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Sample records for subcutaneous sc insulin

  1. Continuous intraperitoneal insulin infusion versus subcutaneous insulin therapy in the treatment of type 1 diabetes: effects on glycemic variability

    NARCIS (Netherlands)

    van Dijk, Peter R.; Groenier, Klaas H.; DeVries, J. Hans; Gans, Reinold O. B.; Kleefstra, Nanno; Bilo, Henk J. G.; Logtenberg, Susan J. J.

    2015-01-01

    As continuous intraperitoneal insulin infusion (CIPII) results in a more physiologic action of insulin than subcutaneous (SC) insulin administration, we hypothesized that CIPII would result in less glycemic variability (GV) than SC insulin therapy among type 1 diabetes mellitus (T1DM) patients. Data

  2. Continue subcutane insuline-infusie

    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

  3. Continuous subcutaneous insulin infusion: practical issues

    Directory of Open Access Journals (Sweden)

    Banshi D Saboo

    2012-01-01

    Full Text Available The growing number of individuals with diabetes mellitus has prompted new way of treating these patients, continuous subcutaneous insulin infusion (CSII or insulin pump therapy is an increasingly form of intensive insulin therapy. An increasing number of individuals with diabetes mellitus individuals of all ages have started using insulin pump therapy. Not everyone is a good candidate for insulin pump therapy, and the clinician needs to be able to determine which patients are able to master the techniques required and to watch for the adverse reactions that may develop. Insulin pump increases quality of life of patient with diabetes mellitus with increasing satisfaction with treatment and decrease impact of diabetes mellitus. Manual errors by insulin pump users may lead to hypo or hyperglycemia, resulting into diabetic ketoacidosis (DKA sometimes. Some of practical aspect is associated with insulin pump therapy such as selection of candidates, handling of pump and selection of site, and pump setting, henceforth this review is prepared to explore and solve the practical problems or issues associated with pump therapy.

  4. Continuous subcutaneous insulin infusion therapy in type 1 diabetes ...

    African Journals Online (AJOL)

    2013-01-14

    Jan 14, 2013 ... Guidelines: Continuous subcutaneous insulin infusion pump therapy in type 1 diabetes. 15. 2013 Volume 18 No 1. JEMDSA. Introduction. The first external insulin pump device to deliver continuous subcutaneous insulin infusion (CSII or “insulin pump”) therapy was used more than 30 years ago.

  5. Transition from intravenous insulin to subcutaneous long-acting insulin in critical care patients on enteral or parenteral nutrition.

    Science.gov (United States)

    Ramos, Analía; Zapata, Lluis; Vera, Paula; Betbese, Antoni J; Pérez, Antonio

    2017-12-01

    The optimal initial dose of subcutaneous (SC) insulin after intravenous (IV) infusion is controversial, especially in patients receiving continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of this study was to evaluate the strategy used at our hospital intensive care unit (ICU) in patients switched from IV insulin to SC insulin glargine while receiving EN or TPN. A retrospective analysis was made of 27 patients on EN and 14 on TPN switched from IV infusion insulin to SC insulin. The initial dose of SC insulin was estimated as 50% of the daily IV insulin requirements, extrapolated from the previous 12h. A corrective dose of short-acting insulin (lispro) was used when necessary. Mean blood glucose (BG) level during SC insulin treatment was 136±35mg/dL in the EN group and 157±37mg/dL in the TPN group (p=0.01). In the TPN group, mean BG was >180mg/dL during the first three days after switching, and a 41% increase in the glargine dose was required to achieve the target BG. In the EN group, mean BG remained <180mg/dL throughout the days of transition and the dose of glargine remained unchanged. In the transition from IV to SC insulin therapy, initial insulin glargine dose estimated as 50% of daily IV insulin requirements is adequate for patients on EN, but inadequate in those given TPN. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration

    OpenAIRE

    D’Souza, Anita; Theis, Jason D.; Vrana, Julie A; Dogan, Ahmet

    2014-01-01

    Protein and peptide drugs administered subcutaneously, such as insulin can be amyloidogenic and result in localized amyloid deposits at the sites of medication injections. These iatrogenic amyloidoses typically present as a localized subcutaneous nodule or skin reaction at the site of administration, and often pose diagnostic challenges. We have analyzed the amyloid proteome in 52 cases of insulin and enfuvirtide associated amyloidosis using laser microdissection/tandem mass spectrometry. We ...

  7. Transitioning from intravenous to subcutaneous insulin in the medical intensive care unit.

    Science.gov (United States)

    Zhou, Keren; Williams, Mia F; Esquivel, Mary Angelynne; Song, Anne; Rahman, Farah; Bena, James; Lam, Simon W; Rathz, Deborah A; Lansang, M Cecilia

    2017-12-01

    There is a paucity of studies on transitions from IV insulin infusion (IVII) to subcutaneous (SC) insulin in the medical ICU (MICU). We conducted a retrospective study of patients admitted to the Cleveland Clinic MICU from June 2013 to January 2014 who received IVII. We compared blood glucose (BG) control between 3 cohorts based on timing of basal insulin dose: (1) NB (no basal), (2) IB (incorrect basal), (3) CB (correct basal) at 5 time points post-IVII discontinuation (1, 4, 8, 12, and 24h). Insulin doses used for transitioning were compared with 80% of estimated 24h IVII total. Analysis was done using chi-square, ANOVA and t-tests. There were 269 patients (NB 166, IB 45, CB 58), 55% male with a mean age 58±16years. 103 patients (38%) had a transition attempted (IB 21%, CB 17%). The NB cohort had better BG than the IB cohort at all time points (p180mg/dL at 4/5 time intervals. However, the dose of basal insulin used was less than 80% of estimated 24h IVII total (IB 21.4 vs 49.6U, CB 25vs 57.1U). Despite this, 15% of patients in the IB cohort and 24% of patients in the CB had hypoglycemic events. The low rates of IV to SC insulin transitions raises the question of challenges to transitions. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Subcutaneous blood flow during insulin-induced hypoglycaemia

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Sestoft, L

    1982-01-01

    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....

  9. Insulin Analogs Applied with Continuous Subcutaneous Insulin Infusion (Pump in the Treatment of Diabetes

    Directory of Open Access Journals (Sweden)

    Ercan Tuncel

    2015-03-01

    Full Text Available Diabetes mellitus (DM is an important health problem that should be treated efficiently because of its high prevalence and high morbidity and mortality due to its complications. In patients with DM, the application of a treatment which provides physiologic insulin secretion as such in healthy individuals is directly related with the prevention of diabetes complications. Insulin analogs, which were developed in recent years and shown to have pharmacokinetic and pharmacodynamic superiority to human insulin, have made it possible to obtain natural insulin pattern in the body. In addition to development of insulin analogs, introduction of insulin application method of “continuous subcutaneous insulin infusion” (insulin pump has led a new era in the treatment of DM. In this review, treatment of type 1 and 2 DM patients with insulin analogs, particularly insulin aspart, applied with insulin pump was discussed in the light of the current literature.

  10. Twenty-four-hour simultaneous subcutaneous basal-bolus administration of insulin and amylin in adolescents with type 1 diabetes decreases postprandial hyperglycemia

    Science.gov (United States)

    The purpose of this study was to examine the effect of continuous subcutaneous (sc) replacement of amylin and insulin for a 24-h period on glucose homeostasis in adolescents with type 1 diabetes. Thirteen adolescents with type 1 diabetes on insulin pump therapy participated in a randomized, controll...

  11. Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.

    Science.gov (United States)

    Almuraikhy, Shamma; Kafienah, Wael; Bashah, Moataz; Diboun, Ilhame; Jaganjac, Morana; Al-Khelaifi, Fatima; Abdesselem, Houari; Mazloum, Nayef A; Alsayrafi, Mohammed; Mohamed-Ali, Vidya; Elrayess, Mohamed A

    2016-11-01

    A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated. Adipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application. Despite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of adipose tissue-derived SVF cells, despite higher frequency of hypertrophied adipocytes. SC pre-adipocytes from these tissues exhibited lower adipogenic capacity accompanied by downregulation of PPARγ (also known as PPARG) and CEBPα (also known as CEBPA) and upregulation of GATA3 expression. Impaired adipogenesis in IR individuals was further associated with increased adipose secretion of IL-6. Treatment of IS-derived SC pre-adipocytes with IL-6 reduced their adipogenic capacity to levels of the IR group. Obesity-associated insulin resistance is marked by impaired SC adipogenesis, mediated, at least in a subset of individuals, by elevated local levels of IL-6. Understanding the molecular mechanisms underlying reduced adipogenic capacity in IR individuals could help target appropriate therapeutic strategies aimed at those at greatest risk of insulin resistance and type 2 diabetes mellitus.

  12. 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

    BACKGROUND: Insertion of an insulin catheter for continuous subcutaneous insulin infusion into the subcutaneous adipose tissue (SAT) causes a tissue trauma that may have consequences for insulin absorption. We evaluated the importance of insulin catheter wear-time on subcutaneous adipose tissue...... 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...

  13. Challenges and recent advances in the subcutaneous delivery of insulin.

    Science.gov (United States)

    Guo, Xiaohui; Wang, Wei

    2017-06-01

    The morbidity of diabetes mellitus is increasing, and subcutaneous injection of exogenous insulin is well established as an effective therapeutic strategy for reducing complications associated with the disease. However, the pain that accompanies repeated injections is an important drawback, and can detrimentally affect the adherence to therapy. Recently, there have been great improvements in injection devices and techniques, including the development of microneedle systems and quantitative injection technologies, which have increased the accuracy of injection, decreased leakage of insulin to the skin surface, and reduced pain. Areas covered: This review highlights some limitations of current techniques for the injection of insulin and its analogs, and describes new methodologies and strategies that have been developed in an attempt to overcome these limitations. Furthermore, novel technologies currently under development that are potential future prospects for insulin delivery are discussed. Expert opinion: New technologies have provided easier and well-tolerated treatment regimens for diabetes patients. However, to further improve patients' satisfaction, self-regulated insulin delivery, automatic adjustment of needle length, memory function to the injection device, use of novel materials could be introduced into insulin injection. Intelligent control of insulin delivery and soluble microneedle arrays may be important areas of future research.

  14. Dose comparison of ultrasonic transdermal insulin delivery to subcutaneous insulin injection

    Science.gov (United States)

    Park, Eun-Joo; Dodds, Jeff; Barrie Smith, Nadine

    2010-03-01

    Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array. In this study the physiologic response to ultrasound mediated transdermal insulin delivery is compared to that of subcutaneously administered insulin. Anesthetized rats (350-550 g) were divided into four groups of four animals; one group representing ultrasound mediated insulin delivery and three representing subcutaneously administered insulin (0.15, 0.20, and 0.25 U/kg). The cymbal array was operated for 60 minutes at 20 kHz with 100 mW/cm2 spatial-peak temporal-peak intensity and a 20% duty cycle. The blood glucose level was determined at the beginning of the experiment and, following insulin administration, every 15 minutes for 90 minutes for both the ultrasound and injection groups. The change in blood glucose from baseline was compared between groups. When administered by subcutaneous injection at insulin doses of 0.15 and 0.20 U/kg, there was little change in the blood glucose levels over the 90 minute experiment. Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190±96 mg/dl (mean±SD) at 90 minutes. The change in blood glucose following ultrasound mediated insulin delivery was -262±40 mg/dl at 90 minutes. As expected, the magnitude of change in blood glucose between the three injection groups was dependant on the dose of insulin administered. The change in blood glucose in the ultrasound group was greater than that observed in the injection groups suggesting that a higher effective dose of insulin was delivered.

  15. Clinical Experience with U-500 Regular Insulin by Multiple Daily Injections and Continuous Subcutaneous Insulin Infusion.

    Science.gov (United States)

    Meade, Lisa T; Tart, Rebecca C; Nuzum, Donnie

    2017-04-01

    The effectiveness of U-500 regular insulin was assessed in patients with type 2 diabetes who were previously treated with U-100 insulin. A retrospective chart review was conducted on all patients who were prescribed U-500 insulin between January 2012 and December 2013. The primary outcome measure was change in glycosylated hemoglobin (A1C) 1 year after switching from U-100 insulin to U-500 regular insulin. Secondary outcomes included change in body weight, total daily insulin dose, number of daily injections, and episodes of hypoglycemia. Sixty-six patients met inclusion criteria: U-500 regular insulin via multiple daily injections (MDI; n = 36) or continuous subcutaneous insulin infusion (CSII; n = 30). The A1C in patients using MDI decreased by 1.8%, whereas patients using CSII experienced an A1C decrease of 0.63% after 1 year of U-500 regular insulin use. There was an increase of 3.1 + 0.73 kg in body weight in both the MDI and CSII groups, which was significant (P insulin in MDI and CSII patients can improve glycemic control, and it does not increase the frequency of hypoglycemia when compared with U-100 insulin hypoglycemic incidence reported in the literature.

  16. Relationship between subcutaneous blood flow and absorption of lente type insulin

    DEFF Research Database (Denmark)

    Hildebrant, P; Mehlsen, J; Birch, K

    1987-01-01

    To study the relationship between the absorption of intermediate acting insulin and the local subcutaneous blood flow (SBF) 8 diabetic patients were given subcutaneous injections of 125I labeled human lente type insulin and 133Xenon in the abdominal wall. External measurements of the tracer...

  17. [Value of combined subcutaneous infusion of insulin and metformin in 10 insulin-dependent obese diabetics].

    Science.gov (United States)

    Leblanc, H; Marre, M; Billault, B; Passa, P

    1987-01-01

    Combined continuous subcutaneous insulin infusion (CSII) and metformin (M) was tested in 10 overweighted insulin requiring diabetic patients (body mass index 27.9 +/- 4.9 kg/m2). They were still poorly controlled (HbA1 9.6 +/- 0.8%) despite large doses of lente insulin (Novo) (51.7 +/- 19.6 IU/24 h) injected once daily. With CSII after two weeks on placebo (P) they were enrolled in a randomized double blind cross-over trial with two successive one month periods of M (2550 mg/day) or P. At the end of the two-weeks period CSII--initial P, the daily regular insulin requirement decreased significantly (40.1 +/- 18.1). During M and P body weight and HbA1 were unchanged (respectively 28.6 +/- 6.0 vs 29.0 +/- 59 kg/m2 and 7.7 +/- 1.1 vs 7.7 +/- 0.8%). With M daily insulin requirements decreased significantly (32.0 +/- 16.8 vs 38.4 +/- 18.2 IU, p less than 0.05). During test-meals, M compared to placebo also reduced peripheral free insulin concentrations (-24.9 +/- 26.0%) while plasma glucose and C peptide remained comparable. In the conditions of this study, combined CSII and M reduced the insulin resistance observed in overweighted insulin requiring diabetic patients.

  18. Evaluation of pharmacokinetic model designs for subcutaneous infusion of insulin aspart

    DEFF Research Database (Denmark)

    Mansell, Erin J.; Schmidt, Signe; Docherty, Paul D.

    2017-01-01

    Effective mathematical modelling of continuous subcutaneous infusion pharmacokinetics should aid understanding and control in insulin therapy. Thorough analysis of candidate model performance is important for selecting the appropriate models. Eight candidate models for insulin pharmacokinetics...... included a range of modelled behaviours, parameters and complexity. The models were compared using clinical data from subjects with type 1 diabetes with continuous subcutaneous insulin infusion. Performance of the models was compared through several analyses: R2 for goodness of fit; the Akaike Information...

  19. 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.

  20. 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.

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

    DEFF Research Database (Denmark)

    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...

  2. Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    M Boering

    2016-06-01

    Full Text Available Aims Elevated sex hormone-binding globulin (SHBG concentrations have been described in patients with type 1 diabetes mellitus (T1DM, probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII, or subcutaneous (SC, influences SHBG concentrations among T1DM patients. Methods Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13 years, diabetes duration 23 (±11 years, and hemoglobin A1c (HbA1c 8.7 (±1.1 (72 (±12 mmol/mol. As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH, and follicle-stimulating hormone (FSH were analyzed. Results Estimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2 during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6 during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3; −12.7nmol/L (95% CI: −25.1, −0.4 for males and −1.7nmol/L (95% CI: −24.6, 21.1 for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5 and −8.3nmol/L (95% CI: −14.4, −2.2, respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2 among males. Conclusions SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

  3. Role of Subcutaneous Adipose Tissue in the Pathogenesis of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Pavankumar Patel

    2013-01-01

    Full Text Available Burden of obesity has increased significantly in the United States over last few decades. Association of obesity with insulin resistance and related cardiometabolic problems is well established. Traditionally, adipose tissue in visceral fat depot has been considered a major culprit in development of insulin resistance. However, growing body of the literature has suggested that adipose tissue in subcutaneous fat depot, not only due to larger volume but also due to inherent functional characteristics, can have significant impact on development of insulin resistance. There are significant differences in functional characteristics of subcutaneous abdominal/truncal versus gluteofemoral depots. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger vicious cycle of inflammation in subcutaneous adipose tissue and subsequent ectopic fat deposition. It is important to shift focus from fat content to functional heterogeneity in adipose tissue depots to better understand the relative role of subcutaneous adipose tissue in metabolic complications of obesity. Therapeutic lifestyle change continues to be the most important intervention in clinical practice at any level of increased adiposity. Future pharmaceutical interventions aimed at improving adipose tissue function in various subcutaneous depots have potential to help maintain adequate insulin sensitivity and reduce risk for development of insulin resistance complications.

  4. Changes in subcutaneous fat cell volume and insulin sensitivity after weight loss.

    Science.gov (United States)

    Andersson, Daniel P; Eriksson Hogling, Daniel; Thorell, Anders; Toft, Eva; Qvisth, Veronica; Näslund, Erik; Thörne, Anders; Wirén, Mikael; Löfgren, Patrik; Hoffstedt, Johan; Dahlman, Ingrid; Mejhert, Niklas; Rydén, Mikael; Arner, Erik; Arner, Peter

    2014-07-01

    Large subcutaneous fat cells associate with insulin resistance and high risk of developing type 2 diabetes. We investigated if changes in fat cell volume and fat mass correlate with improvements in the metabolic risk profile after bariatric surgery in obese patients. Fat cell volume and number were measured in abdominal subcutaneous adipose tissue in 62 obese women before and 2 years after Roux-en-Y gastric bypass (RYGB). Regional body fat mass by dual-energy X-ray absorptiometry; insulin sensitivity by hyperinsulinemic-euglycemic clamp; and plasma glucose, insulin, and lipid profile were assessed. RYGB decreased body weight by 33%, which was accompanied by decreased adipocyte volume but not number. Fat mass in the measured regions decreased and all metabolic parameters were improved after RYGB (P fat cell size correlated strongly with improved insulin sensitivity (P = 0.0057), regional changes in fat mass did not, except for a weak correlation between changes in visceral fat mass and insulin sensitivity and triglycerides. The curve-linear relationship between fat cell size and fat mass was altered after weight loss (P = 0.03). After bariatric surgery in obese women, a reduction in subcutaneous fat cell volume associates more strongly with improvement of insulin sensitivity than fat mass reduction per se. An altered relationship between adipocyte size and fat mass may be important for improving insulin sensitivity after weight loss. Fat cell size reduction could constitute a target to improve insulin sensitivity. © 2014 by the American Diabetes Association.

  5. 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

  6. Safety and efficacy of inhaled insulin (AERx iDMS) compared with subcutaneous insulin therapy in patients with Type 1 diabetes: 1-year data from a randomized, parallel group trial.

    Science.gov (United States)

    Moses, R G; Bartley, P; Lunt, H; O'Brien, R C; Donnelly, T; Gall, M-A; Vesterager, A; Wollmer, P; Roberts, A

    2009-03-01

    Assessment of the long-term safety and efficacy of liquid inhaled insulin via AERx insulin Diabetes Management System (iDMS) in a basal/bolus treatment regimen of adults with Type 1 diabetes. Patients were randomized 2 : 1 to prandial inhaled (n = 205) or subcutaneous (s.c.) (n = 99) insulin, plus one/two daily injections of neutral protamine Hagedorn (NPH) insulin for 12 months. The primary endpoints were pulmonary function tests (PFT) and baseline changes in chest X-rays at 12 months. Safety and efficacy assessments were measured at regular intervals. PFTs after 12 months were comparable between the groups, except for reduced per cent of predicted carbon monoxide lung diffusing capacity with inhaled insulin (difference: -2.03%, P = 0.04) occurring after the first 3 months and then stabilizing. There were no apparent treatment differences in chest X-rays. Overall risk of hypoglycaemia [risk ratio (RR) 1.02, P = 0.83] and adverse events were comparable between groups. Risk of nocturnal hypoglycaemia was higher in the inhaled group (RR 1.58, P = 0.001). Cough [10% (inhaled); 3% (s.c.)] tended to be mild in nature. Inhaled insulin was non-inferior to s.c. insulin for change in glycated haemoglobin (HbA(1c)) after 12 months [difference 0.18% (CI 95%-0.04; 0.39)]. At trial end, mean laboratory measured fasting plasma glucose was lower in the inhaled group (inhaled 9.2 mmol/l; s.c. 11.7 mmol/l; difference: -2.53 mmol/l, P iDMS requires further optimization to reduce nocturnal hypoglycaemia before it has comparable safety and efficacy to s.c. insulin aspart.

  7. Spatial distribution of soluble insulin in pig subcutaneous tissue

    DEFF Research Database (Denmark)

    Thomsen, Maria; Rasmussen, Christian Hove; Refsgaard, Hanne H F

    2015-01-01

    injections. Increasing the injected volume from 0.1ml to 1ml did not increase the intramuscular volume fraction, but gave a significantly higher volume fraction placed in the fascia separating the deep and superficial subcutaneous fat layers. Varying the injection speed from 25l/s up to 300l/s gave...

  8. Portable detectors for 125I-insulin absorption measurement during subcutaneous infusion with portable pumps.

    Science.gov (United States)

    Bojsen, J; Kølendorf, K; Deckert, T

    1984-04-01

    Programmed subcutaneous insulin infusion is a promising method for normalisation of the blood glucose concentration in insulin-dependent diabetics. To evaluate insulin availability the absorption rate from the depot is usually measured intermittently by radioactively-labelled insulin and stationary scintillation detectors. Small portable detectors are an alternative, however, and continuous absorption measurements could be made during normal life conditions. Contrary to conventional single injection therapy, the insulin depot initially expands during infusion treatment, changing the geometry during measurements. In the present study the methodological aspects and geometrical dependences were investigated. Simulated studies were made with various plane disc 125I sources in Perspex phantoms as well as 125I-insulin absorption studies in short-term subcutaneous infusion experiments with anaesthetised rabbits. Results from portable, end-window Geiger-Müller (GM) detectors fixed above the depots and close to the surfaces of phantom or skin were compared with results obtained by a conventional stationary NaI(Tl) detector 15 cm from the phantom or skin surface. With a 125I-insulin infusion site at 5 mm depth in the subcutaneous tissue of rabbits, an overall linear proportionality was found between the results obtained with a NaI(Tl) detector and a GM detector raised 15 mm above the skin surface inside the detector housing.

  9. Comparison between multiple daily insulin injection therapy (MDI) and continuous subcutaneous insulin infusion therapy (CSII), results of the five nations study

    NARCIS (Netherlands)

    Hoogma, Roel P. L. M.; Hoekstra, Joost B.; Michels, Bob P.; Levi, Marcel

    2006-01-01

    Continuous subcutaneous insulin infusion (CSII) is an alternative to multiple daily insulin injections (MDII) as intensive insulin therapy for optimising glycaemic control in type 1 diabetes. The Diabetes Control and Complications Trial (DCCT) showed the benefits of intensive insulin therapy in

  10. Polymorphic Basal Rates of Continuous Subcutaneous Insulin Infusion among Taiwanese Children with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Chia-Hung Lin

    2015-01-01

    Full Text Available Introduction. The basal dose of insulin, proportion of total daily insulin, and circadian variation during continuous subcutaneous insulin infusion (CSII therapy among children with type 1 diabetes mellitus (T1D have not been fully elucidated. Materials and Methods. A total of 45 childhood patients with T1D receiving CSII therapy at Pediatrics Department of Chang Gung Memorial Hospital between 2004 and 2012 were analyzed. Patients were classified according to Tanner stage. Results. HbA1c was significantly reduced in all Tanner groups within three months of CSII therapy (from 67 mmol/mol (8.3% to 54 mmol/mol (7.1%, P<0.05. The actual basal proportion of total daily insulin use was 34–40%. The circadian distribution of basal insulin differed markedly between the five Tanner groups. Basal insulin requirement was highest between 3:00 and 7:00 h in Tanner stages 1-2. In stages 3-4, a lower nocturnal basal insulin that increased gradually until daytime was noted. Adolescents (stage 5 displayed a high insulin peak between 6:00 and 11:00 h, and a smaller peak between 19:00 and 23:00 h. Conclusions. A smaller proportion of basal insulin to total daily insulin use, as well as varied circadian patterns of insulin use, characterized these children with T1D.

  11. Type III Hypersensitivity Reaction to Subcutaneous Insulin Preparations in a Type 1 Diabetic.

    Science.gov (United States)

    Murray, Benjamin R; Jewell, Jolene R; Jackson, Kyle J; Agboola, Olabunmi; Alexander, Brianna R; Sharma, Poonam

    2017-07-01

    Management of type 1 diabetes in patients who have insulin hypersensitivity is a clinical challenge and places patients at risk for recurrent diabetic ketoacidosis (DKA). Hypersensitivity reactions can be due to the patient's response to the insulin molecule itself or one of the injection's non-insulin components. It is therefore crucial for clinicians to quickly recognize the type of hypersensitivity reaction that is occurring and identify potentially immunogenic additives for the purpose of directing therapy as various insulin preparations have differing ingredients. We present the case of a 23-year-old diabetic female with common variable immunodeficiency (CVID) and autoimmune enteropathy who developed a type III hypersensitivity reaction to multiple formulations of subcutaneous insulin after years of use and the challenges of devising a long-term management strategy.

  12. Current trend in drug delivery considerations for subcutaneous insulin depots to treat diabetes.

    Science.gov (United States)

    P V, Jayakrishnapillai; Nair, Shantikumar V; Kamalasanan, Kaladhar

    2017-05-01

    Diabetes mellitus (DM) is a metabolic disorder due to irregularities in glucose metabolism, as a result of insulin disregulation. Chronic DM (Type 1) is treated by daily insulin injections by subcutaneous route. Daily injections cause serious patient non-compliance and medication non-adherence. Insulin Depots (ID) are parenteral formulations designed to release the insulin over a specified period of time, to control the plasma blood glucose level for intended duration. Physiologically, pancreas produces and secretes insulin in basal and pulsatile mode into the blood. Delivery systems mimicking basal release profiles are known as open-loop systems and current marketed products are open-loop systems. Future trend in open-loop systems is to reduce the number of injections per week by enhancing duration of action, by modifying the depot properties. The next generation technologies are closed-loop systems that mimic the pulsatile mode of delivery by pancreas. In closed-loop systems insulin will be released in response to plasma glucose. This review focuses on future trend in open-loop systems; by understanding (a) the secretion of insulin from pancreas, (b) the insulin regulation normal and in DM, (c) insulin depots and (d) the recent progress in open-loop depot technology particularly with respect to nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The smooth and bumpy road of trastuzumab administration: from intravenous (IV) in a hospital to subcutaneous (SC) at home.

    Science.gov (United States)

    Tjalma, Waa; Huizing, M T; Papadimitriou, K

    2017-03-01

    Trastuzumab has become standard of care in the treatment of early and metastatic HER2-positive breast cancer. Initially trastuzumab could only be administered intravenously (IV), however since a few years there is also a subcutaneous (SC) formulation. The efficacy and the safety profile of both formulations is the comparable. The administration logistics however have an impact on the patients, the health care professionals (HCPs), the hospital and the government. The preference for the patients (89%) and the HCPs (77%) is in favour of the SC formulation. The patient chair time per cycle, as defined by the time between entry and exit of infusion chair, is between 53 and 122 minutes shorter for SC administration. Also, the time actively dedicated by the HCP on preparation and administration SC, is between 17 and 50 minutes shorter per cycle. These time savings may increase the capacity of an oncological day clinic and reduce waiting lists. An additional benefit is that the use of SC formulation reduces the consumables and the waste. When the SC form was given at home instead of in the hospital the safety profile remained the same, but the satisfaction rate improved further for both the patients and the HCPs. The next and final step will be potentially to invest in teaching the patients to self-administer the medication. The home administration and the education of the patients and the HCPs will have a cost price and it will be interesting to see how the hospital financial authorities and the government will deal with this situation in the time of budgetary restrictions.

  14. Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes

    DEFF Research Database (Denmark)

    Ranjan, Ajenthen; Schmidt, S; Madsbad, Sten

    2016-01-01

    AIM: To investigate the dose-response relationship of subcutaneous glucagon administration on plasma glucose and on counterregulatory hormone responses during subcutaneous insulin induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. MATERIALS AND METHODS: Eight...... insulin pump treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by a subcutaneous insulin bolus and when plasma glucose reached 3.4 mmol/l (95%CI 3.2-3.5), a subcutaneous bolus of either 100, 200, 300 µg glucagon or saline.......9(6.4-9.3) and 8.7(7.8-9.5) vs 3.6(3.4-3.9) mmol/l, p insulin levels. Area under plasma glucose curve, peak plasma glucose, time to peak and duration of plasma glucose above baseline...

  15. Influence of glutathione on the bioactivity of subcutaneously or orally administered insulin to rats.

    Science.gov (United States)

    Al-Kurdi, Zakieh I; Chowdhry, Babur Z; Leharne, Stephen A; Qinna, Nidal A; Al-Omari, Mahmoud M H; Badwan, Adnan A

    2015-01-01

    The effect of reduced (GSH) and oxidized (GSSG) glutathione on the bioactivity of insulin was studied. A polyelectrolyte complex (PEC) of insulin with low molecular weight chitosan (13 kDa) was prepared and characterized. The PEC was then solubilized, in the presence and absence of GSH and GSSG, in a reverse micelle consisting of oleic acid and two surfactants (PEG-8 caprylic/capric glycerides and polyglycerol-6-dioleate). The in vitro and in vivo performances of the reverse micelle formulations (RMFs) were evaluated in rats. At pH 6.5 the association efficiency of the PEC was 76.2%. In vitro insulin release from the RMs was negligible at pH 1.2 and was markedly increased at pH 6.8. The hypoglycemic activity of insulin in the PEC was reduced when administered via the subcutaneous route, regardless of the GSH content. On the other hand, the presence of GSSG significantly enhanced hypoglycemia. When the RMF was administered via the oral route, the presence of GSH had no effect on the hypoglycemic activity of insulin compared with the GSH free system. However, the presence of GSSG in the oral preparation increased the hypoglycemic activity of insulin; probably by inhibiting insulin degradation, thereby prolonging its effect. Thus, incorporation of GSSG in the RMF reduces blood glucose levels in rats and protects insulin from degradation.

  16. Subcutaneous adipose tissue zinc-α2-glycoprotein is associated with adipose tissue and whole-body insulin sensitivity.

    Science.gov (United States)

    Balaz, Miroslav; Vician, Marek; Janakova, Zuzana; Kurdiova, Timea; Surova, Martina; Imrich, Richard; Majercikova, Zuzana; Penesova, Adela; Vlcek, Miroslav; Kiss, Alexander; Belan, Vitazoslav; Klimes, Iwar; Olejnik, Juraj; Gasperikova, Daniela; Wolfrum, Christian; Ukropcova, Barbara; Ukropec, Jozef

    2014-08-01

    To examine the regulatory aspects of zinc-α2-glycoprotein (ZAG) association with obesity-related insulin resistance. ZAG mRNA and protein were analyzed in subcutaneous adipose tissue (AT) and circulation of lean, obese, prediabetic, and type 2 diabetic men; both subcutaneous and visceral AT were explored in lean and extremely obese. Clinical and ex vivo findings were corroborated by results of in vitro ZAG silencing experiment. Subcutaneous AT ZAG was reduced in obesity, with a trend to further decrease with prediabetes and type 2 diabetes. ZAG was 3.3-fold higher in subcutaneous than in visceral AT of lean individuals. All differences were lost in extreme obesity. Obesity-associated changes in AT were not paralleled by alterations of circulating ZAG. Subcutaneous AT ZAG correlated with adiposity, adipocyte hypertrophy, whole-body and AT insulin sensitivity, mitochondrial content, expression of GLUT4, PGC1α, and adiponectin. Subcutaneous AT ZAG and adipocyte size were the only predictors of insulin sensitivity, independent on age and BMI. Silencing ZAG resulted in reduced adiponectin, IRS1, GLUT4, and PGC1α gene expression in primary human adipocytes. ZAG in subcutaneous, but not in visceral AT, was markedly reduced in obesity. Clinical, cellular, and molecular evidence indicate that ZAG plays an important role in modulating whole-body and AT insulin sensitivity. Copyright © 2014 The Obesity Society.

  17. 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

  18. Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy

    NARCIS (Netherlands)

    Schulten, Ron J; Piet, Jessica; Bruijning-Verhagen, Patricia; de Waal, Wouter J

    2017-01-01

    Objective: The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. Methods: All patients under the age of 18 with type I diabetes

  19. 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

  20. Carbohydrate-to-Insulin Ratio in a Mediterranean Population of Type 1 Diabetic Patients on Continuous Subcutaneous Insulin Infusion Therapy.

    Science.gov (United States)

    Alcántara-Aragón, Valeria; Gonzalez, Cintia; Corcoy, Rosa; Ubeda, Justa; Chico, Ana

    2015-05-01

    The carbohydrate-to-insulin ratio (CIR) is initially calculated from the total daily insulin dose (TDID). However, CIR likely presents variations owing to different population characteristics and intraday variations not being taken into account by most formulas. No information is available concerning the Mediterranean population. We investigated the CIR used by patients with type 1 diabetes (T1DM) using continuous subcutaneous insulin infusion (CSII) therapy in a Mediterranean area, to identify possible intraday variations and establish an adequate formula to calculate CIR. Data from 170 T1DM patients from Barcelona were obtained retrospectively from the Spanish National Registry of CSII Therapy (SNR-CSII). Theoretical CIR was calculated using the formula: 500 divided by TDID. This theoretical CIR was compared to the real CIR. The real CIR was also compared between main meals. Patients with HbA1c insulin requirements. A calculation of 350/TDID for breakfast and 400/TDID for lunch and dinner would be more appropriate for this population. © 2014 Diabetes Technology Society.

  1. Effect of melatonin on expression of leptin in subcutaneous fat tissue in insulin-resistant rats

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2014-03-01

    Full Text Available Objective To investigate the effect of melatonin (MLT on protein and mRNA expression of leptin (Lep in subcutaneous fat tissue in insulin resistance (IR rats. Methods Thirty seven Sprague-Dawley (SD rats were randomly divided into model group (n=27 and control group (CN group, n=10. Rats in model group were fed with high glucose diet for 6 weeks. Twenty rats having developed IR in the model group were further randomly divided into two groups: IR group (n=10 and melatonin group (MLT group, n=10. Rats in CN group and MLT group were fed with 10mg/(kg.d of standard chow or MLT, respectively, for 6 weeks from the beginning of the 7th week. At the end of the 12th week, the subcutaneous fat tissue was harvested from bilateral inguinal areas of the rats for the evaluation of the protein and mRNA expression of Lep by immunohistochemistry and RTPCR. Results Systolic blood pressure (SBP, fasting serum leptin (Lep, triglycerides (TG, low density lipoprotein cholesterol (LDL-C, malondialdehyde (MDA and homeostasis model assessment insulin resistance (HOMA-IR were significantly lower (P0.05. The protein and mRNA expressions of Lep in subcutaneous adipose tissue were significantly higher in IR group than in CN group (P<0.01, while they were significantly lower in MLT group than in IR group (P<0.01. Conclusion MLT may improve IR and the status of oxidation stress, and inhibit the over expression of Lep protein and mRNA in subcutaneous fat tissue in the high-glucose diet-induced IR rats. DOI: 10.11855/j.issn.0577-7402.2014.01.04

  2. Treatment of diabetic ketoacidosis with subcutaneous insulin lispro: a review of the current evidence from clinical studies.

    Science.gov (United States)

    Vincent, M; Nobécourt, E

    2013-09-01

    Low-dose intravenous infusions of regular insulin, usually initiated in the emergency department and continued in the intensive care unit (ICU), are the standard care for patients with diabetic ketoacidosis (DKA) to ensure rapid resolution of hyperglycaemia and ketoacidosis. Several studies have evaluated whether subcutaneous injections of the rapid-acting analogue insulin lispro may be an alternative to intravenous insulin infusion for avoiding ICU admissions of uncomplicated DKA cases. This review summarizes the current clinical evidence for the effectiveness and safety of subcutaneous insulin lispro injections in non-severe DKA patients. Relevant studies were identified by a systematic literature search through the PubMed database. To date, four small randomized studies (156 patients overall; three studies in adults and one in paediatric patients with diabetes) have directly compared subcutaneous insulin lispro injections every 1-2h vs continuous intravenous infusions of regular insulin. Patients with severe complications were excluded. In all studies, the mean time to resolution of DKA was similar in both treatment groups [range (three studies): lispro 10-14.8h; regular insulin 11-13.2h]. The mean time to resolution of hyperglycaemia, total insulin doses required, number of hospitalization days and number of hypoglycaemic episodes were similar in both treatment groups; no severe complications or DKA recurrences were reported, and one study showed a 39% cost reduction for the insulin lispro group. In patients with mild-to-moderate DKA, subcutaneous injections of insulin lispro every 1-2h offer a feasible alternative to continuous intravenous infusions of regular insulin, and should now be evaluated in larger, more appropriately powered studies. Copyright © 2013. Published by Elsevier Masson SAS.

  3. 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.

  4. 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

    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.......01, respectively). The slope of the subcutaneous blood flow autoregulation curves during poor metabolic control (median: 11.6% per 10 mmHg, range: 8.0-30.5% per 10 mmHg) was not significantly different from the slope values during improved metabolic control (13.4% per mmHg, 10.1-24.4% per mmHG). No association...... was demonstrated between the impaired autoregulation of subcutaneous blood flow and the metabolic parameters. Our results indicate that improved metabolic control for 10 weeks has no effect on the impaired autoregulation of subcutaneous blood flow in long-term insulin-dependent diabetic patients with clinical...

  5. [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.

  6. Novel microneedle patches for active insulin delivery are efficient in maintaining glycaemic control: an initial comparison with subcutaneous administration.

    Science.gov (United States)

    Nordquist, Lina; Roxhed, Niclas; Griss, Patrick; Stemme, Göran

    2007-07-01

    Good glycaemic control is essential to minimize the risk for diabetes-induced complications. Also, compliance is likely to be higher if the procedure is simple and painless. This study was designed to validate painless intradermal delivery via a patch-like microneedle array. Diabetes was induced by an intravenous injection of streptozotocin (50 mg/kg bw) in adult male Sprague Dawley rats. Plasma insulin and blood glucose were measured before, during and after subcutaneous or intradermal (microneedles) infusion of insulin (0.2 IU/h) under Inactin-anaesthesia. Before insulin administration, all animals displayed a pronounced hyperglycaemia (19 +/- 1 mM; 359 mg/dl). Administration of insulin resulted in a reduced plasma glucose independently of administration route (subcutaneous 7.5 +/- 4.2, n = 9, and intradermal 11 +/- 1.8, n = 9 after 240 min), but with less errors of the mean in the intradermal group. In the intradermal group, plasma insulin was increased in all latter measurements (72 +/- 22, 81 +/- 34, and 87 +/- 20 microIU/ml), as compared to the first measurement (26 +/- 13). In the subcutaneous group, plasma insulin was elevated during the last measurement (to 154 +/- 3.5 microIU/ml from 21 +/- 18). This study presents a novel possibility of insulin delivery that is controllable and requires minimal training. This treatment strategy could improve compliance, and thus be beneficial for patients' glycaemic control.

  7. Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids.

    Science.gov (United States)

    Lam, Y Y; Hatzinikolas, G; Weir, J M; Janovská, A; McAinch, A J; Game, P; Meikle, P J; Wittert, G A

    2011-01-01

    The study aims to determine the effect of long-chain saturated and polyunsaturated (PUFA) fatty acids, specifically palmitic acid (PA; 16:0), docosahexaenoic acid (DHA; 22:6n-3) and linoleic acid (LA; 18:2n-6), and their interactions with factors from adipose tissue, on insulin sensitivity and lipid metabolism in skeletal muscle. L6 myotubes were cultured with PA, DHA or LA (0.4mmol/l), with or without conditioned media from human subcutaneous (SC) and visceral (IAB) fat. Insulin-stimulated glucose uptake, lipid content, mRNA expression of key genes involved in nutrient utilization and protein expression of inhibitor protein inhibitor kappa B (IκB)-α and mammalian target of rapamycin (mTOR) were measured. PA and IAB fat reduced insulin-stimulated glucose uptake and their combined effect was similar to that of PA alone. PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IκBα degradation or mTOR activation. The PA effect was also partially reversed by DHA and completely by LA in the presence of SC fat. PA increased diacylglycerol content, which was reduced by LA and to a greater extent when either IAB or SC fat was also present. PA increased SCD1 whereas DHA and LA increased AMPKα2 mRNA. In the presence of SC or IAB fat, the combination of PA with either DHA or LA decreased SCD1 and increased AMPKα2 mRNA. PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. PUFAs promote pathways, at a transcriptional level, that increase fat oxidation and synergize with factors from SC fat to abrogate PA-induced insulin resistance. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. 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.

  9. A Comparison of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Insulin Injection in Children with Type I Diabetes in Kuwait: Glycemic Control, Insulin Requirement, and BMI

    Directory of Open Access Journals (Sweden)

    Majedah M. AbdulRasoul

    2015-09-01

    Full Text Available Objective: Continuous subcutaneous insulin infusion (CSII and multiple daily insulin injections (MDI are two methods currently used to manage type I diabetes mellitus (T1DM. Here we compare our experiences with CSII and MDI in a large cohort of pediatric patients in Kuwait. Methods: Data on 326 patients with T1DM who were started on CSII between 2007 and 2012 were retrospectively compared with those of 326 patients on MDI. They were matched for sex, age at diagnosis, T1DM duration, glycemic control, insulin requirement, and body mass index (BMI. Data were collected at baseline and every three months and included glycated hemoglobin (HbA1c, insulin dose, and adverse events (severe hypoglycemia, diabetic ketoacidosis, and skin problems. Results: The main reason for switching to CSII was to achieve better glycemic control (37%, followed by reducing hypoglycemia, and improving the quality of life (13.3% each. Although HbA1c decrease was most significant in the first year, it continued to be significantly lower in the CSII group compared to the MDI throughout the study period. Total daily insulin requirements were significantly lower in the CSII group. BMI increased in both groups, but the difference was significant only at the end of the fifth year. There was no significant change in the rate of diabetic ketoacidosis in either group. The CSII patients had more severe hypoglycemic episodes at baseline; however, it significantly decreased throughout the study period. Only five patients discontinued CSII therapy and two of these restarted within three months. Conclusion: CSII is a safe intensive insulin therapy in youngsters with T1DM and achieved markedly fewer severe hypoglycemic episodes and lower daily insulin requirements

  10. A nationwide study of continuous subcutaneous insulin infusion (CSII) in Denmark

    DEFF Research Database (Denmark)

    Nørgaard, Kirsten

    2003-01-01

    AIMS: To record the number of patients treated with continuous subcutaneous insulin infusion (CSII), the attitude to CSII treatment among diabetes care providers and the characteristics of pump users in Denmark. METHODS: A questionnaire was mailed to all departments of endocrinology, internal...... that no more patients were interested and that it did not significantly improve metabolic control. The mean age of pump users was 48.1 +/- 10.5 years and the mean time wearing a pump 14.1 +/- 6.3 years. Mean HbA1c was 7.9 +/- 1.2% during CSII, with a significant difference among the 15 centres (P ....05) and a tendency to be lower in females (P = 0.07). CONCLUSIONS: CSII is infrequently used in Denmark despite pump users showing reasonably good metabolic control. The most common explanations for these low figures are lack of expertise and funding for CSII. If more patients in Denmark were to be offered pumps...

