitation of the Al3Sc and/or Al3(Sc,Zr) particles and/or their coarsening was slightly facilitated by the previous cold rolling. The presence of Sc,Zr-containing particles has a significant antirecrystallization effect that prevents recrystallization at temperatures minimally up to 420 C. The precipitation of the Al6Mn- and/or Al 6(Mn,Fe) particles of a size ~ 1.0 μm at subgrain boundaries has also an essential antirecrystallization effect and totally suppresses recrystallization during 32 h long annealing at 550 C. The texture development of the alloys seems to be affected by high solid solution strengthening by Mn. The precipitation of the Mn-containing alloy is highly enhanced by a cold rolling. The apparent activation energy of the Al3Sc particles formation and/or coarsening and that of the Al6Mn and/or Al 6(Mn,Fe) particle precipitation in the powder and in the compacted alloys were determined. The cold deformation has no effect on the apparent activation energy values of the Al3Sc-phase and the Al 6Mn-phase precipitation. © 2013 Elsevier Inc.

Precipitation in cold-rolled Al-Sc-Zr and Al-Mn-Sc-Zr alloys prepared by powder metallurgy

KAUST Repository

Vlach, Martin; Stulí ková , Ivana; Smola, Bohumil; Kekule, Tomá š; Kudrnová , Hana; Daniš, Stanislav; Gemma, Ryota; Očená šek, Vladivoj; Má lek, Jaroslav; Tanprayoon, Dhritti; Neubert, Volkmar

2013-01-01

The effects of cold-rolling on thermal, mechanical and electrical properties, microstructure and recrystallization behaviour of the AlScZr and AlMnScZr alloys prepared by powder metallurgy were studied. The powder was produced by atomising in argon with 1% oxygen and then consolidated by hot extrusion at 350 C. The electrical resistometry and microhardness together with differential scanning calorimetry measurements were compared with microstructure development observed by transmission and scanning electron microscopy, X-ray diffraction and electron backscatter diffraction. Fine (sub)grain structure developed and fine coherent Al3Sc and/or Al3(Sc,Zr) particles precipitated during extrusion at 350 C in the alloys studied. Additional precipitation of the Al3Sc and/or Al3(Sc,Zr) particles and/or their coarsening was slightly facilitated by the previous cold rolling. The presence of Sc,Zr-containing particles has a significant antirecrystallization effect that prevents recrystallization at temperatures minimally up to 420 C. The precipitation of the Al6Mn- and/or Al 6(Mn,Fe) particles of a size ~ 1.0 μm at subgrain boundaries has also an essential antirecrystallization effect and totally suppresses recrystallization during 32 h long annealing at 550 C. The texture development of the alloys seems to be affected by high solid solution strengthening by Mn. The precipitation of the Mn-containing alloy is highly enhanced by a cold rolling. The apparent activation energy of the Al3Sc particles formation and/or coarsening and that of the Al6Mn and/or Al 6(Mn,Fe) particle precipitation in the powder and in the compacted alloys were determined. The cold deformation has no effect on the apparent activation energy values of the Al3Sc-phase and the Al 6Mn-phase precipitation. © 2013 Elsevier Inc.

Band structure of the quaternary Heusler alloys ScMnFeSn and ScFeCoAl

Science.gov (United States)

Shanthi, N.; Teja, Y. N.; Shaji, Shephine M.; Hosamani, Shashikala; Divya, H. S.

2018-04-01

In our quest for materials with specific applications, a theoretical study plays an important role in predicting the properties of compounds. Heusler alloys or compounds are the most studied in this context. More recently, a lot of quaternary Heusler compounds are investigated for potential applications in fields like Spintronics. We report here our preliminary study of the alloys ScMnFeSn and ScFeCoAl, using the ab-initio linear muffin-tin orbital method within the atomic sphere approximation (LMTO-ASA). The alloy ScMnFeSn shows perfect half-metallicity, namely, one of the spins shows a metallic behaviour and the other spin shows semi-conducting behaviour. Such materials find application in devices such as the spin-transfer torque random access memory (STT-MRAM). In addition, the alloy ScMnFeSn is found to have an integral magnetic moment of 4 µB, as predicted by the Slater-Pauling rule. The alloy ScFeCoAl does not show half-metallicity.

Penile Subcutaneous Fibrolipoma Postaugmentative Phalloplasty

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Patrizio Vicini

2013-01-01

Full Text Available Fibrolipomas are a rare subtype of lipomas. We describe a case of a man suffering from subcutaneous penile fibrolipoma, who three months earlier has been submitted to an augmentative phalloplasty due to aesthetic dysmorphophobia. After six months from the excision of the mass, the penile elongation and penile enlargement were stable, and the patient was satisfied with his sexual intercourse and sexual life. To our knowledge, this is the first reported penile subcutaneous fibrolipoma case in the literature. The diagnostics and surgical features of this case are discussed.

In Silico Assessment of Literature Insulin Bolus Calculation Methods Accounting for Glucose Rate of Change.

Science.gov (United States)

Cappon, Giacomo; Marturano, Francesca; Vettoretti, Martina; Facchinetti, Andrea; Sparacino, Giovanni

2018-05-01

The standard formula (SF) used in bolus calculators (BCs) determines meal insulin bolus using "static" measurement of blood glucose concentration (BG) obtained by self-monitoring of blood glucose (SMBG) fingerprick device. Some methods have been proposed to improve efficacy of SF using "dynamic" information provided by continuous glucose monitoring (CGM), and, in particular, glucose rate of change (ROC). This article compares, in silico and in an ideal framework limiting the exposition to possibly confounding factors (such as CGM noise), the performance of three popular techniques devised for such a scope, that is, the methods of Buckingham et al (BU), Scheiner (SC), and Pettus and Edelman (PE). Using the UVa/Padova Type 1 diabetes simulator we generated data of 100 virtual subjects in noise-free, single-meal scenarios having different preprandial BG and ROC values. Meal insulin bolus was computed using SF, BU, SC, and PE. Performance was assessed with the blood glucose risk index (BGRI) on the 9 hours after meal. On average, BU, SC, and PE improve BGRI compared to SF. When BG is rapidly decreasing, PE obtains the best performance. In the other ROC scenarios, none of the considered methods prevails in all the preprandial BG conditions tested. Our study showed that, at least in the considered ideal framework, none of the methods to correct SF according to ROC is globally better than the others. Critical analysis of the results also suggests that further investigations are needed to develop more effective formulas to account for ROC information in BCs.

Subcutaneous blood flow in psoriasis

International Nuclear Information System (INIS)

Klemp, P.

1985-01-01

The simultaneously recorded disappearance rates of 133 xe from subcutaneous adipose tissue in the crus were studied in 10 patients with psoriasis vulgaris using atraumatic labeling of the tissue in lesional skin (LS) areas and symmetrical, nonlesional skin (NLS) areas. Control experiments were performed bilaterally in 10 younger, healthy subjects. The subcutaneous washout rate constant was significantly higher in LS, 0.79 +/- 0.05 min-1 x 10(2) compared to the washout rate constant of NLS, 0.56 +/- 0.07 min-1. 10(2), or the washout rate constant in the normal subjects, 0.46 +/- 0.17 min-1 x 10(2). The mean washout rate constant in NLS was 25% higher than the mean washout rate constant in the normal subjects. The difference was, however, not statistically significant. Differences in the washout rate constants might be due to abnormal subcutaneous tissue-to-blood partition (lambda) in the LS--and therefore not reflecting the real differences in the subcutaneous blood flow (SBF). The lambda for 133 Xe was therefore measured--using a double isotope washout method ( 133 Xe and [ 131 I]antipyrine)--in symmetrical sites of the lateral crus in LS and NLS of 10 patients with psoriasis vulgaris and in 10 legs of normal subjects. In LS the lambda was 4.52 +/- 1.67 ml/g, which was not statistically different from that of NLS, 5.25 +/- 2.19 ml/g, nor from that of normal subcutaneous tissue, 4.98 +/- 1.04 ml/g. Calculations of the SBF using the obtained lambda values gave a significantly higher SBF in LS, 3.57 +/- 0.23 ml/100 g/min, compared to SBF in the NLS, 2.94 +/- 0.37 ml/100 g/min. There was no statistically significant difference between SBF in NLS and SBF in the normal subjects. The increased SBF in LS of psoriatics might be a secondary phenomenon to an increased heat loss in the lesional skin

The effect of insulin on amino acid incorporation into exocrine pancreatic cells of the rat

International Nuclear Information System (INIS)

Kramer, M.F.; Poort, C.

1975-01-01

The rate of incorporation of radioactive leucine per cell in the acinar pancreatic cells of the rat increases by 50 per cent within one hour after subcutaneous administration of insulin, an effect that lasts for at least one more hour. The rate of incorporation has been measured by quantitative radioautography and by determination of the radioactivity per μg DNA in TCA-precipitable material from tissue homogenates. The capacity for amino acid (leucine and lysine) incorporation as measured by incubating pancreatic fragments in vitro is not enhanced by insulin treatment of the rat in vivo during one or more hours. Insulin was found to lower the serum concentration of most amino acids significantly, leucine by 50 per cent. The apparent effect of insulin on the incorporation of radioactive leucine in vivo can be explained by the difference in the specific radioactivity of the circulating amino acid in the treated rats as compared to the untreated ones. A change in amino acid concentration in the serum may likewise be the explanation of the decrease in amino acid incorporation rate in alloxan diabetic rats. (orig./GSE) [de

Female adipocyte androgen synthesis and the effects of insulin

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David Cadagan

2014-01-01

Full Text Available The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione in vitro and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.

Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation Impact on Sensor Accuracy.

Science.gov (United States)

Rigla, Mercedes; Pons, Belén; Rebasa, Pere; Luna, Alexis; Pozo, Francisco Javier; Caixàs, Assumpta; Villaplana, Maria; Subías, David; Bella, Maria Rosa; Combalia, Neus

2018-04-01

Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance. Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%. Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm 2 ; P sensor-tissue interface is related with decrease in accuracy of the glucose measure.

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

Science.gov (United States)

Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

2017-12-01

To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.

Science.gov (United States)

Grabovac, Vjera; Föger, Florian; Bernkop-Schnürch, Andreas

2008-02-04

The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo. The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured. The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%. The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.

Recurrent subcutaneous emphysema of the face: a challenging clinical problem.

Science.gov (United States)

Hojjati, Hossein; Davani, Sam Zeraatian Nejad; Johari, Hamed Ghoddusi

2007-01-01

In the neck or face, there are different causes for subcutaneous emphysema such as injury to the sinuses, the hypopharynx, the laryngotracheal complex, the pulmonary parenchyma, the esophagus or the presence of gas-forming organisms. However, factitious subcutaneous emphysema, a rare cause, must be considered in the differential diagnosis. In this clinical report, we discuss a 20-year-old girl who was under follow-up because of recurrent subcutaneous emphysema of the face and periorbital area. After 2 years of work-ups, including a period of close observation in the intensive care unit, self air injection by syringe was found as the cause of recurrent subcutaneous emphysema of the face, and the patient was labeled as having factitious recurrent subcutaneous emphysema. Therefore, when a patient presents with unexplained recurrent subcutaneous emphysema, one should suspect self-infliction and examine for puncture marks.

Effects of a somatostatin derivative (SMS 201-995) on postprandial hyperglycemia in insulin-dependent diabetics studied by means of a closed-loop device.

Science.gov (United States)

Nosari, I; Lepore, G; Querci, F; Maglio, M L; Sileo, F; Pagani, G

1989-06-01

We studied the effects of a premeal sc injection of an analog of somatostatin (SMS 201-995, Sandoz) on the postprandial glycemic excursions, insulin requirement and hormone profiles (GH, glucagon and C-peptide) in 8 IDDM patients (diabetes duration 14.0 +/- 6.5 yr, daily insulin requirement 36 +/- 6.4 U) maintained normoglycemic by connecting them to a closed-loop insulin infusion system (Betalike, Genoa). The morning of the test the patients were connected to the Betalike and their glucose levels stabilized for at least 4 h. At 13:00 h the study was begun with a sc injection of 50 micrograms of SMS 201-995 or placebo (randomly) and a standardized mixed meal (800 Kcal) was given. Blood samples were obtained 0, 15, 30, 60, 120 and 180 min after the injection. Each patient was tested both with SMS 201-995 and placebo. Postmeal glycemic peaks were decreased after SMS 201-995 (119.6 +/- 5.4 mg/dl vs 149.1 +/- 4.2; p less than 0.05) as well as insulin requirements (3.2 +/- 0.8 U vs 13.3 +/- 1.9; p less than 0.01) for the 180 min postprandial period. Similarly, glucagon level was reduced 30 min postprandially (24 +/- 6 pg/ml vs 59 +/- 24; p less than 0.05) and so GH level only 180 min after lunch (p less than 0.05). The premeal injection of SMS decreases postprandial glycemic excursions and the corresponding insulin requirement. The action of SMS 201-995 may be mainly mediated by the suppression of postprandial glucagon peak.

Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats.

Science.gov (United States)

Steagall, P V M; Moutinho, F Q; Mantovani, F B; Passarelli, D; Thomassian, A

2009-02-01

This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2mg/kg (day 2 and 3) and 1mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables.

Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

DEFF Research Database (Denmark)

Plomgaard, P; Nielsen, A R; Fischer, C P

2007-01-01

AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes. METHODS: We obtained blood and biopsy samples from skeletal muscle...... and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). RESULTS: Patients with type 2 diabetes had higher plasma levels of fasting insulin (p ...) uptake (VO2/kg) in the diabetes group (p type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein...