  11. Pascal's wager: combining continuous glucose monitoring and continuous subcutaneous insulin infusion.

    Science.gov (United States)

    Kerr, David; Olateju, Tolu

    2010-06-01

    Pascal's Wager is a suggestion posed by the French Philosopher, Blaise Pascal, that even though the existence of God cannot be determined through reason, a person should wager that God exists because he or she has everything to gain and nothing to lose. In the area of consideration here, the optimum experimental trial of the combined use of continuous subcutaneous insulin infusion and real-time continuous glucose monitoring in free-living individuals with type 1 diabetes providing rock-solid evidence of clinical benefit has not been performed. Nevertheless, there is considerable enthusiasm for combining the technologies among healthcare professionals, patients, and manufacturers based on the belief that this approach to diabetes care must be beneficial beyond the available evidence (i.e., reason).

  12. Converting continuous insulin infusion to subcutaneous insulin glargine after cardiac surgery using percentage-based versus weight-based dosing: a pilot trial.

    Science.gov (United States)

    Silinskie, Kevin M; Kirshner, Ronald; Hite, Mindee S

    2013-01-01

    Most studies report using percentage of total daily insulin (TDI) for converting therapy from continuous insulin infusion to subcutaneous insulin in cardiac surgery patients. Few studies have evaluated the efficacy of using body weight to calculate the basal insulin dose. To compare the efficacy and safety of dosing insulin glargine by weight versus percentage of TDI in cardiac surgery patients transitioning from continuous insulin infusion to subcutaneous insulin. We conducted a prospective, randomized, open-label, pilot study. Study patients who had a preoperative weight less than 100 kg and were receiving at least 6 hours of a continuous insulin infusion were randomized to receive either 50% of their TDI requirement or 0.5 units/kg of glargine as a one-time dose 2 hours before stopping the continuous insulin infusion. All patients were administered subcutaneous corrective insulin. Blood glucose monitoring occurred before each meal, at bedtime, and with morning laboratory tests for 24 hours after administration of the glargine dose. A total of 200 blood glucose measurements were performed in each group. The percentage of blood glucose measurements in target range (80-140 mg/dL) was similar between the weight-based group and the percentage-based group (66% vs 64%, p = 0.75). Median blood glucose after transition was 120 mg/dL (interquartile range [IQR] 99-147) in the weight-based group compared to 127 mg/dL (IQR 107-149; p = 0.03) in the percentage-based group. The median glargine dose was higher in the weight-based group (41 units; IQR 36-44) than in the weight-based group (24 units; IQR 14-30, p weight proved to be safe, but larger scale studies are needed before adopting weight-based dosing in this patient population.

  13. Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.

    Science.gov (United States)

    Jansen, H J; Stienstra, R; van Diepen, J A; Hijmans, A; van der Laak, J A; Vervoort, G M M; Tack, C J

    2013-12-01

    Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight. We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status. ClinicalTrials.gov: NCT00781495. The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.

  14. 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.

  15. Intraperitoneal insulin infusion : treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia

    NARCIS (Netherlands)

    van Dijk, P R; Logtenberg, S J J; Gans, R O B; Bilo, H J G; Kleefstra, N

    2014-01-01

    Continuous intraperitoneal insulin infusion (CIPII) is a treatment option for patients with type 1 diabetes mellitus who fail to reach adequate glycaemic control despite intensive subcutaneous (SC) insulin therapy. CIPII has clear advantages over SC insulin administration in terms of pharmacokinetic

  16. Changes in glycemic control and quality of life in pediatric type 1 diabetics with continuous subcutaneous insulin infusion of insulin aspart following multiple daily injection therapy.

    Science.gov (United States)

    Kawamura, Tomoyuki; Urakami, Tatsuhiko; Sugihara, Shigetaka; Kim, Hey Sook; Mochizuki, Mie; Amamiya, Shin

    2008-01-01

    The efficacy of continuous subcutaneous insulin infusion (CSII) of the rapid-acting insulin analogue, insulin aspart, was evaluated in 26 patients with childhood-onset type 1 diabetes aged between 6 and 18 yr who had been on basal-bolus therapy (multiple daily injection (MDI) of regular human insulin or rapid-acting insulin and intermediate/long-acting insulin). The glycemic control in the patients was evaluated based on changes in the clinical parameters and the patient quality of life (QOL) was evaluated by using the insulin therapy-related QOL questionnaire. Twenty two patients continued CSII during the 6-mo study period. The mean HbA1c was 7.8 ± 1.8% at baseline and it decreased to 7.4 ± 0.8% at 6 mo after the start of the CSII. Overall, no decrease of the QOL post-CSII initiation was noted. The possible superiority of CSII as compared to MDI was suggested for patients who "eat out" or "have to look for an appropriate place for insulin injection." Aside from an inadequate indwelling needle placement detected after the initiation of CSII in several patients, no adverse event associated with NovoRapid(®) was seen. In conclusion, CSII of rapid-acting insulin appears to be a useful therapy for patients with childhood-onset type 1 diabetes.

  17. Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Ning Xu

    2015-09-01

    Conclusions: Differential expression of core insulin signaling pathway components in subcutaneous adipose tissue is not a major contributor to the pathogenesis of PCOS. Correlation between clinical phenotypes and expression of several genes in the mitogenic limb of the insulin signaling pathway suggests mitogenic signaling by insulin may regulate steroidogenesis and glucose homeostasis.

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

    Science.gov (United States)

    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.

  19. ImmunoPET Imaging of Insulin-Like Growth Factor 1 Receptor in a Subcutaneous Mouse Model of Pancreatic Cancer

    Science.gov (United States)

    2016-06-30

    ImmunoPET Imaging of Insulin-Like Growth Factor 1 Receptor in a Subcutaneous Mouse Model of Pancreatic Cancer Christopher G. England,†,# Anyanee...and Weibo Cai*,†,‡,⊥ †Department of Medical Physics, ‡Department of Radiology, and ⊥Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin...Seoul 110-744, Korea ∥NeoClone Biotechnologies International, Madison, Wisconsin 53713, United States *S Supporting Information ABSTRACT: The role of

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

    DEFF Research Database (Denmark)

    Nielsen, Mette Olaf; Hou, Lei; Johnsen, Lærke

    2016-01-01

    Previous studies have shown that fetal life malnutrition affects preferences for fat deposition in the body thereby predisposing for visceral adipocity and associated disorders in glucose-insulin regulation. In this study, we aimed to test the hypotheses that late-gestation undernutrition 1) has ...... long-term differential impacts on development, expandability and metabolic features in subcutaneous as compared to perirenal and mesenteric adipose tissues, which 2) will predispose for visceral obesity upon exposure to an obesogenic diet in early postnatal life....

  1. Comparison of a Multiple Daily Insulin Injection Regimen (Glargine or Detemir Once Daily Plus Prandial Insulin Aspart and Continuous Subcutaneous Insulin Infusion (Aspart in Short-Term Intensive Insulin Therapy for Poorly Controlled Type 2 Diabetes Patients

    Directory of Open Access Journals (Sweden)

    Wen-shan Lv

    2013-01-01

    Full Text Available Aims. To examine the potential differences between multiple daily injection (MDI regimens based on new long-acting insulin analogues (glargine or detemir plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII in patients with poorly controlled type 2 diabetes. Methods. Patients (n=119 with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes.

  2. Treatment Efficacy of Subcutaneous Insulin Infusion Therapy In Type 1 Diabetic Patients - Orijinal Article

    Directory of Open Access Journals (Sweden)

    Soner

    2010-12-01

    Full Text Available Objective: Current goals of treatment of diabetes are to achieve near-normal glycemia, minimize the risk of severe hypoglycemia, limit excessive weight gain, and to improve quality of life. Insulin pump or continuous subcutaneous insulin infusion (CSII therapy provides a treatment option to aid in achieving all of these goals. CSII is a viable alternative to multiple daily injections (MDI therapy for patients with diabetes who are capable and motivated. In this study, we aimed to compare the diabetic control and treatment satisfaction in our patients using CSII and MDI. Materials and Methods: Fifty patients with type 1 diabetes, who had been followed between 2005-2008, were enrolled in the study. Changes in biomedical outcomes (glycated haemoglobin; HbA1c, hypoglycaemia, and weigth gain pre-CSII, during the last year and at the end of the study were analyzed retrospectively. For treatment satisfaction and compliance, we used a questionnaire containing 12 questions. The patients were divided into two groups according to MDI or CSII therapy use for least one year: Group 1 using CSII (n:27 and Group 2 using MDI (n:23. Results: There was no significant difference between the last HbA1c levels in both groups. In CSII group, decrease in HbA1c was 0.79% for average follow-up of 1.66 years ( 9.19%±2.23; 8.40%±1.17. When the two groups were compared in terms of hypoglycemia rates and weight gain over the last year, no statistically significant difference was found, but in CSII group, hypoglycemia rates were lower. Finally, CSII group demonstrated a higher treatment satisfaction rate and higher compliance, while a negative correlation was detected between frequency of home blood glucose monitoring and HbA1c levels in all patients. Conclusion: CSII therapy is effective in improving glycemic control with higher treatment satisfaction when compared with MDI therapy in selected type 1 diabetic patients. Turk Jem 2010; 14: 80-4

  3. Effect of carbohydrate counting using bolus calculators on glycemic control in type 1 diabetes patients during continuous subcutaneous insulin infusion.

    Science.gov (United States)

    Yamada, Eijiro; Okada, Shuichi; Nakajima, Yasuyo; Bastie, Claire C; Tagaya, Yuko; Osaki, Aya; Shimoda, Yoko; Shibusawa, Ryo; Saito, Tsugumichi; Ozawa, Atsushi; Yamada, Masanobu

    2017-07-01

    The present study examined the long-term efficacy of insulin pump therapy for type 1 diabetes patients when carried out using carbohydrate counting with bolus calculators for 1 year. A total of 22 type 1 diabetes patients who had just started continuous subcutaneous insulin infusion were examined and divided into two groups: one that was educated about carbohydrate counting using bolus calculators (n = 14); and another that did not use bolus calculators (n = 8). After 1 year, the hemoglobin A1c levels of the patient group that used bolus calculators decreased persistently and significantly (P = 0.0297), whereas those of the other group did not. The bodyweight, total daily dose of insulin and bolus percentage of both groups did not change. Carbohydrate counting using bolus calculators is necessary to achieve optimal and persistent glycemic control in patients undergoing continuous subcutaneous insulin infusion. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  4. c-Abl inhibition mitigates diet-induced obesity through improving insulin sensitivity of subcutaneous fat in mice.

    Science.gov (United States)

    Wu, Rong; Sun, Jian-Guang; Wang, Ji-Qiu; Li, Binhua; Liu, Qingsong; Ning, Guang; Jin, Wanzhu; Yuan, Zengqiang

    2017-05-01

    High-energy diets are among the main causes of the global epidemic of metabolic disorders, including obesity and type 2 diabetes. The mechanisms of high-energy-diet-induced metabolic disorders are complex and largely unknown. The non-receptor tyrosine kinase c-Abl plays an important role in adipogenesis in vitro but its role in vivo in the regulation of metabolism is still elusive. Hence, we sought to address the role of c-Abl in diet-induced obesity and obesity-associated insulin resistance. The expression of c-Abl in different fat tissues from obese humans or mice fed a high-fat diet (HFD) were first analysed by western blotting and quantitative PCR. We employed conditional deletion of the c-Abl gene (also known as Abl1) in adipose tissue using Fabp4-Cre and 6-week-old mice were fed with either a chow diet (CD) or an HFD. Age-matched wild-type mice were treated with the c-Abl inhibitor nilotinib or with vehicle and exposed to either CD or HFD, followed by analysis of body mass, fat mass, glucose and insulin tolerance. Histological staining, ELISA and biochemical analysis were used to clarify details of changes in physiology and molecular signalling. c-Abl was highly expressed in subcutaneous fat from obese humans and HFD-induced obese mice. Conditional knockout of c-Abl in adipose tissue improved insulin sensitivity and mitigated HFD-induced body mass gain, hyperglycaemia and hyperinsulinaemia. Consistently, treatment with nilotinib significantly reduced fat mass and improved insulin sensitivity in HFD-fed mice. Further biochemical analyses suggested that c-Abl inhibition improved whole-body insulin sensitivity by reducing HFD-triggered insulin resistance and increasing adiponectin in subcutaneous fat. Our findings define a new biological role for c-Abl in the regulation of diet-induced obesity through improving insulin sensitivity of subcutaneous fat. This suggests it may become a novel therapeutic target in the treatment of metabolic disorders.

  5. 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

  6. Effect of 4 years subcutaneous insulin infusion treatment on albuminuria, kidney function and HbA1c compared with multiple daily injections

    DEFF Research Database (Denmark)

    Vestergaard Rosenlund, Signe; Hansen, Tine Willum; Andersen, Steen

    2015-01-01

    AIM: The effect of insulin pump [continuous subcutaneous insulin infusion (CSII)] treatment on diabetes complications in a modern clinical setting is largely unknown. We investigated the effect of 4 years CSII treatment on HbA1c, albuminuria and kidney function compared with multiple daily...

  7. Up-regulation of the complement system in subcutaneous adipocytes from nonobese, hypertriglyceridemic subjects is associated with adipocyte insulin resistance.

    Science.gov (United States)

    van Greevenbroek, M M J; Ghosh, S; van der Kallen, C J H; Brouwers, M C G J; Schalkwijk, C G; Stehouwer, C D A

    2012-12-01

    Dysfunctional adipose tissue plays an important role in the etiology of the metabolic syndrome, type 2 diabetes, and dyslipidemia. However, the molecular mechanisms underlying adipocyte dysfunction are incompletely understood. The aim of the study was to identify differentially regulated pathways in sc adipocytes of dyslipidemic subjects. Whole-genome expression profiling was conducted on sc adipocytes from a discovery group of nine marginally overweight subjects with familial combined hyperlipidemia (FCHL) and nine controls of comparable body sizes as well as two independent confirmation groups. In this study, FCHL served as a model of familial insulin resistance and dyslipidemia, in the absence of frank obesity. Functional analyses and gene set enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes or a custom pathway database identified the complement system and complement regulators as one of the top up-regulated pathways in FCHL [false discovery rate (FDR) complement expression in FCHL was confirmed in the appropriate confirmation group. Higher complement gene expression was associated with lower adipocyte insulin receptor substrate-1 expression as marker of adipocyte insulin resistance, independent of age, sex, or disease status, and this association was corroborated in the two confirmation groups. Additionally, complement gene expression was associated with triglycerides in the discovery set and with triglycerides and/or waist circumference in the confirmation groups. Complement pathway up-regulation did not appear to be driven by hypertriglyceridemia because a 40% pharmacological reduction in triglycerides did not affect complement expression. These findings point to an up-regulation of a complement-related transcriptome in sc adipocytes under metabolically stressed conditions, even in the absence of overt obesity. Such up-regulation may subsequently influence downstream processes, including macrophage infiltration into adipose tissue and

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

    Directory of Open Access Journals (Sweden)

    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.

  9. [Nocturnal continuous subcutaneous insulin infusion--a therapeutic possibility in labile type I diabetes under exceptional conditions].

    Science.gov (United States)

    Bruns, W; Steinborn, F; Menzel, R; Staritz, B; Bibergeil, H

    1990-03-15

    The whole-day continuous subcutaneous insulin infusion (CSII) with portable pumps in daily blood glucose autocontrol guarantees a more stabile and favourable glycaemia than multiple injections in labile type I diabetics. The success is mainly to be traced back to the continuous replacement of the basal secretion, particularly to the nocturnal fasting phase. In this study the effect on the glycaemia is investigated with exclusively nocturnal administration of the CSII under maintenance of multiple insulin injections during this day. In a group of 18 type I diabetics the nocturnal CSII in comparison to intermediate insulin administrations in the evening led to a significant improvement of glycaemia (p less than 0.01), in particular to the decrease of the fasting blood sugars (p less than 0.05). In two casuistic observations in comparison to all the other conventional methods for the compensation of the nocturnal glycaemia (depot insulin, nocturnal injection of normal insulin) the nocturnal CSII proved to be superior. Therefore, the nocturnal CSII is an--though more rarely to be used--alternative, which may be taken into consideration, of a whole-day CSII is temporarily unwished for.

  10. 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.

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

    DEFF Research Database (Denmark)

    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...... glycerol concentrations in the phentolamine-containing probe while no difference in lipolytic response was found in the aminophylline-containing probe. The results suggest that insulin antilipolytic action plays a role in the regulation of lipolysis during exercise in lean as well as in obese subjects...

  12. Differences in parental involvement in the care of children and adolescents with type 1 diabetes mellitus on multiple daily insulin injections versus continuous subcutaneous insulin infusion.

    Science.gov (United States)

    Cemeroglu, Ayse Pinar; Timmer, Scott; Turfe, Zaahir; Davis, Alan T; Koehler, Tracy J; Can, Argun; Kleis, Lora; Daniel, Maala S

    2016-03-01

    Assessing the degree of involvement of caregivers for children with type 1 diabetes mellitus (T1DM) in their diabetes care, differences in the degree of involvement based on the method of insulin administration (multiple daily injections: MDI/continuous subcutaneous insulin infusion: CSII), and its effect on glycemic control. This was a cross-sectional study with T1DM patients, ages 6-13 years using a six question survey derived from the Diabetes Family Responsibility Questionnaire (DFRQ). All caregivers (n=140) and participants between ages 11 and 13 (n=60) completed the survey. Significant differences between MDI and CSII caregiver responses were found for responsibility for giving insulin boluses, as well as for rotation of infusion/injection sites (pparental involvement on last 2-year average HbA1C was found for CSII or MDI groups (p>0.20). Caregiver reported diabetes care responsibility (mostly parent, mostly child, shared between parent and child) varies for certain aspects of diabetes related care for children ages 6-13, depending upon the mode of insulin administration. Based on the reported degree of parental collaboration, HbA1C did not differ significantly. However, long-term effects are yet to be determined in longitudinal studies.

  13. 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.

  14. Hydrophilic poly (ethylene glycol) capped poly (lactic-co-glycolic) acid nanoparticles for subcutaneous delivery of insulin in diabetic rats.

    Science.gov (United States)

    S, Saravanan; S, Malathi; P S L, Sesh; S, Selvasubramanian; S, Balasubramanian; V, Pandiyan

    2017-02-01

    The aim of the present study is to evaluate the effect of insulin loaded poly(ethylene glycol) capped poly(lactic-co-glycolic)acid nanoparticles (ISPPLG NPs) by subcutaneous administration in diabetic rats. A series of biodegradable low molecular weight PLGA [90/10 (PLG2) and 80/20 (PLG4)] copolymers were synthesized by melt polycondensation and their ISPPLG NPs were synthesized by water-oil-water (W/O/W) emulsion solvent evaporation method. The PLGA copolymers and their nanoparticles were characterized. The maximum encapsulation efficiency of ISPPLG4 NPs is 66% and the diameter of the nanoparticles is about 140nm. The in-vivo studies of ISPPLG NPs carried out in diabetic rats by subcutaneous administration show considerable reduction in serum glucose level along with partial restoration of tissue defense systems. Histopathological studies reveal that ISPPLG NPs could restore the damages caused by oxidants during hyperglycaemia. The subcutaneous administration of ISPPLG4 NPs is thus an effective method of reducing hyperglycaemia associated complications. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 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...

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

    DEFF Research Database (Denmark)

    Christensen, Cramer; 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...

  17. Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    Willemse, Peter-Paul M; van der Meer, Rutger W; Burggraaf, Jacobus; van Elderen, Saskia G C; de Kam, Marieke L; de Roos, Albert; Lamb, Hildo J; Osanto, Susanne

    2014-03-01

    Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. We studied 19 testicular cancer patients (age 20-54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m(2) (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development

  18. Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy.

    Science.gov (United States)

    Schulten, Ron J; Piet, Jessica; Bruijning, Patricia Cjl; de Waal, Wouter J

    2017-02-01

    The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. All patients under the age of 18 with type I diabetes mellitus, treated in a general hospital in Utrecht, The Netherlands, who were on CSII therapy between 2000 and 2011 were selected for inclusion. All data as recorded during outpatient visits were retrospectively collected from patients' charts. Analyses were performed using R Statistical Software. Data of 847 outpatient visits of 78 patients [31 males (39.7%) and 47 females (60.3%)] were analyzed. Mean age at diagnosis was 7.1 ± 3.7 yr, mean age at start of pump therapy 10.1 ± 3.8 yr. Mean HbA1c before pump start was 8.3 ± 1.0%, median BMI standard deviation score for age and gender was 0.64 (-1.89-3.79). Median follow-up time per patient was 29 months with an average of 10 visits (range: 3-25). Multivariate analysis revealed that a change of 10% in %BD/T resulted in a decrease or increase of HbA1c of 0.22% [95% confidence interval (CI): 0.15-0.29). No significant effect was observed from SDS BMI, sex, or duration of diabetes. Low dose basal insulin infusion as a percentage of total insulin dose has a positive effect on metabolic outcome as expressed in HbA1c-levels. A change of 10% in %BD/T results in a decrease or increase of HbA1c of 0.22%. This supports the tendency to aim at the lowest basal insulin requirements in pump setting strategy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. 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 (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 (plevel. Pre-adolescents, adolescents and young adults with CSII have also better diabetes-related knowledge. Moreover, in all age-groups, the parents of patients with CSII had mostly a lower unemployment rate and higher educational levels. The present analyses demonstrate that in all age-groups CSII provides convenient and flexible insulin delivery during routine treatment of type 1 diabetes. There is reasonable quality of diabetes control accompanied by a low incidence of hypoglycaemia and ketoacidosis. However, under CSII and MIT 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.

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

    Science.gov (United States)

    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.

  1. 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...... build-up was evaluated indirectly from the changes in the flow rate between subcutaneous injections and air injections. This method enabled the tissue counter pressure to be evaluated without a formal clinical study approval. The measurements were coupled to a model for the pressure evolution...... in subcutaneous tissue, based on mass conservation and flow in a porous medium. From the measurements the flow permeability and bulk modulus of the tissue were determined. In the adipose tissue the drug forms a bolus from where it is absorbed by the blood capillaries. The spatial distribution of the injected...

  2. Improved Glycemic Control With Intraperitoneal Versus Subcutaneous Insulin in Type 1 Diabetes A randomized controlled trial

    NARCIS (Netherlands)

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

    OBJECTIVE - Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump has been available for the past 25 years. CIPII, with its specific pharmacodynamic properties, may be a viable treatment alternative to improve glycemic control in patients with type I diabetes for whom other

  3. Moving beyond subcutaneous insulin: the application of adjunctive therapies to the treatment of type 1 diabetes.

    Science.gov (United States)

    Ang, Kathleen H; Sherr, Jennifer L

    2017-09-01

    With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D. Areas covered: This review focuses on agents that have been utilized, including inhaled insulin preparations, pramlintide, metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dual SGLT1/2 inhibitors. Furthermore, with approval of the first hybrid closed loop (CL) system, the development of dual hormone CL systems is being explored. While the most common agent applied to these dual systems has been glucagon, research has been conducted to assess how some of the adjunctive therapies described above could aide with achieving postprandial glucose control while on CL insulin delivery. Expert opinion: By becoming less insulin-centric and incorporating some of these other agents, it is possible we may be able to better combat T1D.

  4. 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.

  5. 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

    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...... the dynamics. In the first model, the insulin absorption rate parameter is replaced by a random walk. In the second model, the relationship between the absorption rate and exercise is modelled as a linear dependency, while in the third model this linear relationship depends on the intensity. A Lamperti...

  6. Associations of Abdominal Subcutaneous and Visceral Fat with Insulin Resistance and Secretion Differ Between Men and Women: The Netherlands Epidemiology of Obesity Study.

    Science.gov (United States)

    de Mutsert, Renée; Gast, Karin; Widya, Ralph; de Koning, Eelco; Jazet, Ingrid; Lamb, Hildo; le Cessie, Saskia; de Roos, Albert; Smit, Jan; Rosendaal, Frits; den Heijer, Martin

    2018-02-01

    Abdominal obesity is a well-established risk factor for the development of type 2 diabetes. However, sex differences may exist. We aimed to investigate the associations of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with insulin resistance and insulin secretion in men and women. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, fasting and postprandial concentrations of glucose and insulin were measured and abdominal fat depots were assessed using magnetic resonance imaging in 2253 participants (53% women). With linear regression analysis, we examined associations of abdominal SAT and VAT with measures of insulin resistance and insulin secretion in men and women, while adjusting for age, ethnicity, education, smoking habits, alcohol consumption, menopausal state and hormone use in women, and models with VAT additionally for total body fat. Participants had a mean [standard deviation (SD)] age of 56 (6) years, body mass index: 25.9 (3.9) kg/m2, VAT: 89 (55) cm2, and SAT: 235 (95) cm2. In the multivariate models in men, per SD of VAT the homeostatic model assessment of insulin resistance (HOMA-IR) was 20% (95% CI: 14-26) higher, and per SD SAT 21% (15-27) higher. In women, per SD of VAT the HOMA-IR was 40% (29-52) higher, and per SD SAT 12% (6-19) higher. Associations with measures of insulin secretion were weaker than with insulin resistance. In men, abdominal SAT and VAT were associated with insulin resistance to a similar extent, whereas in women particularly VAT was associated with insulin resistance and insulin secretion. Future studies need to unravel the mechanisms underlying the metabolic effects of visceral fat in women. Simple and less expensive measures that can distinct abdominal subcutaneous and visceral fat are needed for an improved metabolic risk stratification.

  7. Continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections in preventing albumin excretion rate increase in Type 1 diabetic patients.

    Science.gov (United States)

    Lepore, G; Bruttomesso, D; Bonomo, M; Dodesini, A R; Costa, S; Meneghini, E; Corsi, A; Nosari, I; Trevisan, R

    2009-06-01

    To compare the effect of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) on albumin excretion rate (AER) in Type 1 diabetic patients. In a 3-year multicentre retrospective observational study, 110 Type 1 diabetic patients treated with CSII were compared with 110 patients treated with MDI matched at baseline for age, sex, diabetes duration and HbA(1c). At entry, 90 patients in each group had normal AER and 20 persistent microalbuminuria. AER, estimated glomerular filtration rate (eGFR), HbA(1c,) lipids and blood pressure were assessed. HbA(1c) was lower in the CSII than in the MDI group (8.1 +/- 0.9 vs. 8.4 +/- 1.3%; P AER [median (95% confidence interval)], similar at baseline [6.0 microg/min (9, 21) in the CSII group vs. 4.4 (8, 16) in the MDI group, NS] was significantly lower in the patients treated with CSII both at year 2 and at year 3 of follow-up [4.7 microg/min (6, 12) vs. 6.4 (13, 29), P therapy may be useful in decreasing the progressive increase in AER in Type 1 diabetic patients.

  8. 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.

  9. [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.

  10. Real-time UV imaging identifies the role of pH in insulin dissolution behavior in hydrogel-based subcutaneous tissue surrogate

    DEFF Research Database (Denmark)

    Jensen, Sabrine S; Jensen, Henrik; Cornett, Claus

    2015-01-01

    in the development of new protein drug formulations. Using insulin as a model compound, the aim of this work was to develop a UV imaging-based method to study the real-time dissolution and diffusion behavior of solid protein drugs under stagnant conditions in a hydrogel matrix mimicking the subcutaneous tissue...... in the vicinity of solid protein drug in a hydrogel matrix with the aim of achieving a better understanding of in vivo dissolution processes....

  11. The effect of subcutaneous Insulin-like Growth Factor-1 (IGF-1 injection on rabbit auricular cartilage autograft viability

    Directory of Open Access Journals (Sweden)

    Guclu Kaan Beriat

    2012-11-01

    Full Text Available Insulin-like Growth Factor-1 (IGF-1 is one of the significant substances affecting the growth and development of cartilage tissue in the body. The aim of this study is to evaluate the possible histopathological effects of local IGF-1 injection on the viability of rabbit auricular cartilage autografts.To this end, the single-piece and sliced cartilage tissues obtained from 20 albino rabbits’ auricula were implanted in the subcutaneous pockets created on the back skins of the experimental animals. Every two weeks IGF-1 (10 mg/ml injections were performed on the autograft implants of one group and normal saline (0.9% injections were performed on the other group. Experimental animals were sacrificed at the end of the third month. A total of 34 tissue samples obtained after dissection were evaluated and scored histopathologically according to their cartilage viability, environmental reaction, and regenerative activities.The intergroup evaluation carried out for the single-piece and sliced cartilage grafts revealed that there was statistically more cartilage viability and less foreign-body reaction in the IGF-1 group than the normal saline group (p<0.05.While there was a statistically significant difference between the groups for single-piece grafts regarding regenerative activity (p<0.05, there was no significant difference for sliced grafts. The IGF-1 group, however, showed more activity.The results we obtained point out to the fact that IGF-1 increases the tissue viability of the implanted auricular autograft and it suppresses immune modulation effect.

  12. 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

    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......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...... an approximately 40 mmHg increase in venous transmural pressure, induced by lowering the lower leg 50 cm below heart level. During lowering of the leg, the subcutaneous blood flow decreased to the same level in long-term IDDM patients (mean: 46%), short-term IDDM patients (53%) and control subjects (53...

  13. 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...... an approximately 40 mmHg increase in venous transmural pressure, induced by lowering the lower leg 50 cm below heart level. During lowering of the leg, the subcutaneous blood flow decreased to the same level in long-term IDDM patients (mean: 46%), short-term IDDM patients (53%) and control subjects (53......%). There was no association between the relative local blood flow during lowering and the degree of terminal arteriolar hyalinosis studied in skin biopsies from the same tissue area. Our results suggest that terminal arteriolar hyalinosis does not interfere with the local sympathetic-mediated veno-arteriolar reflex...

  14. Bisphenol-A impairs insulin action and up-regulates inflammatory pathways in human subcutaneous adipocytes and 3T3-L1 cells.

    Directory of Open Access Journals (Sweden)

    Rossella Valentino

    Full Text Available Current evidence indicates that chemical pollutants may interfere with the homeostatic control of nutrient metabolism, thereby contributing to the increased prevalence of metabolic disorders. Bisphenol-A (BPA is a lipophilic compound contained in plastic which is considered a candidate for impairing energy and glucose metabolism. We have investigated the impact of low doses of BPA on adipocyte metabolic functions. Human adipocytes derived from subcutaneous adipose tissue and differentiated 3T3-L1 cells were incubated with BPA, in order to evaluate the effect on glucose utilization, insulin sensitivity and cytokine secretion. Treatment with 1 nM BPA significantly inhibited insulin-stimulated glucose utilization, without grossly interfering with adipocyte differentiation. Accordingly, mRNA levels of the adipogenic markers PPARγ and GLUT4 were unchanged upon BPA exposure. BPA treatment also impaired insulin-activated receptor phosphorylation and signaling. Moreover, adipocyte incubation with BPA was accompanied by increased release of IL-6 and IFN-γ, as assessed by multiplex ELISA assays, and by activation of JNK, STAT3 and NFkB pathways. Treatment of the cells with the JNK inhibitor SP600125 almost fully reverted BPA effect on insulin signaling and glucose utilization. In conclusion, low doses of BPA interfere with inflammatory/insulin signaling pathways, leading to impairment of adipose cell function.

  15. Pharmacokinetics and metabolic effects of growth hormone injected subcutaneously in growth hormone deficient patients: thich versus abdomen

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Christiansen, Jens Sandahl

    1994-01-01

    Abstract OBJECTIVE: The absorption of insulin following subcutaneous (s.c.) injection is faster in the abdomen than the thigh. We therefore studied the effect of changing the site of injection on the absorption and metabolic effects of human growth hormone. DESIGN AND MEASUREMENTS: In a cross...

  16. 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...

  17. 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

    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......), 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...

  18. Continuous Subcutaneous Insulin Infusion During Pregnancy in Women with Complicated Type 1 Diabetes Is Associated with Better Glycemic Control but Not with Improvement in Pregnancy Outcomes.

    Science.gov (United States)

    Kekäläinen, Päivi; Juuti, Mari; Walle, Tiina; Laatikainen, Tiina

    2016-03-01

    The aim of this study was to evaluate maternal and fetal pregnancy outcomes of women with type 1 diabetes managed on continuous subcutaneous insulin infusion (CSII) compared with multiple daily insulin injections (MDI). Pregnancy outcomes were assessed retrospectively in women with type 1 diabetes who were patients of the Diabetes Clinic of North Karelia Hospital (Joensuu, Finland) between 2000 and 2012. The medical records of 72 women experiencing 135 pregnancies and data of their infants were retrospectively reviewed. In total, 48 pregnancies were treated with CSII and 87 with MDI. Women on CSII treatment were older and had more diabetes complications compared with women on MDI. No significant differences in glycated hemoglobin (HbA1c) levels were observed between the CSII and MDI groups before or during pregnancy. Maternal or fetal outcomes did not differ between the treatment groups. However, among women with complicated diabetes, HbA1c levels were significantly lower in the CSII group until the second trimester (prepregnancy, 7.22% vs. 8.14%, respectively [P = 0.034]; first trimester, 6.85% vs. 7.87% [P Pregnancy outcomes were similar regardless of insulin treatment modality. Although using an insulin pump did not result in improvement of pregnancy outcomes, it allowed for better glycemic control in pregnancies of women with complicated diabetes. Therefore, it is worth considering in high-risk T1DM pregnancies, especially if good glycemic control is not achieved otherwise.

  19. SAFETY AND EFFICACY OF A PERI-OPERATIVE PROTOCOL FOR PATIENTS WITH DIABETES TREATED WITH CONTINUOUS SUBCUTANEOUS INSULIN INFUSION WHO ARE ADMITTED FOR SAME-DAY SURGERY.

    Science.gov (United States)

    Sobel, Sandra I; Augustine, Marilyn; Donihi, Amy C; Reider, Jodie; Forte, Patrick; Korytkowski, Mary

    2015-11-01

    The number of people with diabetes using continuous subcutaneous insulin infusions (CSII) with an insulin pump has risen dramatically, creating new challenges when these patients are admitted to the hospital for surgical or other procedures. There is limited literature guiding CSII use during surgical procedures. The study was carried out in a large, urban, tertiary care hospital. We enrolled 49 patients using insulin pump therapy presenting for 57 elective surgeries. We developed a CSII peri-operative glycemic management protocol (PGMP) to standardize insulin pump management in patients admitted to a same-day surgery unit (SDSU). The purpose was evaluate the safety (% capillary blood glucose (CBG) surgery length, and peri-operative steroid use on postoperative glycemic control. Overall, 63% of patients treated according to the CSII PGMP had a first postoperative CBG ≤200 mg/dL. There were no episodes of intra- or postoperative hypoglycemia. For patients treated with the CSII PGMP, the mean postoperative CBG was lower in patients with anticipated or actual surgical length ≤120 minutes (158.1 ± 53.9 vs. 216 ± 77.7 mg/dL, Psafe and effective for patients admitted for elective surgical procedures and provides an example of a standardized protocol for use in clinical practice.

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

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Haidar, Ahmad

    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 th...

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

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Haidar, Ahmad

    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 glucagon levels. We build a simulation model of the glucose-insulin-glucagon dynamics in man including saturation......-insulin-glucagon dynamics using the Hovorka model with a novel multiplicative description of the effects of insulin and of glucagon on EGP. Bayesian estimation by Maximum a Posteriori using prior knowledge reported in literature was used to estimate the model parameters for each subject. Profile likelihood plots were used...

  2. Pramlintide improved measures of glycemic control and body weight in patients with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion therapy.

    Science.gov (United States)

    Herrmann, Kathrin; Frias, Juan P; Edelman, Steven V; Lutz, Karen; Shan, Kevin; Chen, Steven; Maggs, David; Kolterman, Orville G

    2013-05-01

    To assess the safety and efficacy of the addition of pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM). We conducted a post hoc analysis of 2 studies: a 29-week, multicenter, randomized, double-blind, placebo-controlled trial (referred to as RCT) (pramlintide, n = 82; placebo, n = 73) and an open-ended, multicenter, open-label, single-arm, observational study (referred to as clinical practice trial) (n = 150), which assessed the addition of pramlintide to CSII therapy in patients with T1DM. Pramlintide was initiated at 15 μg and titrated to 30 or 60 μg with major meals. The mealtime insulin dose was reduced by 30% to 50% at initiation, and then adjusted to optimize glycemic control. Endpoints at 29 weeks (RCT) and 6 months (clinical practice trial) included change in glycated hemoglobin (HbA1c) level, insulin dose, body weight, pre- and postprandial blood glucose level, and tolerability and safety. In both studies, mean baseline age was approximately 42 years, duration of diabetes was 20 to 24 years, and HbA1c level was approximately 8%. Pramlintide reduced blood glucose excursions and improved the percentage of recorded postprandial blood glucose levels body weight (RCT: pramlintide, -2.2 kg ± 0.5 kg; placebo, +1.4 kg ± 0.3 kg; P body weight. www.ClinicalTrials.gov identifiers: NCT00042458, NCT00108004.

  3. [Influence of the treatment with continuous subcutaneous insulin infusion (CSII) in the improvement of the quality of life of patients with type 1 diabetes mellitus].

    Science.gov (United States)

    Casas-Oñate, Maria Luisa; Montoya-Martínez, Dolores

    2010-01-01

    To evaluate the influence of the treatment with continuous subcutaneous insulin infusion on the quality of life of type 1 diabetics. An analytical study of cohorts was conducted on 80 patients diagnosed with type 1 diabetes mellitus, with more than five years of evolution and without evidence of micro-macro vascular complications, on treatment with CSII or multiple daily insulin injections (MDII). The quality of life of both groups was evaluated by means of a validated modification of the survey "Diabetes Quality of Life Measure" (DQLM). The SPSS 11.0 software was used to determine Chi(2) and establish statistically significant values for a Pquality of life than the patients with multiple daily insulin injections, although only in 16% (6/36) of the questions, were the scores significantly better in the first group. There were no significant differences in the dimensions studied between both groups, but the patients with CSII obtain better results in many variables of the fe DQLM, and they were more satisfied with the flexibility that their treatment offers them in daily life activities. Copyright 2009 Elsevier España, S.L. All rights reserved.

  4. 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...... not influence insulin sensitivity (P = 0.71) or glucose effectiveness (P = 0.15) derived from Bergman's minimal model. Similarly, the two treatment regimens had no differential impact on lipoprotein levels, bone metabolism, or body composition. In conclusion, continuous and intermittent administrations of GH...... 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....

  5. Glycemic Control During Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Insulin Injections in Type 2 Diabetes: Individual Patient Data Meta-analysis and Meta-regression of Randomized Controlled Trials.

    Science.gov (United States)

    Pickup, John C; Reznik, Yves; Sutton, Alex J

    2017-05-01

    To compare glycemic control during continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) in people with type 2 diabetes to identify patient characteristics that determine those best treated by CSII. Randomized controlled trials were selected comparing HbA1c during CSII versus MDI in people with type 2 diabetes. Data sources included Cochrane database and Ovid Medline. We explored patient-level determinants of final HbA1c level and insulin dose using Bayesian meta-regression models of individual patient data and summary effects using two-step meta-analysis. Hypoglycemia data were unavailable. Five trials were identified, with 287 patients randomized to receive MDI and 303 to receive CSII. Baseline HbA1c was the best determinant of final HbA1c: HbA1c difference (%) = 1.575 - (0.216 [95% credible interval 0.371-0.043] × baseline HbA1c) for all trials, but with largest effect in the trial with prerandomization optimization of control. Baseline insulin dose was best predictor of final insulin dose: insulin dose difference (units/kg) = 0.1245 - (0.382 [0.510-0.254] × baseline insulin dose). Overall HbA1c difference was -0.40% (-0.86 to 0.05 [-4.4 mmol/mol (-9.4 to 0.6)]). Overall insulin dose was reduced by -0.25 units/kg (-0.31 to -0.19) (26% reduction on CSII), and by -24.0 units/day (-30.6 to -17.5). Mean weight did not differ between treatments (0.08 kg [-0.33 to 0.48]). CSII achieves better glycemic control than MDI in people with poorly controlled type 2 diabetes, with ∼26% reduction in insulin requirements and no weight change. The best effect is in those worst controlled and with the highest insulin dose at baseline. © 2017 by the American Diabetes Association.

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

    Science.gov (United States)

    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

  7. Impaired autoregulation of blood flow in subcutaneous tissue of long-term type 1 (insulin-dependent) diabetic patients with microangiopathy

    DEFF Research Database (Denmark)

    Kastrup, J; Nørgaard, T; Parving, H H

    1985-01-01

    Autoregulation of blood flow in subcutaneous tissue was studied at the level of the lateral malleolus in eight long-term Type 1 (insulin-dependent) diabetic patients with clinical microangiopathy, eight short-term Type 1 diabetic patients without clinical microangiopathy and seven healthy control...... subjects. Blood flow was measured by the local 133Xenon washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevating to a maximum of 70 mmHg by head-up tilt; in the latter position venous pressure was kept constant and low...... by activation of the leg muscle vein pump (heel raising). Mean arterial blood pressure was thus varied between 60 and 160 mmHg. In normal and short-term diabetic subjects blood flow remained within 10% of control values during the changes in arterial blood pressure. In six of the eight Type 1 diabetic patients...

  8. 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

    regression analysis, adiponectin correlated negatively with CFM (r = -0.27; P multiple linear regression analysis, HOMA-IR (dependent variable......, 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...

  9. 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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Background: In the development of glucose control algorithms, mathematical models of glucose metabolism are useful for conducting simulation studies and making real-time predictions upon which control calculations can be based. To obtain type 1 diabetes (T1D) data for the modeling of glucose...... 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...... energy expenditure. The sequence of everyday life events was predetermined and included carbohydrate intake, insulin boluses, and bouts of exercise; the events were introduced, temporally separated, in different orders and in different quantities. Throughout the study day, 10-min plasma glucose...

  10. Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue

    NARCIS (Netherlands)

    Jansen, H.J.; Stienstra, R.; Diepen, J.A. van; Hijmans, A.; Laak, J.A.W.M. van der; Vervoort, G.M.M.; Tack, C.J.J.

    2013-01-01

    AIMS/HYPOTHESIS: Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the

  11. Modelling the glucose-insulin-glucagon dynamics after subcutaneous administration of native glucagon and a novel glucagon analogue in dogs

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Boye Knudsen, Carsten; Jørgensen, John Bagterp

    Zealand Pharma has invented a glucagon analogue, ZP-GA-1, with increased stability in liquid formulation for treatment of hypoglycemia. A pharmacodynamic (PD) model is needed to compare ZP-GA-1 with marketed glucagon. We aim to develop a model of the complex glucose-insulin-glucagon dynamics base...

  12. Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue

    NARCIS (Netherlands)

    Jansen, H.J.; Stienstra, R.; Diepen, van J.A.; Hijmans, A.; Laak, van der J.A.; Vervoort, G.M.; Tack, C.J.

    2013-01-01

    Aims/hypothesis Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the

  13. 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

    Directory of Open Access Journals (Sweden)

    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.

  14. Insulin

    Science.gov (United States)

    ... Information by Audience For Women Women's Health Topics Insulin Share Tweet Linkedin Pin it More sharing options ... medicines. You can do it. Back to Top Insulin Safety Tips Never drink insulin. Do not share ...

  15. 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.

  16. 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.

  17. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

    Science.gov (United States)

    Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe

    2016-09-01

    Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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

    Science.gov (United States)

    Wan, Heng; Zhao, Defu; Shen, Jie; Lu, Lu; Zhang, Tong; Chen, Zhi

    2016-01-01

    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.

  19. Epidemiological characterization of diabetic patients on therapy with continuous subcutaneous insulin infusion and continuous glucose monitoring in real time.

    Science.gov (United States)

    Aristizábal, Natalia; Ramírez, Alex; Hincapié-García, Jaime; Laiton, Estefany; Aristizábal, Carolina; Cuesta, Diana; Monsalve, Claudia; Hincapié, Gloria; Zapata, Eliana; Abad, Verónica; Delgado, Maria-Rocio; Torres, José-Luis; Palacio, Andrés; Botero, José

    2015-11-01

    To describe baseline characteristics of diabetic patients who were started on insulin pump and real time continuous glucose monitor (CSII-rtCGM) in a specialized center in Medellin, Colombia. All patients with diabetes with complete data who were started on CSII-rtCGM between February 2010 and May 2014 were included. This is a descriptive analysis of the sociodemographic and clinical characteristics. 141 of 174 patients attending the clinic were included. 90,1% had type 1diabetes (T1D). The average age of T1D patients at the beginning of therapy was 31,4 years (SD 14,1). 75.8% of patients had normal weight (BMI30). The median duration of T1D was 13 years (P25-P75=10.7-22.0). 14,2% of the patients were admitted at least once in the year preceding the start of CSII-rtCGM because of diabetes related complications. Mean A1c was 8.6%±1.46%. The main reasons for starting CSII-rtCGM were: poor glycemic control (50.2%); frequent hypoglycemia, nocturnal hypoglycemia, hypoglycemia related to exercise, asymptomatic hypoglycemia (30.2%); severe hypoglycemia (16.44%) and dawn phenomena (3.1%). Baseline characteristics of patients included in this study who were started on CSII-rtCGM are similar to those reported in the literature. The Clinic starts CSII-rtCGM mainly in T1D patients with poor glycemic control, frequent or severe hypoglycemia despite being on basal/bolus therapy. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  20. 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.

  1. Experiences of continuous subcutaneous insulin infusion in pregnant women with type 1 diabetes during delivery from four Italian centers: a retrospective observational study.

    Science.gov (United States)

    Fresa, Raffaella; Visalli, Natalia; Di Blasi, Vincenzo; Cavallaro, Vincenzo; Ansaldi, Egle; Trifoglio, Oria; Abbruzzese, Santina; Bongiovanni, Marzia; Agrusta, Mariano; Napoli, Angela

    2013-04-01

    An optimized metabolic control during delivery is mandatory to prevent maternal-neonatal complications. The primary aim of this study was to evaluate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) during delivery in pregnant women with type 1 diabetes. The secondary aim was to assess the impact of real-time continuous glucose monitoring (RT-CGM) added to CSII versus CSII alone. This was a multicenter observational retrospective study. A standardized protocol, to use CSII throughout pregnancy and delivery, foresaw three different insulin basal rates according to blood glucose level: profile A, the last basal rate in use; profile B, preventive 50% reduction of the last basal rate in use; and profile C, 0.1-0.2 U/h for blood glucose level <70 mg/dL, activated just before anesthesia or at the beginning of active labor. An alternative intravenous protocol (IVP) was given in case of complications and relevant metabolic deterioration. Blood glucose in the target range (70-140 mg/dL) throughout delivery and percentage of activation of the IVP were primary outcomes. Sixty-five pregnant women with diabetes included in the study (56-86% cesarean section; 9-14% spontaneous/stimulated vaginal delivery). Mean blood glucose level was 102 ± 31 mg/dL at 0 min, 109 ± 42 mg/dL at 30 min, 120 ± 48 mg/dL at 60 min, and 99 ± 34 mg/dL at 24 h. Mean basal rate during delivery was 0.6 ± 0.4 U/h (profile B). Mean capillary blood glucose (CBG) level was lower in the RT-CGM group relative to the CSII-alone group: 80 ± 14 mg/dL versus 111 ± 32 mg/dL at 0 min (P<0.01), 79 ± 11 mg/dL versus 109 ± 42 mg/dL at 30 min (P<0.02), and 98 ± 20 mg/dL versus 125 ± 51 mg/dL at 60 min (difference not significant). Eleven newborns experienced transient neonatal hypoglycemia. None of the women switched to IVP. No major differences were observed according to delivery procedure. CSII is possible and safe in different types of delivery in selected and educated women. RT

  2. The impact of continuous subcutaneous insulin infusion on health-related quality of life in children and adolescents with type 1 diabetes.

    Science.gov (United States)

    Júlíusson, Pétur Benedikt; Graue, Marit; Wentzel-Larsen, Tore; Søvik, Oddmund

    2006-11-01

    To study the impact of continuous subcutaneous insulin infusion (CSII) therapy on health-related quality of life in children and adolescents with type 1 diabetes. 31 children and adolescents with poorly regulated type 1 diabetes (mean HbA1c 10.4%, SD 1.8), mean age 14.4 (1.5) y (range 9.7-17.1) and mean diabetes duration of 6.8 (3.2) y (range 1.3-14.6) were consecutively assigned to CSII therapy. Data for generic (CHQ-CF87) and diabetes-specific quality of life (DQOL) were obtained before initiating pump therapy and twice during 15 mo of treatment. HbA1c, BMI and episodes of severe hypoglycaemia and ketoacidosis were recorded over 15 mo prior to and 15 mo during pump therapy. Analysis showed improvements on the family activity scale (p=0.041) and change in health score (p=0.042) (CHQ-CF87). Mean HbA1c decreased from 10.4% (1.8) to 9.0% (0.9) after 3 mo, increasing to 9.6% (1.2) after 15 mo. The number of overweight and obese children increased from 4 and 2 before CSII, to 6 and 3 after 15 mo (IOTF criteria). There was a reduction in severe hypoglycaemia episodes from 43.8 to 5.2 per 100 patient years, but no change in ketoacidosis episodes. The degree of limitation experienced by families due to adolescents' general health and well-being was significantly reduced. Expected improvement in metabolic control and frequency of severe hypoglycaemia was observed.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Optimization of in vitro conditions for bovine subcutaneous and intramuscular preadipocyte differentiation.

    Science.gov (United States)

    Grant, A C; Ortiz-Colòn, G; Doumit, M E; Buskirk, D D

    2008-01-01

    The objective of these experiments was to develop an in vitro cell culture system for differentiation of bovine preadipocytes, which will permit examination of differences in differentiation between intramuscular (i.m.) and subcutaneous (s.c.) bovine preadipocytes. Stromal-vascular cells from bovine i.m. and s.c. adipose depots were isolated and cultured. Clonally derived s.c. preadipocytes were used to determine the ability of insulin, bovine serum lipids, octanoate, acetic acid, dexamethasone (DEX), and troglitazone (TRO) to elicit differentiation of these cells when added to serum-free medium. Addition of 10 and 20 microL/mL of a commercially available serum lipids supplement to low-glucose Dulbecco's modified Eagle's medium containing 280 nM insulin increased glycerol-3-phosphate dehydrogenase (GPDH) activity (P insulin and 20 microL/ mL serum lipids supplement also increased GPDH activity (P insulin, 1 mM octanoate, and 10 mM acetic acid, with 48 h exposure to 0.25 microM DEX caused morphological differentiation in a small number of cells but did not stimulate GPDH activity (P = 0.99). When used together, 280 nM insulin, 20 microL/mL of serum lipids supplement, 40 microM TRO, and 0.25 microM DEX stimulated differentiation compared with the aforementioned treatment (P insulin from this medium reduced GPDH activity by 68% (P insulin, serum lipids, DEX, and TRO. Although TRO enhanced differentiation of bovine preadipocytes, no differential effects of TRO on the differentiation of s.c. and i.m. cells were detected.

  5. Maternal and perinatal outcomes in pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion and real time continuous glucose monitoring in two specialized centers in Medellin, Colombia.

    Science.gov (United States)

    Restrepo-Moreno, Mónica; Ramírez-Rincón, Alex; Hincapié-García, Jaime; Palacio, Andrés; Monsalve-Arango, Claudia; Aristizabal-Henao, Natalia; Restrepo-Zapata, Camila; Botero-Arango, José Fernando

    2017-03-06

    We assessed maternal and perinatal outcomes in pregnant women with type 1 diabetes, treated with continuous subcutaneous insulin infusion and real time continuous glucose monitoring. This is a retrospective study, analyzing the basal characteristics, glycemic control, maternal and perinatal outcomes of pregnant women with type 1 diabetes, who were on an insulin pump with continuous glucose monitoring between 2011 and 2015. Fourteen patients were included. The median age was 33 and disease duration 12 years. Indications for therapy were mainly poor glycemic control and severe hypoglycemia. The median A1c decrease was 1.02% between the first and third trimester. Pregnancies were associated with complications: 7.1% of the patients had diabetic ketoacidosis, 7.1% had an abortion, 28.5% gestational hypertension and 12.2% preeclampsia. The median gestational age at birth was 37 weeks and four days; the frequency of preterm birth was 7.1% and macrosomia 21.4%. There were no congenital malformations or perinatal death. Baseline characteristics and results of patients in this study were similar to those reported in the previous literature. Continuous subcutaneous insulin infusion with continuous glucose monitoring is an alternative treatment option for pregnant women with type 1 diabetes before or during pregnancy.

  6. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency

    Directory of Open Access Journals (Sweden)

    Jolles S

    2013-09-01

    Full Text Available Stephen Jolles Department of Immunology, University Hospital of Wales, Cardiff, UK Abstract: Immunoglobulin (Ig-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either intravenously (IVIg or subcutaneously (SCIg. While hyaluronidase has been used in clinical practice for over 50 years, the development of a high-purity recombinant form of this enzyme (recombinant human hyaluronidase PH20 has recently enabled the study of repeated and more prolonged use of hyaluronidase in facilitating the delivery of SC medicines. It has been used in a wide range of clinical settings to give antibiotics, local anesthetics, insulin, morphine, fluid replacement, and larger molecules, such as antibodies. Hyaluronidase has been used to help overcome the limitations on the maximum volume that can be delivered into the SC space by enabling dispersion of SCIg and its absorption into lymphatics. The rate of facilitated SCIg (fSCIg infusion is equivalent to that of IVIg, and the volume administered at a single site can be greater than 700 mL, a huge increase over conventional SCIg, at 20–40 mL. The use of fSCIg avoids the higher incidence of systemic side effects of IVIg, and it has higher bioavailability than SCIg. Data on the long-term safety of this approach are currently lacking, as fSCIg has only recently become available. fSCIg may help several areas of patient management in primary antibody deficiency, and the extent to which it may be used in future will depend on long-term safety data and cost–benefit analysis. Keywords: enzyme facilitated IgG infusion, recombinant human hyaluronidase PH20, subcutaneous immunoglobulin, intravenous immunoglobulin, primary immunodeficiency disease

  7. Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes : experience of the PedPump Study in 17 countries

    NARCIS (Netherlands)

    Danne, T.; Battelino, T.; Jarosz-Chobot, P.; Kordonouri, O.; Pankowska, E.; Ludvigsson, J.; Schober, E.; Kaprio, E.; Saukkonen, T.; Nicolino, M.; Tubiana-Rufi, N.; Klinkert, C.; Haberland, H.; Vazeou, A.; Madacsy, L.; Zangen, D.; Cherubini, V.; Rabbone, I.; Toni, S.; de Beaufort, C.; Waarde, W. Bakker-van; van den Berg, N.; Volkov, I.; Barrio, R.; Hanas, R.; Zumsteg, U.; Kuhlmann, B.; Aebi, C.; Schumacher, U.; Gschwend, S.; Hindmarsh, P.; Torres, M.; Shehadeh, N.; Phillip, M.

    Aims/hypothesis To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. Methods Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European

  8. Effects of Liraglutide Combined with Short-Term Continuous Subcutaneous Insulin Infusion on Glycemic Control and Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Weijian Ke

    2016-01-01

    Full Text Available The objective of this paper is to investigate the effects of liraglutide in combination with short-term continuous subcutaneous insulin infusion (CSII therapy on glycemic control and beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM. Thirty-nine eligible newly diagnosed T2DM patients were recruited and randomized to receive either of two therapies: short-term CSII alone (CSII alone group or CSII in combination with liraglutide (CSII + Lira group for 12 weeks. Blood glucose control, homeostasis model assessment (HOMA indices, and acute insulin response (AIR were compared between the two groups. The patients in CSII + Lira group achieved euglycemia with equivalent insulin dosage in shorter time (1 (0 versus 2 (3 days, P=0.039. HbA1c at the end of study was comparable between two groups (6.3±0.7% versus 6.0±0.5%, for CSII alone group and CSII + Lira group, resp., P=0.325. The increment of AIR was higher in CSII + Lira group (177.58 (351.57 μU·min/mL versus 58.15 (51.30 μU·min/mL, P<0.001. However, after stopping liraglutide, its effect on beta cell function disappeared completely. Liraglutide combined with short-term CSII was effective in further improving beta cell function, but the beneficial effects did not sustain after suspension of the therapy.

  9. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet?induced obesity rats

    OpenAIRE

    Torres?Villalobos, Gonzalo; Hamdan?P?rez, Nashla; D?az?Villase?or, Andrea; Tovar, Armando R.; Torre?Villalvazo, Ivan; Ordaz?Nava, Guillermo; Mor?n?Ramos, Sof?a; Noriega, Lilia G.; Mart?nez?Ben?tez, Braulio; L?pez?Garibay, Alejandro; Torres?Landa, Samuel; Ceballos?Cant?, Juan C.; Tovar?Palacio, Claudia; Figueroa?Ju?rez, Elizabeth; Hiriart, Marcia

    2016-01-01

    Abstract Long?term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90?days. The study was performed using two different ...

  10. 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: ...

  11. The relationship between the frequency of self-monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections.

    Science.gov (United States)

    Murata, Takashi; Tsuzaki, Kokoro; Yoshioka, Fumi; Okada, Hiroshi; Kishi, Junichiro; Yamada, Kazunori; Sakane, Naoki

    2015-11-01

    We investigated the relationship between the frequency of self-monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software. We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNET™ SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients' hemoglobin A1c (HbA1c) levels was analyzed using the χ(2)-test and linear regression analysis was carried out to clarify their relationship. The odds ratio of achieving a target HbA1c level of diabetes mellitus patients on CSII.

  12. PK/PD modelling of glucose-insulin-glucagon dynamics in healthy dogs after a subcutaneous bolus administration of native glucagon or a novel glucagon analogue

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Boye Knudsen, Carsten

    Objective We aim to develop a simulation model of the complex glucose-insulin-glucagon dynamics based on physiology and data. Furthermore, we compare pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of marketed reconstituted glucagon with a stable liquid glucagon analogue invented by...

  13. Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Koppo, Katrien; Siklová-Vitková, Michaela; Klimcáková, Eva

    2012-01-01

    low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined...... the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM......, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α(2)-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned...

  14. 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

  15. Nutritional education and carbohydrate counting in children with type 1 diabetes treated with continuous subcutaneous insulin infusion: the effects on dietary habits, body composition and glycometabolic control.

    Science.gov (United States)

    Marigliano, Marco; Morandi, Anita; Maschio, Maddalena; Sabbion, Alberto; Contreas, Giovanna; Tomasselli, Francesca; Tommasi, Mara; Maffeis, Claudio

    2013-12-01

    Carbohydrate counting (CHC) in combination with nutritional education has been used to optimize the insulin dose in patients with type 1 diabetes (T1D). The aim of this study was to test the impact of CHC and nutritional education on changes in dietary habits, body composition and body fat distribution in children with T1D treated with insulin pumps (CSII). Twenty-five children with T1D and CSII were recruited and valuated at baseline and after 18 months of follow-up. They were trained in CHC and following standard nutrition education program (based on American Diabetes Association and International Society of Pediatric and Adolescent Diabetes guidelines); clinical, biochemical and nutritional variables were measured. In the total population, body composition, body fat distribution and biochemical variables did not change, at follow-up; HbA1c was significantly reduced (8.50 ± 0.77 vs 7.92 ± 0.74 %; p dietary habits, body composition and body fat distribution in children with T1D treated with CSII. Moreover, the sub-group of subjects showing a significant improvement in glycometabolic control reported an increase in CHO intake and a reduction in fat and protein intake.

  16. Evaluation of a Novel Continuous Glucose Monitoring-Based Method for Mealtime Insulin Dosing—the iBolus—in Subjects with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Controlled Trial

    Science.gov (United States)

    Ampudia-Blasco, F. Javier; Laguna, Alejandro; Revert, Ana; Vehì, Josep; Ascaso, Juan F.; Bondia, Jorge

    2012-01-01

    Abstract Objective Prandial insulin dosing is an empirical practice associated frequently with poor reproducibility in postprandial glucose response. Based on continuous glucose monitoring (CGM), a method for prandial insulin administration (iBolus) is presented and evaluated for people with type 1 diabetes using CSII therapy. Subjects and Methods An individual patient's model for a 5-h postprandial period was obtained from 6-day ambulatory CGM and used for iBolus calculation in 12 patients with type 1 diabetes. In a double-blind, crossover study each patient underwent four meal tests with 40 g or 100 g of carbohydrates (CHOs), both on two occasions. For each meal, the iBolus or the traditional bolus (tBolus) was given before mealtime (t0) in a randomized order. We measured the postprandial glycemic response as the area under the curve of plasma glucose (AUC-PG0–5h) and variability as the individual coefficient of variation (CV) of AUC-PG0–5h. The contribution of the insulin-to-CHO ratio, CHO, plasma glucose at t0 (PGt0), and insulin dose to AUC-PG0–5h and its CV was also investigated. Results AUC-PG0–5h was similar with either bolus for 40-g (iBolus vs. tBolus, 585.5±127.5 vs. 689.2±180.7 mg/dL·h) or 100-g (752.1±237.7 vs. 760.0±263.2 mg/dL·h) CHO meals. A multiple regression analysis revealed a significant model only for the tBolus, with PGt0 being the best predictor of AUC-PG0–5h explaining approximately 50% of the glycemic response. Observed variability was greater with the iBolus (CV, 16.7±15.3% vs. 10.1±12.5%) but independent of the factors studied. Conclusions A CGM-based algorithm for calculation of prandial insulin is feasible, although it does not reduce unpredictability of individual glycemic responses. Causes of variability need to be identified and analyzed for further optimization of postprandial glycemic control. PMID:23003329

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Bioavailability and variability of biphasic insulin mixtures

    DEFF Research Database (Denmark)

    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...

  19. Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats.

    Science.gov (United States)

    Hamishehkar, Hamed; Emami, Jaber; Najafabadi, Abdolhossien Rouholamini; Gilani, Kambiz; Minaiyan, Mohsen; Hassanzadeh, Kambiz; Mahdavi, Hamid; Koohsoltani, Maryam; Nokhodchi, Ali

    2010-03-01

    The pulmonary route is an alternative route of administration for the systemic delivery of peptide and proteins with short-half lives. A long-acting formulation of insulin was prepared by encapsulation of protein into respirable, biodegradable microcapsules prepared by an oil in oil emulsification/solvent evaporation method. Insulin-loaded PLGA microcapsules prepared as a dry powder inhaler formulation were administered via the pulmonary route to diabetic rats and serum insulin and glucose concentrations were monitored. Control treatments consisted of respirable spray-dried insulin (RSDI) powder administered by intratracheal insufflation, insulin-loaded PLGA microcapsules and NPH (long-acting) insulin administered by subcutaneous (SC) administration. Pharmacokinetic analysis demonstrated that insulin administered in PLGA microcapsules illustrated a sustained release profile which resulted in a longer mean residence time, 4 and 5 fold longer than those after pulmonary administration of RSDI and SC injection of NPH insulin, respectively. Accordingly, the hypoglycemic profile followed a stable and sustained pattern which remained constant between 10 and 48 h. Results of the in vitro experiments were in good agreement with those of in vivo studies. Bronchoalveolar lavage fluid analysis indicated that microcapsules administration did not increase the activities of lactate dehydrogenase and total protein. However, histological examination of the lung tissue indicated a minor but detectable effect on the normal physiology of the rat lung. These findings suggest that the encapsulation of peptides and proteins into PLGA microcapsules technique could be a promising controlled delivery system for pulmonary administration. Copyright (c) 2010 John Wiley & Sons, Ltd.

  20. 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....... 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 (safety signals for trastuzumab were observed. CONCLUSIONS: PrefHer revealed...... that switching from IV to SC trastuzumab (hand-held syringe or SID) or vice versa did not impact the known safety profile of trastuzumab....

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

    Science.gov (United States)

    Jin, Jing-Fen; Zhu, Ling-Ling; Chen, Meng; Xu, Hui-Min; Wang, Hua-Fen; Feng, Xiu-Qin; Zhu, Xiu-Ping; Zhou, Quan

    2015-01-01

    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. 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. "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 immu-noglobulin, 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 governing the choice of injection route. Safety and efficacy must be the preferred principles to be considered (eg, epinephrine should be given intramuscularly during an episode of systemic anaphylaxis). If the safety and efficacy of two injection routes are equivalent, clinicians should consider more about patient preference and pharmacoeconomics because patient preference will

  2. Oral Insulin - Fact or Fiction?

    Indian Academy of Sciences (India)

    Insulin is a major protein hormone secreted by the p-cells of the pancreas and is important for the control of diabetes. Insulin is usually administered to diabetic patients through subcutaneous injection. This mode of therapy has certain inherent disadvantages such as local pain, itching and insulin lipodystrophy around the ...

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

    OpenAIRE

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

    2010-01-01

    Objective: 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 ...

  4. Subcutaneous granuloma annulare

    Directory of Open Access Journals (Sweden)

    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.

  5. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-08-01

    Full Text Available BACKGROUND: Over the past 50 years, scientists have recognized that not all adipose tissue is alike, and that health risk is associated with the location as well as the amount of body fat. Different depots are sufficiently distinct with respect to fatty-acid storage and release as to probably play unique roles in human physiology. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. CONTENT: The limited expandability of the subcutaneous adipose tissue leads to inappropriate adipose cell expansion (hypertrophic obesity with local inflammation and a dysregulated and insulin-resistant adipose tissue. The inability to store excess fat in the subcutaneous adipose tissue is a likely key mechanism for promoting ectopic fat accumulation in tissues and areas where fat can be stored, including the intra-abdominal and visceral areas, in the liver, epi/pericardial area, around vessels, in the myocardium, and in the skeletal muscles. Many studies have implicated ectopic fat accumulation and the associated lipotoxicity as the major determinant of the metabolic complications of obesity driving systemic insulin resistance, inflammation, hepatic glucose production, and dyslipidemia. SUMMARY: In summary, hypertrophic obesity is due to an impaired ability to recruit and differentiate available adipose precursor cells in the subcutaneous adipose tissue. Thus, the subcutaneous adipose tissue may be particular in its limited ability in certain individuals to undergo adipogenesis during weight increase. Inability to promote subcutaneous adipogenesis under periods of affluence would favor lipid overlow and ectopic fat accumulation with negative metabolic consequences. KEYWORDS: obesity, adipogenesis, subcutaneous adipose tissue, visceral adipose tissue, adipocyte dysfunction.

  6. Subcutaneous Injection Volume of Biopharmaceuticals-Pushing the Boundaries.

    Science.gov (United States)

    Mathaes, Roman; Koulov, Atanas; Joerg, Susanne; Mahler, Hanns-Christian

    2016-08-01

    Administration into the subcutaneous (SC) tissue is a typical route of delivery for therapeutic proteins, especially for frequent treatments, long-term regimens, or self-administration. It is currently believed that the maximum volume for SC injections is approximately 1.5 mL. Larger SC injection volumes are considered to be associated with injection pain and adverse events at the injection site. However, no controlled clinical studies and actual evidence exist to support this assumption. In this review, we discuss current and publically available data related to SC administration volumes. We conclude that injection volumes higher than 3.5 mL are worth exploring if required for the development of efficacious drug treatments. Studying tissue back pressure, injection site leakage, local tolerability, and injection-related adverse events, such as injection pain, should be considered for the development of higher SC injection volumes. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Cross-Validation of a Glucose-Insulin-Glucagon Pharmacodynamics Model for Simulation using Data from Patients with Type 1 Diabetes

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Ranjan, Ajenthen; Møller, Jan Kloppenborg

    2017-01-01

    a validated glucoregulatory model including the effect of glucagon. Methods: Eight type 1 diabetes (T1D) patients each received a subcutaneous (SC) bolus of insulin on four study days to induce mild hypoglycemia followed by a SC bolus of saline or 100, 200, or 300 µg of glucagon. Blood samples were analyzed...... PK/PD model including equations and fitted parameters allows for in silico experiments that may help improve diabetes treatment involving glucagon for prevention of hypoglycemia....... three PD model test fits in each of the seven subjects. Thus, we successfully validated the PD model by leave-one-out cross-validation in seven out of eight T1D patients. Conclusions: The PD model accurately simulates glucose excursions based on plasma insulin and glucagon concentrations. The reported...

  8. 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...

  9. Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase.

    Science.gov (United States)

    Shpilberg, O; Jackisch, C

    2013-09-17

    Rituximab and trastuzumab were the first therapeutic monoclonal antibodies (mAbs) approved in oncology. Both antibodies are delivered by the intravenous (IV) route, but recently subcutaneous (SC) formulations have been developed. Subcutaneous administration of mAbs can offer substantial patient and resource benefits compared with IV, but SC administration of some mAbs can be limited by drug volume. Recombinant human hyaluronidase (rHuPH20) temporarily degrades hyaluronan, allowing SC delivery of drug volumes that might not otherwise be feasible. Clinical trials assessing coformulation of rituximab or trastuzumab with rHuPH20 for SC administration were reviewed. Phase I trials of rituximab SC maintenance therapy in patients with follicular lymphoma and trastuzumab SC in healthy volunteers and patients with early breast cancer have demonstrated substantially shorter administration times and comparable tolerability and pharmacokinetics compared with IV formulations. Rituximab SC 1400-mg and trastuzumab SC 600-mg doses were identified for further study. Phase III clinical data for rituximab SC 1400 mg have shown comparable efficacy to rituximab IV, and initial clinical data suggest comparable efficacy of trastuzumab SC 600 mg and the IV formulation. Coformulation with rHuPH20 may enable effective, well-tolerated, cost-effective, and convenient SC administration of rituximab and trastuzumab. Additional studies are ongoing.

  10. Subcutaneous Zygomycosis Basidiobolomycosis

    Directory of Open Access Journals (Sweden)

    Sethuraman G

    2001-01-01

    Full Text Available Subcutaneous zygomycosis, also known as basidiobolomycosis, is a rare disease caused by the fungus Basidiobolus ranarum. Since its first description in 1954, may cases have been reported. In India, so far only few cases have been described. We report this entity in a 3 year- old female child who had firm to hard swelling of the right upper extremely and chest. Histopathology showed short aseptate hyphae surrounded by eosinophilic material within the granulomatous tissue response, in the subcutaneous tissue. She responded dramatically to saturated solution of potassium iodide.

  11. Site-dependent differences in both prelamin A and adipogenic genes in subcutaneous adipose tissue of patients with type 2 familial partial lipodystrophy.

    Science.gov (United States)

    Araújo-Vilar, D; Lattanzi, G; González-Méndez, B; Costa-Freitas, A T; Prieto, D; Columbaro, M; Mattioli, E; Victoria, B; Martínez-Sánchez, N; Ramazanova, A; Fraga, M; Beiras, A; Forteza, J; Domínguez-Gerpe, L; Calvo, C; Lado-Abeal, J

    2009-01-01

    Type 2 familial partial lipodystrophy (FPLD2) is characterised by loss of fat in the limbs and buttocks and results from mutations in the LMNA gene. To evaluate the role of several genes involved in adipogenesis in order to better understand the underlying mechanisms of regional loss of subcutaneous adipose tissue (scAT) in patients with FPLD2. In total, 7 patients with FPLD2 and 10 healthy control participants were studied. A minimal model was used to calculate the insulin sensitivity (IS). scAT was obtained from abdomen and thigh by biopsy. Relative gene expression was quantified by real-time reverse transcription PCR in a thermal cycler. Prelamin A western blot analysis was carried out on scAT and prelamin A nuclear localisation was determined using immunofluorescence. Adipocyte nuclei were examined by electron microscopy. Patients with FPLD2 were found to have significantly lower IS. The expression of LMNA was similar in both groups. The expression of PPARG2, RB1, CCND3 and LPL in thigh but not in abdomen scAT was significantly reduced (67%, 25%, 38% and 66% respectively) in patients with FPLD2. Significantly higher levels of prelamin A were found in peripheral scAT of patients with FPLD2. Defects in the peripheral heterochromatin and a nuclear fibrous dense lamina were present in the adipocytes of patients with FPLD2. In FPLD2 participants, prelamin A accumulation in peripheral scAT is associated with a reduced expression of several genes involved in adipogenesis, which could perturb the balance between proliferation and differentiation in adipocytes, leading to less efficient tissue regeneration.

  12. Delivering needle-free insulin using AERx iDMS (insulin diabetes management system) technology.

    Science.gov (United States)

    Wollmer, Per; Pieber, Thomas R; Gall, Mari-Anne; Brunton, Stephen

    2007-06-01

    Inhaled insulin has recently emerged as an alternative to subcutaneous insulin administration. One inhaled insulin device, AERx (a registered trademark of Aradigm Corp., Hayward, CA, or its affiliates in the United States and other countries) insulin diabetes management system (iDMS) (Novo Nordisk A/S, Bagsvaerd, Denmark), uses a unique liquid human insulin strip to deliver an aerosol of insulin to the lungs. AERx iDMS enables 1-unit increment dosing, and the device ensures that the insulin dose is released at the optimal point of inhalation for delivery to the lungs. Compared with subcutaneous human insulin, the pharmacokinetic and pharmacodynamic profile of inhaled insulin with AERx iDMS is similar, but with a more rapid onset of action. Data from these pharmacokinetic studies have also demonstrated that inhaled insulin dosing with AERx iDMS is as consistent and reproducible as subcutaneous human insulin. In individuals with diabetes, prandial inhaled insulin with AERx iDMS is as effective and well tolerated as subcutaneous prandial human insulin or insulin aspart in terms of glycemic control and overall hypoglycemia. No major safety concerns have been raised with respect to pulmonary function tests. Other clinical studies using AERx iDMS in special populations, such as smokers, people with asthma, or people suffering from upper respiratory tract infections, have provided important information regarding the use of inhaled insulin in these circumstances. Overall, pulmonary insulin delivery with the AERx iDMS device appears to be a promising safe and efficacious alternative to subcutaneous insulin injections.

  13. Subcutaneous encapsulated fat necrosis

    DEFF Research Database (Denmark)

    Aydin, Dogu; Berg, Jais O

    2016-01-01

    We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help...

  14. Subcutaneous granuloma annulare

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. Species Composition (SC)

    Science.gov (United States)

    John F. Caratti

    2006-01-01

    The FIREMON Species Composition (SC) method is used to provide ocular estimates of cover and height measurements for plant species on a macroplot. The SC method provides plant species composition and coverage estimates to describe a stand or plant community and can be used to document changes over time. It is suited for a wide variety of vegetation types and is...

  17. c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals

    DEFF Research Database (Denmark)

    Sourris, Karly C; Lyons, Jasmine G; de Courten, Maximilian

    2009-01-01

    Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between...

  18. Massive subcutaneous emphysema with pneumoscrotopenis ...

    African Journals Online (AJOL)

    Chest injury commonly leads to subcutaneous emphysema of the chest, neck and face. It is usually non-life threatening. Massive subcutaneous emphysema may occur and very rarely may spread to involve the scrotal sac and subcutaneous tissue planes of the penis to cause pneumoscrotopenis. This case report presents ...

  19. Subcutaneous bronchogenic cyst

    Directory of Open Access Journals (Sweden)

    Vivek Manchanda

    2010-01-01

    Full Text Available Bronchogenic cysts occur due to the anomalous development of the primitive tracheobronchial tree early in fetal life. They are usually present in middle mediastinum. Rarely, they have been found in other locations. We describe two patients with subcutaneous bronchogenic cysts located over manubrium sterni with special emphasis on the difficulties in pre-operative diagnosis. The two boys were managed by complete excision of the cysts. The children are well on follow-up.

  20. Insulin Secretagogues

    Science.gov (United States)

    ... the Spikes Is mealtime insulin right for you? Insulin Secretagogues September 2017 Download PDFs English Espanol Editors ... Additional Resources Affordable Insulin Project FDA What are insulin secretagogues? Insulin secretagogues are one type of medicine ...

  1. Insulin and Insulin Resistance

    Science.gov (United States)

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  2. Subcutaneous Phycomycosis in a Child

    Directory of Open Access Journals (Sweden)

    Manjiri R. Naniwadekar

    2009-11-01

    Full Text Available Subcutaneous phycomycosis is a rare entity. We hereby report a case of subcutaneous phycomycosis in 18 months old female child who presented with a painless, non-tender swelling on the thigh. Skin biopsy showed eosinophilic granuloma lying deep in the subcutaneous tissue, with sparse hyphae. Culture on Sabouraud's dextrose agar showed characteristic colonies. Patient was started on oral potassium iodide. The swelling was completely resolved after one month of treatment.

  3. Tolerance of subcutaneously administered antibiotics: a French national prospective study.

    Science.gov (United States)

    Roubaud-Baudron, Claire; Forestier, Emmanuel; Fraisse, Thibaut; Gaillat, Jacques; de Wazières, Benoit; Pagani, Leonardo; Ingrand, Isabelle; Bernard, Louis; Gavazzi, Gaëtan; Paccalin, Marc

    2017-01-08

    Although poorly documented, subcutaneous (SC) administration of antibiotics is common practice in France especially in Geriatrics Departments. The aim of this study was to determine the tolerance of such a practice. Prospective observational multicentre study. Sixty-six physicians accepted to participate from 50 French Infectious Diseases and Geriatrics Departments. From May to September 2014, patients treated at least one day with SC antibiotics could be included. Modalities of subcutaneous administration, occurrence of local and systemic adverse effects (AE) and clinical course were collected until the end of the treatment. Two hundred-nineteen patients (83.0 [19–104] yo) were included. Ceftriaxone (n = 163, 74.4%), and ertapenem (n = 30, 13.7%) were the most often prescribed antibiotics. The SC route was mainly used because of poor venous access (65.3%) and/or palliative care (32.4%). Fifty patients (22.8%) experienced at least one local AE that led to an increased hospital stay for two patients (4.0%) and a discontinuation of the SC infusion in six patients (12.0%). A binary logistic regression for multivariate analysis identified the class of antibiotic (p = 0.002) especially teicoplanin and the use of rigid catheter (p = 0.009) as factors independently associated with AE. In over 80% of cases, SC antibiotics were well tolerated and associated with clinical recovery. SC administration of antibiotics leads to frequent but local and mild AE. Use of non-rigid catheter appears to be protective against AE. As it appears to be a safe alternative to the intravenous route, more studies are needed regarding efficacy and pharmacokinetics.

  4. 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...... of adverse events with minocycline versus placebo. CONCLUSION: Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy....

  5. Subcutaneous adipose tissue classification

    Directory of Open Access Journals (Sweden)

    A. Sbarbati

    2010-11-01

    Full Text Available The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT, structural WAT (sWAT and fibrous WAT (fWAT. dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical. In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for

  6. Insulin Basics

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Insulin Basics There are different types of insulin depending ... you may be experiencing a reaction. Types of Insulin Rapid-acting insulin , begins to work about 15 ...

  7. SC tuning fork

    CERN Multimedia

    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...

  8. Macromolecular confinement of therapeutic protein in polymeric particles for controlled release: insulin as a case study

    Directory of Open Access Journals (Sweden)

    Luiz Henrique Guerreiro

    2017-06-01

    Full Text Available ABSTRACT Sustained release systems for therapeutic proteins have been widely studied targeting to improve the action of these drugs. Molecular entrapping of proteins is particularly challenging due to their conformational instability. We have developed a micro-structured poly-epsilon-caprolactone (PCL particle system loaded with human insulin using a simple double-emulsion w/o/w method followed by solvent evaporation method. This formulation is comprised by spheric-shaped microparticles with average size of 10 micrometers. In vitro release showed a biphasic behavior such as a rapid release with about 50% of drug delivered within 2 hours and a sustained phase for up to 48 h. The subcutaneous administration of microencapsulated insulin showed a biphasic effect on glycemia in streptozotocin-induced diabetic mice, compatible with short and intermediate-acting behaviors, with first transition peak at about 2 h and the second phase exerting effect for up to 48h after s.c. administration. This study reveals that a simplified double-emulsion system results in biocompatible human-insulin-loaded PCL microparticles that might be used for further development of optimized sustained release formulations of insulin to be used in the restoration of hormonal levels.

  9. Nanoemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats.

    Science.gov (United States)

    Li, Xiaoyang; Qi, Jianping; Xie, Yunchang; Zhang, Xi; Hu, Shunwen; Xu, Ying; Lu, Yi; Wu, Wei

    2013-01-01

    This study aimed to prepare nanoemulsions coated with alginate/chitosan for oral insulin delivery. Uncoated nanoemulsions were prepared by homogenization of a water in oil in water (w/o/w) multiple emulsion that was composed of Labrafac(®) CC, phospholipid, Span™ 80 and Cremorphor(®) EL. Coating of the nanoemulsions was achieved based on polyelectrolyte cross-linking, with sequential addition of calcium chloride and chitosan to the bulk nanoemulsion dispersion that contained alginate. The particle size of the coated nanoemulsions was about 488 nm and the insulin entrapment ratio was 47.3%. Circular dichroism spectroscopy proved conformational stability of insulin against the preparative stress. In vitro leakage study indicated well-preserved integrity of the nanoemulsions in simulated gastric juices. Hypoglycemic effects were observed in both normal and diabetic rats. The relative pharmacological bioavailability of the coated nanoemulsion with 25 and 50 IU/kg insulin were 8.42% and 5.72% in normal rats and 8.19% and 7.84% in diabetic rats, respectively. Moreover, there were significantly prolonged hypoglycemic effects after oral administration of the coated nanoemulsions compared with subcutaneous (sc) insulin. In conclusion, the nanoemulsion coated with alginate/chitosan was a potential delivery system for oral delivery of polypeptides and proteins.

  10. 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

  11. The effect of insulin to decrease neointimal growth after arterial injury is endothelial nitric oxide synthase-dependent.

    Science.gov (United States)

    Guo, June; Breen, Danna M; Pereira, Troy J; Dalvi, Prasad S; Zhang, Hangjun; Mori, Yusaku; Ghanim, Husam; Tumiati, Laura; Fantus, I George; Bendeck, Michelle P; Dandona, Paresh; Rao, Vivek; Dolinsky, Vernon W; Heximer, Scott P; Giacca, Adria

    2015-07-01

    In vitro, insulin has mitogenic effects on vascular smooth muscle cells (VSMC) but also has protective effects on endothelial cells by stimulating nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) expression. Furthermore, NOS inhibition attenuates the effect of insulin to inhibit VSMC migration in vitro. Using an in vivo model, we have previously shown that insulin decreases neointimal growth and cell migration and increases re-endothelialization after arterial injury in normal rats. Since insulin can stimulate NOS, and NO can decrease neointimal growth, we hypothesized that NOS, and more specifically eNOS was required for the effects of insulin in vivo. Rats were given subcutaneous insulin implants (3 U/day) alone or with the NOS inhibitor l-NAME (2 mg kg(-1) day(-1)) 3 days before arterial (carotid or aortic) balloon catheter injury. Insulin decreased both neointimal area (P < 0.01) and cell migration (P < 0.01), and increased re-endothelialization (P < 0.05). All of these effects were prevented by the co-administration of l-NAME. Insulin was found to decrease inducible NOS expression (P < 0.05) but increase eNOS phosphorylation (P < 0.05). These changes were also translated at the functional level where insulin improved endothelial-dependent vasorelaxation. To further study the NOS isoform involved in insulin action, s.c. insulin (0.1 U/day) was given to wild-type and eNOS knockout mice. We found that insulin was effective at decreasing neointimal formation in wild-type mice after wire injury of the femoral artery, whereas this effect of insulin was absent in eNOS knockout mice. These results show that the vasculoprotective effect of insulin after arterial injury is mediated by an eNOS-dependent mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Effect of Insulin on Visuo-Spatial Memory and Histology of Cerebral Cortex in the Presence or Absence of Nitric Oxide Inhibition.

    Science.gov (United States)

    Yarube, I U; Ayo, J O; Fatihu, M Y; Magaji, R A; Umar, I A; Alhassan, A W; Saleh, M Ia

    2017-03-06

    Insulin has emerged from its traditional 'peripheral' glucose-lowering function to become increasingly regarded as a brain hormone that controls a wide range of functions including learning and memory. Insulin action on learning and memory is linked to nitric oxide (NO) signalling, but its effects on memory and histology of cerebral cortex in conditions of varied NO availability is unclear. This research sought to determine the effect of insulin on visuo-spatial learning, memory and histology of cerebral cortex during NO deficiency. Twenty-four mice weighing 21-23 g, were divided into four groups (n = 6) and treated daily for seven days with 0.2 ml distilled water subcutaneously (s.c.) (control), 10 I.U/kg insulin s.c., 10 I.U/kg insulin + 50 mg/kg L-NAME intraperitoneally (i.p.), and 50 mg/kg i.p. L-NAME s.c., respectively. The 3-day MWM paradigm was used to assess memory. Brain tissue was examined for histological changes. There was no significant difference between day 1 and day 2 latencies for all the groups. The mice in all (but L-NAME) groups spent more time in the target quadrant, and the difference was significant within but not between groups. There was significant reduction in number of platform site crossings (4.83 ± 0.5, 0.67 ± 0.3, 0.50 ± 0.3 and 0.50 ± 0.3 for control, insulin, insulin+L-NAME and L-NAME groups, respectively) in all the groups compared to control. Normal histology of the cortex and absence of histological lesions were observed in brain slides of control and treatment groups. It was concluded that insulin administration impairs visuo-spatial memory to a greater extent in the presence of NO block, and to a lesser extent in the absence of NO block. Nitric oxide has a role in insulin-induced memory impairment. Insulin administration in the presence or absence of NO block had no effect on histology of cortex.

  13. Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist degarelix

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

    Purpose. The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone (GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose......-concentration dependent absorption. Methods. The PK analysis is made in NONMEM through joint analysis of data from two phase I clinical studies; an intravenous infusion study and a single SC dose escalation study. The SC absorption is modeled using an approximation to Ficks' second law of diffusion out of a spherical...

  14. Population Pharmacokinetic Modeling of a Subcutaneous Depot for GnRH Antagonist Degarelix

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

    2004-01-01

    Purpose. The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone ( GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose......-concentration dependent absorption. Methods. The PK analysis is made in NONMEM through joint analysis of data from two phase I clinical studies; an intravenous infusion study and a single SC dose escalation study. The SC absorption is modeled using an approximation to Ficks' second law of diffusion out of a spherical...

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

    Science.gov (United States)

    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

  16. DiSC

    DEFF Research Database (Denmark)

    Pedersen, Rasmus; Sloth, Christoffer; Bruun Andresen, Gorm

    2015-01-01

    This paper presents the MATLAB simulation framework, DiSC, for verifying voltage control approaches in power distribution systems. It consists of real consumption data, stochastic models of renewable resources, flexible assets, electrical grid, and models of the underlying communication channels....... The simulation framework makes it possible to validate control approaches, and thus advance realistic and robust control algorithms for distribution system voltage control. Two examples demonstrate the potential voltage issues from penetration of renewables in the distribution grid, along with simple control...

  17. Efficacy and safety of inhaled insulin in the treatment of diabetes mellitus.

    NARCIS (Netherlands)

    Galan, B.E. de; Simsek, S.; Tack, C.J.J.; Heine, R.J.

    2006-01-01

    Many patients with diabetes mellitus view subcutaneous injections of insulin as a daily burden. Pulmonary delivery of insulin offers an alternative route of administration and may as such improve diabetes treatment. Inhaled insulin provides a rapid absorption of insulin, but with low

  18. Identification of Primo-Vascular System in Abdominal Subcutaneous Tissue Layer of Rats

    Directory of Open Access Journals (Sweden)

    Chae Jeong Lim

    2015-01-01

    Full Text Available The primo-vascular system (PVS is a novel network identified in various animal tissues. However, the PVS in subcutaneous tissue has not been well identified. Here, we examined the putative PVS on the surface of abdominal subcutaneous tissue in rats. Hemacolor staining revealed dark blue threadlike structures consisting of nodes and vessels, which were frequently observed bundled with blood vessels. The structure was filled with various immune cells including mast cells and WBCs. In the structure, there were inner spaces (20–60 µm with low cellularity. Electron microscopy revealed a bundle structure and typical cytology common with the well-established organ surface PVS, which were different from those of the lymphatic vessel. Among several subcutaneous (sc PVS tissues identified on the rat abdominal space, the most outstanding was the scPVS aligned along the ventral midline. The distribution pattern of nodes and vessels in the scPVS closely resembled that of the conception vessel meridian and its acupoints. In conclusion, our results newly revealed that the PVS is present in the abdominal subcutaneous tissue layer and indicate that the scPVS tissues are closely correlated with acupuncture meridians. Our findings will help to characterize the PVS in the other superficial tissues and its physiological roles.