Predicting Insulin Absorption and Glucose Uptake during Exercise in Type 1 Diabetes

Science.gov (United States)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Szeri, Andrew; Basu, Ananda

2017-11-01

A dose of insulin infused into subcutaneous tissue has been shown to absorb more quickly during exercise, potentially causing hypoglycemia in persons with type 1 diabetes. We develop a model that relates exercise-induced physiological changes to enhanced insulin-absorption (k) and glucose uptake (GU). Drawing on concepts of the microcirculation we derive a relationship that reveals that k and GU are mainly determined by two physiological parameters that characterize the tissue: the tissue perfusion rate (Q) and the capillary permeability surface area (PS). Independently measured values of Q and PS from the literature are used in the model to make predictions of k and GU. We compare these predictions to experimental observations of healthy and diabetic patients that are given a meal followed by rest or exercise. The experiments show that during exercise insulin concentrations significantly increase and that glucose levels fall rapidly. The model predictions are consistent with the experiments and show that increases in Q and PS directly increase k and GU. This mechanistic understanding provides a basis for handling exercise in control algorithms for an artificial pancreas. Now at University of British Columbia.

Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects

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Soronen Jarkko

2012-04-01

Full Text Available Abstract Background To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. Methods Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 hours of intravenously maintained euglycemic hyperinsulinemia from 9 insulin-resistant and 11 insulin-sensitive females. Gene expression was measured using Affymetrix HG U133 Plus 2 microarrays and qRT-PCR. Microarray data and pathway analyses were performed with Chipster v1.4.2 and by using in-house developed nonparametric pathway analysis software. Results The most prominent difference in gene expression of the insulin-resistant group during hyperinsulinemia was reduced transcription of nuclear genes involved in mitochondrial respiration (mitochondrial respiratory chain, GO:0001934. Inflammatory pathways with complement components (inflammatory response, GO:0006954 and cytokines (chemotaxis, GO:0042330 were strongly up-regulated in insulin-resistant as compared to insulin-sensitive subjects both before and during hyperinsulinemia. Furthermore, differences were observed in genes contributing to fatty acid, cholesterol and triglyceride metabolism (FATP2, ELOVL6, PNPLA3, SREBF1 and in genes involved in regulating lipolysis (ANGPTL4 between the insulin-resistant and -sensitive subjects especially during hyperinsulinemia. Conclusions The major finding of this study was lower expression of mitochondrial respiratory pathway and defective induction of lipid metabolism pathways by insulin in insulin-resistant subjects. Moreover, the study reveals several novel genes whose aberrant regulation is associated with the obese insulin-resistant phenotype.

Subcutaneous granuloma annulare

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Dhar Sandipan

1994-01-01

Full Text Available Two cases of subcutaneos granuloma annulare are reported. Clinical presentation was in the form of hard subcutaneous nodules; histopathology confirmed the clinical diagnosis. The cases were unique because of onset in adult hood, occurrence over unusual sites and absence of classical lesions of granuloma annulare elsewhere.

Exenatide with Metformin Ameliorated Visceral Adiposity and Insulin Resistance

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Xuan Du

2018-01-01

Full Text Available Background. To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods. 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups. Adipose distribution was quantified with computerized tomography according to anatomy, dividing into visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT, adding up to total adipose tissue (TAT. Results. The 6-month exenatide treatment dramatically ameliorated the glucose and lipid profile, improved insulin sensitivity, and mainly decreased VAT and also the ratio of VAT/SAT (RVS. The following 6-month glargine treatment increased VAT. The whole 12-month sequential treatment with exenatide and glargine added to metformin basically improved the insulin sensitivity and glucolipid control though VAT rebounded at the end, however without deteriorating the other parameters. Conclusion. Exenatide is an ideal treatment for obese type 2 diabetic patients in the aspect of adipose tissue distribution. Sequential treatment of exenatide and glargine could be an alternative for low-income patients who cannot afford GLP-1 agonist for long time. This trial is registered with ChiCTR-OOC-17013679.