  19. Insulin Therapy

    Science.gov (United States)

    ... Your Health Resources Drugs, Procedures & Devices Prescription Medicines Insulin Therapy Insulin Therapy Share Print When you digest food, your ... you eat into glucose (a form of sugar). Insulin allows this glucose to enter all the cells ...

  20. The effects of crocin, insulin and their co-administration on the heart function and pathology in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Amir Farshid

    2016-11-01

    Full Text Available Objective: Crocinisa saffron constituent with a potent anti-oxidant activity. The present study investigated the effects of crocin and insulin treatments (alone or in combination on cardiac function and pathology in diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (i.p. injection of streptozotocin (STZ, 50 mg/kg. Thereafter, crocin (5, 10 and 20 mg/kg, i.p., subcutaneous (s.c. injection of insulin (4 IU/kg and their combination were administeredfor eight weeks. Blood glucose level andwhole heart and body weights were measured. Electrocardiography (ECG was carried out using the lead II. Serum concentrations of lactate dehydrogenase (LDH, creatine kinase-MB isoenzyme (CK-MB, and the heart tissue malodialdehyde (MDA and superoxide dismutase (SOD contents were determined. The heart lesions were evaluated by light microscopy. Results: STZ decreased body weight and increased whole heart weight/body weight ratio. It also decreased heart rate, and increased RR and QT intervals and T wave amplitude. STZ increased blood glucose, serum LDH andCK-MB levels, augmentedheart tissue MDA content, decreased SOD content of heart tissue, and produced hemorrhages, degeneration, interstitial edema, and fibroblastic proliferation in the heart tissue. Crocin (10 and 20 mg/kg, i.p., insulin (4 IU/kg, s.c. and their combination (5 mg/kg of crocin with 4 IU/kg of insulin treatments recovered the ECG, biochemical and histopathological changes induced by STZ. Conclusion: The results showed cardioprotective  effects of crocin and insulin in STZ-induced diabetic rats. The antioxidant and anti-hyperglycemic properties of crocin and insulin may be involved in their cardioprotective actions.

  1. Evolution of subcutaneous adipose tissue fibrosis after bariatric surgery.

    Science.gov (United States)

    Chabot, K; Gauthier, M-S; Garneau, P Y; Rabasa-Lhoret, R

    2017-04-01

    Obesity is associated with the development of metabolic complications such as insulin resistance (IR). The mechanisms leading to IR remain unclear. This study aimed to investigate the relationship between adipose tissue fibrosis and IR in obese patients before and after bariatric surgery. Thirty-five obese patients awaiting bariatric surgery (12 with type 2 diabetes) were included in the study. Non-diabetic patients were classified as either insulin-sensitive (n=11) or insulin-resistant (n=12), based on the Matsuda insulin sensitivity index (ISI Matsuda ). Homoeostasis model assessment (HOMA-IR) was used for longitudinal evaluation of insulin resistance. Fibrosis was quantified by Masson's trichrome staining on microscopy, and mRNA levels of fibrosis-related genes were examined in subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies collected during and 6 months after bariatric surgery (SAT only). Despite their similar age, body mass index and fat mass, SAT fibrosis was significantly higher in diabetic vs insulin-sensitive patients (Psurgery and significant weight loss, fibrosis levels remained unchanged in SAT, although IR was significantly reduced in all groups (Psurgery. Overall, these results show a significant but, most likely, transient association between SAT fibrosis and IR in obese humans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. The Effectiveness and Durability of an Early Insulin Pump Therapy in Children and Adolescents with Type 1 Diabetes Mellitus

    OpenAIRE

    Brancato, Davide; Fleres, Mattia; Aiello, Vito; Saura, Gabriella; Scorsone, Alessandro; Ferrara, Lidia; Provenzano, Francesca; Di Noto, Anna; Spano, Lucia; Provenzano, Vincenzo

    2014-01-01

    Background: This study evaluated the predictors of effectiveness and durability of insulin pump therapy in children and adolescents who have initiated continuous subcutaneous insulin infusion (CSII) within 2 years after the diagnosis of type 1 diabetes mellitus (T1DM).

  3. Subcutaneous Fluid Administration: A Potentially Useful Tool in Prehospital Care

    Directory of Open Access Journals (Sweden)

    Annette O. Arthur

    2012-01-01

    Full Text Available Mass casualty incidents (MCIs and disaster medical situations are ideal settings in which there is need for a novel approach to infusing fluids and medications into a patient’s intravascular space. An attractive new approach would avoid the potentially time-consuming needlestick and venous cannulation requiring a trained practitioner. In multiple-patient situations, trained practitioners are not always available in sufficient numbers to enable timely placement of intravenous catheters. The novel approach for intravascular space infusion, described in this paper involves the preadministration of the enzyme, human recombinant hyaluronidase (HRH, into the subcutaneous (SC space, via an indwelling catheter. The enzyme “loosens” the SC space effectively enhancing the absorption of fluids and medication.

  4. Subcutaneous granuloma annulare: radiologic appearance

    Energy Technology Data Exchange (ETDEWEB)

    Kransdorf, M.J. [Saint Mary`s Hospital, Richmond, VA (United States). Dept. of Radiol.]|[Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Murphey, M.D. [Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)]|[Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States)]|[Department of Radiology, School of Medicine, University of Maryland, Baltimore, Maryland (United States); Temple, H.T. [Department of Orthopedic Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia (United States)]|[Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)

    1998-05-01

    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.) With 3 figs., 17 refs.

  5. Transdermal delivery of insulin via microneedles.

    Science.gov (United States)

    Narayan, Roger J

    2014-09-01

    Treatment of insulin-dependent diabetes mellitus, also known as Type 1 diabetes mellitus, requires delivery of exogenous insulin via injection or pump. An alternative to syringe-based subcutaneous delivery of insulin involves use of microneedles. These delivery of insulin. Benefits associated with microneedle-based delivery of insulin include minimal training for use, painless insertion, as well as the potential to combine microneedles with sensors and drug delivery devices to create an autonomous artificial pancreas. In this review, the efforts of academic and industrial researchers over the past decade to examine the functionality of microneedles for delivery of insulin, including insulin-containing nanomaterials, via in vitro, ex vivo, and in vivo studies are considered.

  6. Subcutaneous adipose tissue from obese and lean adults does not release hepcidin in vivo.

    Science.gov (United States)

    Tussing-Humphreys, Lisa; Frayn, Keith N; Smith, Steven R; Westerman, Mark; Dennis, A Louise; Nemeth, Elizabeta; Thomson, Jessica; Pusatcioglu, Cenk

    2011-01-01

    Hepcidin is the main regulator of systemic iron homeostasis and is primarily produced by the liver but is also expressed, at the mRNA-level, in periphery tissues including the subcutaneous and visceral adipose tissue. Obesity is associated with elevated hepcidin concentrations and iron depletion suggesting that the exaggerated fat mass in obesity could contribute significantly to circulating hepcidin levels consequently altering iron homeostasis. The objective of this study was to determine if abdominal subcutaneous adipose tissue (AbScAT) releases hepcidin in vivo and if release is modified by obesity. Arterio-venous differences in concentrations of hepcidin were measured across AbScAT in 9 obese and 9 lean adults. Overall (n = 18), mean plasma hepcidin concentrations were significantly higher in arterialized compared to AbScAT venous samples [mean difference (arterialized-AbScAT venous plasma hepcidin) = 4.9 ± 9.6 ng/mL, P = 0.04]. Net regional release was not calculated because mean venous plasma hepcidin concentrations were lower than mean arterialized concentrations indicating no net release. Significant correlations between AbScAT venous and arterialized plasma hepcidin concentrations with anthropometric variables were not observed. Findings from this vein drainage study suggest there is no net release of hepcidin from the AbScAT depot and thereby no ability to signal systemically, even in obesity.

  7. Subcutaneous Adipose Tissue from Obese and Lean Adults Does Not Release Hepcidin In Vivo

    Directory of Open Access Journals (Sweden)

    Lisa Tussing-Humphreys

    2011-01-01

    Full Text Available Hepcidin is the main regulator of systemic iron homeostasis and is primarily produced by the liver but is also expressed, at the mRNA-level, in periphery tissues including the subcutaneous and visceral adipose tissue. Obesity is associated with elevated hepcidin concentrations and iron depletion suggesting that the exaggerated fat mass in obesity could contribute significantly to circulating hepcidin levels consequently altering iron homeostasis. The objective of this study was to determine if abdominal subcutaneous adipose tissue (AbScAT releases hepcidin in vivo and if release is modified by obesity. Arterio-venous differences in concentrations of hepcidin were measured across AbScAT in 9 obese and 9 lean adults. Overall (n=18, mean plasma hepcidin concentrations were significantly higher in arterialized compared to AbScAT venous samples [mean difference (arterialized-AbScAT venous plasma hepcidin = 4.9±9.6 ng/mL, P=0.04]. Net regional release was not calculated because mean venous plasma hepcidin concentrations were lower than mean arterialized concentrations indicating no net release. Significant correlations between AbScAT venous and arterialized plasma hepcidin concentrations with anthropometric variables were not observed. Findings from this vein drainage study suggest there is no net release of hepcidin from the AbScAT depot and thereby no ability to signal systemically, even in obesity.

  8. Insulin Modulates Cytokine Release, Collagen and Mucus Secretion in Lung Remodeling of Allergic Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Sabrina S. Ferreira

    2017-06-01

    Full Text Available IntroductionThe role of insulin in lung remodeling in a model of asthma in healthy and diabetic mice was evaluated.Material and methodsDiabetic male BALB/c mice (alloxan, 50 mg/kg, intravenous and controls were sensitized by subcutaneous (s.c. injection of ovalbumin (OA, 20 µg in aluminum hydroxide (Al(OH3, 2 mg 10 days after the alloxan injection and received the same dose 12 days later. Six days after the last sensitization, animals were nebulized with OA solution for 7 days. The first set of diabetic and control mice received 2 and 1 IU, respectively, of s.c. neutral protamine Hagedorn (NPH insulin and were analyzed 8 h later. The second set of diabetic and control mice received 2 and 1 IU, respectively, of insulin 12 h before the OA challenge and half doses of insulin 2 h before each the seven OA challenges. Twenty-four hours after the last challenge, the following analyses were performed: (a quantification of the cells in the bronchoalveolar lavage fluid (BALF, the white cell count, and blood glucose; (b morphological analysis of lung tissues by hematoxylin and eosin staining; (c quantification of collagen deposition in lung tissues and mucus by morphometric analysis of histological sections stained with Masson’s trichrome and periodic acid-Schiff (PAS, respectively; and (d quantification of the cytokine concentrations (IL-4, IL-5, and IL-13 in the BALF supernatant.ResultsCompared to controls, diabetic mice had significantly reduced inflammatory cells (81% in the BALF, no eosinophils in the BALF and peripheral blood and reduced collagen deposition and mucus in the lungs. BALF concentrations of IL-4 (48% and IL-5 (31% decreased and IL-13 was absent. A single dose of insulin restored peripheral blood eosinophils and BALF mononuclear cells but not BALF eosinophils, collagen deposition, and mucus levels. However, multiple doses of insulin restored both total cells and eosinophils in the BALF and peripheral blood, BALF

  9. Insulin Modulates Cytokine Release, Collagen and Mucus Secretion in Lung Remodeling of Allergic Diabetic Mice.

    Science.gov (United States)

    Ferreira, Sabrina S; Nunes, Fernanda P B; Casagrande, Felipe B; Martins, Joilson O

    2017-01-01

    The role of insulin in lung remodeling in a model of asthma in healthy and diabetic mice was evaluated. Diabetic male BALB/c mice (alloxan, 50 mg/kg, intravenous) and controls were sensitized by subcutaneous (s.c.) injection of ovalbumin (OA, 20 µg) in aluminum hydroxide (Al(OH)3, 2 mg) 10 days after the alloxan injection and received the same dose 12 days later. Six days after the last sensitization, animals were nebulized with OA solution for 7 days. The first set of diabetic and control mice received 2 and 1 IU, respectively, of s.c. neutral protamine Hagedorn (NPH) insulin and were analyzed 8 h later. The second set of diabetic and control mice received 2 and 1 IU, respectively, of insulin 12 h before the OA challenge and half doses of insulin 2 h before each the seven OA challenges. Twenty-four hours after the last challenge, the following analyses were performed: (a) quantification of the cells in the bronchoalveolar lavage fluid (BALF), the white cell count, and blood glucose; (b) morphological analysis of lung tissues by hematoxylin and eosin staining; (c) quantification of collagen deposition in lung tissues and mucus by morphometric analysis of histological sections stained with Masson's trichrome and periodic acid-Schiff (PAS), respectively; and (d) quantification of the cytokine concentrations (IL-4, IL-5, and IL-13) in the BALF supernatant. Compared to controls, diabetic mice had significantly reduced inflammatory cells (81%) in the BALF, no eosinophils in the BALF and peripheral blood and reduced collagen deposition and mucus in the lungs. BALF concentrations of IL-4 (48%) and IL-5 (31%) decreased and IL-13 was absent. A single dose of insulin restored peripheral blood eosinophils and BALF mononuclear cells but not BALF eosinophils, collagen deposition, and mucus levels. However, multiple doses of insulin restored both total cells and eosinophils in the BALF and peripheral blood, BALF cytokines, and collagen deposition and mucus

  10. Upregulation of Early and Downregulation of Terminal Pathway Complement Genes in Subcutaneous Adipose Tissue and Adipocytes in Acquired Obesity

    Directory of Open Access Journals (Sweden)

    Sanna Kaye

    2017-05-01

    Full Text Available Inflammation is an important mediator of obesity-related complications such as the metabolic syndrome but its causes and mechanisms are unknown. As the complement system is a key mediator of inflammation, we studied whether it is activated in acquired obesity in subcutaneous adipose tissue (AT and isolated adipocytes. We used a special study design of genetically matched controls of lean and heavy groups, rare monozygotic twin pairs discordant for body mass index (BMI [n = 26, within-pair difference (Δ in body mass index, BMI >3 kg/m2] with as much as 18 kg mean Δweight. Additionally, 14 BMI-concordant (BMI <3 kg/m2 served as a reference group. The detailed measurements included body composition (DEXA, fat distribution (MRI, glucose, insulin, adipokines, C3a and SC5b-9 levels, and the expression of complement and insulin signaling pathway-related genes in AT and adipocytes. In both AT and isolated adipocytes, the classical and alternative pathway genes were upregulated, and the terminal pathway genes downregulated in the heavier co-twins of the BMI-discordant pairs. The upregulated genes included C1q, C1s, C2, ficolin-1, factor H, receptors for C3a and C5a (C5aR1, and the iC3b receptor (CR3. While the terminal pathway components C5 and C6 were downregulated, its inhibitor clusterin was upregulated. Complement gene upregulation in AT and adipocytes correlated positively with adiposity and hyperinsulinemia and negatively with the expression of insulin signaling-related genes. Plasma C3a, but not SC5b-9, levels were elevated in the heavier co-twins. There were no differences between the co-twins in BMI-concordant pairs. Obesity is associated with increased expression of the early, but not late, complement pathway components and of key receptors. The twins with acquired obesity have therefore an inflated inflammatory activity in the AT. The results suggest that complement is likely involved in orchestrating clearance of apoptotic debris

  11. Inhaled insulin using AERx insulin Diabetes Management System (AERx iDMS).

    Science.gov (United States)

    Mudaliar, Sunder

    2007-10-01

    Diabetes is a chronic, debilitating disease that afflicts millions of people worldwide and poor glycemic control in this disease leads to numerous microvascular and macrovascular complications. There is growing evidence that tight glycemic control prevents the development, and delays the progression, of microvascular complications and possibly macrovascular disease in patients with diabetes. All patients with Type 1 diabetes and many patients with Type 2 diabetes require intensive insulin therapy to achieve optimal glucose control. Although subcutaneous insulin therapy is the mainstay of insulin therapy, there are patients who fear needles and often refuse to start insulin therapy despite suboptimal glucose control. In these patients, inhaled insulin represents a non-invasive, painless method to administer intensive insulin treatment. The Novo Nordisk AS AERx iDMS (insulin Diabetes Management System) for inhaled insulin is a novel device that administers an aerosol of liquid insulin into the deep lung with dose adjustments as precise as one subcutaneous unit. Initial pharmacokinetic and pharmacodynamic studies demonstrate that the device delivers liquid insulin in a clear dose-response manner and with a rapid onset of action similar to the fast-acting analog insulins. At present, large, long-term Phase III studies are in progress to document not only the efficacy, but also the safety and feasibility of this device in the treatment of patients with diabetes.

  12. Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

    Science.gov (United States)

    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.

  13. Effectiveness of Subcutaneous Methotrexate in Chronic Plaque Psoriasis.

    Science.gov (United States)

    Yesudian, Paul Devakar; Leman, Joyce; Balasubramaniam, Periasamy; Macfarlane, Andy W; Al-Niaimi, Firas; Griffiths, Christopher E M; Burden, Arthur David; Warren, Richard B

    2016-03-01

    Oral methotrexate (MTX) has been a first line systemic agent in the treatment of chronic plaque psoriasis (CPP) for more than 50 years. Parenteral MTX, administered as a subcutaneous (SC) injection has gained favour in recent years. The effectiveness of SC MTX has been proven in rheumatological conditions but there has been no assessment of its role in CPP. We retrospectively reviewed case notes of 85 patients prescribed SC MTX for psoriasis in three dermatology centres in the UK (Betsi Cadwaladr University Health Board, Western Infirmary, Glasgow, and Salford Royal NHS Foundation Trust). Audit department approval was sought and granted. A total of 85 patients (44 male; 41 female; age range 14 - 78 years, mean 44 years; 79 Caucasian, 6 Asian) with CPP were identified. The average duration of psoriasis was 19 years [range 3 - 60 years]. Co-morbidities included depression, diabetes mellitus, hypertension, epilepsy, obesity, ischaemic heart disease, and hyperlipidaemia; 29 patients had no associated co-morbidities. Psoriatic arthritis was noted in 18 patients. Previous treatments included phototherapy (both narrow band ultraviolet B [TLO1] and psoralen and ultraviolet A [PUVA])(n=60), oral MTX (n=82), ciclosporin (n=37), acitretin (n=19), fumaric acid esters (n=20), hydroxycarbamide (n=6), mycophenolate mofetil (n=2), and repeated in-patient admissions (n=2). Oral MTX was stopped due to nausea (n=43), ineffectiveness (n=13) or partial response (n=11), headache (n=3), increased liver enzymes (n=2), and lethargy (n=2). The median number of systemic agents used prior to SC MTX was 3 (mean 2.65, range 1 to 6 agents). The weekly dose of SC MTX varied between 7.5mg to 30 mg (mean 18.5mg, median 20mg) and had been used for 2 months to 67 months (mean 14 months; median 9 months). Folic acid supplementation was used in every patient. The patients were reviewed between 6 weeks to 3 months once treatment was fully established. Using a pre-determined "adjective list" (where

  14. SUBCUTANEOUS BASIDIOBOLOMYCOSIS: A CASE REPORT

    African Journals Online (AJOL)

    2013-07-09

    Jul 9, 2013 ... E-mail: sackey@sky.com. Conflict of interest: None declared. SUMMARY. Basidiobolomycosis is an uncommon chronic deep fungal infection in which gradually enlarging granulomas form, usually in the subcutaneous fat tissues of the limbs, chest or trunk of immunocompetent hosts, primarily children.

  15. Pneumomediastinum and subcutaneous cervical emphysema ...

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2012-09-08

    Sep 8, 2012 ... department with a history of increasing difficulty with breathing and ... ward and commenced on intravenous antibiotics and high flow oxygen. He made remarkable improvement with complete resolution of subcutaneous emphysema on the 4th day ... the left lateral decubitus position.18 Our patient met most.

  16. Pyrexial therapy in subcutaneous phycomycosis

    Directory of Open Access Journals (Sweden)

    Reddy BSN

    1992-01-01

    Full Text Available A case of subcutaneous phycomycosis occurring in a 2 ½ year old child is reported for its rarity, clinical interest and paucity of literature. The condition failed to resolve with conventional antimycotics but improved with the administration of concomitant pyrexial therapy.

  17. Pneumomediastinum and subcutaneous cervical emphysema ...

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2012-09-08

    Sep 8, 2012 ... to trauma or pathological disease state3, with gastroin- testinal and respiratory diseases most commonly impli- cated.4,5. The respiratory disease commonly associated with pneu- momediastinum and subcutaneous cervical emphysema is bronchial asthma.6 Pneumonia, though a very com- mon childhood ...

  18. Assessing the impact of a new delivery method of insulin on glycemic control using a novel trial design

    Directory of Open Access Journals (Sweden)

    Thomas Strack

    2009-01-01

    Full Text Available Thomas Strack1, Luc Martinez2, Stefano Del Prato3, Larry Blonde4, Burkhard Göke5, Vincent Woo6, Ann Millward7, Ramon Gomis8, Bill Canovatchel1, David Lawrence1, Nick Freemantle9 on behalf of the EXPERIENCE Trial Team1Pfizer Inc., New York, NY, USA; 2Société Française de Médecine Générale, Issy les Moulineaux, France; 3University of Pisa, Pisa, Italy; 4Ochsner Medical Center, New Orleans, LO, USA; 5University of Munich, Munich, Germany; 6Health Sciences Centre, Winnipeg, Canada; 7Peninsula Medical School, Plymouth, UK; 8University of Barcelona, Barcelona, Spain; 9University of Birmingham, Birmingham, UKObjective: The purpose of the trial was to examine the impact of inhaled human insulin (INH on patient or physician willingness to adopt insulin after oral diabetes agent failure.Research design and methods: The EXPERIENCE trial was a one-year randomized controlled trial conducted at primary, secondary and tertiary care facilities in Europe and North America. The primary study endpoint was difference in glycated hemoglobin (A1c between randomized groups at 26 weeks, and results from that phase have been reported previously. The present report concerns results from the second 26-week extension phase. We also consider the applicability of the design. The trial recruited 727 patients with type 2 diabetes mellitus who, prior to randomization, were using two or more oral diabetes agents and whose A1c was ≥8.0%. Patients were randomized to two treatment settings: Group 1 (usual care with the option of INH or Group 2 (usual care only. Usual care included adjusting oral therapy (optimizing current regimen or adding/deleting agents and/or initiating subcutaneous (SC insulin.Results: At baseline, insulin was initiated by more (odds ratio [OR] 6.0;95% confidence interval [CI] 4.2 to 8.8; P < 0.0001 patients in Group 1 (86.2%; 76.7% INH plus 9.5% SC than in Group 2 (50.7%; SC insulin only. The largest reduction from baseline in A1c was in Group 1 (

  19. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure

    National Research Council Canada - National Science Library

    Wu, Michelle V; Bikopoulos, George; Hung, Steven; Ceddia, Rolando B

    2014-01-01

    ...) and subcutaneous inguinal (SC Ing) white adipose tissue (WAT) and how it affects whole-body energy expenditure in sedentary and endurance-trained rats fed ad libitum either low fat or high fat (HF) diets...

  20. Metabolic Control with Insulin Pump Therapy: Preliminary Experience

    Directory of Open Access Journals (Sweden)

    Shang-Ren Hsu

    2008-07-01

    Conclusion: Our preliminary experience demonstrated the effectiveness of insulin pump therapy for both type 1 and type 2 diabetic patients. The reduction in their HbA1C values was both statistically and clinically significant. This treatment should be considered for patients poorly controlled by subcutaneous insulin injection therapy.

  1. Fetal subcutaneous cells have potential for autologous tissue engineering.

    Science.gov (United States)

    Ekblad, Åsa; Westgren, Magnus; Fossum, Magdalena; Götherström, Cecilia

    2018-01-11

    Major congenital malformations affect up to 3% of newborns. Infants with prenatally diagnosed soft tissue defects should benefit from having autologous tissue readily available for surgical implantation in the perinatal period. In this study, we investigate fetal subcutaneous cells (fSC) as cellular source for tissue engineering. Fetal subcutaneous biopsies were collected from elective terminations at gestational week 20-21. Cells were isolated, expanded and characterized in vitro. To determine cell coverage, localization, viability and proliferation in different constructs, the cells were seeded onto a matrix (small intestine submucosa (SIS)) or in collagen gel with or without poly(ε-caprolactone) (PCL) mesh and were kept in culture for up to 8 weeks before analysis. Angiogenesis was analyzed through a tube-forming assay. fSC could be expanded until 43±3 population doublings, expressed mesenchymal markers and readily differentiate into adipogenic and osteogenic lineages. The cells showed low adherence to SIS and did not migrate deep into the matrix. However, in collagen gels the cells migrated into the gel and proliferated with sustained viability for up to 8 weeks. The cells in the matrices expressed Ki67, CD73 and α-smooth muscle actin but not cytokeratin or CD31. Fetal cells derived from subcutaneous tissue demonstrated favorable characteristics for preparation of autologous tissue transplants before birth. Our study supports the theory that cells could be obtained from the fetus during pregnancy for tissue engineering purposes after birth. In a future clinical situation, autologous transplants could be used for reconstructive surgery in severe congenital malformations. This article is protected by copyright. All rights reserved.

  2. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

    Science.gov (United States)

    Carrasco-Benso, Maria P; Rivero-Gutierrez, Belen; Lopez-Minguez, Jesus; Anzola, Andrea; Diez-Noguera, Antoni; Madrid, Juan A; Lujan, Juan A; Martínez-Augustin, Olga; Scheer, Frank A J L; Garaulet, Marta

    2016-09-01

    In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. © FASEB.

  3. Intradermal Insulin Delivery

    Science.gov (United States)

    Hultström, Michael; Roxhed, Niclas

    2014-01-01

    The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines. PMID:24876605

  4. Does switching from oral to subcutaneous administration of methotrexate influence on patient reported gastro-intestinal adverse effects?

    DEFF Research Database (Denmark)

    Kromann, Charles B; Lage-Hansen, Philip R; Koefoed, Mette

    2015-01-01

    INTRODUCTION: When treating patients with methotrexate (MTX) the most frequently reported adverse effects (AE) are gastrointestinal (GI) with nausea being reported by 10-20%. If intolerable AE of oral MTX persist, switching from oral to subcutaneous (SC) or intramuscular (IM) administration...... is common. However, this approach is largely empirical and the evidence is inconsistent. To our knowledge, this will be the first study to estimate the change in GI AE of switching from oral to SC MTX. METHODS: A retrospective postal survey was sent to patients who had changed from oral MTX to SC MTX. GI AE...

  5. 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...

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

    OpenAIRE

    Jin JF; Zhu LL; Chen M; Xu HM; Wang HF; Feng XQ; Zhu XP; Zhou Q

    2015-01-01

    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 ver...

  7. Behandeling van patiënten met diabetes mellitus door middel van inhalatie-insuline

    NARCIS (Netherlands)

    Simsek, S.; Galan, B.E. de; Tack, C.J.J.; Heine, R.J.

    2006-01-01

    Good glycaemic control of diabetes mellitus is still hampered by the fear of insulin injections. Particularly in patients with type 2 diabetes, inhaled insulin as a novel therapeutic option for glycaemic control could be an alternative to subcutaneous insulin. Phase III clinical studies have shown

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  9. Injectable agents affecting subcutaneous fats.

    Science.gov (United States)

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. ©2015 Frontline Medical Communications.

  10. Principles of subcutaneous port placement.

    Science.gov (United States)

    Gonda, Shaun J; Li, Ruizong

    2011-12-01

    The introduction of totally implantable subcutaneous devices in the early 1980s provided patients with secure, reliable venous access and also gave them the ability to move more freely and have a more normal lifestyle with these devices in place. The most common totally implantable device used today is the subcutaneous port. These ports consist of an injection port connected to a catheter. Ports provide a number of advantages compared with other venous catheters; the most important is the reduced risk of infection. These devices have significantly lower rates of infection than nontunneled and tunneled catheters. Additional advantages include less frequent irrigation and minimal home care, and they are less prone to environmental or cutaneous contamination when not being accessed. This article will focus on the placement of these ports. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL amyloidosis.

    Directory of Open Access Journals (Sweden)

    Surbhi Sidana

    Full Text Available Randomized studies have shown that bortezomib (BTZ can be given weekly via intravenous (IV route or twice weekly via subcutaneous (SC route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001 while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15. Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008 while the likelihood of not achieving a response (= partial response or better was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56 for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001.Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.

  12. Subcutaneous emphysema during status astmaticus

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, E.

    1985-09-01

    Spontaneous subcutaneous accumulations of air in the soft parts of the thorax during an asthmatic crisis (status asthmaticus) are rarely seen. The pathomechanism of the phenomenon, which may lead to the formation of an emphysema of the soft parts via the pneumomediastinum, is discussed, and the possible complications which must be taken into account are pointed out. The value of radiological examination of the thorax in children suffering from asthma bronchiale, is explained briefly. (orig.).

  13. Epidural, paraspinal, and subcutaneous lipomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Sener, R. Nuri [Department of Radiology, Ege University Hospital, Bornova, Izmir (Turkey)

    2003-09-01

    A unique case of idiopathic diffuse lipomatosis is reported. The patient was an 11-year-old boy with diffuse lipomatosis in the epidural space, paraspinal muscles, and thoracolumbar subcutaneous regions. Epidural lipomatosis involved the entire thoracolumbar spine and was associated with filar thickening and lipoma. In addition, paraspinal muscles, especially the erector spinae group, had diffuse fatty infiltration. The ultimate clinical effect of this fatty tissue was urinary dysfunction, radicular pain and hypoesthesia in both legs and difficulty walking. (orig.)

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

    DEFF Research Database (Denmark)

    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...

  15. Monitor of SC beam profiles

    CERN Multimedia

    CERN PhotoLab

    1977-01-01

    A high-resolution secondary emission grid for the measurement of SC beam profiles. Modern techniques of metal-ceramic bonding, developed for micro-electronics, have been used in its construction. (See Annual Report 1977 p. 105 Fig. 12.)

  16. First coil for the SC

    CERN Multimedia

    CERN PhotoLab

    1955-01-01

    The coils for the SC magnet were stored in the large hangar of the Cointrin Airport (to make sure that they would be available before snow and ice would block the roads and canals from Belgium, where they were built).

  17. Slip points of subcutaneous adipose tissue lipids do not predict beef marbling score or percent intramuscular lipid.

    Science.gov (United States)

    Carvalho, Victor V; Smith, Stephen B

    2018-02-07

    We hypothesized that slip points of subcutaneous (s.c.) adipose tissue lipids would predict USDA beef marbling scores or percent intramuscular lipid (%IML). M. longissimus dorsi (LD) muscle and s.c. adipose tissue from 79 feedlot-finished Angus steers were analyzed for lipid slip point, %IML, and fatty acid composition. The s.c. monounsaturated:saturated fatty acid (MUFA:SFA) ratio and s.c. lipid slip points were highly correlated (R 2  = 0.557; P  0.05). These data indicate s.c. adipose tissue lipid slip point did not predict USDA marbling scores or %IML in the conventionally fed Angus steers of this study. Copyright © 2018. Published by Elsevier Ltd.

  18. Sodium retention and insulin treatment in insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Nørgaard, K; Feldt-Rasmussen, B

    1994-01-01

    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...... 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...

  19. 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

    Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin-dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose-insulin-glucagon model was used to describe seven virtual patients with insulin pump......-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...

  20. A Systematic Review of Patients' Perspectives on the Subcutaneous Route of Medication Administration.

    Science.gov (United States)

    Ridyard, Colin H; Dawoud, Dalia M M; Tuersley, Lorna V; Hughes, Dyfrig A

    2016-08-01

    Subcutaneous injections allow for self-administration, but consideration of patients' perspectives on treatment choice is important to ensure adherence. Previous systematic reviews have been limited in their scope for assessing preferences in relation to other routes of administration. Our objective was to examine patients' perspectives on subcutaneously administered self-injectable medications when compared with other routes or methods of administration for the same medicines. Nine electronic databases were searched for publications since 2000 using terms pertaining to methods of administration, choice behavior, and adverse effects. Eligibility for inclusion was determined through reference to specific criteria by two independent reviewers. Results were described narratively. Of the 1726 papers screened, 85 met the inclusion criteria. Studies were focused mainly on methods of insulin administration for diabetes but also included treatments for pediatric growth disorders, multiple sclerosis, HIV, and migraine. Pen devices and autoinjectors were favored over administration with needle and syringe, particularly with respect to ergonomics, convenience, and portability. Inhalation appeared to be more acceptable than subcutaneous injection (in the case of insulin), but how subcutaneous infusion, intramuscular injection, and needle-free injection devices compare with subcutaneous injections in terms of patient preference is less certain. The review identified a number of studies showing the importance of the methods and routes of drug delivery on patient choice. However, studies were prone to bias, and further robust evidence based on methodologically sound approaches is required to demonstrate how patient choice might translate to improved adherence.

  1. Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery

    Science.gov (United States)

    Matteucci, Elena; Giampietro, Ottavio; Covolan, Vera; Giustarini, Daniela; Fanti, Paolo; Rossi, Ranieri

    2015-01-01

    Insulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients’ (and diabetologists’) ideal requirements that organic chemistry could meet. PMID:26124635

  2. Subcutaneous Leiomyosarcoma of the Frenulum

    Directory of Open Access Journals (Sweden)

    D. Mendis

    2005-01-01

    Full Text Available Leiomyosarcomas of the penis are rare, with only 29 reported cases to date. We record the case of a patient who presented with a 2-year history of a seemingly indolent penile skin lesion. On histopathology of the local resection, a diagnosis of subcutaneous leiomyosarcoma was made. Specifically, leiomyosarcoma of the penile frenulum has not been clearly reported previously. The patient underwent a further excision to ensure an adequate resection margin and has had no disease recurrence at subsequent follow-up. Our case was of a lesion that, although clinically benign, was malignant and this possibility should be borne in mind when assessing patients.

  3. 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

  4. Presternal subcutaneous bronchogenic cyst in adolescence

    Science.gov (United States)

    Moon, Sung Mo; Lee, Sang Min; Kang, Haeyoun; Choi, Hye Jeong

    2017-01-01

    Abstract Subcutaneous bronchogenic cysts have been described rarely, particularly among adolescents. Only a few reports have described the ultrasonographic features of bronchogenic cysts, characterizing them as nonspecific cystic masses with or without internal echogenic foci or debris. Therefore, it is hard to differentiate subcutaneous bronchogenic cysts from other subcutaneous cystic tumors ultrasonographically. We report a case of presternal subcutaneous bronchogenic cyst in an 18-year-old man with unusual ultrasonographic findings. Ultrasonography revealed a small, oval, cystic mass containing a well-circumscribed, heterogeneously hypoechoic, egg-shaped lesion in the dependent portion of the mass within the subcutaneous fat layer overlying the sternum. Surgical excision was performed, and the cystic mass was diagnosed as a bronchogenic cyst. On pathological examination, the internal, heterogeneously hypoechoic, ball-like lesion was found to be mucous material within the cyst. To our knowledge, this is the first reported case of a presternal subcutaneous bronchogenic cyst presenting with a ball-like lesion inside of the cyst. This unusual ultrasonographic feature can be a clue to the diagnosis of subcutaneous bronchogenic cyst. In conclusion, if an anechoic cyst containing an internal, well-circumscribed, hypoechoic ball-like lesion is seen in the presternal subcutaneous fat layer, subcutaneous bronchogenic cyst should be considered in the differential diagnosis of subcutaneous cystic masses. PMID:28151916

  5. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Rask-Madsen, C; Ihlemann, N; Krarup, T

    2001-01-01

    Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n......, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease....... after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high...

  6. Insulin degludec is a new ultra-long-acting insulin analogue

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-06-01

    Full Text Available Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba® is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

  7. Tolerability and Plasma Drug Level Monitoring of Prolonged Subcutaneous Teicoplanin Treatment for Bone and Joint Infections.

    Science.gov (United States)

    El Samad, Youssef; Lanoix, Jean-Philippe; Bennis, Youssef; Diouf, Momar; Saroufim, Carlo; Brunschweiler, Benoit; Rousseau, Florence; Joseph, Cédric; Hamdad, Farida; Ait Amer Meziane, Mohamed; Routier, Simon; Schmit, Jean-Luc

    2016-10-01

    Teicoplanin is a key drug for the treatment of multiresistant staphylococcal bone and joint infections (BJI), yet can only be administered via a parenteral route. The objective of this study was to evaluate the safety and tolerability of subcutaneous (s.c.) teicoplanin for that indication over 42 days. Thirty patients with Gram-positive cocci BJI were included. Once the target of 25 to 40 mg/liter trough serum concentration was achieved, treatment was switched from an intravenous to an s.c. route. No discontinuation of teicoplanin related to injection site reaction and no severe local adverse event were observed. On multivariate analysis, better tolerability was observed at the beginning of treatment, in patients over 70 years old, and for dosages less than 600 mg. In conclusion, we recommend s.c. administration of teicoplanin when needed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Tolerability and Plasma Drug Level Monitoring of Prolonged Subcutaneous Teicoplanin Treatment for Bone and Joint Infections

    Science.gov (United States)

    Bennis, Youssef; Diouf, Momar; Saroufim, Carlo; Brunschweiler, Benoit; Rousseau, Florence; Joseph, Cédric; Hamdad, Farida; Ait Amer Meziane, Mohamed; Routier, Simon; Schmit, Jean-Luc

    2016-01-01

    Teicoplanin is a key drug for the treatment of multiresistant staphylococcal bone and joint infections (BJI), yet can only be administered via a parenteral route. The objective of this study was to evaluate the safety and tolerability of subcutaneous (s.c.) teicoplanin for that indication over 42 days. Thirty patients with Gram-positive cocci BJI were included. Once the target of 25 to 40 mg/liter trough serum concentration was achieved, treatment was switched from an intravenous to an s.c. route. No discontinuation of teicoplanin related to injection site reaction and no severe local adverse event were observed. On multivariate analysis, better tolerability was observed at the beginning of treatment, in patients over 70 years old, and for dosages less than 600 mg. In conclusion, we recommend s.c. administration of teicoplanin when needed. PMID:27458228

  9. 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

  10. [Subcutaneous teicoplanin for children with infectious endocarditis].

    Science.gov (United States)

    Carpentier, E; Roméo, B; El Samad, Y; Geslin-Lichtenberger, L; Maingourd, Y; Tourneux, P

    2013-07-01

    Infectious endocarditis in children requires prolonged antibiotic therapy. In adults, antibiotics administrated subcutaneously such as teicoplanin are an alternative to intravenous treatment. We report the use of subcutaneous teicoplanin, after an initial antibiotic treatment administrated intravenously, for 2 children treated for infectious endocarditis following an initial cardiac surgery. Serum concentrations of teicoplanin were within the target range after the adaptation in the teicoplanin subcutaneous dosages. The treatment was effective for both cases. No specific side effects related to the treatment were reported. Subcutaneous administration could be used for prolonged antibiotic therapy for the treatment of infectious endocarditis in children, after an initial intravenous treatment. Variability of the bioavailability of antibiotics administrated subcutaneously requires regular testing. Prospective, randomized trials comparing intravenous and subcutaneous administration of teicoplanin should be conducted to assess the efficacy and safety of this treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Subcutaneous Emphysema—Beyond the Pneumoperitoneum

    OpenAIRE

    Ott, Douglas E.

    2014-01-01

    Background: Subcutaneous emphysema and gas extravasation outside of the peritoneal cavity during laparoscopy has consequences. Knowledge of the circumstances that increase the potential for subcutaneous emphysema is necessary for safe laparoscopy. Methods: A literature review and a PubMed search are the basis for this review. Conclusions: The known risk factors leading to subcutaneous emphysema during laparoscopy are multiple attempts at abdominal entry, improper cannula placement, loose fitt...

  12. Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty?Two?Week Randomized, Double?Blind, Placebo?Controlled Study

    OpenAIRE

    Stohl, William; Schwarting, Andreas; Okada, Masato; Scheinberg,Morton; Doria, Andrea; Hammer, Anne E.; Kleoudis, Christi; Groark, James; Bass, Damon; Fox, Norma Lynn; Roth, David; Gordon, David

    2017-01-01

    Objective To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE). Methods Patients with moderate?to?severe SLE (score of ?8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Respon...

  13. Rotary condenser for SC2

    CERN Multimedia

    1975-01-01

    During 1975 the SC2 performance was improved among other things by redesigning some of the elements of the ROTCO (Annual Report 1975, p. 55). The photo shows an interior wiew of the housing of the rotary condenser and of the sixteen sets of shaped stator blades.

  14. and Deltamethrin 1% SC (Pali)

    African Journals Online (AJOL)

    control. During the experimental period (10 to 29 January 2011), the three groups of cattle were attended separately to avoid contacts. A high degree of efficacy of. Deltamethrin 1% pour-on (Smash) and Deltamethrin 1% SC (Pali) against single- and multi-host ticks was achieved by a single application of each product.

  15. Body Fat Distribution and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Nicola Abate

    2013-06-01

    Full Text Available The burden of obesity has increased globally over the last few decades and its association with insulin resistance and related cardio-metabolic problems have adversely affected our ability to reduce population morbidity and mortality. Traditionally, adipose tissue in the visceral fat depot has been considered a major culprit in the development of insulin resistance. However, there is a growing body of evidence supporting the role of subcutaneous truncal/abdominal adipose tissue in the development of insulin resistance. There are significant differences in the functional characteristics of subcutaneous abdominal/truncal vs. intraabdominal vs. gluteo-femoral fat depots. More recently, mounting evidence has been supporting the role of adipose tissue function in the development of metabolic complications independent of adipose tissue volume or distribution. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger a vicious cycle of inflammation leading to subcutaneous adipose tissue dysfunction and ectopic fat deposition. Therapeutic lifestyle change continues to be the most important intervention in clinical practice to improve adipose tissue function and avoid development of insulin resistance and related cardio-metabolic complications.

  16. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    Directory of Open Access Journals (Sweden)

    Vasiliki Valla

    2010-01-01

    Full Text Available Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.

  17. Model Predictive Control Algorithms for Pen and Pump Insulin Administration

    DEFF Research Database (Denmark)

    Boiroux, Dimitri

    Despite recent developments within diabetes management such as rapidacting insulin, continuous glucose monitors (CGM) and insulin pumps, tight blood glucose control still remains a challenge. A fully automated closedloop controller, also known as an artificial pancreas (AP), has the potential...... to ease the life and reduce the risk of acute and chronic diabetic complications. However, the noise associated to CGMs, the long insulin action time for continuous subcutaneous infusion of insulin (CSII) pumps, and the high intra- and inter-patient variability significantly limits the performance...

  18. 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

    during cooling and rewarming and to measure the effect of scalp cooling on subcutaneous scalp blood flow, subcutaneous blood flow and epi- and subcutaneous temperatures were measured in the frontal region at the hairline border before and during cooling with a cooling helmet, during spontaneous rewarming...

  19. 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).

  20. Insulin pump therapy in transient neonatal diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Joong Heum Park

    2013-09-01

    Full Text Available Neonatal diabetes mellitus (NDM is a rare disease requiring insulin treatment. Its treatment is primarily focused on maintaining adequate glycemic control and avoiding hypoglycemia. Although insulin pump therapy is frequently administered to adults and children, there is no consensus on the use of insulin pumps in NDM. A 10 day-old female infant was referred to us with intrauterine growth retardation and poor weight gain. Hyperglycemia was noted, and continuous intravenous insulin infusion was initiated. However, the patient's serum glucose levels fluctuated widely, and maintaining the intravenous route became difficult within the following weeks. Continuous subcutaneous insulin infusion with an insulin pump was introduced on the twenty-fifth day of life, and good glycemic control was achieved without any notable adverse effects including hypoglycemia. We suggest that the insulin pump is a safe and effective mode for treating NDM and its early adoption may shorten the length of hospital stays in patients with NDM.