Enfisema subcutâneo maciço - Tratamento com drenos subcutâneos Massive subcutaneous emphysema - Management using subcutaneous drains

Directory of Open Access Journals (Sweden)

Maria Sucena

2010-04-01

Full Text Available O enfisema subcutâneo é uma complicação relativamente comum na sequência de técnicas invasivas, procedimentos cirúrgicos e algumas patologias médicas. Na maior parte dos casos apenas causa sintomatologia minor e o tratamento é habitualmente conservador. Mesmo quando grave, raramente tem consequências patofisiológicas significativas, apesar de ser extremamente desconfortável para o doente. Os autores descrevem um caso clínico de enfisema subcutâneo maciço, de rápida instalação, após saída acidental de tubo de drenagem torácica, em doente com pneumotórax espontâneo secundário e fístula broncopleural. O enfisema foi tratado através da colocação, sob anestesia local, de dois drenos subcutâneos na parede anterossuperior do tórax, conectados a sacos de drenagem. Após a colocação dos drenos subcutâneos verificou-se uma franca melhoria clínica do doente, com descompressão eficaz do enfisema subcutâneo. No presente caso clínico, a técnica de drenagem do enfisema maciço mostrou-se simples, segura e eficaz, permitindo o alívio sintomático imediato.Massive subcutaneous emphysema is a relatively common complication in invasive techniques, surgical practice and some medical conditions. Subcutaneous emphysema is usually treated conservatively and may only cause minimal symptoms. Even when it is severe, subcutaneous emphysema rarely has pathophysiologic consequences, but it is extremely uncomfortable for the patient. The authors report a case of massive and rapid developing subcutaneous emphysema following chest tube displacement in a patient with spontaneous secondary pneumothorax and large air leak. The emphysema was treated with two subcutaneous drains, inserted using local anesthesia, on both sides of the chest (antero-superior thoracic wall, connected to drainage bags. The drains produced a dramatic clinical improvement and provided effective decompression of the subcutaneous emphysema. In this clinical case, the

Effects of Endogenous Androgens and Abdominal Fat Distribution on the Interrelationship Between Insulin and Non-Insulin-Mediated Glucose Uptake in Females

Science.gov (United States)

Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Dey, Damini; Berman, Daniel; Chen, Ida Y.; Dumesic, Daniel A.

2013-01-01

Background: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. Glucose disposal occurs via noninsulin-mediated glucose uptake (NIMGU) and insulin-mediated glucose uptake (IMGU). It is unknown whether in PCOS NIMGU increases to compensate for declining IMGU and whether androgens and fat distribution influence this relationship. Objectives: The objective of the study was to compare in women with PCOS and controls the interrelationship between NIMGU [ie, glucose effectiveness (Sg)] and IMGU [ie, the insulin sensitivity index (Si)] and the role of androgens and fat distribution. Participants: Twenty-eight PCOS (by National Institutes of Health 1990 criteria) and 28 control (age, race, and body mass index matched) women were prospectively studied. A subset of 16 PCOS subjects and 16 matched controls also underwent abdominal computed tomography. Main Outcome Measures: Glucose disposal (by a frequently sampled iv glucose tolerance test), circulating androgens, and abdominal fat distribution [by waist to hip ratio and visceral (VAT) and sc (SAT) adipose tissue content] were measured. Results: PCOS women had lower mean Si and similar Sg and abdominal fat distribution compared with controls. PCOS women with Si below the PCOS median (more insulin resistant) had a lower mean Sg than controls with Si above the control median (more insulin sensitive). In PCOS only, body mass index, free T, modified Ferriman-Gallwey score, and waist to hip ratio independently predicted Sg, whereas Si did not. In PCOS, VAT and SAT independently and negatively predicted Si and Sg, respectively. Conclusion: The decreased IMGU in PCOS is not accompanied by a compensatory increase in NIMGU or associated with excessive VAT accumulation. Increased general obesity, SAT, and hyperandrogenism are primary predictors of the deterioration of NIMGU in PCOS. PMID:23450052

The colours of Hubble Sc galaxy nuclei

International Nuclear Information System (INIS)

Iskudaryan, S.G.

1975-01-01

The colorimetric data on the nuclei of the Sc galaxies are given. Comparison of the following parameters: color of a nucleus, integral color of a galaxy, Byurakan class, and spectral type of normal spirals gives the possibility to conclude: (1) The colors of the nuclei of the Sc galaxies have a high dispersion in its values. In all Byurakan classes the galaxies with intensely red and blue nuclei occur; (2) Some Sc galaxies exhibit a discrepancy between the spectral and morphological types. The results of colorimetry of nuclei indicate that almost all such Sc galaxies have intensely red nuclei which, naturally, provide for these late spectral types. It can be assumed that the intensely red color of the nuclei of such Sc galaxies is a result of a new type of activity of these nuclei; and (3) some Sc galaxies show the characteristics of the Markarian objects

Insulin resistance, hepatic lipid and adipose tissue distribution in HIV infected men

Science.gov (United States)

He, Qing; Engelson, Ellen S.; Ionescu, Gabriel; Glesby, Marshall J.; Albu, Jeanine B.; Kotler, Donald P.

2010-01-01

Background A large proportion of HIV-infected subjects on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. Design and methods We performed a cross-sectional analysis of baseline data from twenty-three HIV-infected participants in 3 prospective clinical studies. Magnetic resonance spectroscopy was applied to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole body adipose tissue compartments, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes as well as inter-muscular adipose tissue (IMAT) subcompartment, and omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. Homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Results Hepatic lipid content correlated significantly with total VAT (r=0.62, p=0.0014) but not with SAT (r=0.053, p=0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r=0.67, p=0.0004) and RPAT (r=0.53, p=0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r=0.61, p=0.057 and 0.68, p=0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. Conclusion Hepatic lipid content is associated with VAT volume, especially the omental-mesenteric subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men. PMID:18572755

Insulin resistance, hepatic lipid and adipose tissue distribution in HIV-infected men.

Science.gov (United States)

He, Qing; Engelson, Ellen S; Ionescu, Gabriel; Glesby, Marshall J; Albu, Jeanine B; Kotler, Donald P

2008-01-01

A large proportion of HIV-infected patients on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. We performed a cross-sectional analysis of baseline data from 23 HIV-infected participants in three prospective clinical studies. Magnetic resonance spectroscopy was used to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole-body adipose tissue compartments: that is, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes, as well as the intermuscular adipose tissue (IMAT) subcompartment and the omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. The homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Hepatic lipid content correlated significantly with total VAT (r = 0.62, P = 0.0014), but not with SAT (r = 0.053, P = 0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r = 0.67, P = 0.0004) and RPAT (r = 0.53, P = 0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r = 0.61, P = 0.057 and r = 0.68, P = 0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. Hepatic lipid content is associated with VAT volume, especially the OMAT subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men.

An Audit of Clinical Practice in a Single Centre in Kuwait: Management of Children on Continuous Subcutaneous Insulin Infusion and Cardiovascular Risk Factors Screening.

Science.gov (United States)

Omar, Dina; Alsanae, Hala; Al Khawari, Mona; Abdulrasoul, Majedah; Rahme, Zahraa; Al Refaei, Faisal; Behbehani, Kazem; Shaltout, Azza

2017-01-01

To audit the current clinical practice of continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetes mellitus (T1D) in children and adolescents attending a single centre in Kuwait. A one year retrospective audit was performed in children and adolescents with T1D on CSII, who attended the paediatric diabetes clinic, Dasman Diabetes Institute during 2012. The primary outcome measure was glycaemic control as evidenced by glycated haemoglobin (HbA1c) level and the secondary outcome measures were the frequency of monitoring of the risk for microvascular complications and occurrence of acute complications and adverse events. 58 children and adolescents (mean age ± SD: 12.6 ± 4.1 years) were included. Mean HbA1c at baseline was 8.8% (72.7 mmol/mol) and 8.9% (73.8 mmol/mol) at the end of a 12 months observation period. Children with poor control (HbA1c >9.5% (80 mmol/mol) had a significant 1.4% reduction in HbA1c compared with the overall reduction of 0.1% (p=0.7). Rate of screening for cardiovascular risk factors and for long term complications were well documented. However, there was underreporting of acute complications such as severe hypoglycaemia and diabetic ketoacidosis. Only 1.7% of patients discontinued the pump. There was no significant change in HbA1c values at the end of 12 months follow up. However, HbA1c values in poorly controlled children improved. CSII requires care by skilled health professionals as well as education and selection of motivated parents and children.

Role of Liposuction Combined with Subcutaneous Mastectomy in ...

African Journals Online (AJOL)

deformity in two other patients. Conclusions: Liposuction combined with subcutaneous mastectomy is a reliable, versatile, less time consuming and valid procedure for the treatment of gynecomastia. This procedure provides satisfactory aesthetic results. KEY WORDS: Gynecomastia, liposuction, subcutaneous mastectomy.

Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

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Krishnan, Navasona; Bonham, Christopher A; Rus, Ioana A; Shrestha, Om Kumar; Gauss, Carla M; Haque, Aftabul; Tocilj, Ante; Joshua-Tor, Leemor; Tonks, Nicholas K

2018-01-18

The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

Caloric restriction and diet-induced weight loss do not induce browning of human subcutaneous white adipose tissue in women and men with obesity

DEFF Research Database (Denmark)

Barquissau, Valentin; Léger, Benjamin; Beuzelin, Diane

2018-01-01

Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white...... variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent...

Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity.