  1. 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

    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...... by elevated levels of plasma visfatin. Recombinant human IL-6 infusion to mimic the exercise-induced IL-6 response (n = 6) had no effect on visfatin mRNA expression in adipose tissue compared with the effect of placebo infusion (n = 6). The finding that exercise enhances subcutaneous adipose tissue visfatin mRNA...... 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...

  2. Model study of the pressure build-up during subcutaneous injection.

    Directory of Open Access Journals (Sweden)

    Maria Thomsen

    Full Text Available 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 of a porous medium. For equivalent injection forces we measure the change in the infusion rate between injections in air at atmospheric pressure and in tissue. From a best fit with our model, we then determine the flow permeability as well as the bulk modulus of the tissue, estimated to be of the order 10-11-10-10 m2 and 105 Pa, respectively. The permeability is in good agreement with reported values for adipose porcine tissue. We suggest our model as a general way to estimate the pressure build-up in tissue during subcutaneous injection.

  3. 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...... of a porous medium. For equivalent injection forces we measure the change in the infusion rate between injections in air at atmospheric pressure and in tissue. From a best fit with our model, we then determine the flow permeability as well as the bulk modulus of the tissue, estimated to be of the order 10......-11-10-10 m2 and 105 Pa, respectively. The permeability is in good agreement with reported values for adipose porcine tissue. We suggest our model as a general way to estimate the pressure build-up in tissue during subcutaneous injection....

  4. Gentamicin concentrations in human subcutaneous tissue

    DEFF Research Database (Denmark)

    Lorentzen, Hanne; Kallehave, Finn Lasse; Kolmos, Hans Jørn Jepsen

    1996-01-01

    in human subcutaneous adipose tissue by a microdialysis technique. Seven healthy young volunteers each had four microdialysis probes placed in the fat (subcutaneous) layer of the abdominal skin. After the administration of a 240-mg gentamicin intravenous bolus, consecutive measurements of the drug...

  5. 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...

  6. Gentamicin concentrations in human subcutaneous tissue

    DEFF Research Database (Denmark)

    Lorentzen, Hanne; Kallehave, Finn Lasse; Kolmos, Hans Jørn Jepsen

    1996-01-01

    Wound infections frequently originate from the subcutaneous tissue. The effect of gentamicin in subcutaneous tissue has, however, normally been evaluated from concentrations in blood or wound fluid. The aim of the present study was to investigate the pharmacokinetic properties of gentamicin in hu...... the presence of sufficient concentrations in the adipose tissue to be effective against common bacteria....

  7. Subcutaneous Emphysema—Beyond the Pneumoperitoneum

    Science.gov (United States)

    2014-01-01

    Background: Subcutaneous emphysema and gas extravasation outside of the peritoneal cavity during laparoscopy has consequences. Knowledge of the circumstances that increase the potential for subcutaneous emphysema is necessary for safe laparoscopy. Methods: A literature review and a PubMed search are the basis for this review. Conclusions: The known risk factors leading to subcutaneous emphysema during laparoscopy are multiple attempts at abdominal entry, improper cannula placement, loose fitting cannula/skin and fascial entry points, use of >5 cannulas, use of cannulas as fulcrums, torque of the laparoscope, increased intra-abdominal pressure, procedures lasting >3.5 hours, and attention to details. New additional risk factors acting as direct factors leading to subcutaneous emphysema risk and occurrence are total gas volume, gas flow rate, valveless trocar systems, and robotic fulcrum forces. Recognizing this spectrum of factors that leads to subcutaneous emphysema will yield greater patient safety during laparoscopic procedures. PMID:24680136

  8. 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

  9. 2010 ARRA Lidar: Bamberg County (SC)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Provide high density LiDAR elevation data map of Bamberg County, SC. Provide Bare Earth DEM (vegetation removal) of Bamberg County, SC.

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

    Science.gov (United States)

    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

  11. Effects of subcutaneous calcium administration at calving on mineral status, health, and production of Holstein cows.

    Science.gov (United States)

    Amanlou, H; Akbari, A P; Farsuni, N E; Silva-Del-Río, N

    2016-11-01

    The objective of this study was to determine effects of subcutaneous (s.c.) infusions of Ca at calving day on serum concentrations of Ca, P, Mg, β-hydroxybutyrate (BHB), glucose, body condition score (BCS), milk yield, and health in fresh cows receiving a dietary cation-anion difference diet during the dry period. Three hundred seventy-five fresh Holstein cows were blocked based on parity (143 cows in first parity, 108 cows in second parity, and 124 cows in third or greater parity) and randomly assigned to 1 of 4 experimental treatments immediately after calving. Treatments were control group without infusion (control; n=190); 1 s.c. infusion of 250mL of 40% Ca borogluconate (1SC250; n=72) at calving; 1 s.c. infusion of 500mL of 40% Ca borogluconate (1SC500; n=63) at calving; 2 s.c. infusions of 250mL of 40% Ca borogluconate, one immediately after calving and the second 12 to 18h after first infusion (2SC250; n=50). Blood samples were collected immediately after parturition and at 1, 2, 4, and 7d in milk (DIM) for Ca, P, and Mg determination. Milk production, milk composition, and somatic cell count were recorded monthly up to 90 DIM. The evaluation of BCS was performed at calving and at 38 DIM. A subset of 9 cows per treatment group was randomly chosen to measure serum concentration of glucose and BHB at 2, 4, and 7 DIM. Total serum Ca in 1SC250 (8.95mg/dL), 1SC500 (9.27mg/dL), and 2SC250 (9.07mg/dL) was greater during the first week postpartum compared with control (8.45mg/dL). Serum concentrations of P, Mg, BHB, glucose, and milk yield were not affected by treatments. The dry matter intake during the first 24h after calving was higher for treatments 1SC250 (13.5kg), 1SC500 (15.0kg), and 2SC250 (15.6kg) relative to control (12.5kg). Milk somatic cell counts were lower for 1SC500 (90.5 cells/mL) and 2SC250 (82.2 cells/mL) than control (132.8 cells/mL). Risk ratio was >1 for development of metritis, and clinical and subclinical endometritis in control cows

  12. Co-infusion of adipose tissue derived mesenchymal stem cell-differentiated insulin-making cells and haematopoietic cells with renal transplantation: a novel therapy for type 1 diabetes mellitus with end-stage renal disease.

    Science.gov (United States)

    Dave, Shruti D; Vanikar, Aruna V; Trivedi, Hargovind L

    2013-05-23

    Type 1 diabetes mellitus (T1DM) is a common cause of end-stage renal disease (ESRD). Various factors contribute to wide fluctuations in blood glucose levels and exogenous insulin requirement in such patients even after renal transplantation (RT). Simultaneous pancreas-kidney transplantation is one of the therapies for these patients. Stem cell (SC) therapy for T1DM and for minimisation of immunosuppression after RT has shown encouraging results. We report a 30-year-old-man with T1DM since 15 years and ESRD since 2 years, who underwent living donor RT and co-infusion of in vitro generated insulin-making cells differentiated from donor adipose tissue derived mesenchymal stem cells and bone marrow -derived haematopoietic SC into subcutaneous tissue, portal and thymic circulation under non-myeloablative conditioning. Over follow-up of 13 months he has stable graft function with serum creatinine, 1.2 mg/dl, zero rejection and glycosylated haemoglobin level of 6.1% on calcineurin-inhibitor based therapy.

  13. Insulin Test

    Science.gov (United States)

    ... involves changes in diet and lifestyle. The American Diabetes Association recommends losing excess weight, getting regular amounts of moderate intensity physical activity, and increasing dietary fiber to lower blood insulin levels and increase the ...

  14. Insulin Test

    Science.gov (United States)

    ... to come strictly from animal sources (cow and pig pancreas cells). Most insulin used today is synthetic, ... developing type 2 diabetes , hypertension , hyperlipidemia , and/or heart disease several years down the road. Abdominal obesity, ...

  15. The use of subcutaneous infusion in medication administration.

    Science.gov (United States)

    Gabriel, Janice

    The subcutaneous administration of medications is an area that receives little attention compared with other types of parenteral therapy. Parenteral administration is used by many thousands of patients who self-administer their medication on a daily basis-for example, those using insulin to manage diabetes, recipients of some types of hormone therapy and so on. It is also an effective route for the continuous administration of medication(s) in individuals who are terminally ill. Patients approaching the end of their life may be unable to tolerate the administration of oral medication to control their symptoms and make them more comfortable. This paper will discuss how subcutaneous infusion can be used to deliver these medications, but at the same time how important the selection of the most appropriate subcutaneous infusion device is to the overall comfort of the patient, and to reduce the potential for sharps-related injuries to healthcare workers. Appropriate device selection, together with its management, is an important contributing factor to patient safety and comfort. It will diminish the potential for premature device loss, which can lead to repeated insertion procedures for the patient, as well as delaying their medication. There is also a resource implication for the NHS, as the replacement of any device involves the use of additional equipment and staff time. Additionally, the use of any infusion device poses a risk to healthcare workers of acquiring a bloodborne infection should they experience a percutaneous injury. Knowledge of what equipment is available will reduce the potential risk to these staff.

  16. Pharmacokinetics of liposome-encapsulated meglumine antimonate after intramuscular and subcutaneous administration in dogs.

    Science.gov (United States)

    Valladares, J E; Freixas, J; Alberola, J; Franquelo, C; Cristofol, C; Arboix, M

    1997-10-01

    Controlling canine leishmaniasis may reduce the incidence of human leishmaniasis, which affect immunocompromised persons, especially those with human immunodeficiency virus infection. Thus, the pharmacokinetics of liposome-encapsulated meglumine antimonate (LMA) in dogs was studied after intramuscular (I.M.) and subcutaneous (S.C.) administration. Serum concentration-time data for both forms of administration were best described by a triexponential open model. The absorption phase showed statistically significant differences between I.M. and S.C. administrations (K01(I.M.) = 0.046/min, K01(S.C.) = 0.025/min). The first phase of decrease of plasma concentrations showed a longer half-life for S.C. than for I.M. administration, with the delay being caused by the slow absorption process after S.C. injection. Mean terminal phase half-lives after administration of I.M. and S.C. were 904.1 min and 637.4 min, respectively. Peak plasma concentrations after administration of I.M. (Cmax = 43.8 microg/ml) and S.C. (Cmax = 24.9 microg/ml) were detected at 42.8 min and 79.8 min, respectively. Urinary excretion of antimony for both routes surpassed 80% during the first 6 hr, with the rest of the drug being excreted slowly over the following 18 hr. The results obtained with this formulation suggest that for treating canine leishmaniasis, it would be more advisable to inject LMA intramuscularly if we assume that the significantly higher Cmax observed after I.M. administration is more relevant to dog's clinical outcome than is maintenance of concentrations over longer periods.

  17. 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...

  18. Acute dermatomyositis associated with generalized subcutaneous edema.

    Science.gov (United States)

    Lee, Ki-Hong; Lim, Sung-Ryoun; Kim, Yeon-Joo; Lee, Kyung-Ju; Myung, Dae-Seong; Jeong, Hae-Chang; Yoon, Woong; Lee, Shin-Seok; Park, Yong-Wook

    2008-06-01

    Generalized subcutaneous edema is an uncommon manifestation of inflammatory myopathy. We report a 48-year-old female patient who presented with severe generalized edema, an erythematous skin rash, dysphagia and proximal muscle weakness. She was diagnosed with dermatomyositis from the clinical signs, increased muscle enzymes, electromyographic findings and a muscle biopsy. Magnetic resonance imaging revealed increased signal intensity in the muscular and subcutaneous layers. The conditions causing generalized edema were excluded. It was concluded that the generalized edema was secondary to dermatomyositis. Aggressive treatments with high-dose glucocorticoids and immunosuppressive agents were used to control the severe subcutaneous edema.

  19. Insulin Requirements in Relation to Insulin Pump Indications in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Gabriela GHIMPEŢEANU

    2015-09-01

    Full Text Available The purpose of the current research was to assess changes in daily insulin requirements in type 1 diabetic patients transitioning from multiple daily injections (MDI of insulin to continuous subcutaneous insulin infusion (CSII using an external insulin pump, according to clinical indications for changing therapy. The charts of 70 patients with type 1 diabetes (T1D initiating insulin pump therapy were retrospectively reviewed before CSII and after optimization of glycaemic profile with CSII during hospital admission. Daily insulin doses, basal/bolus distributions, dose changes during treatment transition and glycaemic outcomes with MDI and optimized CSII according to insulin pump indications were evaluated. Daily insulin doses were not significantly different among indication groups, with both MDI and CSII; likewise, the overall daily distribution of basal/rapid insulin ratio was similar, around 40/60. With optimized CSII, significant differences were found only in basal/bolus distribution in patients initiating CSII for recurrent hypoglycemia, who had a significantly lower basal (6.4% lower and a complementary higher bolus requirement, compared to patients initiating CSII for HbA1c ≥ 8.5%. At transition, basal insulin needs declined similarly in the high HbA1c and impractical/inflexible MDI groups by approximately 20%, and up to 30% in the recurrent hypoglycaemia group; bolus doses decreased by 20% when the indication was high HbA1c and by approximately 15% for the other indications. Glycaemic control was significantly improved only in patients initiating CSII for high HbA1c (≥8.5%. Insulin pump indication should be considered when starting T1D patients on CSII. These findings may support clinicians in decision making regarding insulin dose changes when initiating insulin pump therapy.

  20. Acceleration of Insulin Pharmacodynamic Profile by a Novel Insulin Infusion Site Warming Device

    Science.gov (United States)

    Cengiz, Eda; Weinzimer, Stuart A.; Sherr, Jennifer L.; Tichy, Eileen; Martin, Melody; Carria, Lori; Steffen, Amy; Tamborlane, William V.

    2012-01-01

    Background and Objective Subcutaneously injected rapid-acting insulin analogs do not replicate physiologic insulin action due to delays in their onset and peak action resulting in post-prandial glucose excursions. The InsuPatch (IP) is a novel insulin infusion site warming device developed to accelerate insulin action by increasing blood flow to the area of insulin absorption. 13 adolescents with type 1 diabetes (mean age 14±4 years) were enrolled in this study to investigate the effect of the IP on the pharmacodynamics and pharmacokinetics of a 0.2u/kg bolus dose of aspart insulin using the euglycemic clamp technique. Research Design and Methods Each subject underwent two euglycemic clamp procedures on separate occasions: one with and one without IP activation in random order. Results When the insulin bolus was given with IP activation as compared to without IP activation, time to reach maximum insulin action (TGIRmax) and to reach 50% maximum action (T 50%GIRmax) were 35 and 18 minutes earlier (125±8 min vs. 90±6min, p=0.002 and 58±5min. vs. 40±3min, p=0.01, respectively), and the AUC GIR 0-90min, reflecting early glucodynamic action, was significantly greater (p=0.001). IP activation also accelerated the rise in plasma insulin levels after the bolus (p=0.03) and resulted in a higher peak (p=0.04) and greater overall increase (p=0.02) in plasma insulin levels. Conclusions Our results demonstrate that insulin infusion site warming with IP activation accelerates the time action profile of aspart insulin which may be of benefit to current open-loop and future closed-loop insulin delivery in patients with type 1 diabetes. PMID:23107353

  1. Safety and efficacy of subcutaneous and continuous intravenous infusion of rIL-2 in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Geertsen, P.F.; Gore, M.E.; Negrier, S.

    2004-01-01

    A retrospective analysis was conducted on data from four open-label, nonrandomised, phase II trials of recombinant interleukin-2 (rIL-2) in patients with metastatic renal cell carcinoma to compare the safety and efficacy of administration by subcutaneous (s.c.) and continuous intravenous (c...

  2. Safety and immunogenicity of subcutaneous or intramuscular administration of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae in healthy volunteers

    NARCIS (Netherlands)

    Laurichesse, H.; Gourdon, F.; Smits, H. L.; Abdoe, T. H.; Estavoyer, J. M.; Rebika, H.; Pouliquen, P.; Catalina, P.; Dubray, C.; Beytout, J.

    2007-01-01

    The safety and immunogenicity of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae was evaluated in 84 volunteers according to the route of administration, i.e., subcutaneous (SC) or intramuscular (IM), in a double-blind randomised trial. The volunteers

  3. Intracerebral and subcutaneous xenografts of human sclc in the nude rat - comparison of monoclonal-antibody localization and tumor-infiltrating lymphocytes

    NARCIS (Netherlands)

    Bulte, J. W. M.; Go, K. Gwan; Zuiderveen, F.; The, T. Hauw; de Leij, Lou

    In the WAG/Rij nude rat, subcutaneous (s.c.) and intracerebral (i.c.) xenografts of the human SCLC cell line GLC-28 were evaluated for their growth behavior, in vivo monoclonal antibody binding and presence of tumor infiltrating lymphocytes. For the i.c. xenografts, two models of cerebral tumor

  4. Metabolic syndrome and insulin resistance in obese adolescents

    OpenAIRE

    Amanda Oliva Gobato; Vasques,Ana Carolina J.; Mariana Porto Zambon; Antonio de Azevedo Barros Filho; Gabriel Hessel

    2014-01-01

    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 ...

  5. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  6. Massive Subcutaneous Emphysema in Robotic Sacrocolpopexy

    Science.gov (United States)

    Celik, Hatice; Cremins, Angela; Jones, Keisha A.

    2013-01-01

    The advent of robotic surgery has increased the popularity of laparoscopic sacrocolpopexy. Carbon dioxide insufflation, an essential component of laparoscopy, may rarely cause massive subcutaneous emphysema, which may be coincident with life-threatening situations such as hypercarbia, pneumothorax, and pneumomediastinum. Although the literature contains several reports of massive subcutaneous emphysema after a variety of laparoscopic procedures, we were not able to identify any report of this complication associated with laparoscopic or robotic sacrocolpopexy. Massive subcutaneous emphysema occurred in 3 women after robotic sacrocolpopexy in our practice. The patients had remarkable but reversible physical deformities lasting up to 1 week. A valveless endoscopic dynamic pressure system was used in all 3 of our cases. Our objective is to define the risk of massive subcutaneous emphysema during robotic sacrocolpopexy in light of these cases and discuss probable predisposing factors including the use of valveless endoscopic dynamic pressure trocars. PMID:23925018

  7. Recurrent, giant subcutaneous leiomyosarcoma of the thigh

    Directory of Open Access Journals (Sweden)

    Gao Chuanping, MD

    2015-10-01

    Full Text Available We present a case of recurrent, massive subcutaneous leiomyosarcoma involving the left thigh in a 29-year-old male from Madagascar. The patient had earlier undergone local resection of subcutaneous leiomyosarcoma a half year before. After surgical intervention, local recurrence developed at this site and was rapidly growing. The patient was surgically treated with a 2-cm-wide margin local excision in our hospital. The patient has remained recurrence free at 1-year follow-up.

  8. 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...

  9. Diabetes and Insulin

    Science.gov (United States)

    ... in the abdomen just behind the stomach, produces insulin. Insulin is a hormone that takes glucose from the ... occurs when the pancreas does not produce enough insulin or when the body doesn’t use insulin ...

  10. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... After Your Baby is Born Monogenic Diabetes Prediabetes & Insulin Resistance What is insulin? Insulin is a hormone made in the pancreas, ... body absorb glucose and use it for energy. Insulin's Role in Blood Glucose Control When blood glucose ...

  11. Postthrombotic or non-postthrombotic severe venous insufficiency: impact of removal of superficial venous reflux with or without subcutaneous fasciotomy.

    Science.gov (United States)

    Christenson, Jan T

    2007-08-01

    Severe chronic venous insufficiency is often associated with therapy-resistant or recurrent venous leg ulcers, either as a result of deep vein thrombosis (DVT)- (postthrombotic syndrome [PTS]) or superficial venous insufficiency (SVI). Frequently present dermatoliposclerosis affects the skin as well as the subcutaneous and subfascial structures, which may impact tissue pressures and compromise skin perfusion. This study was undertaken to measure tissue pressures in PTS and SVI limbs and to evaluate the impact of removal of superficial venous reflux with or without concomitant subcutaneous fasciotomy. In eight patients with recurrent, therapy-resistant venous leg ulcers, due to PTS (11 limbs, 12 ulcers) and 14 patients with severe SVI (14 limbs, 14 ulcers), subcutaneous fasciotomy was performed in addition to removal of superficial reflux. They were compared with eight patients with PTS (11 limbs, 11 ulcers) and 10 patients with SVI (13 limbs, 13 ulcers) who did not have fasciotomy in addition to removal of their superficial venous reflux. Intramuscular (i.m.) and subcutaneous (s.c.) tissue pressures and transcutaneous oxygen tension (TcPO(2)) were measured prior to, immediately after, and 3 months following the surgical intervention. Healing of ulcer (spontaneous or by skin grafting) at 3 months was also observed. There were no statistical differences between the groups regarding gender and age distribution or ulcer age at the time of surgery. All patients had in addition to surgery compression stockings class II (30 mm Hg). The i.m. tissue pressure was higher in patients with PTS compared with SVI patients, while s.c. tissue pressure and TcPO(2) did not differ between the groups. When fasciotomy was performed, i.m. and s.c. tissue pressures decreased and TcPO(2) increased significantly. Without fasciotomy, only s.c. tissue pressure decreased first at 3 months postoperatively. In the SVI-group, i.m tissue pressure was significantly decreased at 3 months in the

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration.

    Science.gov (United States)

    Schiff, Michael H; Jaffe, Jonathan S; Freundlich, Bruce

    2014-08-01

    To compare the relative bioavailability, safety and tolerability of oral methotrexate (MTX) and subcutaneous (SC) MTX administered via an auto-injector (MTXAI) in patients with rheumatoid arthritis (RA). In this randomised, multicenter, open-label, three-way crossover study, patients ≥18 years with adult RA undergoing treatment with MTX for ≥3 months were assigned to receive MTX 10, 15, 20 and 25 mg weekly in a random sequence of three treatments: oral, SC into the abdomen and SC into the thigh. For 24 h after administration of each treatment, blood samples were collected for pharmacokinetic analysis and injection sites were assessed. Forty-seven patients completed the study. Systemic exposure of oral MTX plateaued at doses ≥15 mg/week. In contrast, SC MTX demonstrated a linear increase in systemic exposure that was greater than oral MTX at each dose. No unexpected AEs were noted for either formulation. Unlike oral MTX, the systemic exposure of SC MTX did not plateau over the doses studied, particularly at doses ≥15 mg/week. In this study, higher systemic MTX exposure was not associated with increases in AEs. Patients with an inadequate clinical response to oral MTX may benefit from higher drug exposure by switching to SC MTX. NCT01618968. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Subcutaneous Fat Necrosis of the Newborn: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Kyung Sik; Cho, Bum Sang; Bae, Il Hun; Lee, Seung Young; Jeon, Min Hee; Lee, Ok Jun; Kim, Mi Jung [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2007-09-15

    Subcutaneous fat necrosis in the newborn is an uncommon transient disorder of the subcutaneous adipose tissue that develops after birth. We describe the characteristic ultrasonography and CT findings of a case of pathologically confirmed subcutaneous fat necrosis located at the subcutaneous fat layer of the neck, back, and shoulders with a review of the literature

  15. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...

  16. Postoperative analgesic effects of intravenous, intramuscular, subcutaneous or oral transmucosal buprenorphine administered to cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Giordano, Tatiana; Steagall, Paulo V M; Ferreira, Tatiana H; Minto, Bruno W; de Sá Lorena, Sílvia Elaine Rodolfo; Brondani, Juliana; Luna, Stelio P L

    2010-07-01

    To compare the postoperative analgesic effects of intravenous (IV), intramuscular (IM), subcutaneous (SC) or oral transmucosal (OTM) buprenorphine administered to cats undergoing ovariohysterectomy. Randomized, prospective and blinded clinical trial. 100 female cats. Cats were assigned to receive 0.01 mg kg(-1) of buprenorphine administered by the IV, IM, SC or OTM route (n = 25/group). Buprenorphine was made up to 0.3 mL with 0.9% saline. DIVAS (0-100 mm) and simple descriptive scale (SDS) (from 0 to 4) pain and sedation scores were assigned to each cat before and 1, 2, 3, 4, 6, 8, 12 and 24 hours after ovariohysterectomy. Buprenorphine and carprofen were administered for rescue analgesia. Data were analyzed using anova and Fisher's exact test (p 0.05). There were no significant differences between groups for sedation scores at any time. SDS pain scores did not detect any differences between groups (p > 0.05). DIVAS pain scores after OTM administration were significantly higher than IV and IM administration at 1 hour and at 3, 4, 6, 8 and 12 hours, respectively (p buprenorphine required rescue analgesia, respectively. There was a significantly higher incidence of treatment failure in cats that received SC and OTM buprenorphine compared with cats that received IV and IM buprenorphine (p buprenorphine provided better postoperative analgesia than SC or OTM administration of the drug and these routes of administration should be preferred when buprenorphine is administered to cats.

  17. The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial.

    Science.gov (United States)

    Lane, W; Weinrib, S; Rappaport, J; Hale, C

    2014-09-01

    Patients with type 2 diabetes and insulin resistance may require high insulin doses to control hyperglycaemia. The addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin therapy has been shown to reduce insulin requirement while reducing insulin-associated weight gain [1,2]. The effect of GLP-1 RA therapy added to intensive (basal/bolus) insulin therapy has not been studied in a prospective trial. This trial evaluated the effect of the addition of liraglutide to high-dose intensive insulin therapy compared with standard insulin up-titration in obese insulin-resistant patients with type 2 diabetes requiring high-dose insulin therapy. Thirty-seven subjects with type 2 diabetes requiring >100 units of insulin daily administered either by continuous subcutaneous insulin infusion (CSII) or by multiple daily injections (MDIs) with or without metformin were randomized to receive either liraglutide plus insulin (LIRA) or intensive insulin only (controls). Liraglutide was initiated at 0.6 mg subcutaneously (sq) per day and increased to either 1.2 or 1.8 mg daily in combination with intensive insulin therapy. Controls received intensive insulin up-titration only. At 6 months, subjects receiving liraglutide plus insulin experienced statistically significant reductions in HbA1c, weight, insulin dose and glycaemic variability (GV) by continuous glucose monitor (CGM) compared with the control group receiving insulin only. Adding liraglutide to intensive high-dose (basal/bolus) insulin therapy results in greater improvement in glycaemic control than insulin therapy alone, with additional benefits of weight loss and reduced GV. © 2014 John Wiley & Sons Ltd.

  18. Academic Training - Pulsed SC Magnets

    CERN Multimedia

    Françoise Benz

    2006-01-01

    2005-2006 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 2, 3, June 29, 30, 31 May, 1, 2 June 11:00-12:00 - Auditorium, bldg 500 Pulsed SC Magnets by M. Wilson Lecture 1. Introduction to Superconducting Materials Type 1,2 and high temperature superconductors; their critical temperature, field & current density. Persistent screening currents and the critical state model. Lecture 2. Magnetization and AC Loss How screening currents cause irreversible magnetization and hysteresis loops. Field errors caused by screening currents. Flux jumping. The general formulation of ac loss in terms of magnetization. AC losses caused by screening currents. Lecture 3. Twisted Wires and Cables Filamentary composite wires and the losses caused by coupling currents between filaments, the need for twisting. Why we need cables and how the coupling currents in cables contribute more ac loss. Field errors caused by coupling currents. Lecture 4. AC Losses in Magnets, Cooling and Measurement Summary of all loss mech...

  19. 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 d...

  20. 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 southernmost extremity of Folly Island to latitude 32°35′ N. longitude 79°58.2′ W. (Stono Inlet Lighted Whistle...

  1. Subcutaneous epinephrine vs nebulized salbutamol in asthma.

    Science.gov (United States)

    Sharma, A; Madan, A

    2001-12-01

    This study was conducted to compare the efficacy of the subcutaneous epinephrine with nebulized salbutamol. Fifty asthmatic children in the age range of 6-14 years were divided into two equal groups. Group I children were given subcutaneous epinephrine and Group II were nebulized with salbutamol. Patients were observed at 15, 20, 30, 60, 120, 180 and 240 minute intervals. Both the groups had comparable mean increase in peak expiratory flow rate (PEFR %) (Group I 27.7 +/- 0.7; Group II 28.8 +/- 0.06, p >0.05). In Group I there was significant increase in systolic blood pressure, 30 minutes after the start of treatment, however it settled on its own by 60 minutes. Both the groups had satisfactory improvement in clinical parameters which continued upto 4 hours after start of treatment. Subcutaneous epinephrine can be safely used if nebulizers are not available.

  2. Electromagnetic switches, NEO SC Series; Denji kaiheiki NEO SC series

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-01-10

    The medium to large size electromagnetic switches, NEO SC Series were developed under the following five concepts: 'internationality,' 'safety,' 'practical applicability,' 'compactness' and 'environmentality'. Under the circumstances that safety and environmentality are given greater importance, internationalization of the JIS standard is in progress. These switches are the global products that are based on the newly established JIS standard and the international standard, and have acquired certification for the overseas standards in the standard products. Assurance of quick supply of the products including maintenance parts contribute to convenience of the customers. Enhancement was made on the performance to prevent consequential accident in the event of short circuit accident, as well as on the arc space free structure and safety as a result of making a full product line, including terminal covers and intra-phase barriers. Practical applicability was enhanced by expanding models attached with rails, and increasing the operating ambient temperature to 55 degrees C, and the coverage of additional auxiliary contacts. (translated by NEDO)

  3. Metabolic syndrome and insulin resistance in obese adolescents.

    Science.gov (United States)

    Gobato, Amanda Oliva; Vasques, Ana Carolina J; Zambon, Mariana Porto; Barros Filho, Antonio de Azevedo; Hessel, Gabriel

    2014-03-01

    To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. 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. 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 (pinsulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. 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.

  4. Pregnancy complicated by obesity induces global transcript expression alterations in visceral and subcutaneous fat.

    Science.gov (United States)

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

    2014-08-01

    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 not much 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 the 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 led to identification of indolethylamine N-methyltransferase, tissue factor pathway inhibitor-2, and ephrin type-B receptor 6, not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis as compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity.

  5. Insulin detemir in the treatment of type 1 and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Philips

    2006-09-01

    Full Text Available Jean-Christophe Philips, André ScheenDivision of Diabetes, Nutrition & Metabolic Disorders, Department of Medicine, CHU Sart-Tilman, University of Liège, Liège, Belgium Abstract: Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime. Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients.Keywords: diabetes mellitus, insulin detemir, hypoglycemia, insulin analogue, insulin therapy

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  8. The Insuline Analogues

    OpenAIRE

    Garrido Carrasco, Elizabeth; Servicio de Endocrinología, Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú

    2014-01-01

    Insulin analogues are a new pharmaceutical family, designed to overcome deficiencies that still exist with the rDNA insulin. There are rapid-acting insulin analogues such as lispro insulin and insulin aspart. They avoid postprandial and nocturnal hypoglycemia. There are also intermediate-acting insulin analogues like NPL and Mix 25 (a mixture between NPL and lispro), which join the neutral protamine insulin length of action and the fast onset of the rapid-acting analogue lispro. Finally, ther...

  9. Combined subcutaneous, intrathoracic and abdominal splenosis.

    Science.gov (United States)

    Javadrashid, Reza; Paak, Neda; Salehi, Ahad

    2010-09-01

    We report a case of combined subcutaneous, intrathoracic, and abdominal splenosis who presented with attacks of flushing, tachycardia and vague abdominal pain. The patient's past medical history included a splenectomy due to abdominal trauma and years later, a lung lobectomy due to recurrent pneumonia. An enhancing solid mass adjacent to the upper pole of the left kidney and nodular pleural based lesions in the left hemi-thorax along with nodular lesions in subcutaneous tissue of the left chest wall suggested possible adrenal malignancy with multiple metastases. Histopathologic examination demonstrated benign lesions of ectopic splenic tissue.

  10. A dose-equivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients

    DEFF Research Database (Denmark)

    Naimi, R M; Madsen, K B; Askov-Hansen, C

    2013-01-01

    Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated en...... effects of continuous, subcutaneous (s.c.), exogenous GLP-2 infusion (CONT-GLP-2) versus three daily s.c. GLP-2 injections (TID-GLP-2) on intestinal absorption in SBS patients....

  11. Detemir insulin for the treatment of diabetes mellitus in dogs.

    Science.gov (United States)

    Fracassi, Federico; Corradini, Sara; Hafner, Michaela; Boretti, Felicitas S; Sieber-Ruckstuhl, Nadia S; Reusch, Claudia E

    2015-07-01

    To investigate the effects of insulin detemir in dogs with diabetes mellitus. Prospective, uncontrolled clinical trial. 10 client-owned dogs with naturally occurring diabetes mellitus. Dogs were treated with insulin detemir SC every 12 hours for 6 months. Follow-up evaluations were done at 1, 2, 4, 12, and 24 weeks and included evaluation of clinical signs and measurement of blood glucose concentration curves and serum fructosamine concentrations. Insulin detemir administration resulted in a significant decrease in blood glucose and serum fructosamine concentrations at 6 months, compared with pretreatment values. Median insulin dosage at the end of the study was 0.12 U/kg (0.055 U/lb; range, 0.05 to 0.34 U/kg [0.023 to 0.155 U/lb], SC, q 12 h). Hypoglycemia was identified in 22% (10/45) of the blood glucose concentration curves, and 6 episodes of clinical hypoglycemia in 4 dogs were recorded. A subjective improvement in clinical signs was observed in all dogs during the 6-month study period. On the basis of clinical signs and blood glucose concentration curves, efficacy of insulin detemir at the end of the study was considered good in 5 dogs, moderate in 3, and poor in 2. Results suggested that SC injection of insulin detemir every 12 hours may be a viable treatment for diabetes mellitus in dogs. Insulin detemir dosages were lower than reported dosages of other insulin types needed to maintain glycemic control, suggesting that insulin detemir should be used with caution, especially in small dogs.

  12. Radiation Protection Section (SC/SL/RP)

    CERN Multimedia

    2006-01-01

    We should like to inform you that the Radiation Protection Section (SC/SL/RP) located on the Prévessin site has moved from Building 865 (ground floor) to new premises in Wing A of Building 892 (second floor). Telephone numbers remain the same. SC/SL/RP section

  13. rotor of the SC rotating condenser

    CERN Multimedia

    1974-01-01

    The rotor of the rotating condenser was installed instead of the tuning fork as the modulating element of the radiofrequency system, when the SC accelerator underwent extensive improvements between 1973 to 1975 (see object AC-025). The SC was the first accelerator built at CERN. It operated from August 1957 until it was closed down at the end of 1990.

  14. Peripheral Insulin Doesn’t Alter Appetite of Broiler Chicks

    Directory of Open Access Journals (Sweden)

    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.

  15. Dose responsive effects of subcutaneous pentosan polysulfate injection in mucopolysaccharidosis type VI rats and comparison to oral treatment.

    Directory of Open Access Journals (Sweden)

    Michael Frohbergh

    Full Text Available BACKGROUND: We previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS treatment in a rat model of mucopolysaccharidosis (MPS type VI. Herein we compare these effects to once weekly, subcutaneous (s.c. injection. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Injected PPS also effectively treats osteoarthritis in animals, and has shown success in osteoarthritis patients. METHODOLOGY/PRINCIPAL FINDINGS: One-month-old MPS VI rats were given once weekly s.c. injections of PPS (1, 2 and 4 mg/kg, human equivalent dose (HED, or daily oral PPS (4 mg/kg HED for 6 months. Serum inflammatory markers and total glycosaminoglycans (GAGs were measured, as were several histological, morphological and functional endpoints. Overall, weekly s.c. PPS injections led to similar or greater therapeutic effects as daily oral administration. Common findings between the two treatment approaches included reduced serum inflammatory markers, improved dentition and skull lengths, reduced tracheal deformities, and improved mobility. Enhanced effects of s.c. treatment included GAG reduction in urine and tissues, greater endurance on a rotarod, and better improvements in articular cartilage and bone in some dose groups. Optimal therapeutic effects were observed at 2 mg/kg, s.c.. No drug-related increases in liver enzymes, coagulation factor abnormalities or other adverse effects were identified following 6 months of s.c. PPS administration. CONCLUSIONS: Once weekly s.c. administration of PPS in MPS VI rats led to equal or better therapeutic effects than daily oral administration, including a surprising reduction in urine and tissue GAGs. No adverse effects from s.c. PPS administration were observed over the 6-month study period.

  16. Long-acting insulin allergy in a diabetic child.

    Science.gov (United States)

    Mastrorilli, Carla; Rizzuti, Laura; Cangelosi, Antonina Marta; Iovane, Brunella; Chiari, Giovanni; Caffarelli, Carlo

    2017-06-01

    Insulin allergy has been uncommon since the introduction of human recombinant insulin preparations; the prevalence is 2.4%. Insulin injection could elicit immediate reactions, which are usually induced by an IgE-mediated mechanism, within the first hour after drug administration. In the present study, we describe the case of a child who experienced immediate urticaria after long-acting insulin injection. A 9-year-old girl affected by type I diabetes mellitus referred a history of three episodes of urticaria 30 min after insulin subcutaneous injection. During the first week of insulin therapy, she developed generalized immediate urticaria twice after long-acting insulin glargine first and then once after insulin degludec administration. Symptoms resolved within a few hours after treatment with oral antihistamine. She tolerated rapid insulin lispro. Her personal allergological history was negative. Skin prick tests with degludec, glargine and detemir were performed, showing negative results. Intradermal 1:100000-diluted tests were immediately positive for both degludec and glargine but not for detemir. In light of these findings, detemir was administered without any reaction. Our results show that detemir is tolerated by patients with clinical hypersensitivity reactions to degludec and glargine. Although reactions could be attributable to additives allergy, such as zinc or metacresol, this was excluded since all three preparations contain the same components. So, insulin itself acted as offending allergen. Detemir differs from degludec and glargine in a few aminoacids. Therefore, it is possible that the conformational rather than the linear epitope may be responsible for the reaction. This result suggests integrating intradermal tests in the diagnostic flowchart for insulin allergy. Insulin allergy should always be suspected in patients with immediate symptoms after drug injection. As allergologic work-up, prick by prick test and intradermal test to insulin

  17. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue

    DEFF Research Database (Denmark)

    Nielsen, Ninna Bo; Højbjerre, Lise; Sonne, Mette P

    2009-01-01

    Adipokines play important regulatory roles in the pathophysiology of obesity and insulin resistance. We measured plasma and interstitial concentrations of the adipokines adiponectin, resistin, leptin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8...... found for the remaining adipokines (P>0.05). Adiponectin and leptin concentrations were higher in plasma than subcutaneous adipose tissue (approximately 25-fold and approximately 2-fold, respectively, P... investigated adipokines as well as of ATBF were substantial (coefficient of variation: 4-177%). In conclusion, interstitial leptin concentrations are approximately 2.5-fold higher in subcutaneous, femoral than abdominal adipose tissue, which might be a potential mechanism behind the health-benefits of "pear...

  18. Loss of autoregulation of blood flow in subcutaneous tissue in juvenile diabetes

    DEFF Research Database (Denmark)

    Henriksen, O; Kastrup, J; Parving, H H

    1984-01-01

    The autoregulation of blood flow in subcutaneous tissue was investigated at the level of the lateral malleolus by the local 133Xenon washout technique. We have investigated eight long-term insulin-dependent diabetics and seven healthy controls. All diabetics had moderate diabetic nephropathy...... and retinopathy. The blood flow remained constant in all normal subjects, when the arterial perfusion pressure was varied between 70 and 150 mm Hg. All diabetics had impaired or reduced autoregulation of the subcutaneous blood flow. The blood flow increased and decreased almost linearly with the changes...... in arterial perfusion pressure. The mechanism underlying the defect autoregulation of blood flow in diabetics is uncertain; possibilities include structural changes of the arterioles and/or alterations of local metabolic factors....

  19. A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.

    Science.gov (United States)

    Reilly, Shannon M; Ahmadian, Maryam; Zamarron, Brian F; Chang, Louise; Uhm, Maeran; Poirier, BreAnne; Peng, Xiaoling; Krause, Danielle M; Korytnaya, Evgenia; Neidert, Adam; Liddle, Christopher; Yu, Ruth T; Lumeng, Carey N; Oral, Elif A; Downes, Michael; Evans, Ronald M; Saltiel, Alan R

    2015-01-12

    The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified IKK-ε and TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute inhibition of IKK-ε and TBK1 with amlexanox treatment increases cAMP levels in subcutaneous adipose depots of obese mice, promoting the synthesis and secretion of the cytokine IL-6 from adipocytes and preadipocytes, but not from macrophages. IL-6, in turn, stimulates the phosphorylation of hepatic Stat3 to suppress expression of genes involved in gluconeogenesis, in the process improving glucose handling in obese mice. Preliminary data in a small cohort of obese patients show a similar association. These data support an important role for a subcutaneous adipose tissue-liver axis in mediating the acute metabolic benefits of amlexanox on glucose metabolism, and point to a new therapeutic pathway for type 2 diabetes.

  20. Palmitoleic acid reduces intramuscular lipid and restores insulin sensitivity in obese sheep

    Directory of Open Access Journals (Sweden)

    Duckett SK

    2014-11-01

    Full Text Available Susan K Duckett, Gabriela Volpi-Lagreca, Mariano Alende, Nathan M LongAnimal and Veterinary Sciences Department, Clemson University, Clemson, SC, USAAbstract: Obese sheep were used to assess the effects of palmitoleic (C16:1 cis-9 acid infusion on lipogenesis and circulating insulin levels. Infusion of 10 mg/kg body weight (BW/day C16:1 intravenously in obese sheep reduced (P<0.01 weight gain by 77%. Serum palmitoleic levels increased (P<0.05 in a linear manner with increasing levels of C16:1 infusion. Cis-11 vaccenic (C18:1 cis-11 acid, a known elongation product of palmitoleic acid, was also elevated (P<0.05 in serum after 14 days and 21 days of infusion. Plasma insulin levels were lower (P<0.05 (10 mg/kg BW/day C16:1 than controls (0 mg/kg BW/day C16:1 at 14 days and 28 days of infusion. Infusion of C16:1 resulted in linear increases in tissue concentrations of palmitoleic, cis-11 vaccenic, eicosapentaenoic, and docosapentaenoic acids in a dose-dependent manner. Total lipid content of the semitendinosus (ST muscle and mesenteric adipose tissue was reduced (P<0.01 in both 5 mg/kg and 10 mg/kg BW C16:1 dose levels. Total lipid content and mean adipocyte size in the longissimus muscle was reduced (P<0.05 in the 10 mg/kg BW C16:1 dose level only, whereas total lipid content and adipocyte size of the subcutaneous adipose tissue was not altered. Total lipid content of the liver was also unchanged with C16:1 infusion. Palmitoleic acid infusion upregulated (P<0.05 acetyl-CoA carboxylase (ACC, fatty acid elongase-6 (ELOVL6, and Protein kinase, AMP-activated, alpha 1 catalytic subunit, transcript variant 1 (AMPK mRNA expressions in liver, subcutaneous adipose, and ST muscle compared to the controls. However, mRNA expression of glucose transporter type 4 (GLUT4 and carnitine palmitoyltransferase 1b (CPT1B differed between tissues. In the subcutaneous adipose and liver, C16:1 infusion upregulated (P<0.05 GLUT4 and CPT1B, whereas these genes were

  1. Subcutaneous Midazolam with and without Ketamine for Sedation In Children Undergoing Dental Treatment: A Pilot Study.

    Science.gov (United States)

    Flores-Castillo, D; Martínez-Rider, R; Ruiz-Rodríguez, S; Garrocho-Rangel, A; Lara-Guevara, J; Pozos-Guillén, A

    2015-01-01

    The objective of this study was to evaluate the efficacy of subcutaneous (SC) sedation using midazolam with and without ketamine in non-cooperative pediatric patients undergoing dental treatment. A prospective, randomized, controlled, double-blind, crossover pilot clinical trial was carried out in 13 children, aged between 17-46 months, ASA l, Frankl 1. Two sedation schemes were administered SC: Midazolam alone (M), and a combination of Midazolam-Ketamine (MK). Both regimens were administered to the same patient in two consecutive treatment sessions, in accordance with a random assignment. Overall behavior, movement, and crying were assessed according to the modified Houpt scale. Heart rate, blood pressure, blood oxygen saturation, and possible side effects were also monitored. The percentage of non-crying children was always higher in the treatment with MK compared with the treatment with M, but without a significant statistical difference. Regarding variable body movement, the percentage of children without movement was higher in the MK group, although only up to minute 10; no significant differences were found at 20, 30, and 40 minutes, and from minute 40, body movement was lower in the M group. Midazolam alone and the midazolam-ketamine combination administered subcutaneously resulted in a safe and efficient pharmacological method for providing moderate sedation to non-cooperative pediatric patients undergoing dental treatment.