Science.gov (United States)

Schwarz, Jean-Marc; Noworolski, Susan M; Erkin-Cakmak, Ayca; Korn, Natalie J; Wen, Michael J; Tai, Viva W; Jones, Grace M; Palii, Sergiu P; Velasco-Alin, Moises; Pan, Karen; Patterson, Bruce W; Gugliucci, Alejandro; Lustig, Robert H; Mulligan, Kathleen

2017-09-01

Consumption of sugar is associated with obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis [DNL]) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/d). Children (9-18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child. Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (interquartile range [IQR], 2.5%-14.8%) to 3.8% (IQR, 1.7%-15.5%) (P fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov Number: NCT01200043. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

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Xiuyuan Zhang

2016-12-01

Full Text Available Background/Aims: The endocannabinoid signalling (ECS system has been known to regulate glucose homeostasis. Previous studies have suggested that the cannabinoid 2 (CB2 receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance. Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD/streptozotocin (STZ-induced mice. Methods: Diabetes was induced in male ICR mice by HFD/STZ and exposed to a CB2 receptor agonist, SER601, for 2- or 4-weeks via subcutaneous implantation of osmotic minipumps. Glucose and insulin tolerance tests were performed at the end of treatment. Islets were isolated for assessment of β-cell function. Pancreases and skeletal muscles were also obtained for histological analyses. Results: Despite a lack of impact on glucose tolerance, substantial improvement on insulin sensitivity was observed in SER601-treated mice, which could partly be attributed to improved islet β-cell function, shown as increased glucose-induced insulin secretion and insulin content. No changes on islet macrophage infiltration or skeletal muscle fat deposition were detectable from SER601-treated mice. However, a major decrease in body weight was recorded at the end of 4-week SER601 exposure, accompanied by a lack of epididymal adipose mass in SER601-treated mice. Conclusion: Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity. Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

Science.gov (United States)

2014-01-01

Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

Soybean and sunflower oil-induced insulin resistance correlates with impaired GLUT4 protein expression and translocation specifically in white adipose tissue.

Science.gov (United States)

Poletto, Ana Cláudia; Anhê, Gabriel Forato; Eichler, Paula; Takahashi, Hilton Kenji; Furuya, Daniela Tomie; Okamoto, Maristela Mitiko; Curi, Rui; Machado, Ubiratan Fabres

2010-03-01

Free fatty acids are known for playing a crucial role in the development of insulin resistance. High fat intake is known for impairing insulin sensitivity; however, the effect of vegetable-oil injections have never been investigated. The present study investigated the effects of daily subcutaneous injections (100 microL) of soybean (SB) and sunflower (SF) oils, during 7 days. Both treated groups developed insulin resistance as assessed by insulin tolerance test. The mechanism underlying the SB- and SF-induced insulin resistance was shown to involve GLUT4. In SB- and SF-treated animals, the GLUT4 protein expression was reduced approximately 20% and 10 min after an acute in vivo stimulus with insulin, the plasma membrane GLUT4 content was approximately 60% lower in white adipose tissue (WAT). No effects were observed in skeletal muscle. Additionally, both oil treatments increased mainly the content of palmitic acid ( approximately 150%) in WAT, which can contribute to explain the GLUT4 regulations. Altogether, the present study collects evidence that those oil treatments might generate insulin resistance by targeting GLUT4 expression and translocation specifically in WAT. These alterations are likely to be caused due to the specific local increase in saturated fatty acids that occurred as a consequence of oil daily injections. 2010 John Wiley & Sons, Ltd.

Concentrated insulins: the new basal insulins

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Lamos EM

2016-03-01

Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

Science.gov (United States)

Winkelman, L A; Overton, T R

2013-01-01

This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

Saccharomyces cerevisiae Differential Functionalization of Presumed ScALT1 and ScALT2 Alanine Transaminases Has Been Driven by Diversification of Pyridoxal Phosphate Interactions

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Erendira Rojas-Ortega

2018-05-01

Full Text Available Saccharomyces cerevisiae arose from an interspecies hybridization (allopolyploidiza-tion, followed by Whole Genome Duplication. Diversification analysis of ScAlt1/ScAlt2 indicated that while ScAlt1 is an alanine transaminase, ScAlt2 lost this activity, constituting an example in which one of the members of the gene pair lacks the apparent ancestral physiological role. This paper analyzes structural organization and pyridoxal phosphate (PLP binding properties of ScAlt1 and ScAlt2 indicating functional diversification could have determined loss of ScAlt2 alanine transaminase activity and thus its role in alanine metabolism. It was found that ScAlt1 and ScAlt2 are dimeric enzymes harboring 67% identity and intact conservation of the catalytic residues, with very similar structures. However, tertiary structure analysis indicated that ScAlt2 has a more open conformation than that of ScAlt1 so that under physiological conditions, while PLP interaction with ScAlt1 allows the formation of two tautomeric PLP isomers (enolimine and ketoenamine ScAlt2 preferentially forms the ketoenamine PLP tautomer, indicating a modified polarity of the active sites which affect the interaction of PLP with these proteins, that could result in lack of alanine transaminase activity in ScAlt2. The fact that ScAlt2 forms a catalytically active Schiff base with PLP and its position in an independent clade in “sensu strictu” yeasts suggests this protein has a yet undiscovered physiological function.