  2. Lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling

    DEFF Research Database (Denmark)

    Høeg, Louise D; Sjøberg, Kim Anker; Jeppesen, Jacob

    2011-01-01

    AbstractObjective: We have previously shown that overnight fasted women have higher insulin stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism...... (60%) after intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates...... ratio was decreased by intralipid. Conclusion: Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation or direct inhibition of glucose...

  3. Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese type 2 diabetes patients

    DEFF Research Database (Denmark)

    Thondam, Sravan K; Daousi, Christina; Wilding, John P H

    2017-01-01

    is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean (n...... correlated with adipose tissue insulin resistance for all subjects (Pearson, r = 0.56, P = 0.005). There were no significant gene expression changes in key SAT lipid metabolism enzymes. In conclusion, GIP appears to promote fat accretion and thus may exacerbate obesity and insulin resistance in T2DM....

  4. Transmissible Venereal Tumor with Subcutaneous and Bone ...

    African Journals Online (AJOL)

    A five year old entire mixed breed dog was admitted to the University of Nairobi's small animal clinic with a 5-months history of subcutaneous masses. Physical examination revealed firm and mobile masses in the subcuticular tissues, on the mandible and the transverse processes of the lumbar vertebrae. Visual inspection ...

  5. Radiological case: subcutaneous and mediastinal enfisema

    OpenAIRE

    Nascimento, J.; Gomes, M.; Moreira, C.; Macedo, F.

    2012-01-01

    ABSTRACT We present the case of a 5 year old asmathic girl admitted to the hospital for acute non traumatic edema and crepitus of the face, neck and upper thorax. Thoracic x-ray (not shown) and thoracic and neck CT were performed, showing extensive subcutaneous and mediastinal enfisema. These are rare complications of asthma. The imaging features are described.

  6. Case Report Pneumomediastinum and Subcutaneous Emphysema ...

    African Journals Online (AJOL)

    wheezing and neck pain. He was diagnosed asthmatic at the age of eleven and had been admitted on a few occasions for acute exacerbations in the prior ten years. He had salbutamol tablets regularly. At this index presentation, he was noted to have subcutaneous swelling and crepitus over the neck and upper anterior ...

  7. Thoracic duct lymphography by subcutaneous contrast agent ...

    African Journals Online (AJOL)

    A 4-year-old male Japanese Shiba Inu presented with recurrent chylothorax. The thoracic duct was successfully imaged using computed tomography after the injection of an iodine contrast agent into the subcutaneous tissue surrounding the anus. The thoracic duct was successfully ligated and pericardectomy performed via ...

  8. Anthropometrical Profile, Skinfold Tickness and Subcutaneous Fat ...

    African Journals Online (AJOL)

    Background: The threatening health problems resulting from excess subcutaneous fat depositions have been reported by the world Health Organization. Also noteworthy is that childhood obesity is a pointer to adult obesity. This necessitated a study on the anthropometrical profiles of adolescents of Southeast Nigeria using ...

  9. Case Report: Pneumomediastinum and subcutaneous cervical ...

    African Journals Online (AJOL)

    The occurrence of pneumomediastinum and subcutaneous cervical emphysema as complications of childhood pneumonia is very unusual. They results most often from respiratory manoeuvres that produce high intrathoracic pressure. Although they are largely benign, pneumomediastinum can cause compression of major ...

  10. Insulin dose during glucocorticoid treatment for fetal lung maturation in diabetic pregnancy: test of an algorithm [correction of analgoritm

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Christensen, Ann-Birgitte L; Hellmuth, Ellinor

    2002-01-01

    Poor glycemic control is often a serious clinical problem during glucocorticoid treatment for fetal lung maturation in pregnant women with diabetes. An algorithm for improved subcutaneous insulin treatment during glucocorticoid treatment in insulin-dependent diabetic women was developed and tested....

  11. Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women.

    Directory of Open Access Journals (Sweden)

    Cacylde Amouzou

    Full Text Available Obesity is associated with insulin-resistance (IR, the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity.We compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development.30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT and obese (grade I insulin-sensitive (OIS or insulin-resistant (OIR according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression.Systemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR.Our results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle

  12. Results of the Prolonged Use of Subcutaneous Continuous Infusion of Hydrocortisone in a Man with Congenital Adrenal Hyperplasia

    OpenAIRE

    Sonnet, Emmanuel; Roudaut, Nathalie; Kerlan, V?ronique

    2011-01-01

    This is a case report study of a young man with Congenital Adrenal Hyperplasia (CAH) who has been treated during 2 years by a subcutaneous continuous infusion hydrocortisone (SCIH) to optimize his treatment. Hydrocortisone was delivered via an insulin infusion device. We also studied the evolution of testicular adrenal rest tumors (TARTs) and the quality of life through SF36 survey. Four rates were determined, with a total of 47 mg per day. Biochemical parameters were normalized at 2 months. ...

  13. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... with IR independent of weight gain. In conclusion, the data presented in the current thesis, supported by a thorough review of available literature, advocate that 1) Inflammation is a triggering event fueling IR; 2) Commensal microbes can, when mistreated, aggravate IR and glucose intolerance; and 3) Diet...

  14. A review of biodegradable polymeric systems for oral insulin delivery.

    Science.gov (United States)

    Luo, Yue Yuan; Xiong, Xiang Yuan; Tian, Yuan; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

    2016-07-01

    Currently, repeated routine subcutaneous injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, patients' poor compliance for injections often fails to achieve the stable concentration of blood glucose. As a protein drug, the oral bioavailability of insulin is low due to many physiological reasons. Several carriers, such as macromolecules and liposomes have been used to deliver drugs in vivo. In this review article, the gastrointestinal barriers of oral insulin administration are described. Strategies for increasing the bioavailability of oral insulin, such absorption enhancers, enzyme inhibitors, enteric coatings are also introduced. The potential absorption mechanisms of insulin-loaded nanoparticles across the intestinal epithelium, including intestinal lymphatic route, transcellular route and paracellular route are discussed in this review. Natural polymers, such as chitosan and its derivates, alginate derivatives, γ-PGA-based materials and starch-based nanoparticles have been exploited for oral insulin delivery; synthetic polymers, such as PLGA, PLA, PCL and PEA have also been developed for oral administration of insulin. This review focuses on recent advances in using biodegradable natural and synthetic polymers for oral insulin delivery along with their future prospects.

  15. Subcutaneous bortezomib in multiple myeloma patients induces similar therapeutic response rates as intravenous application but it does not reduce the incidence of peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Jiri Minarik

    Full Text Available Subcutaneous (SC application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM patients treated using either intravenous (IV or subcutaneous (SC route of administration.During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly - 63% or twice weekly - 27% in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥ 3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN. PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥ 2 was present in 20% vs 18% and PN grade ≥ 3 was present in 6% vs 4%.We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

  16. Clinical utility of insulin and insulin analogs

    Science.gov (United States)

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  17. Hyperglycemia in critical patients: Determinants of insulin dose choice

    Directory of Open Access Journals (Sweden)

    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.

  18. Degludec: the new ultra-long insulin analogue.

    Science.gov (United States)

    Tambascia, Marcos Antonio; Eliaschewitz, Freddy Goldberg

    2015-01-01

    The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, "De") and the attachment, via a glutamic acid linker ("glu"), of a 16-carbon fatty diacid (hexadecanoic diacid, "dec") to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26-52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia.

  19. Hyperglycemia in critical patients: Determinants of insulin dose choice.

    Science.gov (United States)

    Paliosa, Aline Klitzke; Teixeira, Cassiano; Rosa, Regis Goulart; Blatt, Carine Raquel

    2017-05-01

    To identify factors that can determine the choice of intermittent subcutaneous regular insulin dose in critically ill patients with hyperglycemia. 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. 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. 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.

  20. Forkhead box O-1 modulation improves endothelial insulin resistance in human obesity.

    Science.gov (United States)

    Karki, Shakun; Farb, Melissa G; Ngo, Doan T M; Myers, Samantha; Puri, Vishwajeet; Hamburg, Naomi M; Carmine, Brian; Hess, Donald T; Gokce, Noyan

    2015-06-01

    Increased visceral adiposity has been closely linked to insulin resistance, endothelial dysfunction, and cardiometabolic disease in obesity, but pathophysiological mechanisms are poorly understood. We sought to investigate mechanisms of vascular insulin resistance by characterizing depot-specific insulin responses and gain evidence that altered functionality of transcription factor forkhead box O-1 (FOXO-1) may play an important role in obesity-related endothelial dysfunction. We intraoperatively collected paired subcutaneous and visceral adipose tissue samples from 56 severely obese (body mass index, 43 ± 7 kg/m(2)) and 14 nonobese subjects during planned surgical operations, and characterized depot-specific insulin-mediated responses using Western blot and quantitative immunofluorescence techniques. Insulin signaling via phosphorylation of FOXO-1 and consequent endothelial nitric oxide synthase stimulation was selectively impaired in the visceral compared with subcutaneous adipose tissue and endothelial cells of obese subjects. In contrast, tissue actions of insulin were preserved in nonobese individuals. Pharmacological antagonism with AS1842856 and biological silencing using small interfering RNA-mediated FOXO-1 knockdown reversed insulin resistance and restored endothelial nitric oxide synthase activation in the obese. We observed profound endothelial insulin resistance in the visceral adipose tissue of obese humans which improved with FOXO-1 inhibition. FOXO-1 modulation may represent a novel therapeutic target to diminish vascular insulin resistance. In addition, characterization of endothelial insulin resistance in the adipose microenvironment may provide clues to mechanisms of systemic disease in human obesity. © 2015 American Heart Association, Inc.

  1. Preparation and evaluation of mucinated sodium alginate microparticles for oral delivery of insulin.

    Science.gov (United States)

    Builders, Philip F; Kunle, Olobayo O; Okpaku, Larry C; Builders, Modupe I; Attama, Anthony A; Adikwu, Michael U

    2008-11-01

    Effective oral insulin delivery remains a challenge to the pharmaceutical industry. In this study, insulin-loaded microparticles for oral delivery were prepared with mucin and sodium alginate combined at different ratios using a novel method based on polymer coacervation and diffusion filling. Some physical characteristics of the various insulin-loaded microparticles such as particle size, morphology and compressibility indices were determined. The microparticles were filled into hard gelatin capsules and the in vitro insulin release as well as the blood glucose reduction after oral administration to diabetic rabbits were determined. The microparticles formed were generally multi-particulate, discrete and free flowing. Before insulin loading, microparticles were round and smooth, becoming fluffier, less spherical and larger with rough and pitted surface after insulin loading. The insulin content of the microparticles increased with increase in their sodium alginate content. The various insulin-loaded microparticles prepared with the mucinated sodium alginate when encapsulated exhibited lag time before insulin release. The time taken to reach maximum insulin release from the various formulations varied with the mucin-sodium alginate ratio mix. The mean dissolution time of insulin from the microparticles prepared with sodium alginate, mucin, sodium alginate: mucin ratios of 1:1, 3:1 and 1:3 was 11.21+/-0.75, 3.3+/-0.42, 6.69+/-023, 8.52+/-0.95 and 3.48+/-0.65 (min.), respectively. The percentage blood glucose reduction for the subcutaneously administered insulin was significantly (porally administered insulin-loaded microparticles prepared with three parts of sodium alginate and one part of mucin after 5h was, however, equal to that produced by the subcutaneously administered insulin solution, an indication that it is an effective alternative for the delivery of insulin.

  2. Inflammation and Insulin Resistance

    OpenAIRE

    de Luca, Carl; Olefsky, Jerrold M.

    2007-01-01

    Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Pro-inflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but t...

  3. Pharmacokinetics of a Sustained Release Formulation of Buprenorphine After Intramuscular and Subcutaneous Administration to American Kestrels ( Falco sparverius ).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Knych, Heather K; Olsen, Glenn H; Paul-Murphy, Joanne R

    2017-06-01

    Previous studies have validated the clinical use of opioids with μ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study. A total of 12 birds (6 males and 6 females) were assigned randomly to 3 groups of 4 birds each. A single dose of Buprenorphine SR-LAB (1.8 mg/kg) was administered intramuscularly (IM), and blood samples were collected at 0.25, 3, and 24 hours (n = 4); 1, 6, and 48 hours (n = 4); and 2, 12, and 72 hours (n = 4) after drug administration. Plasma buprenorphine concentrations were measured by tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After 1 year, the same dose of buprenorphine was administered subcutaneously (SC) to 12 birds divided into 3 groups as previously, and blood samples were collected at the same times after drug administration. Maximum plasma buprenorphine concentration was measured at 15 minutes after IM and SC administration. Mean plasma buprenorphine concentrations were >1 ng/mL for 48 hours after IM and SC administration. The elimination half-life was 13.5 and 11.1 hours for IM and SC administration, respectively. Depending on the severity and type of pain, adjunctive therapy, and the individual response, Buprenorphine SR-LAB administered at 1.8 mg/kg IM or SC to American kestrels would require administration every 12 to 72 hours to manage pain. Further pharmacodynamic and clinical evaluations are warranted in kestrels and

  4. z206sc_video_observations

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents video observations from cruise Z206SC for the Santa Barbara Channel region and beyond in southern California. The vector data file is...

  5. Bandwidth challenge teams at SC2003 conference

    CERN Multimedia

    2003-01-01

    Results from the fourth annual High-Performance Bandwidth Challenge, held in conjunction with SC2003, the international conference on high-performance computing and networking which occurred last week in Phoenix, AZ (1 page).

  6. Subcutaneous implantable defibrillator: State-of-the art 2013

    OpenAIRE

    Akerström, Finn; Arias, Miguel A; Pachón, Marta; Puchol, Alberto; Jiménez-López, Jesús

    2013-01-01

    The subcutaneous implantable cardioverter-defibrillator (S-ICD) has recently been approved for commercial use in Europe, New Zealand and the United States. It is comprised of a pulse generator, placed subcutaneously in a left lateral position, and a parasternal subcutaneous lead-electrode with two sensing electrodes separated by a shocking coil. Being an entirely subcutaneous system it avoids important periprocedural and long-term complications associated with transvenous implantable cardiove...

  7. Pharmacokinetics of meloxicam in adult goats: a comparative study of subcutaneous, oral and intravenous administration.

    Science.gov (United States)

    Karademir, U; Erdogan, H; Boyacioglu, M; Kum, C; Sekkin, S; Bilgen, M

    2016-05-01

    To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5 mg/kg bodyweight. Five healthy Saanen goats, aged 12-14 months and weighing 35-40 kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5 mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group. Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (pmeloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.

  8. Pharmacokinetics of the novel atypical opioid tapentadol after intravenous, intramuscular and subcutaneous administration in cats.

    Science.gov (United States)

    Lee, H-K; Lebkowska-Wieruszewska, B; Kim, T-W; Kowaski, C-J; Giorgi, M

    2013-12-01

    Drugs that provide effective analgesia in cats are limited. The aim of the present study was to investigate the pharmacokinetics of the novel atypical drug tapentadol (TAP) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) injection in six healthy cats using a 3 × 3 Latin square crossover study design. The dose rate used was 5mg/kg and the concentrations of TAP in plasma were evaluated using high-performance liquid chromatography. Some adverse effects including salivation, agitation and panting, were noted, especially following IV administration. In all three administration groups, TAP concentrations were detectable in plasma for up to 8h. Bioavailability for each route was almost complete, accounting for 94% and 90% after IM and SC administrations, respectively. Drug absorption was faster after IM than SC administration (0.25 h vs. 0.63 h). The half-life of the terminal portion of the plasma concentration curve was not significantly different between the three routes of administrations (2-3h). TAP appears to have some variation in its pharmacokinetic features in cats compared to other animal species. Further studies are needed to evaluate whether TAP would be suitable for use in cats that are experiencing moderate to severe pain, but are sensitive to the adverse effects of commonly prescribed opioids. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Subcutaneous filariasis: An unusual case report

    Directory of Open Access Journals (Sweden)

    Valand Arvindbhai

    2007-01-01

    Full Text Available Wuchereria bancrofti presented in subcutaneous nodule is a very rare presentation. Wuchereria bancrofti first reported by Bancrofti in Brisbane in 1876 and the name filaria Bancrofti was given in 1877 and the generic name was given in 1878. A 15-year-old male patient′s known case of pulmonary Koch′s with incidentally detected subcutaneous nodule on right arm pit, cytology from the nodule shows many sheathed microfilaria along with segment of an adult female worm. Wet mount peripheral blood smear shows nocturnal motile microfilaria. The Wuchereria bancrofti is known to be associated with pulmonary Koch′s. Nocturnal motility and cytomorphological features differentiate Wuchereria bancrofti from Wuchereria loa loa . After giving diethyl carbamazine (DEC 6 mg/kg for 21 days without disturbing anti Koch′s treatment schedule and microfilaria disappeared from peripheral blood.

  12. Primary Sonographic Diagnosis of Subcutaneous Cysticercosis

    Directory of Open Access Journals (Sweden)

    M E Shivu

    2011-01-01

    Full Text Available We present the case of a 40-year-old woman with a small diffuse swelling on the left side of her face. She was diagnosed with intramuscular cysticercosis in the masseter muscle (case of disseminated cysticercosis involving the muscular system and subcutaneous tissues with surrounding phlegmon on high-resolution ultrasound and managed conservatively. To our knowledge, the imaging findings of disseminated muscular cysUcercosis have been reported before only a few numbers of times. In this case, the correct diagnosis was made on the basis of high-resolution sonography of the subcutaneous tissue and muscles. It showed multiple oval to circular, predominantly anechoic lesions, which were around 1 cm in diameter. Most of these cystic lesions showed a hyperechoic focus within suggestive of a scolex. There was no increased vascularity surrounding the lesions. Thus, sonography can primarily make the correct diagnosis of disseminated muscular cysticercosis if such lesions are seen. In endemic areas, cysticercosis should be considered one of the differential diagnosis of the subcutaneous swellings.

  13. Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression.

    Science.gov (United States)

    Thackeray, James T; Pietzsch, Stefan; Stapel, Britta; Ricke-Hoch, Melanie; Lee, Chun-Wei; Bankstahl, Jens P; Scherr, Michaela; Heineke, Jörg; Scharf, Gesine; Haghikia, Arash; Bengel, Frank M; Hilfiker-Kleiner, Denise

    2017-05-18

    Advanced cancer induces fundamental changes in metabolism and promotes cardiac atrophy and heart failure. We discovered systemic insulin deficiency in cachectic cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with marked cardiac atrophy, metabolic impairment, and function. B16F10 and C26 tumors decrease systemic insulin via high glucose consumption, lowering pancreatic insulin production and producing insulin-degrading enzyme. As tumor cells consume glucose in an insulin-independent manner, they shift glucose away from cardiomyocytes. Since cardiomyocytes in both tumor models remained insulin responsive, low-dose insulin supplementation by subcutaneous implantation of insulin-releasing pellets improved cardiac glucose uptake, atrophy, and function, with no adverse side effects. In addition, by redirecting glucose to the heart in addition to other organs, the systemic insulin treatment lowered glucose usage by the tumor and thereby decreased tumor growth and volume. Insulin corrected the cancer-induced reduction in cardiac Akt activation and the subsequent overactivation of the proteasome and autophagy. Thus, cancer-induced systemic insulin depletion contributes to cardiac wasting and failure and may promote tumor growth. Low-dose insulin supplementation attenuates these processes and may be supportive in cardio-oncologic treatment concepts.

  14. Sc3N and Sc2C2 encapsulated B40: Smarter than its carbon analogue

    Science.gov (United States)

    Shah, Esha V.; Roy, Debesh R.

    2016-10-01

    A detailed comparative investigation on the recently synthesised B40 and C40 along with their metal nitride (Sc3N)and carbide (Sc2C2) encapsulated endohedral fullerenes, is performed under density functional theory for the first time. The structures, electronic, thermodynamic and magnetic properties of all the considered compounds are explored in detail. The present study identifies borospherene (B40) and its encapsulated nitride (Sc3N@B40) and carbide (Sc2C2@B40) endohedral borofullerenes as the better candidates for future novel nano-applications compared to their carbon bucky ball analogues.

  15. ScPd2Al3 - New polymorphic phase in Al-Pd-Sc system

    Science.gov (United States)

    Pospíšil, Jiří; Haga, Yoshinori; Nakajima, Kunihisa; Ishikawa, Norito; Císařová, Ivana; Tateiwa, Naoyuki; Yamamoto, Etsuji; Yamamura, Tomoo

    2017-12-01

    We have discovered a new compound of the composition ScPd2Al3 crystallizing in unknown structure type. Moreover, ScPd2Al3 reveals polymorphism. We have found an orthorhombic crystal structure at room temperature and a high temperature cubic phase. The polymorphic phases are separated by a reversible first order transition at 1053 °C with a hysteresis of 19 °C. ScPd2Al3 exists as a very stable intermetallic phase just in the vicinity of the icosahedral quasicrystal Tsai-type i-phase Al54Pd30Sc16.

  16. Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral prednisone: a case report

    Directory of Open Access Journals (Sweden)

    Chantelau Ernst A

    2011-12-01

    Full Text Available Abstract Introduction Circumscript, progressing lipoatrophy at the insulin injection sites is an unexplained, however rare condition in diabetes mellitus. Case presentation We report a case of severe localised lipoatrophy developing during insulin pump-treatment (continuous subcutaneous insulin infusion with the insulin analogue lispro (Humalog® in a woman with type-1 diabetes mellitus. After 11 months of progressing lipoatrophy at two spots on the abdomen, low-dose prednisone (5-10 mg p.o. was given at breakfast for 8 months, whereby the atrophic lesions centripetally re-filled with subcutaneous fat tissue (confirmed by MRI despite ongoing use of insulin lispro. However, 4 weeks after cessation of prednisone, lipoatrophy relapsed, but resolved after another 2 months of low-dose prednisone. No further relapse was noted during 12 months of follow-up on insulin-pump therapy with Humalog®. Conclusion Consistent with an assumed inflammatory nature of the condition, low-dose oral prednisone appeared to have cured the lipoatrophic reaction in our patient. Our observation suggests a temporary intolerance of the subcutaneous fat tissue to insulin lispro (Humalog®, triggered by an unknown endogenous mechanism.

  17. Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological delivery

    Directory of Open Access Journals (Sweden)

    Matteucci E

    2015-06-01

    Full Text Available Elena Matteucci,1 Ottavio Giampietro,1 Vera Covolan,2 Daniela Giustarini,3 Paolo Fanti,4 Ranieri Rossi3 1Department of Clinical and Experimental Medicine, 2Department of Chemistry and Industrial Chemistry, University of Pisa, 3Department of Life Sciences, Laboratory of Pharmacology and Toxicology, University of Siena, Siena, Italy; 4Division of Nephrology, University of Texas Health Science Center San Antonio, South Texas Veteran Health Care System, San Antonio, Texas, USA Abstract: Insulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients’ (and diabetologists’ ideal requirements that organic chemistry could meet. Keywords: type 1 diabetes mellitus, drug formulations, drug administration routes, insulin, portal system, nanoparticles, biodegradable polymers

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

    Directory of Open Access Journals (Sweden)

    Mark K Nøhr

    Full Text Available Low-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS resulting in endotoxemia could be a candidate. Here 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 an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin/delta0-15glucose from 13.73 to 22.40 pmol/mmol (P < 0.001. This aberration in insulin and glucose homeostasis was normalized by resveratrol.Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin secretion.

  19. Expression profiling of PPARγ-regulated microRNAs in human subcutaneous and visceral adipogenesis in both genders.

    Science.gov (United States)

    Yu, Jing; Kong, Xiaocen; Liu, Juan; Lv, Yifan; Sheng, Yunlu; Lv, Shan; Di, Wenjuan; Wang, Chen; Zhang, Feng; Ding, Guoxian

    2014-06-01

    Clinical evidence shows that visceral fat accumulation decreases whereas sc fat increases in patients treated with thiazolidinediones (TZDs), a type of peroxisome proliferator-activated receptor (PPAR)γ agonist. To clarify the molecular mechanism of the differential effects of PPARγ agonists on sc and visceral adipose, we investigated expression profiling of PPARγ-regulated micro-RNAs (miRNAs) using miRNA microarray. The level of 182 miRNAs changed in human sc adipose treated with pioglitazone, whereas only 46 miRNAs changed in visceral adipose. Among these miRNAs, 27 miRNAs changed in both human sc and visceral adipocytes. Specifically, 7 miRNAs changed at the same direction in sc and visceral adipocytes, whereas 20 miRNAs changed at opposite directions in these two fat depots. Bioinformatics analysis showed that these miRNAs and the predicted target genes were involved in TGF-β-, Wnt/β-catenin-, and insulin-signaling pathways and related to metabolic regulation or cell cycle. Among the miRNAs changed at the same direction in sc and visceral adipocytes, miR-378, located in the first intron of PPARγ coactivator 1β (PGC1β), was coordinately expressed with PGC1β during adipogenesis. Moreover, miR-378 and PGC1β were both up-regulated by PPARγ agonist. We also provided evidence that miR-378 promoted adipogenesis in sc fat, but not in visceral fat. These results display miRNAs expression profiling altered in sc and visceral adipogenesis regulated by PPARγ and suggest a potential mechanism underlying the differential effects of TZDs on the 2 fat depot accumulations.

  20. Differential Development of Inflammation and Insulin Resistance in Different Adipose Tissue Depots Along Aging in Wistar Rats: Effects of Caloric Restriction.

    Science.gov (United States)

    Sierra Rojas, Johanna X; García-San Frutos, Miriam; Horrillo, Daniel; Lauzurica, Nuria; Oliveros, Eva; Carrascosa, Jose María; Fernández-Agulló, Teresa; Ros, Manuel

    2016-03-01

    The prevalence of insulin resistance and type 2 diabetes increases with aging and these disorders are associated with inflammation. Insulin resistance and inflammation do not develop at the same time in all tissues. Adipose tissue is one of the tissues where inflammation and insulin resistance are established earlier during aging. Nevertheless, the existence of different fat depots states the possibility of differential roles for these depots in the development of age-associated inflammation and insulin resistance. To explore this, we analyzed insulin signaling and inflammation in epididymal, perirenal, subcutaneous, and brown adipose tissues during aging in Wistar rats. Although all tissues showed signs of inflammation and insulin resistance with aging, epididymal fat was the first to develop signs of inflammation and insulin resistance along aging among white fat tissues. Subcutaneous adipose tissue presented the lowest degree of inflammation and insulin resistance that developed latter with age. Brown adipose tissue also presented latter insulin resistance and inflammation but with lower signs of macrophage infiltration. Caloric restriction ameliorated insulin resistance and inflammation in all tissues, being more effective in subcutaneous and brown adipose tissues. These data demonstrate differential susceptibility of the different adipose depots to the development of age-associated insulin resistance and inflammation. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. [Adverse reactions to insulin].

    Science.gov (United States)

    Liñana, J J; Montoro, F J; Hernández, M D; Basomba, A

    1997-07-01

    The prevalence of allergic reactions to insuline has decreased during the last few years. Probably this is due to the use of the newly-developed recombinant human insuline. At present, adverse reactions to insuline occur in 5-10% of patients on therapy with insuline. Adverse reactions may be local (more frequent) or systemic (rare). Insuline resistance consists in a different type of immunological reaction. Diagnosis of allergy to insuline is based on clinical history and cutaneous and serological tests. Treatment depends upon the severity of the reaction. When insuline is indispensable despite a previous allergic reaction, a desensitization protocol may be implemented.

  2. Sonographic Appearance of Dermal and Subcutaneous Sarcoidosis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ja Yoon; Bae, Young A; Hong, Hyeok Jin; Kwon, Kye Won [Dept. of Radiology, Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of)

    2012-08-15

    Sarcoidosis is a systemic granulomatous disease of unknown origin that mainly involves lung and skin, but rarely involves subcutaneous tissue. While some studies have reported on CT or MR imaging findings of subcutaneous sarcoidosis, there is only one report on sonographic findings of subcutaneous sarcoidosis, recently published in the US. Familiarity with ultrasonographic findings of subcutaneous sarcoidosis might be helpful for the early diagnosis in patient with palpable nodules and image follow-up for subcutaneous sarcoidosis. Here we report on the sonographic appearance of subcutaneous sarcoidosis involving dermal and subcutaneous tissue over axilla and sole, a case diagnosed as sarcoidosis and improved by steroid treatment, along with a review of the relevant literature.

  3. Interrelations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance: effect of moderate weight loss in older women.

    Science.gov (United States)

    Mazzali, Gloria; Di Francesco, Vincenzo; Zoico, Elena; Fantin, Francesco; Zamboni, Giulia; Benati, Claudia; Bambara, Valentina; Negri, Mauro; Bosello, Ottavio; Zamboni, Mauro

    2006-11-01

    Interrelations between fat distribution, muscle lipid infiltration, adipocytokines, insulin resistance, and moderate weight loss have not been investigated in obese older subjects. The objective was to evaluate relations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance in older women and the effects of moderate weight loss. In 35 healthy women aged 58-83 y, body mass index, waist circumference, sagittal abdominal diameter (SAD), and body composition measured by dual-energy X-ray absorptiometry were evaluated. A midthigh single computed tomography scan was performed to determine subcutaneous adipose tissue (AT), intermuscular AT (IAT), muscular tissue, and muscle lipid infiltration, evaluated as low-density lean tissue. Metabolic variables, insulin resistance measured by homeostasis model assessment, adiponectin, leptin, and high-sensitivity C-reactive protein were measured in all subjects and after weight loss in a subgroup of 15 obese women. Waist circumference and SAD were positively correlated with leptin and insulin resistance and negatively correlated with adiponectin. Adiponectin was associated negatively with insulin resistance and positively with HDL cholesterol, whereas leptin was positively associated with insulin resistance and triacylglycerols. Midthigh subcutaneous AT was associated with insulin resistance and leptin, whereas IAT was associated with triacylglycerols. Stepwise regression with insulin resistance as the dependent variable and body mass index, SAD, triacylglycerols, HDL cholesterol, adiponectin, leptin, high-sensitivity C-reactive protein, and midthigh subcutaneous AT as independent variables showed that SAD entered the regression first (R(2) = 0.492) followed by adiponectin (R(2) = 0.63). After moderate weight loss, midthigh subcutaneous AT, IAT, low-density lean tissue, leptin, and insulin resistance decreased significantly; no significant changes in adiponectin were observed. Fat distribution

  4. Insulin causes insulin-receptor internalization in human erythrocyte ghosts.

    OpenAIRE

    Kelleher, R S; Murray, E F; Peterson, S W

    1987-01-01

    The effect of incubation with insulin on insulin-receptor internalization by erythrocyte ghosts was investigated. The number of surface insulin receptors decreased by 30-40% after incubation of ghosts with insulin. Total insulin-receptor binding to solubilized ghosts was the same in insulin-incubated and control ghosts, whereas insulin binding to an internal vesicular fraction was substantially increased in insulin-incubated ghosts. Our findings suggest that erythrocyte-ghost insulin receptor...

  5. Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats.

    Science.gov (United States)

    Steagall, Paulo V M; Pelligand, Ludovic; Giordano, Tatiana; Auberger, Christophe; Sear, John W; Luna, Stelio P L; Taylor, Polly M

    2013-01-01

    To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (SC) buprenorphine in cats. Randomized, prospective, blinded, three period crossover experiment. Six healthy adult cats weighing 4.1±0.5 kg. Buprenorphine (0.02 mg kg(-1)) was administered i.v., i.m. or s.c.. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (pbuprenorphine concentration-time data decreased curvilinearly. S.c. PK could not be modeled due to erratic absorption and disposition. I.v. buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t(1/2) k(e0)=47.4 minutes) and receptor binding (k(on)=0.011 mL ng(-1) minute(-1)). Persistence of thermal antinociception was due to slow receptor dissociation (t(1/2) k(off)=18.2 minutes). I.v. and i.m. data followed classical disposition and elimination in most cats. Plasma concentrations after i.v. administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the i.v. route should be preferred over the i.m. and s.c. routes when buprenorphine is administered to cats. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  8. 33 CFR 80.707 - Cape Romain, SC to Sullivans Island, SC.

    Science.gov (United States)

    2010-07-01

    ... Island, SC. 80.707 Section 80.707 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... to Sullivans Island, SC. (a) A line drawn from the western extremity of Cape Romain 292° true to... southernmost extremity of Bull Island to the easternmost extremity of Capers Island. (d) A line formed by the...

  9. 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 Island, SC. 80.712 Section 80.712 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Seventh District § 80.712 Morris Island...

  10. Enhancing insulin oral absorption by using mucoadhesive nanoparticles loaded with LMWP-linked insulin conjugates.

    Science.gov (United States)

    Sheng, Jianyong; He, Huining; Han, Limei; Qin, Jing; Chen, Sunhui; Ru, Ge; Li, Ruixiang; Yang, Pei; Wang, Jianxin; Yang, Victor C

    2016-07-10

    Although significant progress has been achieved, effective oral delivery of protein drugs such as insulin by nanoparticle-based carrier systems still faces certain formidable challenges. Considerable amount of protein drug is released from the nanoparticles (NPs) in the gastrointestinal (GI) tract. Because of their low permeability through the intestinal mucosa, the released protein would be soon degraded by the large amount of proteases in the GI tract. Herein, we report an oral insulin delivery system that can overcome the above-mentioned problems by mucoadhesive NPs (MNPs) loaded with cell penetrating peptide-linked insulin conjugates. On one hand, after conjugation with low molecular weight protamine (LMWP), a cell penetrating peptide (CPP), insulin showed greatly improved permeability through intestinal mucus layer and epithelia. On the other hand, the mucoadhesive N-trimethyl chitosan chloride-coated PLGA nanoparticles (MNPs) that were loaded with conjugates enhanced the retention in the intestinal mucus layer. By adopting this delivery strategy, the LMWP-insulin conjugates released from the MNPs could be deprived from enzymatic degradation, due to the short distance in reaching the epithelia and the high permeation of the conjugates through epithelia. The oral delivery system of insulin designed by us showed a long-lasting hypoglycemia effect with a faster onset in diabetic rats. The pharmacological availability of orally delivered conjugates-loaded MNPs was 17.98±5.61% relative to subcutaneously injected insulin solution, with a 2-fold higher improvement over that by MNPs loaded with native insulin. Our results suggested that conjugation with CPP followed by encapsulation in MNPs provides an effective strategy for oral delivery of macromolecular therapeutics. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Insulin Detemir in the Treatment of Type 1 and Type 2 Diabetes

    Science.gov (United States)

    Philips, Jean-Christophe; Scheen, André

    2006-01-01

    Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients. PMID:17326333

  12. Surgical management of subcutaneous Colletotrichum gloeosporioides

    Science.gov (United States)

    Allton, David R; Parvez, Najma; Ranganath, Sangeetha; Jinadatha, Chetan

    2015-01-01

    A 52-year-old male patient with a history of sarcoidosis and over 10 years of chronic low-dose glucocorticoid use, cirrhosis and type 2 diabetes mellitus presented with two painful, enlarging subcutaneous nodules ultimately identified as Colletotrichum gloeosporioides. Two attempts at needle aspiration of the larger nodule resulted in rapid reaccumulation. Complete surgical excision of both nodules resulted in complete resolution without the use of any concomitant antifungals. Patient had no recurrence at 2 years of follow-up. PMID:25737220

  13. Subcutaneous myiasis caused by Dermatobia hominis.

    Science.gov (United States)

    Logar, J; Beović, B; Triller, C; Rakovec, S

    2001-01-01

    A case of subcutaneous myiasis caused by the larvae of the Dermatobia hominis fly is described, involving the ankle region of a 25-y-old man who had returned from Peru. After removal of 4 larvae from the affected sites, the lesions healed in 2 weeks without further treatment. Because of the increasing number of people travelling to tropical America, physicians in Slovenia will have to consider Dermatobia myiasis in the differential diagnosis of furuncular lesions in patients with a relevant travel history.

  14. Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

    Directory of Open Access Journals (Sweden)

    Berteau C

    2015-11-01

    Full Text Available Cecile Berteau,1 Orchidée Filipe-Santos,1 Tao Wang,2 Humberto E Rojas,2 Corinne Granger,1 Florence Schwarzenbach1 1Becton-Dickinson Medical Pharmaceutical Systems, Le Pont de Claix, France; 2Eli Lilly and Company, Indianapolis, IN, USA Aim: The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC injection pain tolerance. Methods: The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8–10, and 15–20 cP combined with two different injection flow rates (0.02 and 0.3 mL/s. All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS (0 mm/no pain, 100 mm/extreme pain. The location and depth of the injected fluid was assessed through 2D ultrasound echography images. Results: Viscosity levels had significant impact on perceived injection pain (P=0.0003. Specifically, less pain was associated with high viscosity (VAS =12.6 mm than medium (VAS =16.6 mm or low (VAS =22.1 mm viscosities, with a significant difference between high and low viscosities (P=0.0002. Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89. Slow (0.02 mL/s or fast (0.30 mL/s injection rates also showed no significant impact on perceived pain during SC injection (P=0.79. In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. Conclusion: The results of this study suggest that solutions of up to 3 mL and up to 15–20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High

  15. 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.

  16. Autotaxin Is Regulated by Glucose and Insulin in Adipocytes.

    Science.gov (United States)

    D'Souza, Kenneth; Kane, Daniel A; Touaibia, Mohamed; Kershaw, Erin E; Pulinilkunnil, Thomas; Kienesberger, Petra C

    2017-04-01

    Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid. Despite recent studies implicating adipose-derived ATX in metabolic disorders including obesity and insulin resistance, the nutritional and hormonal regulation of ATX in adipocytes remains unclear. The current study examined the regulation of ATX in adipocytes by glucose and insulin and the role of ATX in adipocyte metabolism. Induction of insulin resistance in adipocytes with high glucose and insulin concentrations increased ATX secretion, whereas coincubation with the insulin sensitizer, rosiglitazone, prevented this response. Moreover, glucose independently increased ATX messenger RNA (mRNA), protein, and activity in a time- and concentration-dependent manner. Glucose also acutely upregulated secreted ATX activity in subcutaneous adipose tissue explants. Insulin elicited a biphasic response. Acute insulin stimulation increased ATX activity in a PI3Kinase-dependent and mTORC1-independent manner, whereas chronic insulin stimulation decreased ATX mRNA, protein, and activity. To examine the metabolic role of ATX in 3T3-L1 adipocytes, we incubated cells with the ATX inhibitor, PF-8380, for 24 hours. Whereas ATX inhibition increased the expression of peroxisome proliferator-activated receptor-γ and its downstream targets, insulin signaling and mitochondrial respiration were unaffected. However, ATX inhibition enhanced mitochondrial H2O2 production. Taken together, this study suggests that ATX secretion from adipocytes is differentially regulated by glucose and insulin. This study also suggests that inhibition of autocrine/paracrine ATX-lysophosphatidic acid signaling does not influence insulin signaling or mitochondrial respiration, but increases reactive oxygen species production in adipocytes. Copyright © 2017 Endocrine Society.

  17. Effects of insulin on placental, fetal and maternal outcomes in gestational diabetes mellitus

    OpenAIRE

    Arshad, Rabia; Karim, Nasim; Ara Hasan, Jahan

    2014-01-01

    Objective: To observe the effects of exogenous insulin on placental, fetal and maternal outcomes in Gestational Diabetes Mellitus (GDM). Methods: After screening and diagnoses(WHO criteria) 30 GDM patients(Group A) were kept on diet control and 39 GDM (Group B) who did not achieve glycemic targets were added subcutaneous insulin. Term placental weight, size, shape, consistency, fibrinoid necrosis, hemorrhages, cord color, length of the cord, completeness of membranes, weight and condition of ...

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

    Science.gov (United States)

    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.

  19. 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.

  20. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  1. Insulin therapy in critically ill patients

    Science.gov (United States)

    Ellahham, Samer

    2010-01-01

    Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients. Even patients who are normoglycemic can develop hyperglycemia in response to acute metabolic stress. An expanding body of literature describes the benefits of normalizing hyperglycemia with insulin therapy in hospitalized patients. As a result, both the American Diabetes Association and the American College of Endocrinology have developed guidelines for optimal control of hyperglycemia, specifically targeting critically ill, hospitalized patients. Conventional blood glucose values of 140–180 mg/dL are considered desirable and safely achievable in most patients. More aggressive control to insulin administration, which can then be transitioned to subcutaneous insulin therapy in those patients who require continued insulin maintenance. This article reviews the data establishing the link between hyperglycemia and its risks of morbidity and mortality, and describes strategies that have proven effective in maintaining glycemic control in high-risk hospitalized patients. PMID:21191429

  2. 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

    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...

  3. No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

    DEFF Research Database (Denmark)

    Lerche, Susanne; Soendergaard, Liselotte; Rungby, Joergen

    2008-01-01

    glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min. RESULTS: Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) ... of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT. CONCLUSION: The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long...

  4. Red blood cell trans-18:1 isomeric profile correlates with subcutaneous fat and muscle profiles in beef cattle.

    Science.gov (United States)

    Aldai, Noelia; Dugan, Michael E R; Rolland, David C; Aalhus, Jennifer L

    2012-06-01

    Due to significant variation in polyunsaturated fatty acid biohydrogenation products in beef it would be useful to determine if levels of trans-18:1 isomers in samples collected ante-mortem are correlated with those collected post-mortem. Beef blood (RBC), subcutaneous fat (SC) and muscle (intramuscular fat; IM) samples were collected from an experiment with dietary vitamin E with/without flaxseed (n=80) and fatty acids analyzed. Across treatments, correlation analysis of total and individual trans-18:1 isomers were performed between tissues. Correlations between SC and IM were highly significant for all individual and total trans-18:1. RBC trans-18:1 were also well correlated with other tissues except for vaccenic acid. Levels of 10t-, 12t- and 13t/14t- were amongst the best correlated between RBC and SC and IM profiles. Levels of 6t/7t/8t-, 9t-, and 15t-18:1 showed significant but lower correlation factors particularly between RBC and SC. These results confirm the possibility of utilizing blood as a non-destructive sample to predict the total and isomeric profile of trans-18:1 in beef. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  5. Evaluation of the absolute bioavailability of pegylated interferon alfa-2a after subcutaneous administration to healthy male volunteers: an open-label, randomized, parallel-group study.

    Science.gov (United States)

    Brennan, Barbara J; Xu, Zhi-Xin; Grippo, Joseph F

    2012-09-01

    Interferon (IFN)-based therapy is the recommended treatment for hepatitis C virus. Because pegylated IFN (PEG-IFN) alfa-2a is administered subcutaneously, it is of interest to determine the proportion of the dose that is absorbed from the subcutaneous (SC) tissue and ultimately reaches systemic circulation. The goal of this study was to characterize the absolute bioavailability of PEG-IFN alfa-2a (40 kDa) after SC dosing (180 μg) and to evaluate the pharmacokinetics of PEG-IFN alfa-2a after intravenous (IV) and SC administration. In this parallel-group study, 18 participants were given a single IV dose of PEG-IFN alfa-2a 90 μg and 18 participants received PEG-IFN alfa-2a 180 μg SC. Serum concentrations of PEG-IFN alfa-2a were measured predose and serially until 312 hours after the first dose. Pharmacokinetic parameters (CL/F, volume of distribution, C(max), and T(max)) were estimated using noncompartmental methods. Bioavailability was calculated by using the following formula: (AUC(SC)/AUC(IV)) · (dose(IV)/dose(SC)). Eighteen healthy males received IV PEG-IFN alfa-2a, and an additional 18 healthy males received SC PEG-IFN alfa-2a. Subjects in each group had comparable mean weight, height, and body mass index. After IV administration of PEG-IFN alfa-2a (90 μg), there was a slow decline in serum concentration, the mean rate of systemic clearance was low at 126 mL/h, and the estimated mean volume of distribution at steady state was 9 L. After SC administration of PEG-IFN alfa-2a 180 μg, absorption was sustained, with mean T(max) occurring 102 hours after administration. The mean absolute bioavailability was 84%. A higher rate of influenza-like symptoms was observed after IV administration, along with decreased neutrophil counts, compared with subjects who underwent SC dosing. Approximately 84% of a SC-administered dose of PEG-IFN alfa-2a reached the systemic circulation in these male healthy volunteers. The slow absorption, restricted distribution, and slow

  6. Effect of traditional plant medicines (Cinnamomum zeylanicum and Syzygium cumini on oxidative stress and insulin resistance in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Khaled Sharafeldin

    2015-10-01

    Both CZ and SC possessed antioxidant activity as shown by elevated SOD and GPx activities and reduction in LPO. CZ and SC are functioning to improve the level of insulin, hyperglycemia, hyperlipidemia, oxidative stress and kidney and liver dysfunctions in STZ-induced diabetic rats.

  7. Pharmacokinetics of a Single Dose of Oral and Subcutaneous Meloxicam in Caribbean Flamingos ( Phoenicopterus ruber ruber).

    Science.gov (United States)

    Lindemann, Dana M; Carpenter, James W; KuKanich, Butch

    2016-03-01

    To determine the pharmacokinetics of meloxicam in Caribbean flamingos ( Phoenicopterus ruber ruber), a pilot study was performed first, followed by a complete pharmacokinetic study. Four healthy birds were divided into 2 groups and administered 1 mg/kg of either oral (n = 2) or subcutaneous (n = 2) meloxicam. Plasma meloxicam concentrations were determined with liquid chromatography-mass spectrometry. Based on the pilot study results, 12 healthy birds were assigned into 2 groups and administered either 3 mg/kg PO (n = 6) or 1.5 mg/kg SC (n = 6) of meloxicam. Blood samples were collected at baseline and at 9 time intervals per group after administration of meloxicam in all flamingos. Plasma concentrations after administration of 3 mg/kg PO meloxicam reached a mean maximum plasma concentration of 1.449 μg/mL at 2.35 hours with a terminal half-life of 1.832 hours. After administration of 1.5 mg/kg SC meloxicam, maximum plasma concentration was 4.059 μg/mL at 0.91 hour with a terminal half-life of 1.104 hours. The plasma profile from the main oral study (3 mg/kg PO) differed markedly from the pilot study (1 mg/kg PO), suggesting a delayed absorption with the higher dose and lack of dose proportionality. The different doses for subcutaneous administration resulted in a proportional change in plasma concentrations. Further studies are needed to evaluate the effects of the drug volume administered and fasting status when oral dosing is used. Future studies are also needed to investigate multiple-dose pharmacokinetics of meloxicam and to determine the therapeutic meloxicam plasma concentration in Caribbean flamingos.

  8. Closed-loop insulin delivery for treatment of type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Elleri Daniela

    2011-11-01

    Full Text Available Abstract Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed.

  9. Early decrease in resting energy expenditure with bedtime insulin therapy.

    Science.gov (United States)

    Fagour, C; Gonzalez, C; Suberville, C; Higueret, P; Rabemanantsoa, C; Beauvieux, M-C; Gin, H; Rigalleau, V

    2009-09-01

    In type 2 diabetes (T2D), insulin-induced weight gain may stem from a reduction in resting energy expenditure (REE). We sought to determine the early effects of insulin introduction on REE in 20 poorly controlled T2D patients. After improving the glycaemia, REE was measured on Day 0 and Day 4 during two treatment regimens: bedtime insulin (n=10, group 1); and one off (3-day) intravenous insulin infusion (n=10, group 2). Both groups were similar in age, gender, BMI, C-peptide, HbA(1c) and initial REE. By Day 4, fasting glycaemia had similarly improved in both groups: group 1: -5.3+/-2.7mmol/L vs group 2: -5.8+/-4.2 mmol/L. In group 2, the second REE was measured 12h after stopping the intravenous insulin infusion, whereas subcutaneous insulin was maintained in group 1. REE did not change in group 2 (-1.3+/-6.5%), whereas it decreased significantly in group 1 (-8.0+/-7.0%; PBedtime insulin led to an early and specific reduction in REE.

  10. Magnet measuring equipment of SC2

    CERN Multimedia

    1974-01-01

    Checking the positioning of the magnet measuring equipment installed between the poles of SC2. The steel structure in front of the magnet is designed to house the rotary condenser and to shield it from the stray magnetic field of the accelerator. On the left, Marinus van Gulik. (See Photo Archive 7402005 and Annual Report 1974, p. 44.)

  11. Final Scientific Report: DE-SC0008580

    Energy Technology Data Exchange (ETDEWEB)

    Seidler, Gerald T. [Univ. of Washington, Seattle, WA (United States)

    2017-03-16

    We report scientific, technical, and organizational accomplishments under DE-SC0008580. This includes 10 publications, 5 patent or provisional patent applications, beamtime with important results at both LCLS and APS, and new progress in understanding target design for x-ray heating experiments at x-ray heating facilities.

  12. The Synchrocyclotron (SC) in building 300

    CERN Multimedia

    Maximilien Brice

    2012-01-01

    The red magnet of CERN's first accelerator, the Synchrocyclotron (SC), has occupied a large part of Hall 300 since it was installed in the late 1950s. The remaining part of the 300-square-metre building has been used as a storage room since the accelerator was shut down in 1990. Now a public exhibition will breathe new life into the hall.

  13. Magnet measuring equipment of SC2

    CERN Multimedia

    CERN PhotoLab

    1974-01-01

    Checking the positioning of the magnet measuring equipment installed between the poles of SC2. The steel structure in front of the magnet is designed to house the rotary condenser and to shield it from the stray magnetic field of the accelerator.

  14. 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.

  15. 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.

  16. Developing a Commercial Air Ultrasonic Ceramic Transducer to Transdermal Insulin Delivery.

    Science.gov (United States)

    Jabbari, Nasrollah; Asghari, Mohammad Hossein; Ahmadian, Hassan; Mikaili, Peyman

    2015-01-01

    The application of low-frequency ultrasound for transdermal delivery of insulin is of particular public interest due to the increasing problem of diabetes. The purpose of this research was to develop an air ultrasonic ceramic transducer for transdermal insulin delivery and evaluate the possibility of applying a new portable and low-cost device for transdermal insulin delivery. Twenty-four rats were divided into four groups with six rats in each group: one control group and three experimental groups. Control group (C) did not receive any ultrasound exposure or insulin (untreated group). The second group (T1) was treated with subcutaneous insulin (Humulin(®) R, rDNA U-100, Eli Lilly and Co., Indianapolis, IN) injection (0.25 U/Kg). The third group (T2) topically received insulin, and the fourth group (T3) received insulin with ultrasound waves. All the rats were anesthetized by intraperitoneal injection of ketamin hydrochloride and xylazine hydrochloride. Blood samples were collected after anesthesia to obtain a baseline glucose level. Additional blood samples were taken every 15 min in the whole 90 min experiment. In order for comparison the changes in blood glucose levels" to " In order to compare the changes in blood glucose levels. The statistical multiple comparison (two-sided Tukey) test showed a significant difference between transdermal insulin delivery group (T2) and subcutaneous insulin injection group (T1) during 90 min experiment (P = 0.018). In addition, the difference between transdermal insulin delivery group (T2) and ultrasonic transdermal insulin delivery group (T3) was significant (P = 0.001). Results of this study demonstrated that the produced low-frequency ultrasound from this device enhanced the transdermal delivery of insulin across hairless rat skin.

  17. Allergic anaphylaxis due to subcutaneously injected heparin

    Directory of Open Access Journals (Sweden)

    Anders Diana

    2013-01-01

    Full Text Available Abstract Heparins are one of the most used class of anticoagulants in daily clinical practice. Despite their widespread application immune-mediated hypersensitivity reactions to heparins are rare. Among these, the delayed-type reactions to s.c. injected heparins are well-known usually presenting as circumscribed eczematous plaques at the injection sites. In contrast, potentially life-threatening systemic immediate-type anaphylactic reactions to heparins are extremely rare. Recently, some cases of non-allergic anaphylaxis could be attributed to undesirable heparin contaminants. A 43-year-old patient developed severe anaphylaxis symptoms within 5–10 minutes after s.c. injection of enoxaparin. Titrated skin prick testing with wheal and flare responses up to an enoxaparin dilution of 1:10.000 indicated a probable allergic mechanism of the enoxaparin-induced anaphylaxis. The basophil activation test as an additional in-vitro test method was negative. Furthermore, skin prick testing showed rather broad cross-reactivity among different heparin preparations tested. In the presented case, history, symptoms, and results of skin testing strongly suggested an IgE-mediated allergic hypersensitivity against different heparins. Therefore, as safe alternative anticoagulants the patient could receive beneath coumarins the hirudins or direct thrombin inhibitors. Because these compounds have a completely different molecular structure compared with the heparin-polysaccharides.

  18. Suicide by Insulin?

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_165701.html Suicide by Insulin? Self-harm and suicidal behavior may ... higher rates of depression, the researchers explained. And suicide or suicide attempts using insulin or other diabetes ...

  19. Insulin C-peptide

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003701.htm Insulin C-peptide test To use the sharing features ... a product that is created when the hormone insulin is produced and released into the body. The ...

  20. High-mix insulins

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use.

  1. Insulin pump (image)

    Science.gov (United States)

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  2. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen....

  3. Polymer-based nanoparticles for oral insulin delivery: Revisited approaches.

    Science.gov (United States)

    Fonte, Pedro; Araújo, Francisca; Silva, Cátia; Pereira, Carla; Reis, Salette; Santos, Hélder A; Sarmento, Bruno

    2015-11-01

    Diabetes mellitus is a high prevalence and one of the most severe and lethal diseases in the world. Insulin is commonly used to treat diabetes in order to give patients a better life condition. However, due to bioavailability problems, the most common route of insulin administration is the subcutaneous route, which may present patients compliance problems to treatment. The oral administration is thus considered the most convenient alternative to deliver insulin, but it faces important challenges. The low stability of insulin in the gastrointestinal tract and low intestinal permeation, are problems to overcome. Therefore, the encapsulation of insulin into polymer-based nanoparticles is presented as a good strategy to improve insulin oral bioavailability. In the last years, different strategies and polymers have been used to encapsulate insulin and deliver it orally. Polymers with distinct properties from natural or synthetic sources have been used to achieve this aim, and among them may be found chitosan, dextran, alginate, poly(γ-glutamic acid), hyaluronic acid, poly(lactic acid), poly(lactide-co-glycolic acid), polycaprolactone (PCL), acrylic polymers and polyallylamine. Promising studies have been developed and positive results were obtained, but there is not a polymeric-based nanoparticle system to deliver insulin orally available in the market yet. There is also a lack of long term toxicity studies about the safety of the developed carriers. Thus, the aims of this review are first to provide a deep understanding on the oral delivery of insulin and the possible routes for its uptake, and then to overview the evolution of this field in the last years of research of insulin-loaded polymer-based nanoparticles in the academic and industrial fields. Toxicity concerns of the discussed nanocarriers are also addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. [ANSYS simulation of subcutaneous pustule electrical characteristics].

    Science.gov (United States)

    Liu, Baohua; Wang, Xuan; Zhu, Honglian; Wang, Guoyong

    2011-12-01

    With the growing number of clinical surgery, post-operative surgical wound infection has become a very difficult clinical problem. In the treatments of it, non-invasive test of wound infection and healing status has a significance in clinical medicine practice. In this paper, beginning with the electrical properties of skin tissue structure and on the basis of the electromagnetism and the human anatomy, using the finite element analysis software, we applied safe voltage on the 3D skin model, performed the subcutaneous pustule simulation study and gained the relational curve between depth and radius of the pustule model. The simulation results suggested that the method we put forward could be feasible, and it could provide basis for non-invasive detection of wound healing and wound infection status.

  5. 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

  6. 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...

  7. Insulin action in adipose tissue in type 1 diabetes

    Directory of Open Access Journals (Sweden)

    F Arrieta-Blanco

    2011-02-01

    Full Text Available F Arrieta-Blanco1, JI Botella-Carretero1, P Iglesias1, JA Balsa1, I Zamarrón1, C De la Puerta1, JJ Arrieta2, F Ramos3, C Vázquez1, A Rovira21Unit of Clinical Nutrition and Dietetics, Department of Endocrinology and Nutrition, Hospital Ramóny, Cajal, Madrid, Spain, Irycis, Ciberobn; 2Fundación Jimenez Díaz. Madrid, Spain; 3Hospital Sureste de ArgandaBackground: Insulin action has been reported to be normal in type 1 diabetic patients. However, some studies have reported an insulin resistance state in these patients. The aim of this study was to investigate insulin resistance in a group of type 1 diabetic patients. We studied the insulin action in adipose tissue and analyzed the effects of duration of disease, body mass index (BMI, and glycosylated hemoglobin on insulin action at the receptor and postreceptor levels in adipocytes.Methods: Nine female type 1 diabetic patients with different durations of disease and eight nondiabetic female patients of comparable age and BMI were studied. 125I-insulin binding and U-[14C]-D-glucose transport was measured in a sample of subcutaneous gluteus adipose tissue obtained by open surgical biopsy from each subject.Results: The duration of disease was negatively correlated with both 125I-insulin binding capacity (r = -0.70, P < 0.05 and basal and maximum insulin-stimulated glucose transport (r = -0.87, P < 0.01, and r = -0.88, P < 0.01, respectively. Maximum specific 125I-insulin binding to the receptors in adipocytes was higher in the group of patients with a shorter duration of disease (P < 0.01. Basal and maximum insulin-stimulated glucose transport was significantly higher in the group with less than 5 years of disease (P < 0.01. No correlation was found between BMI and insulin action.Conclusion: Female type 1 diabetic patients have normal insulin action. There is a high glucose uptake in the early phase of the disease, although a longer duration of disease appears to be a contributing factor to a

  8. 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.

  9. BMP4 Gene Therapy in Mature Mice Reduces BAT Activation but Protects from Obesity by Browning Subcutaneous Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Jenny M. Hoffmann

    2017-08-01

    Full Text Available We examined the effect of Bone Morphogenetic Protein 4 (BMP4 on energy expenditure in adult mature mice by targeting the liver with adeno-associated viral (AAV BMP4 vectors to increase circulating levels. We verified the direct effect of BMP4 in inducing a brown oxidative phenotype in differentiating preadipocytes in vitro. AAV-BMP4-treated mice display marked browning of subcutaneous adipocytes, with increased mitochondria and Uncoupling Protein 1 (UCP1. These mice are protected from obesity on a high-fat diet and have increased whole-body energy expenditure, improved insulin sensitivity, reduced liver fat, and reduced adipose tissue inflammation. On a control diet, they show unchanged body weight but improved insulin sensitivity. In contrast, AAV-BMP4-treated mice showed beiging of BAT with reduced UCP1, increased lipids, and reduced hormone-sensitive lipase (HSL. Thus, BMP4 exerts different effects on WAT and BAT, but the overall effect is to enhance insulin sensitivity and whole-body energy expenditure by browning subcutaneous adipose tissue.

  10. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria....

  11. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the

  12. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    Langeveld, Mirjam; Aerts, Johannes M. F. G.

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple

  13. 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.

  14. [Is Herceptin(®) (trastuzumab) by subcutaneous a mini revolution? Pharmaco-economic study].

    Science.gov (United States)

    Lieutenant, Vincent; Toulza, Émilie; Pommier, Martine; Lortal-Canguilhem, Barbara

    2015-03-01

    Herceptin(®) injected by intravenous (IV) is one of the key treatment of breast cancer HER2+. The improvement of galenic form allowed a new way of administration, the sub-cutaneous way (SC), authorized by EMEA in 2013. This new way enables a 5-minute infusion, a fixed dose and a fixed volume of preparation. On 2012, saving-time and financial impacts were calculated by extrapolation of the IV way in a cancer treatment center. The study showed a preparing time-saving of 7.5min/loading dose and of 6.5min/maintenance dose, and a nurse time-saving of 4.5min/loading dose and 4.25min/maintenance dose. Moreover, it can be added a saving of consumable of 13,31€ per injection in case of monotherapy. The SC leads to a new adaptation and reorganization in the preparation of monoclonal antibodies and day hospitals. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  15. Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines.

    Science.gov (United States)

    Kashiwagi, Yasuyo; Maeda, Mika; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-06-05

    Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice. Aluminum-adjuvanted vaccines induced inflammatory nodules at the injection site, which expanded into the intra-muscular space without any muscle degeneration or necrosis, whereas non-adjuvanted vaccines did not. These nodules consisted of polymorph nuclear neutrophils with some eosinophils within the initial 48h, then monocytes/macrophages 1 month later. Inflammatory nodules were observed 6 months after IM, had decreased in size, and were absorbed 12 months after IM, which was earlier than that after SC. Cytokine production was examined in the injected muscular tissues and AS04 adjuvanted HPV induced higher IL-1β, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytokine profiles were observed to those induced by the other vaccines. Currently available vaccines did not induce muscular degeneration or fibrotic scar as observed with muscle contracture caused by multiple IMs of antibiotics in the past. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

    1999-01-01

    OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore...... sought to evaluate the effect of infusion of GLP-1 for 48 h in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We infused GLP-1 (2.4 pmol.kg-1.min-1) or saline subcutaneously for 48 h in randomized order in six patients with type 2 diabetes to evaluate the effect on appetite during fixed...... under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration, whereas glucagon levels were unchanged. Neither triglycerides nor free fatty acids were affected. GLP-1 administration decreased hunger and prospective food intake and increased satiety, whereas...

  17. 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

    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...... determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free oestradiol and testosterone were decreased...... 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...

  18. 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

    determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free oestradiol and testosterone were decreased......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...... 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...

  19. Home care use of intravenous and subcutaneous immunoglobulin for primary immunodeficiency in the United States.

    Science.gov (United States)

    Huang, Faith; Feuille, Elizabeth; Cunningham-Rundles, Charlotte

    2013-01-01

    Utilization reports on immunoglobulin (Ig) use for immunodeficiency in the United States (U.S.) have focused on prescribing practices in hospitals. There have been no large-scale reports on Ig use for immune deficiency in the home. We investigated the use of Ig in 3,187 subjects diagnosed with primary immunodeficiency. Cross-sectional data on 4,580 subjects in the U.S. receiving Ig in 2011 was obtained from a major home care provider. Demographics, route, dose, and frequency of Ig use by subjects with ICD-9 coded primary immunodeficiencies were analyzed. Of 4,580 subjects, 3,187 had ICD-9 codes suggesting primary immunodeficiencies; 1,939 (60.8 %) were females and 1,248 (39.2 %) were males, with age ranging from 0 to 95 years. The predominant diagnoses were: common variable immunodeficiency (279.06; n=1,764; 55.3 %), hypogammaglobulinemia (279.00; n=635; 19.9 %), unspecified immunity deficiency (279.3; n=286; 9 %), other selective Ig deficiencies (279.03; n=171; 5.4 %), and agammaglobulinemia (279.04; n=127; 4 %). 54 % of subjects received Ig by the subcutaneous (SC) route, and 46 % by intravenous (IV) route, with more SC use by older subjects. The mean dose prescribed was 483 mg/kg/month, but less Ig was ordered for subjects on SCIg (409 mg/kg/month), as compared to subjects on IVIg (568 mg/kg/month). A highly significant inverse correlation between increasing age and dosage of Ig ordered was found (P= <.0001). Analysis of home care use of Ig in primary immune deficiency revealed that the SC route was prescribed more than the IV route, especially for older patients. By either method of administration, less immunoglobulin was prescribed for older subjects.

  20. The safety of high-dose buprenorphine administered subcutaneously in cats.

    Science.gov (United States)

    Sramek, M K; Haas, M C; Coleman, G D; Atterson, P R; Hamlin, R L

    2015-10-01

    The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol-specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine-treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug-related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats. © 2015 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  1. Hemoglobin C, S-C, and E Diseases

    Science.gov (United States)

    ... more quickly than others, resulting in chronic anemia. Hemoglobin C disease Hemoglobin C disease occurs mostly in ... are a common complication of hemoglobin C disease. Hemoglobin S-C disease Hemoglobin S-C disease occurs in people ...

  2. Maraviroc shows differential effects on glucose uptake and lipolysis in human subcutaneous cultured adipocytes in comparison with omental adipocytes

    Directory of Open Access Journals (Sweden)

    P Perez-Matute

    2012-11-01

    Full Text Available Maraviroc (MVC, the first approved CC-chemokine receptor 5 (CCR5 antagonist, is used for treating HIV-1-infected patients with CCR5 tropism. MVC has been proved safe in all respects and showed beneficial effects on lipid profile of HIV patients with dislipidemia. Adipocyte dysfunction seems to be responsible for many metabolic alterations such as insulin resistance and dislipidemia. Subcutaneous and visceral fat depots are not only physiologically but also metabolically different and metabolic disturbances are more closely associated with visceral than subcutaneous fat accumulation. It has been suggested that antiretrovirals affect both fat depots in a different extent. Thus, whether isolated human adipocytes display regio-specific sensitivity to the metabolic effects of MVC have been tested in this study. Human subcutaneous and omental preadipocytes were used as the source of human adipocytes. These cells were treated with therapeutic concentrations of MVC (0.5–25 µM at day 14 post-differentiation (4 and 24 hours of treatment. Glucose utilization, lactate production and glycerol released into the media were measured using an autoanalyzer. Adiponectin secretion was determined by an ELISA array. A dose-dependent increase in glucose uptake was observed in subcutaneous adipocytes treated with MVC (+72% of stimulation for MVC 25 µM, p < 0.01. This stimulatory effect was tissue specific, as no effects were observed in omental adipocytes. MVC did not exert any significant effect on adiponectin secretion. No significant effects were observed on lactate production neither in subcutaneous nor omental adipocytes. Interestingly, 4 hours of treatment with MVC induced a significant increase in the amount of glycerol released into the media by subcutaneous adipocytes (p < 0.001, but this effect disappeared with longer exposure of adipocytes to MVC (24 h. No effects were observed on lipolysis in omental adipocytes although a slight tendency to

  3. LHCb Data Replication During SC3

    CERN Multimedia

    Smith, A

    2006-01-01

    LHCb's participation in LCG's Service Challenge 3 involves testing the bulk data transfer infrastructure developed to allow high bandwidth distribution of data across the grid in accordance with the computing model. To enable reliable bulk replication of data, LHCb's DIRAC system has been integrated with gLite's File Transfer Service middleware component to make use of dedicated network links between LHCb computing centres. DIRAC's Data Management tools previously allowed the replication, registration and deletion of files on the grid. For SC3 supplementary functionality has been added to allow bulk replication of data (using FTS) and efficient mass registration to the LFC replica catalog.Provisional performance results have shown that the system developed can meet the expected data replication rate required by the computing model in 2007. This paper details the experience and results of integration and utilisation of DIRAC with the SC3 transfer machinery.

  4. 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

  5. Hypercalcemia in Association With Subcutaneous Fat Necrosis of ...

    African Journals Online (AJOL)

    The case of a four weeks-old girl with subcutaneous fat necrosis and associated hypercalcemia is presented. Subcutaneous Fat Necrosis of the New born (SCFN) is an uncommon disorder which is rarely complicated with life threatening hypercalcemia. Though it is reported from many parts of the world this is the first case ...

  6. 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.

    2017-01-01

    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

  7. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  8. [Insulin resistance in children].

    Science.gov (United States)

    Witek, Joanna; Witek, Przemysław; Pańkowska, Ewa

    2011-01-01

    Insulin resistance is characterized by decreased tissue sensitivity to insulin. The hallmark of insulin resistance is decreased tissue glucose uptake despite normal or elevated insulin concentration. There has been an upward trend in the incidence of insulin resistance in developed countries, although in pediatric population it is difficult to assess. Both genetic and environmental factors play an important role in the etiology of insulin resistance, namely increased diet caloricity and decreased physical activity. Gradually, this leads to adipose tissue build-up. The role of visceral adipose tissue is of particular importance, mainly due to its significant endocrine activity, leading to adverse metabolic effects. The most important consequences of insulin resistance in children include increased incidence of type 2 diabetes, atherogenic dyslipidemia and arterial hypertension, which lead to increased cardiovascular risk. Children with insulin resistance can develop nonalcoholic steatohepatitis and sleep apnea syndrome. In case of female pediatric patients a higher incidence of polycystic ovary syndrome (PCOS) is observed. Furthermore, the authors reviewed opinions on risk factors for insulin resistance, as well as direct and indirect insulin resistance assessment methods. The article presents the principles of primary and secondary prevention of insulin resistance in children, with particular allowance for dietary recommendations and recommendations to increase physical activity, and, in selected cases, current guidelines on pharmacological treatment.

  9. Single chain Fab (scFab fragment

    Directory of Open Access Journals (Sweden)

    Brenneis Mariam

    2007-03-01

    Full Text Available Abstract Background The connection of the variable part of the heavy chain (VH and and the variable part of the light chain (VL by a peptide linker to form a consecutive polypeptide chain (single chain antibody, scFv was a breakthrough for the functional production of antibody fragments in Escherichia coli. Being double the size of fragment variable (Fv fragments and requiring assembly of two independent polypeptide chains, functional Fab fragments are usually produced with significantly lower yields in E. coli. An antibody design combining stability and assay compatibility of the fragment antigen binding (Fab with high level bacterial expression of single chain Fv fragments would be desirable. The desired antibody fragment should be both suitable for expression as soluble antibody in E. coli and antibody phage display. Results Here, we demonstrate that the introduction of a polypeptide linker between the fragment difficult (Fd and the light chain (LC, resulting in the formation of a single chain Fab fragment (scFab, can lead to improved production of functional molecules. We tested the impact of various linker designs and modifications of the constant regions on both phage display efficiency and the yield of soluble antibody fragments. A scFab variant without cysteins (scFabΔC connecting the constant part 1 of the heavy chain (CH1 and the constant part of the light chain (CL were best suited for phage display and production of soluble antibody fragments. Beside the expression system E. coli, the new antibody format was also expressed in Pichia pastoris. Monovalent and divalent fragments (DiFabodies as well as multimers were characterised. Conclusion A new antibody design offers the generation of bivalent Fab derivates for antibody phage display and production of soluble antibody fragments. This antibody format is of particular value for high throughput proteome binder generation projects, due to the avidity effect and the possible use of

  10. Implications of subcutaneous or intravenous delivery of trastuzumab; further insight from patient interviews in the PrefHer study.

    Science.gov (United States)

    Fallowfield, L; Osborne, S; Langridge, C; Monson, K; Kilkerr, J; Jenkins, V

    2015-04-01

    The 2 Cohort randomised PrefHer trial examined the preferences of HER2+ve primary breast cancer patients for intravenous (IV) or subcutaneous (SC) delivery of trastuzumab via a Single Injectable Device (SID) or hand-held syringe (HHS). The novel approach and design of the study permitted an in-depth exploration of patients' experiences, the impact that different modes of delivery had on patients' well-being and implications for future management. The preferences, experiences and general comments of patients in the PrefHer study were collected via specific semi-structured interview schedules. Exploratory analyses of data were conducted using standard methodology. The final question invited patients to make further comments, which were divided into 9 thematic categories - future delivery, compliments, time/convenience, practical considerations, pain/discomfort, study design, side-effects, psychological impact, and perceived efficacy. 267/467 (57%) patients made 396 additional comments, 7 were neutral, 305 positive and 86 negative. The three top categories generating the largest number of comments were compliments and gratitude about staff and being part of PrefHer (75/396; 19%), the potential future delivery of SC trastuzumab (73/396; 18%), and practical considerations about SC administration (60/396; 15%). Eliciting patient preferences about routes of administration of drugs via comprehensive interviews within a randomised cross-over trial yielded rich and important information. The few negative comments made demonstrated a need for proper staff training in SC administration Patients were grateful to have been part of the trial, and would have liked to continue with SC delivery. The possibility of home administration in the future also seemed acceptable. 2010-024099-25. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jean O'Connell

    Full Text Available 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

  12. 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

  13. 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....

  14. The SC gets ready for visitors

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    Hall 300, which houses the Synchrocyclotron (SC), CERN’s first accelerator, is getting ready to host a brand-new exhibition. The site will be one of the stops on the new visit itineraries that will be inaugurated for the 2013 CERN Open Day.   The Synchrocyclotron through the years. Just as it did in the late 1950s, when the accelerator was first installed, the gigantic red structure of the Synchrocyclotron's magnet occupies a large part of the 300-square-metre hall. “We have completed the first phase of the project that will give the SC a new lease of life,” says Marco Silari, the project leader and a member of CERN’s Radiation Protection Group. “We have removed all the equipment that was not an integral part of the accelerator. The hall is now ready for the civil-engineering work that will precede the installation of the exhibition.” The SC was witness to a big part of the history of CERN. The accelerator produced ...

  15. Enhancement of the intranasal delivery of insulin via a novel mucoadhesive Carbopol gel.

    Science.gov (United States)

    El-Dakrouri, Walaa Ahmed; Ibrahim, Howida Kamal; Ghorab, Mohamed Khaled; Ghorab, Mahmoud Mohamed

    2010-07-01

    The objectives of this study were to develop an intranasal insulin gel using Carbopol homogenization rather than neutralization and to examine the effectiveness of the gel compared with a subcutaneous injection. Four factors, namely the molecular weight of polyethylene glycol (PEG), the concentration of Carbopol, the temperature of preparation and the type of absorption enhancer, were evaluated for their effect on viscosity and in-vitro insulin release. Bioavailability of insulin from selected formulations was compared with an intranasal solution and subcutaneous injection in rabbits. Increasing the molecular weight of PEG and Carbopol concentration increased the gel viscosity and changed the release mechanism from diffusion to case II transport. Applying heat during preparation resulted in a lower viscosity gel and increased the in-vitro insulin release. Among the two enhancers studied, sodium deoxycholate resulted in a higher viscosity gel than Tween 80. In vivo, the intranasal gel showed a stronger and longer hypoglycaemic effect with 1.7- and 3.1-fold higher maximum decrease in blood glucose level and area above the curve, respectively, compared with the subcutaneous injection. The homogenized Carbopol intranasal gel could be an efficient noninvasive way for insulin delivery but selection of gel components and method of preparation are critical for achieving the most desired effect.

  16. 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.

  17. Effects of exercise training on subcutaneous and visceral adipose tissue in normal- and high-fat diet-fed rats

    OpenAIRE

    Gollisch, Katja S. C.; Brandauer, Josef; Jessen, Niels; Toyoda, Taro; Nayer, Ali; Hirshman, Michael F.; Goodyear, Laurie J.

    2009-01-01

    Regular physical activity improves glucose tolerance and decreases adiposity. Our aim was to investigate the effects of exercise training on subcutaneous (inguinal) and visceral (parametrial) adipose tissue in rats that were fed a chow diet (13% fat) or made insulin resistant by a high-fat diet (60% fat). Sprague-Dawley rats performed 4 wk of voluntary wheel running or were kept as sedentary controls. The training groups fed chow and the high-fat diet achieved similar running distances (8.8 ±...

  18. Acetoacetate and beta-hydroxybutyrate in combination with other metabolites release insulin from INS-1 cells and provide clues about pathways in insulin secretion.

    Science.gov (United States)

    MacDonald, Michael J; Longacre, Melissa J; Stoker, Scott W; Brown, Laura J; Hasan, Noaman M; Kendrick, Mindy A

    2008-02-01

    Mitochondrial anaplerosis is important for insulin secretion, but only some of the products of anaplerosis are known. We discovered novel effects of mitochondrial metabolites on insulin release in INS-1 832/13 cells that suggested pathways to some of these products. Acetoacetate, beta-hydroxybutyrate, alpha-ketoisocaproate (KIC), and monomethyl succinate (MMS) alone did not stimulate insulin release. Lactate released very little insulin. When acetoacetate, beta-hydroxybutyrate, or KIC were combined with MMS, or either ketone body was combined with lactate, insulin release was stimulated 10-fold to 20-fold the controls (almost as much as with glucose). Pyruvate was a potent stimulus of insulin release. In rat pancreatic islets, beta-hydroxybutyrate potentiated MMS- and glucose-induced insulin release. The pathways of their metabolism suggest that, in addition to producing ATP, the ketone bodies and KIC supply the acetate component and MMS supplies the oxaloacetate component of citrate. In line with this, citrate was increased by beta-hydroxybutyrate plus MMS in INS-1 cells and by beta-hydroxybutyrate plus succinate in mitochondria. The two ketone bodies and KIC can also be metabolized to acetoacetyl-CoA and acetyl-CoA, which are precursors of other short-chain acyl-CoAs (SC-CoAs). Measurements of SC-CoAs by LC-MS/MS in INS-1 cells confirmed that KIC, beta-hydroxybutyrate, glucose, and pyruvate increased the levels of acetyl-CoA, acetoacetyl-CoA, succinyl-CoA, hydroxymethylglutaryl-CoA, and malonyl-CoA. MMS increased incorporation of (14)C from beta-hydroxybutyrate into citrate, acid-precipitable material, and lipids, suggesting that the two molecules complement one another to increase anaplerosis. The results suggest that, besides citrate, some of the products of anaplerosis are SC-CoAs, which may be precursors of molecules involved in insulin secretion.

  19. 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).

  20. Feasibility of closed-loop insulin delivery in type 2 diabetes: a randomized controlled study.

    Science.gov (United States)

    Kumareswaran, Kavita; Thabit, Hood; Leelarathna, Lalantha; Caldwell, Karen; Elleri, Daniela; Allen, Janet M; Nodale, Marianna; Wilinska, Malgorzata E; Evans, Mark L; Hovorka, Roman

    2014-01-01

    Closed-loop insulin delivery offers a promising treatment option, but to date, it has only been evaluated in type 1 diabetes. Our aim was to evaluate the feasibility of fully closed-loop subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes. Twelve subjects (seven males, age 57.2 years, BMI 30.5 kg/m2) with noninsulin-treated type 2 diabetes (HbA1c 8.4% [68 mmol/mol], diabetes duration 7.6 years) underwent two 24-h visits (closed-loop and control) in a randomized crossover design. During closed-loop visits, the subjects' routine diabetes therapy was replaced with model predictive control algorithm-driven subcutaneous insulin pump delivery based on real-time continuous glucose monitoring. Meals were unannounced, and no additional insulin was administered for carbohydrates consumed. During control visits, the usual diabetes regimen was continued (metformin 92%, sulfonylureas 58%, dipeptidyl peptidase-4 inhibitors 33%). On both visits, subjects consumed matched 50- to 80-g carbohydrate meals and optional 15-g carbohydrate snacks and remained largely sedentary. Plasma glucose measurements evaluated closed-loop performance. Compared with conventional therapy, 24 h of closed-loop insulin delivery increased overall the median time in target plasma glucose (3.9-8.0 mmol/L) from 24 to 40% (P = 0.016), despite sensor under-reading by a median of 1.2 mmol/L. The benefit of the closed-loop system was more prominent overnight, with greater time in target glucose (median 78 vs. 35%; P = 0.041) and less time in hyperglycemia (22 vs. 65%; P = 0.041). There was no hypoglycemia during either intervention. A closed-loop system without meal announcement and using subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes appears feasible and safe. Improvement in postprandial glucose control may require further optimization of system performance.

  1. 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)].......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...

  2. Synthesis and characterization of reduced scandium halide containing one- and two-dimensional metal bonded arrays. [Sc--ScCl3; Cs3Sc2Cl9; CsScCl3

    Energy Technology Data Exchange (ETDEWEB)

    Poeppelmeier, K.R.

    1978-08-01

    The stabilization effect of metal-metal bond formation on reduced scandium compounds was studied. The binary compounds Sc/sub 7/Cl/sub 12/, Sc/sub 5/Cl/sub 8/, Sc/sub 7/Cl/sub 10/ and ScCl were prepared by high temperature techniques and were characterized by single crystal x-ray diffraction. The respective metal arrays in these compounds can be viewed as fragments of scandium metal ranging from discrete six atom metal cluster species (Sc(Sc/sub 6/Cl/sub 12/)), through intermediate single and double infinite chain configurations ((ScCl/sub 2/)(Sc/sub 4/Cl/sub 6/)) and ((ScCl/sub 2/)(Sc/sub 6/Cl/sub 8/)) to double metal close-packed sheets (ScCl). The halogen atoms effectively isolate the clusters, chains and sheets by bonding face, edge or exo positions on the metal arrays. The common occurrence of isolated scandium (III) ions emphasizes that a minimum number of bonding electrons is required to stabilize what are formally anionic metal arrays. The distribution of the reduction electrons in these anisotropic materials was studied by magnetic susceptibility, EPR and uv-X photoelectron spectroscopy. The ternary compounds studied were Cs/sub 3/Sc/sub 2/Cl/sub 9/ and CsScCl/sub 3/. The anion-bridged metal chain of the hexagonal perovskite structure was found to stabilize scandium (II). CsScCl/sub 3/ was found to be grossly nonstoichiometric on the transition metal site and the effects of the mixed valence character were studied between the single valence extremes Cs/sub 3/Sc/sub 2 + x/Cl/sub 9/; 0< x < 1.0.

  3. Safety of subcutaneous microinjections (mesotherapy) in musicians.

    Science.gov (United States)

    Navarte, Danik Arana; Rosset-Llobet, Jaume

    2011-06-01

    Determine the safety and tolerance of mesotherapy as a technique for the treatment of musculoskeletal complaints in musicians. 67 patients (55.2% women) were subjected to a total of 267 mesotherapy sessions. A mesotherapy needle or normal needle was used randomly. The drugs employed were thiocolchicoside and diazepam as muscular relaxants, pentoxifylline or buflomedil as vasodilators, and piroxicam as an anti-inflammatory, as directed. A visual analogue scale was used to quantify the pain produced by the microinjections as well as the degree of immediate and midterm side effects as reported on a standard questionnaire. A mean of 155.5 microinjections were performed per session, of which 45.6% were perceived as painful by the patient with a mean severity of 4.3 out of 10. The pain reduced to 0.5 out of 10 after 24 hours. The most sensitive areas were the levator scapulae and splenius muscles. Systemic symptoms were reported by 5.99% of the musicians after the mesotherapy sessions (muscular weakness 1.5%, rash 1.5%, drowsiness 1.1% and itching 1.1%, being the most frequent). The mean severity of these symptoms was 2.77 out of 10. In all cases the symptoms had completely disappeared after 24 hours. No patient referred to signs of local or systemic infection. The application of drugs by means of subcutaneous injections (mesotherapy) in musicians is a technique that is safe, well tolerated, and without any severe complications.

  4. INSULIN THERAPY TODAY

    Directory of Open Access Journals (Sweden)

    Saša Živić

    2002-05-01

    Full Text Available The insulin classification regarding the duration of its effect gradually be-comes outdated; it is necessary to speak first about the insulin therapy regimes. The intensified insulin therapy regarding the type of multiple daily insulin injections be-comes an indisputable standard. The progress in the "protein engineering" with the formation of a wide spectrum of insulin analogues provides for moving forward to-wards modern diabetology and the concept of strict individualization of the insulin therapy. The experience becomes a pattern in creating two existing formulas of the insulin "short" analogues, namely HUMALAG with the replacement of the proline and lysinane places with those of 28 and 29, and NOVORAPID with aspartic acid at the 28th place in the B chain. The most recent long-effect analogues are created by amino acid changes with the glycine residual at the position A21 and two ariginines added to the positions B31 and B32 - insulin "glargin" - LANTUS. The development of short and long effect analogues imposed the logical need for formulating "new" fixed insulin combination's as well. New combination's are made of two kinds of ac-tual insulin, namely, the fast-effect analogues of the aspart type or lystroinsulin and protamine-retarded preparations - neutral protamine - lystroinsulin. Three kinds of combinations are made.

  5. Treatment of Refractory Postural Tachycardia Syndrome with Subcutaneous Octreotide Delivered Using an Insulin Pump

    Directory of Open Access Journals (Sweden)

    Muhammad Khan

    2015-01-01

    Full Text Available Postural Tachycardia Syndrome (PoTS represents a disorder of the autonomic nervous system that results in symptoms of orthostatic intolerance. Despite having a severe impact on the patient’s quality of life, the current treatment options for PoTS are based on limited evidence. Subsequently, this results in clinicians having to utilise a variety of treatment regimens in the hope of successfully providing symptomatic relief. However, the options available for PoTS are not without significant side effects that can worsen an already debilitating condition. Our cases provide a further novel treatment option for clinicians to consider in PoTS refractory to established treatments.

  6. Assessment and validation of a defined fluid restriction protocol in the use of subcutaneous desmopressin for children with inherited bleeding disorders.

    Science.gov (United States)

    Mason, J A; Robertson, J D; McCosker, J; Williams, B A; Brown, S A

    2016-09-01

    Despite the availability of subcutaneous desmopressin (1-deamino-8-d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration. Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting. We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol. Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed. Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre. © 2016 John Wiley & Sons Ltd.

  7. The SWITCH study (sensing with insulin pump therapy to control HbA(1c))

    DEFF Research Database (Denmark)

    Conget, Ignacio; Battelino, Tadej; Giménez, Marga

    2011-01-01

    studies investigating the effect of real-time continuous glucose monitoring (CGM) combined with pump therapy on glycemic outcomes in type 1 diabetes are increasing. Pump therapy is well established as a "gold standard" for insulin delivery, offering improvements over multiple daily insulin...... injections. However, there is still a proportion of subjects using continuous subcutaneous insulin infusion in whom goals for metabolic control are far from achieved or benefits of this type of insulin therapy are transient. The SWITCH (Sensing With Insulin pump Therapy to Control HbA(1c) [hemoglobin A1c......]) study is a multicenter, randomized, controlled, crossover study to evaluate if adding CGM to experienced pump patients with suboptimal metabolic control will provide additional insight enabling clinical and therapeutic benefit....

  8. Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro.

    Science.gov (United States)

    Cigolini, M; Bosello, O; Zancanaro, C; Orlandi, P G; Fezzi, O; Smith, U

    1984-12-01

    To study the mechanism(s) of action of metformin, fragments of human subcutaneous adipose tissue were incubated with therapeutic blood concentrations of metformin. In the absence of insulin no effect of metformin was seen on either lipolysis or glucose metabolism. When insulin was present, however, metformin stimulated glucose conversion into both triglycerides and CO2. In marked contrast, no effect of metformin was observed on the antilipolytic effect of insulin. In agreement with this selective effect no change in insulin binding was found. In conclusion, metformin seems to exert its effect on glucose metabolism by potentiating the action of insulin at a post-receptor level, possibly on the rate of glucose transport.

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

    Directory of Open Access Journals (Sweden)

    Paul Pijush Kumar

    2017-06-01

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

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

    Science.gov (United States)

    Paul, Pijush Kumar; Treetong, Alongkot; Suedee, Roongnapa

    2017-06-27

    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.

  11. Implantable batteryless device for on-demand and pulsatile insulin administration

    Science.gov (United States)

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

    2017-04-01

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

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

    Science.gov (United States)

    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.

  13. Reduced insulin secretion in normoglycaemic patients with beta-thalassaemia major.

    Science.gov (United States)

    Angelopoulos, N G; Zervas, A; Livadas, S; Adamopoulos, I; Giannopoulos, D; Goula, A; Tolis, G

    2006-12-01

    To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with beta-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload. We measured fasting glucose, insulin and C-peptide levels in 24 patients with beta-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated. Fasting glucose levels in patients were increased compared with control subjects (5.5 +/- 0.12 vs. 4.7 +/- 0.13 mmol/l, mean +/- SEM, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SC(HOMA)) was lower in thalassaemic patients (SC(HOMA) 88.5 +/- 11.11 vs. 184.3 +/- 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SC(HOMA) was higher in the patients with NFG compared with those with IFG patients (110.6 +/- 17.63 vs. 66.3 +/- 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISI(HOMA)) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SC(HOMA) (r = 0.45, P = 0.02) and negatively with ISI(HOMA) (r = -0.43, P = 0.03). These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in beta-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent.