Saccharomyces cerevisiae Differential Functionalization of Presumed ScALT1 and ScALT2 Alanine Transaminases Has Been Driven by Diversification of Pyridoxal Phosphate Interactions

Science.gov (United States)

Rojas-Ortega, Erendira; Aguirre-López, Beatriz; Reyes-Vivas, Horacio; González-Andrade, Martín; Campero-Basaldúa, Jose C.; Pardo, Juan P.; González, Alicia

2018-01-01

Saccharomyces cerevisiae arose from an interspecies hybridization (allopolyploidiza-tion), followed by Whole Genome Duplication. Diversification analysis of ScAlt1/ScAlt2 indicated that while ScAlt1 is an alanine transaminase, ScAlt2 lost this activity, constituting an example in which one of the members of the gene pair lacks the apparent ancestral physiological role. This paper analyzes structural organization and pyridoxal phosphate (PLP) binding properties of ScAlt1 and ScAlt2 indicating functional diversification could have determined loss of ScAlt2 alanine transaminase activity and thus its role in alanine metabolism. It was found that ScAlt1 and ScAlt2 are dimeric enzymes harboring 67% identity and intact conservation of the catalytic residues, with very similar structures. However, tertiary structure analysis indicated that ScAlt2 has a more open conformation than that of ScAlt1 so that under physiological conditions, while PLP interaction with ScAlt1 allows the formation of two tautomeric PLP isomers (enolimine and ketoenamine) ScAlt2 preferentially forms the ketoenamine PLP tautomer, indicating a modified polarity of the active sites which affect the interaction of PLP with these proteins, that could result in lack of alanine transaminase activity in ScAlt2. The fact that ScAlt2 forms a catalytically active Schiff base with PLP and its position in an independent clade in “sensu strictu” yeasts suggests this protein has a yet undiscovered physiological function. PMID:29867852

Subcutaneous tissue flaps for hallux covering.

Science.gov (United States)

Vaienti, Luca; Urzola, Victor; Scotti, Andrea; Masetto, L

2010-03-01

With the understanding of the extensive vascular supply of the subcutaneous tissue, of its efficacy in the protection of the anatomical structures and of its capability of promoting the adequate functioning of very stressed regions of the human body, the use of subcutaneous adipose flaps has become a valid and sometimes the only reasonable therapeutic weapon in the treatment of small and medium-sized tissue loss. Such a defect represents a common complication of great toe injuries and surgery. Here subcutaneous flap reconstruction is proposed for the treatment of dorsal and medial soft tissue losses of the hallux complicated with infection. Two case are reported. To the best of the authors' knowledge, this application has not been reported in this anatomical site so far. The technique might be worth knowing both for orthopedic and plastic surgeons, as it may represent a safe, less invasive solution for most tegumentary problems of the dorso-medial side of the first ray.

Cost-minimization of mabthera intravenous versus subcutaneous administration

NARCIS (Netherlands)

Bax, P.; Postma, M.J.

2013-01-01

Objectives: To identify and compare all costs related to preparing and administrating MabThera for the intravenous and subcutaneous formulations in Dutch hematological patients. The a priori notion is that the costs of subcutaneous MabThera injections are lower compared to intravenous infusion due

The ternary systems Sc-Sm(Dy)-Si at 870 K

International Nuclear Information System (INIS)

Kotur, B.Ya.; Mokra, I.Ya.; Toporinskij, A.Ya.

1991-01-01

Isothermal cross sections of the ternary systems Sc-Sm-Si and Sc-Dy-Si at 870 K have been plotted. Investigation of scandium and disprosium in ternary systems have been examined by X-ray diffraction and microstructure analysis. Besides literary data on binary systems Sc-Si, Sm-Si, Dy-Si have been used. Formation of limited (Sc-Sm-Si, Sc-Dy-Si) and continuous (Sc-Dy-Si) solid solutions based on bisilicides of Sc and Sm(Dy) is discovered. Two and five ternary compounds in Sc-Sm-Si and Sc-Dy-Si systems have been determined and their crystal structure has been established. When investigating of Sc-(rare earth element)-Si ternary systems and should take into account the specific interaction of scandium and samarium with REE

Iatrogenic Lower Extremity Subcutaneous Emphysema after Prolonged Robotic-Assisted Hysterectomy

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