  14. Cardiovascular risk score is linked to subcutaneous adipocyte size and lipid metabolism.

    Science.gov (United States)

    Rydén, M; Arner, P

    2017-09-01

    Although white adipose tissue mass and distribution correlates with cardiovascular disease, the fat cell-specific perturbations underlying this association are not known. We determined the relationship between adipocyte size and lipid metabolism with cardiovascular risk. Adipocyte size as well as spontaneous (basal) and hormone-stimulated effects on adipocyte lipid metabolism (lipolysis and lipogenesis) were investigated in abdominal subcutaneous adipose tissue of 304 men and 775 women. Subjects were classified into five categories according to Adult Treatment Panel III (ATPIII) metabolic syndrome criteria. Adipocyte size increased with increasing ATPIII score (P ATPIII (P ATPIII classes. Basal and insulin-stimulated lipogenesis decreased with increasing score (P ATPIII score and lipolysis but negatively with lipogenesis. All these differences were independent of age, sex and body weight status (P ATPIII in score. Independently of sex, age and body weight status, a high cardiovascular risk score associates with increased circulating free fatty acid levels and hormone-specific alterations of lipolysis/lipogenesis in enlarged subcutaneous fat cells. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  15. Changes to medication-use processes after overdose of U-500 regular insulin.

    Science.gov (United States)

    Monroe, P Sayer; Heck, Wendy D; Lavsa, Stacey M

    2012-12-01

    Modifications made to medication-use processes after an overdose of U-500 regular insulin are described. After a medication error occurred with U-500 regular insulin, a multidisciplinary team of physicians, nurses, advanced-practice nurses, and pharmacists was created to review and improve the ordering, dispensing, and administration processes associated with U-500 regular insulin. The group determined that current safety practices for managing insulin were inadequate. New safety processes specific to U-500 regular insulin were developed and implemented. Vials of U-500 regular insulin are no longer dispensed to nursing units and are stored only in the pharmacy and separated from other insulins. The ordering of U-500 regular insulin is limited to the endocrinology service, and all orders are written using a specialized U-500 regular insulin order set. The option for i.v. administration for U-500 regular insulin was removed from the pharmacy order-entry system; thus, only the subcutaneous route is entered by the pharmacist. In addition, patient-specific doses of U-500 regular insulin are prepared in the pharmacy using only tuberculin syringes that require a double check by two pharmacists. These syringes are delivered to patient care areas in a bag distinguishing the medication as "high alert." One last safety check involving a two-nurse check at the bedside to confirm correct medication administration is performed. Lastly, patient education material specifically for U-500 regular insulin is available online. A multidisciplinary team recommended modifications to the medication-use system regarding U-500 regular insulin after review of a medication error. No errors involving U-500 regular insulin have been reported since implementation of the changes.

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

    Directory of Open Access Journals (Sweden)

    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

  17. Comparison of subcutaneous and transdermal administration of buprenorphine for pre-emptive analgesia in dogs undergoing elective ovariohysterectomy.

    Science.gov (United States)

    Moll, Xavier; Fresno, Laura; García, Félix; Prandi, David; Andaluz, Anna

    2011-01-01

    The clinical efficacy of a 70 microg/h transdermal buprenorphine patch and of 20 microg/kg of buprenorphine administered subcutaneously (SC) for the relief of post-operative pain was determined in 24 healthy female dogs undergoing elective ovariohysterectomy (OHE). Dogs were randomly assigned to three groups: (1) a control group that received no analgesics, (2) a BSC group that received buprenorphine SC (20 microg/kg), and (3) a BP group that received buprenorphine by a 70 microg/h transdermal patch. Dogs were scored for signs of pain at 0, 2, 4, 6, 8, 10, 14, 20, 26, 32 and 38 h after extubation using the Numerical Rating Scale (NRS) and a modified University of Melbourne Pain Scale (UMPS). Mean NRS and UMPS scores for dogs in the BSC group (2.56 ± 0.23 and 3.05 ± 0.27, respectively) and the BP group (2.02 ± 0.24 and 2.67 ± 0.23, respectively) were significantly lower (Pbuprenorphine treatment groups were not significant. The results indicated that the analgesia produced by the 70 microg/h patch was similar to that induced by SC administration of 20 microg/kg of buprenorphine in dogs undergoing OHE, suggesting that the transdermal buprenorphine patch may be a useful alternative for pain management in dogs. 2009 Elsevier Ltd. All rights reserved.

  18. Subcutaneous injections of low doses of humanized anti-CD20 veltuzumab: a phase I study in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kalaycio, Matt E; George Negrea, O; Allen, Steven L; Rai, Kanti R; Abbasi, Rashid M; Horne, Heather; Wegener, William A; Goldenberg, David M

    2016-01-01

    To evaluate the potential of subcutaneous (SC) injections with anti-CD20 antibody veltuzumab in chronic lymphocytic leukemia (CLL), 21 patients received 80, 160, or 320 mg injections every 2 weeks × 4 doses (n = 11) or 160 or 320 mg twice-weekly × 16 doses (n = 10). Treatment was well tolerated with only occasional, mild-moderate, transient injection reactions. Lymphocytosis decreased in all patients (maximum decrease, 5-91%), with 12 patients obtaining >50% decreases. Of 14 patients with lymphadenopathy on CT imaging, 5 (36%) achieved 14-61% reductions (sum of perpendicular diameters). By NCI-WG criteria, two patients achieved partial responses (10%). SC veltuzumab appeared active in all dose groups, with no obvious exposure-response relationship, despite cumulative doses ranging from 320-5120 mg. Overall median progression-free survival was 7.7 months; three patients remained progression-free >1 year (2 ongoing at 2-year study completion). These data suggest further studies of SC veltuzumab in CLL are warranted.

  19. [Insulin therapy and sports].

    Science.gov (United States)

    Aigner, A

    1997-01-01

    Physical work effects a transitory enhanced affinity of insulin to its receptor in the stressed muscles and thereby a better efficiency. Therefore, in sports lasting for 30 min and more the basal and/or bolus doses of insulin have to be reduced in order to prevent hypoglycemia. An alternative supply of additional carbohydrates prior to physical work is often not practicable. Injections of insulin into areas of the body not involved in muscular work do not give sufficient warranty against hypoglycemic reactions. A new short-acting insulin-analogue (Lispro) shows a reduced effect on blood glucose levels after 3 h as compared to regular insulin. Therefore, it could be of advantage for insulin dependent diabetics doing their exercise at this time.

  20. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... of the patient's reaction to exercise is desirable, which necessitates frequent self-monitoring of plasma glucose. It may often be necessary to diminish the insulin dose before exercise, and/or to ingest additional carbohydrate during or after exercise. In non-insulin-dependent (type II) diabetes, exercise...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so...

  1. Flexibility in insulin prescription

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  2. Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs.

    Science.gov (United States)

    Hwang, J-H; Jeong, J-W; Song, G-H; Koo, T-S; Seo, K-W

    2017-05-01

    Esomeprazole is an S-enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported. To determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study). Seven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively. Both studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs. The bioavailability of esomeprazole administered as PO enteric-coated granules and as SC injections was 71.4 and 106%, respectively. The half-life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05). The PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals

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

    Directory of Open Access Journals (Sweden)

    Erwin De Cock

    Full Text Available 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.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.Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p <0.0001. By country, relative reduction in 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 <0.0001. By country, relative reduction was 53-91%. Absolute reduction in extrapolated chair time for the first year of treatment was 3.1-5.5 eight-hour days.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.ClinicalTrials.gov NCT01200758.

  4. A Nodular Type of Subcutaneous Sarcoidosis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kyu Ho; Choi, Yun Sun; Kim, Byoung Suck; Joo, Jong Eun; Jung, Yoon Young; Cho, Young Kwon; An, Jin Kyung; Kim, Hyun Sook; Woo, Jung Joo [Eulji University Hospital, Daejeon (Korea, Republic of)

    2009-01-15

    Sarcoidosis is a granulomatous multisystemic disorder that rarely involves subcutaneous tissue. We describe the MR imaging findings of a subcutaneous sarcoidosis in a patient that presented with a nontender, palpable soft tissue mass on the left buttock, which was confirmed after surgical excision. The MR images showed the presence of a subcutaneous mass that breached the adjacent fascia with an irregular outline and homogeneous, slightly higher signal intensity than the surrounding muscle as seen on a T2-weighted image and with homogeneous enhancement after contrast injection. The lesion could not be differentiated from a sarcoma or a malignancy.

  5. Iatrogenic subcutaneous cervicofacial emphysema with pneumomediastinum after class V restoration.

    Science.gov (United States)

    Lee, Sang-Woon; Huh, Yoon-Hyuk; Cha, Min-Sang

    2017-02-01

    Subcutaneous facial emphysema after dental treatment is an uncommon complication caused by the invasion of high-pressure air; in severe cases, it can spread to the neck, mediastinum, and thorax, resulting in cervical emphysema, pneumomediastinum, and pneumothorax. The present case showed subcutaneous cervicofacial emphysema with pneumomediastinum after class V restoration. The patient was fully recovered after eight days of conservative treatment. The cause of this case was the penetration of high-pressure air through the gingival sulcus, which had a weakened gingival attachment. This case indicated that dentists should be careful to prevent subcutaneous emphysema during common dental treatments using a high-speed hand piece and gingival retraction cord.

  6. Metastatic breast cancer 42 years after bilateral subcutaneous mastectomies.

    Science.gov (United States)

    Jameson, M B; Roberts, E; Nixon, J; Probert, J C; Braatvedt, G D

    1997-01-01

    Subcutaneous mastectomy has a possible role as prophylaxis in patients at high risk of developing breast cancer. A case history is presented of a woman who developed metastatic breast carcinoma 42 years after bilateral subcutaneous mastectomies for non-malignant disease. This case is presented to draw attention to the persistent risk of developing breast cancer even decades after subcutaneous mastectomy and to point out that the role of such surgery in preventing breast cancer has still not been clarified. The appropriateness of prophylactic mastectomy for an individual is better assessed on the absolute risk of breast cancer developing over a defined period rather than the relative risk.

  7. History of insulin

    Directory of Open Access Journals (Sweden)

    Celeste C. Quianzon

    2012-07-01

    Full Text Available The advancement of diabetes treatment has gone from crude extracts of insulin and accidental discovery of sulfa-like drugs in antibiotics to the development of drugs based on improved understanding of the pathophysiology of diabetes mellitus. This article will review the history of the discovery and development of insulin. A companion focusing on non-insulin diabetes agents will follow in the next issue of JCHIMP.

  8. Insulin resistance and atherosclerosis

    OpenAIRE

    Semenkovich, Clay F.

    2006-01-01

    Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent fi...

  9. A comparison of the pharmacodynamic profiles of insulin detemir and insulin glargine: a single dose clamp study in people with type 2 diabetes.

    Science.gov (United States)

    Luzio, S D; Dunseath, G J; Atkinson, M D; Owens, D R

    2013-12-01

    The pharmacodynamic properties of a single dose of 0.5 U/kg insulin detemir and insulin glargine were compared during two 24-h isoglycaemic clamps, one week apart. The order of treatments was randomised. At approximately 0830 h, persons with T2DM received subcutaneous administration of a 0.5 U/kg dose of either insulin detemir or insulin glargine into the anterior abdominal wall. Plasma glucose was measured at 10-min intervals throughout the 24-h clamp period and isoglycaemia was maintained by variable infusion of 20% glucose. Glucose infusion rates (GIR) and plasma C-peptide were determined throughout each 24-h period. Eleven persons with type 2 diabetes (8 male) with mean (SD) age 58.5 years (8.5), BMI 30.8 kg/m² (2.8) and HbA1c 7.5% (0.6) were studied. Plasma glucose remained constant during the clamp (CV: insulin detemir 3.7%; insulin glargine 3.8%). Following injection of insulin detemir, GIR increased, reaching a mean peak of 2.29 mg/kg/min (95% CI 1.64, 2.94) at 11.6h (range 8.9 to 14.3) compared to 1.71 mg/kg/min (95% CI 1.4, 2.0) at 10.2 h (8.1 to 12.3) for insulin glargine (P=0.025 for GIR(max)). Plasma C-peptide decreased during the study period, remaining significantly lower than the fasting level at the study end after both analogues, insulin detemir (P=0.01) and insulin glargine (P=0.02). In persons with T2DM, no difference in duration of action following a single subcutaneous dose of insulin detemir and insulin glargine could be observed. Insulin detemir showed greater between subject variability and achieved a significantly higher maximum GIR than insulin glargine. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. TAGE-SC-L Branch Predictors Again

    OpenAIRE

    Seznec, André

    2016-01-01

    International audience; Outline In this study, we explore the performance limits of these TAGE-SC-L predictors for respectively 8Kbytes and 64Kbytes of storage budget. For a 8KB storage budget, our submitted predictor used most of its storage budget on the TAGE predictor, features a very small loop predictor LP and a neural statistical cor-rector exploiting global history path and very limited local history. The submitted 8Kbytes predictor achieves 4.991 MPKI on the CBP-5 train traces. With a...

  11. Subcutaneous implantable cardioverter-defibrillator: Initial experience.

    Science.gov (United States)

    Galvão, Pedro; Cavaco, Diogo; Adragão, Pedro; Costa, Francisco; Carmo, Pedro; Morgado, Francisco; Bernardo, Ricardo; Nunes, Manuela; Abecasis, Miguel; Neves, José; Mendes, Miguel

    2014-09-01

    Implantable cardioverter-defibrillators (ICDs) are important tools in the prevention of sudden death, but implantation requires transvenous access, which is associated with complications. Subcutaneous implantable cardioverter-defibrillators (S-ICDs) may prevent some of these complications. To evaluate the therapeutics and complications associated with S-ICD systems. S-ICD implantation was planned in 23 patients, for whom the indications were vascular access problems, increased risk of infection or young patients with long predicted follow-up. The population consisted of four patients with ischemic heart disease, three of them on hemodialysis (two with subclavian vein thrombosis), five with left ventricular noncompaction, four with Brugada syndrome, three with arrhythmogenic right ventricular cardiomyopathy, one with transposition of the great vessels, two with dilated cardiomyopathy and four with hypertrophic cardiomyopathy. S-ICDs were implanted in 21 patients, two having failed to fulfil the initial screening criteria. Mean implantation time was 77 minutes, with no complications. Defibrillation tests were performed, and in one patient the generator had to be repositioned to obtain an acceptable threshold. In a mean follow-up of 14 months, 10 patients had S-ICD shocks, which were appropriate in half of them; one developed infection, one needed early replacement due to loss of telemetry and one patient died of noncardiac cause. S-ICD implantation can be performed by cardiologists with a high success rate. Initial experience appears favorable, but further studies are needed with longer follow-up times to assess the safety and efficacy of this strategy compared to conventional devices. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  12. Insulin, cognition, and dementia

    Science.gov (United States)

    Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

    2015-01-01

    Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

  13. Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

    Science.gov (United States)

    Berteau, Cecile; Filipe-Santos, Orchidée; Wang, Tao; Rojas, Humberto E; Granger, Corinne; Schwarzenbach, Florence

    2015-01-01

    Aim The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC) injection pain tolerance. Methods The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8–10, and 15–20 cP) combined with two different injection flow rates (0.02 and 0.3 mL/s). All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS) (0 mm/no pain, 100 mm/extreme pain). The location and depth of the injected fluid was assessed through 2D ultrasound echography images. Results Viscosity levels had significant impact on perceived injection pain (P=0.0003). Specifically, less pain was associated with high viscosity (VAS =12.6 mm) than medium (VAS =16.6 mm) or low (VAS =22.1 mm) viscosities, with a significant difference between high and low viscosities (P=0.0002). Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89). Slow (0.02 mL/s) or fast (0.30 mL/s) injection rates also showed no significant impact on perceived pain during SC injection (P=0.79). In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. Conclusion The results of this study suggest that solutions of up to 3 mL and up to 15–20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High viscosity injections were shown to be the most tolerated, whereas injection volume and flow rates did not impact perceived pain. PMID:26635489

  14. Needle-free subcutaneous sumatriptan (Sumavel DosePro): bioequivalence and ease of use.

    Science.gov (United States)

    Brandes, Jan Lewis; Cady, Roger K; Freitag, Fred G; Smith, Timothy R; Chandler, Patricia; Fox, Anthony W; Linn, Lawrence; Farr, Stephen J

    2009-01-01

    Subcutaneous (s.c.) injection of sumatriptan is currently associated with needle aversion in some patients, and sharps disposal issues. To investigate whether a needle-free system can deliver s.c. sumatriptan. If so, to examine whether needle-free administration is bioequivalent to a 26-gauge needle-based auto-injector. Lastly, to assess the needle-free system for clinical acceptability and ease of use during migraine attacks. Two clinical trials. Study A: Pharmacokinetics and bioequivalence was studied in normal adult volunteers (n = 57 total), directly comparing needle-free (Sumavel DosePro) with needle-based (Imitrex STATdose System) administration of 6 mg s.c. sumatriptan. An incomplete, randomized, partial factorial, crossover design was used. Each subject received 2 administrations of each product, at 2 of the 3 anatomical sites (abdomen, thigh or arm). There were appropriate "washout" periods between each. Pharmacokinetic sampling was at standard time points, and tests for bioequivalence then followed. Study B: The term "ease of use" was used for clinical acceptability and utility of the needle-free system when it was assessed among 52 outpatients treating migraine attacks. Instructional materials were used as would be provided after ordinary prescription. The primary endpoint was successful use of the needle-free system to administer sumatriptan at the first attempt, including appropriate injection site selection. Second and subsequent uses of the needle-free system were also documented. For administration sites in the thigh and the abdomen, but not the arm, the needle-free and needle-based systems were bioequivalent (for all pharmacokinetic endpoints the mean ratios between the 2 devices were always between 90.1% and 115%). Among outpatients treating a migraine attack with the needle-free system, 51 of 52 on first attempt used the needle-free system successfully when treating a migraine attack. Sumavel DosePro needle-free delivery system is a new

  15. Increases in seizure latencies induced by subcutaneous docosahexaenoic acid are lost at higher doses.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Taha, Ameer Y; Mantha, Rebecca L; Ciobanu, Flaviu A; Zeng, Qiudi H; Tchkhartichvili, George M; Domenichiello, Anthony F; Bazinet, Richard P; Burnham, W M

    2012-05-01

    Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid (PUFA) which has been found to have anticonvulsant properties. Our group has previously reported in a pilot study that the acute administration of subcutaneous (s.c.) DHA increases seizure latencies in the maximal pentylenetetrazole (PTZ) seizure test, however it loses its effect at higher doses. The purpose of the present experiments was (1) to confirm that DHA loses its effect at higher doses, (2) to correlate the anticonvulsant properties of DHA with DHA levels in the different lipid pools of serum and (3) to evaluate whether an anticonvulsant dose of DHA resulted in an increase in DHA release from the brain phospholipids following induction of seizure. In the first experiment, male Wistar rats were injected s.c. with 200, 300, 400 or 600 mg/kg of DHA, or 400mg/kg oleic acid (OA, isocaloric control), and seizure tested with the maximal PTZ test 1h post injection (Experiment 1). In a second experiment, subjects received either: (1) an effective dose of DHA (400mg/kg), (2) a higher, non-effective dose (600 mg/kg; based on the findings of Experiment 1), or (3) OA (400mg/kg). Subjects were sacrificed 1h post injection and blood was collected for fatty acid analysis (Experiment 2). In the third experiment, subjects were injected with either the effective dose of DHA (400mg/kg) or OA (400mg/kg). One hour post lipid injection, animals received either PTZ or saline, and animals were euthanized via microwave fixation. Brain were extracted and unesterified fatty acid concentrations were measured (Experiment 3). Experiment 1 confirmed that DHA loses its effects at higher doses in the maximal PTZ test. The 400mg/kg dose was maximally effective but effects were lost at 600 mg/kg. Experiment 2 showed that only the unesterified DHA pool in serum was statistically increased by an acute injection of s.c. DHA (P0.05). Curiously, unesterified DHA levels were similar in both the 400mg/kg and 600 mg/kg dosage groups

  16. BOOK REVIEW: Assessing Sc1 for GCSE

    Science.gov (United States)

    Reynolds, H.

    2000-01-01

    It is well known that investigations that `fit' the National Curriculum or examination board criteria are few in number. The fair testing emphasis means that pupils all over the country are finding out what affects the rate of a chemical reaction, the rate of photosynthesis or, in the case of Physics, the resistance of a wire. This book focuses on nine of the most common Sc1 investigations and how to prepare for them, manage and assess them. The author, a GCSE examiner, has turned his expertise into a handbook for improving Sc1 performance in the classroom. He has produced a book that would be extremely useful to both newly qualified teachers and experienced teachers. The first aim of the book, however, is to explain the requirements of Sc1. This is done comprehensively with examples of what the jargon means in practice. By breaking down the elements of planning, obtaining evidence, analysing evidence and evaluating, it is easy to see the subtleties of the mark descriptors. At first glance there seems to be little difference between the type of scientific knowledge needed for planning at level 6 and level 8. However, the level 8 statement specifies `detailed' scientific knowledge and understanding, which would mean a student should use equations from physics or symbolic chemical equations to support their arguments. One of the most useful sections in the book details the marking problems that can arise with some investigations. For example, in an investigation into electromagnets it is difficult for students to provide sufficient relevant scientific theory to satisfy the requirements of planning at level 6. One of the problems with Sc1 is that certain requirements, such as graph plotting, are difficult for many students. This book provides exercises that can be given to students to improve those skills. Each of the nine investigations is covered in great detail. Each investigation begins with an introduction detailing the rationale for choosing it, whether students

  17. Severe subcutaneous generalized edema in a patient with dermatomyositis.

    Science.gov (United States)

    Ito, Yoshinaga; Kawabata, Daisuke; Yukawa, Naoichiro; Yoshifuji, Hajime; Usui, Takashi; Tanaka, Masao; Fujii, Takao; Mimori, Tsuneyo

    2007-01-01

    Subcutaneous generalized edema associated with dermatomyositis (DM)/polymyositis (PM) is extremely rare. Herein we report a case of severe subcutaneous generalized edema complicating DM. A 78-year-old woman was hospitalized in our department because of massive edema in the four limbs. Elevated muscle enzymes, heliotrope rash, results of electromyography, and muscle biopsy confirmed the diagnosis of DM. The absence of other diseases that could cause the symptoms indicated that massive edema was correlated with the pathophysiology of DM. Although myopathy and edema responded well to oral prednisolone, dysphagia persisted. We conclude that subcutaneous generalized edema can occur during the course of DM/PM, and subcutaneous vasculopathy may be involved in the pathogenesis of DM/PM.

  18. Effect of sonication parameters on transdermal delivery of insulin to hairless rats.

    Science.gov (United States)

    Boucaud, Alain; Garrigue, Marie Ange; Machet, Laurent; Vaillant, Loïc; Patat, Frédéric

    2002-05-17

    Application of low-frequency ultrasound has been shown to enhance transdermal drug transport of large molecules such as insulin. In this study, we investigated the dependence of ultrasound-induced transdermal delivery of insulin on ultrasound parameters. Insulin was delivered in vivo to hairless rats using 20 kHz ultrasound applied over a range of ultrasound intensity, application time and pulse length. Change in blood glucose levels of the animals was monitored to assess insulin transport. The results showed a threshold below which no detectable changes in blood glucose level was observed for each ultrasound parameter. Moreover, our findings indicated that sonophoretic enhancement is dependent on energy dose and length of ultrasound pulse that is consistent with a cavitation-based mechanism. The more significant effect of lowering glycemia was obtained with application of less than 15 min ultrasound and was similar to subcutaneous injection of 0.5 U of insulin. Pretreatment of hairless rat skin with ultrasound followed by application of insulin resulted in no significant modification in blood glucose level, indicating that transdermal transport of insulin mainly occurred during sonication. Sonophoresis may therefore potentially be applied for non-invasive and painless delivery of insulin in the treatment of insulin-dependent diabetes.

  19. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    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.

  20. Stark broadening parameter tables for Sc X, Sc XI, Ti XI and Ti XII

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.

    1998-01-01

    Full Text Available By using the semiclassical-perturbation formalism, we have calculated electron-, proton-, and He III-impact line widths and shifts for 4 Sc X, 10 Sc XI, 4 Ti XI and 27 Ti XII multiplets, significant for investigation and modeling of different plasmas in astrophysics and physics. For Sc X calculations have been performed within the temperature range from 200,000 K to 5,000,000 K, and for perturber densities 1019cm−3 - 1022cm−3. Stark broadening data for Sc XI are tabulated for temperatures from 500,000 K to 5,000,000 K, and perturber densities 1018cm−3 - 1022cm−3. For Ti XI calculations were performed within the temperature range from 500,000 K to 5,000,000 K, and perturber densities 1018cm−3 - 1022cm−3, while for Ti XII results are given for temperatures from 500,000 K to 6,000,000 K, and perturber densities 1018cm−3 - 1023cm−3.

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

    Science.gov (United States)

    Pepper, Andrew R; Pawlick, Rena; Bruni, Antonio; Wink, John; Rafiei, Yasmin; O'Gorman, Doug; Yan-Do, Richard; Gala-Lopez, Boris; Kin, Tatsuya; MacDonald, Patrick E; Shapiro, A M James

    2017-06-06

    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. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. 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.

  3. Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance.

    Science.gov (United States)

    Shaker, Olfat G; Sadik, Nermin Abdel Hamid

    2013-01-01

    Visceral adipose fat has been claimed to be the link between obesity and insulin resistance through the released adipokines. This study aimed to assess the expression of vaspin as one of the recent adipokines in rats abdominal subcutaneous and visceral fat in diet-induced obese (DIO) and in DIO performing 3 weeks swimming exercise (DIO + EXE) compared to control and control + exercise (C + EXE) groups. Vaspin mRNA and protein expression assessed using RT-PCR and Western blotting analysis revealed vaspin expression in DIO and DIO + EXE but not in controls groups. In DIO group, visceral vaspin expression was higher than in that of subcutaneous fat and was positively correlated with body weight. Upregulation of visceral vaspin expression in DIO was concomitant with the development of insulin resistance (increase in fasting serum insulin and HOMA-IR) and rise in serum leptin level. Unchanged visceral vaspin mRNA in DIO + EXE rats, with significant improvements of insulin resistance parameters and serum leptin compared to DIO group was found. In conclusion, increased visceral vaspin expression in obesity was associated with insulin resistance. Further investigations into the molecular links between vaspin and obesity may unravel innovative therapeutic strategies in people affected by obesity-linked insulin resistance, metabolic syndrome, and type 2 diabetes.

  4. 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 (pobese 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 (pobese 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.

  5. Visceral Fat Accumulation, Insulin Resistance, and Elevated Depressive Symptoms in Middle-Aged Japanese Men.

    Directory of Open Access Journals (Sweden)

    Shuichiro Yamamoto

    Full Text Available To investigate visceral fat accumulation and markers of insulin resistance in relation to elevated depressive symptoms (EDS.Participants were 4,333 male employees (mean age, 49.3 years who underwent abdominal computed tomography scanning, measured fasting insulin, and did not self-report diabetes and mental disorders under treatment and history of cancer, myocardial infarction, and stroke. Multivariable logistic regression was used to assess the association of EDS with abdominal fat deposition and markers of insulin resistance.Visceral fat area (VFA and fasting insulin were significantly, positively associated with EDS. Multivariable-adjusted odds ratios (95% confidence interval of high VFA for the lowest through highest quartile of depression score were 1 (reference, 1.18 (0.97-1.42, 1.25 (1.02-1.54, 1.23 (1.01-1.51, respectively, and corresponding figures for high fasting insulin were 1 (reference, 0.98 (0.80-1.19, 1.12 (0.91-1.38, and 1.29 (1.06-1.57, respectively. Subcutaneous fat area was not associated with EDS.Results suggest that EDS is related to visceral, but not subcutaneous, fat accumulation and insulin resistance in middle-aged Japanese men.

  6. Amyloidoma secondary to insulin injection: Cytologic diagnosis and pitfalls

    Directory of Open Access Journals (Sweden)

    Dianne Grunes

    2015-01-01

    Full Text Available Amyloidomas are rare tumors composed of deposits of amyloid protein not associated with systemic amyloidosis. They can present as an initial manifestation of a systemic disease process or can be a completely localized phenomenon. We present a case of amyloidoma associated with insulin injection site found incidentally in an 80-year-old male with multiple co-morbidities who presented with diverticulitis associated bleeding. A subcutaneous abdominal mass was found on physical examination. Imaging revealed a 5 cm Χ 1.6 cm homogenous subcutaneous lesion. A fine-needle aspiration (FNA and core biopsy were performed under ultrasound guidance to reveal amorphous material proven to be amyloidosis at insulin injection sites (AIns type amyloid. The patient had no treatment for this lesion and has had his care triaged to his more serious health problems. This is the first case of AIns type amyloidoma associated with insulin injection site reported in cytology literature. We highlight the cytologic findings and diagnostic pitfalls. As the incidence of diabetes is increasing, cytopathologists may encounter this lesion more often on FNA.

  7. Diurnal variations in subcutaneous allergen immunotherapy reactions.

    Science.gov (United States)

    Bavishi, Aakash A; Grammer, Leslie C; Pongracic, Jacqueline; Rychlik, Karen; Kumar, Rajesh; Zee, Phyllis; Greenberger, Paul A; Fishbein, Anna B

    2017-01-01

    Circadian rhythms underlie many immune responses and allergic diseases. Subcutaneous immunotherapy (SCIT) can result in adverse reactions; however, it is unclear whether such reactions have a diurnal pattern. To assess whether the timing of SCIT affects the rate of adverse reactions. This study was a retrospective medical record review of adult patients (n = 289) who received SCIT at the Northwestern Medical Faculty Foundation, Chicago, Illinois, during a 10-year period (2004-2014). Injections were given in the outpatient setting. There were a total of 17,457 injections with 574 reactions. Covariates included age, sex, median income, asthma status, vial contents, number of injections, and previous immunotherapy reactions. Logistical regression was used to calculate the odds of having a reaction with time of SCIT administration as the primary determinate. Immunotherapy reactions occurred more frequently after afternoon or evening (pm) injections (328/8721 = 3.8%) vs morning (am) injections (246/8736 = 2.8%), (χ2 = 12.26, P < .01). Systemic reactions, defined as World Allergy Organization grade 1 or higher, did not have diurnal variation (59/8721 = 0.67% for pm vs am 56/8736 = 0.64% for morning; χ2 = 0.08; P = .77). pm injections resulted in higher odds of reaction compared with am injection in a fully adjusted logistic regression model (odds ratio = 1.43; 95% confidence interval, 1.20-1.70; P < .01). When considering time as 4 categories, the highest odds of reaction were noted for the period from 15:01 to 17:30 (odds ratio, 1.55; 95% confidence interval, 1.21-2.00; P < .01). pm injections of SCIT are associated with increased cutaneous reaction rates when compared with am injections. In patients experiencing bothersome local reactions, it may be beneficial to administer SCIT in the morning. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Intravenous and subcutaneous immunoglobulin G replacement therapy.

    Science.gov (United States)

    Bonilla, Francisco A

    2016-11-01

    Human polyclonal immunoglobulin G (IgG) for therapeutic use has been available for decades. This drug was developed for treatment of antibody deficiency (replacement therapy), although its use has expanded into many anti-inflammatory and immunomodulatory applications in recent years. This review focuses on IgG prescribing for replacement therapy. IgG for replacement is most often administered via the intravenous IgG (IVIG) or subcutaneous IgG (SCIG) routes. IVIG is usually administered every 34 weeks, and SCIG is usually administered weekly, although variations may be considered in all cases. Recently, a new product became available that uses hyaluronidase to facilitate absorption of large doses of SCIG less frequently (every 34 weeks, as with IVIG). There are important differences between the pharmacokinetics of these three routes of administration. IVIG therapy leads to high peaks and low troughs between infusions. IgG concentration fluctuates much less over time with SCIG. Hyaluronidase-facilitated SCIG is intermediate. SCIG may have lower bioavailability in comparison with IVIG and may require higher doses over time; this is not true for hyaluronidase SCIG. However, there are large variations in IgG half-life among individuals and with different products. Therefore, individualization of therapy is essential. Mild systemic flu-like adverse effects may affect up to 2025% of patients who receive IVIG, smaller fractions may experience more-severe symptoms, whereas anaphylaxis is exceedingly rare. General flu-like systemic adverse effects are minimal with SCIG (intermediate with hyaluronidase SCIG), but transient (24 hours), mild, local inflammatory symptoms at infusion sites are relatively common with both forms. Additional rare but important complications of IgG therapy include thrombotic events and hemolysis that can be seen at high doses with any route of administration. Renal adverse effects may occur with IVIG as well. The variety of IgG products and routes of

  9. Subcutaneous autologous serum therapy in chronic spontaneous urticaria

    Directory of Open Access Journals (Sweden)

    Kiran Vasant Godse

    2017-01-01

    Full Text Available Background: There is a felt need for trying newer therapeutic modalities in patients with chronic spontaneous urticaria, especially in the subset of patients classified as non-responders to antihistamines. Autologous serum therapy is an upcoming modality of treatment, and we decided to study its efficacy by subcutaneous route. Aims: To evaluate the effectiveness of subcutaneous autologous serum therapy (AST in CSU. Methods: This was a single blind, placebo-controlled parallel group, randomized, controlled study. Twenty-four patients with CSU (11M: 13 F were given subcutaneous AST and seventeen patients (7 M: 10F patients were given subcutaneous injection normal saline (placebo, along with levocetirizine in an on-demand basis in both groups. Results: Urticaria activity score (UAS came down from 35.74 to 7 at the end of 9 weeks and the patients' requirement of antihistamines also reduced remarkably from 5.8 to 1.7 per week in the serum group. Sub-cutaneous saline group did not show statistically significant fall in UAS. Saline group showed UAS 32.8 at zero week to 22.1 at the end of 9 weeks. DLQI showed significant fall in serum group, from 14.26 to 4 at the end of 9 weeks. Conclusion: Subcutaneous autoserum therapy is effective in treatment of CSU.

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

    DEFF Research Database (Denmark)

    Asmar, Meena; Simonsen, Lene; Asmar, Ali

    2016-01-01

    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....../kg/min) in combination with 1) euglycemic-high insulinemic clamp (Eugluc-Hiinsu), raising plasma insulin concentrations to postprandial levels, 2) hyperglycemic-euinsulinemic clamp (Hygluc-Euinsu), and 3) hyperglycemic-hyperinsulinemic clamp, raising plasma insulin concentrations to supraphysiological levels. During...... the hyperglycemic clamps, endogenous insulin and C-peptide secretion were inhibited by infusion of the somatostatin analogue octreotide. RESULTS: During GIP infusion, Eugluc-Hiinsu, and hyperglycemic-hyperinsulinemic clamps, sc abdominal adipose tissue blood flow (ATBF) was similar and increased from 2.1 ± 0...

  11. Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice.

    Directory of Open Access Journals (Sweden)

    Laura J den Hartigh

    Full Text Available Widely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA promotes fat loss in obese mice and humans, but has also been associated with insulin resistance.We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%, an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism.Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured.By design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT. Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation.These results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss.

  12. [Implantable insulin pumps: evaluation after more than 3 years experience].

    Science.gov (United States)

    Keipes, M; Michel, G; Pinget, M

    1994-01-01

    Since the beginning of insulin therapy the improvement of treatment in IDDM is mainly for acute metabolic complications than for chronic degenerative complications. The DCCT could recently prove for the first time that the incidence of chronic complications (retinopathy, nephropathy and neuropathy) could be diminished by reaching glycemic control in more than 700 patients. One of the problems explaining the failure of classical treatment is due to the variability of absorption in the sub-cutaneous tissue. The patients treated by insulin pumps are all IDDM. The aim of this study is to evaluate safety and feasibility of implantable programmable pumps with intraperitoneal insulin infusion. We found three cases of irreversible catheter obstruction. Defects of external communicators and the slow-downs of insulin infusion in infusaid pumps were observed. No acceleration in insulin infusion was found. Acute metabolic complications were two severe hypoglycemic events, but no acito-cetosis. After more than two years for most of the patients we observed a global improvement in glycemic control, demonstrated by a better mean glycemia and lower HbA1c values. The standard deviation of the glycemia was lowered significantly, this value reflects daily fluctuability. The number of hypoglycemias was also lowered. Our study shows a more stable glycemic control than the one in the DCCT study. The safety and feasibility seem to be highly satisfying.

  13. Cyclotron Produced 44gSc from Natural Calcium

    Science.gov (United States)

    Severin, G.W.; Engle, J.W.; Valdovinos, H.F.; Barnhart, T.E.; Nickles, R.J.

    2012-01-01

    44gSc was produced by 16 MeV proton irradiation of unenriched calcium metal with radionuclidic purity greater than 95%. The thick target yield at saturation for 44gSc was 213 MBq/μA, dwarfing the yields of contaminants 43Sc,44mSc, 47Sc and 48Sc for practical bombardment times of 1–2 h. Scandium was isolated from the dissolved calcium target by filtration, and reconstituted in small volumes of dilute HCl. Reactions with the chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) indicated a reactivity of 54±14 Gbq/μmol at end-of-bombardment. PMID:22728844

  14. 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 glucos...

  15. Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes

    Science.gov (United States)

    Dhindsa, Sandeep; Ghanim, Husam; Batra, Manav; Kuhadiya, Nitesh D.; Abuaysheh, Sanaa; Sandhu, Sartaj; Green, Kelly; Makdissi, Antoine; Hejna, Jeanne; Chaudhuri, Ajay; Punyanitya, Mark

    2016-01-01

    OBJECTIVE One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. RESEARCH DESIGN AND METHODS A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. RESULTS Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (−3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat. PMID:26622051

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

    Science.gov (United States)

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

    2017-11-01

    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 sensitivity. We therefore studied the effects of scFOS supplementation on insulin sensitivity in heavy veal calves. Forty male Holstein-Friesian calves (BW = 190 ± 2.9 kg; age = 162 ± 1.4 d at the start of the trial) were fed either a control milk replacer (MR) diet or a diet in which one-third of the lactose was replaced by glucose, fructose, or glycerol for 10 wk prior to the start of the trial. At the start of the trial, calves were subjected to a frequently sampled intravenous glucose tolerance test to assess whole-body insulin sensitivity (muscle and hepatic insulin sensitivity). Calves within each dietary treatment group were ranked based on their insulin sensitivity value. Half of the calves received scFOS (12 mg/kg of BW) with the MR for 6 wk (supplementation was equally distributed over the insulin sensitivity range). Subsequently, a second frequently sampled intravenous glucose tolerance test was conducted to assess the effect of scFOS. In addition, fasting plasma levels of glucose, insulin, triglycerides, and cholesterol were determined to calculate the quantitative insulin sensitivity check index and triglyceride:high-density lipoprotein cholesterol ratio (fasting indicators of insulin sensitivity). Whole-body insulin sensitivity was low at the start of the trial and remained low in all groups [1.0 ± 0.1 and 0.8 ± 0.1 (mU/L)-1 · min-1 on average, respectively]. Supplementation of scFOS did not improve insulin sensitivity in any of the treatment groups. The quantitative insulin sensitivity check index and the triglyceride:high-density lipoprotein cholesterol ratio also did not differ between scFOS and non-scFOS calves and averaged 0.326 ± 0.003 and 0.088

  17. Exploring branch predictability limits with the MTAGE+SC predictor *

    OpenAIRE

    Seznec, André

    2016-01-01

    International audience; In the previous championship CBP-4, the winner of the unlimited storage track [5], poTAGE-SC was combining several TAGE based predictors using different forms of histories (local, global, and frequency), a COLT inspired [3] prediction combiner and a statistical corrector (SC) predictor [8, 10] fed with various forms of branch histories. With MTAGE-SC, we improve this predictor in two ways. First through incorporating new forms of branch histories, adding a new TAGE com...

  18. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    Science.gov (United States)

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  19. SC2: Secure Communication over Smart Cards

    DEFF Research Database (Denmark)

    Dragoni, Nicola; Lostal, Eduardo; Papini, Davide

    2012-01-01

    The Security-by-Contract (S×C) framework has recently been proposed to support software evolution in open multi-application smart cards. The key idea lies in the notion of contract, a specification of the security behavior of an application that must be compliant with the security policy...... of the card hosting the application. In this paper we address a key issue to realize the S×C idea, namely the outsourcing of the contractpolicy matching service to a Trusted Third Party (TTP). In particular, we present the design and implementation of (SC)2 (Secure Communication over Smart Cards), a system...... securing the communication between a smart card and the TTP which provides the S×C matching service....

  20. Final Scientific Report: DE-SC0002194

    Energy Technology Data Exchange (ETDEWEB)

    Seidler, Gerald [Univ. of Washington, Seattle, WA (United States)

    2017-04-07

    We provide the final scientific report for DE-SC0002194. During the term of this grant, 28 publications spanning a variety of topics were addressed under the rubric of advanced x-ray methods and their application to extreme conditions of time-resolution or x-ray intensities. Notable accomplishments include a new observation of XANES features associated with f-shell reconfiguration in lanthanides, size-dependent x-ray heating effects under XFEL illumination conditions, theoretical development of improved treatments of inelastic x-ray scattering for 'warm dense matter' conditions, and several new instrument develop efforts for atomic, molecular, and condensed phase studies in the lab and at major facility lightsources.

  1. The SC State NSF PAARE Program

    Science.gov (United States)

    Walter, Donald; Ajello, Marco; Brittain, Sean; Cash, Jennifer; Fogle, Bryan; Hartmann, Dieter; Ho, Shirley; Howell, Steve; King, Jeremy; Leising, Mark; Smith, Daniel

    2018-01-01

    We report on the activities of our NSF PAARE program during Year 3 of the project. Our partnership under this award includes South Carolina State University (a Historically Black College/University), Clemson University (a Ph.D. granting institution) and individual investigators at NASA Ames and elsewhere. Our partnership with the Citizen CATE Experiment and involvement in the total solar eclipse which passed through our campus on August 21, 2017, will be discussed. The PAARE project continues to strengthen our partnership with Clemson. We are close to completing a memorandum of agreement between the two institutions that will allow for the seamless transfer of an undergraduate from SC State to Clemson’s graduate program in physics and astronomy. Additionally, we have worked together under the Citizen CATE project and through other research activities. SC State is a member of the National Astronomy Consortium (NAC) and participates through its faculty and undergraduates, one of whom (Wesley Red) is reporting on his summer internship at this conference. We also served as the state coordinator for South Carolina for the Citizen CATE Experiment. The August 21st path of totality crossed through our campus and the campus of our partner Clemson University. Additional colleges, universities and citizen scientist groups partnered with us to provide 7 sites of coverage across South Carolina from the foothills of the Appalachian mountains to the Atlantic Ocean near the site of departure of the shadow from the continental U.S. Support for this work includes our NSF PAARE award AST-1358913 as well as resources and support provided by Clemson University and the National Optical Astronomy Observatory. CATE work has been supported by NASA SMD award NNX16AB92A to the National Solar Observatory. Additional details can be found at: http://physics.scsu.edu

  2. Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.

    Science.gov (United States)

    Kimble, B; Black, L A; Li, K M; Valtchev, P; Gilchrist, S; Gillett, A; Higgins, D P; Krockenberger, M B; Govendir, M

    2013-10-01

    The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate. © 2013 John Wiley & Sons Ltd.

  3. Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin

    Directory of Open Access Journals (Sweden)

    Satheesh Jogala

    2015-01-01

    Full Text Available The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c. nanoparticles of low molecular weight heparin (LMWH. The nanoparticles were prepared by water-in-oil in-water (w/o/w emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15, and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1% aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetry (DSC and X-ray diffraction (XRD studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16-38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH.

  4. Differential effects of insulin injections and insulin infusions on levels ...

    African Journals Online (AJOL)

    Studies have shown that while injections of insulin cause an increase in fat mass, infusions of insulin increase fat mass. The aim of this paper was to test the hypothesis that if an increase in glycogen is an indicator of an impending increase in adipose mass, then insulin infusions should not increase glycogen, while insulin ...

  5. Insulin in diabetes prevention.

    Science.gov (United States)

    Ramiya, V K; Maclaren, N K

    1997-01-01

    Insulin-dependent diabetes (IDD) is a chronic immune-endocrine disease in which there is a progressive destruction of insulin-secreting pancreatic beta cells, caused primarily by autoreactive T cells. Many islet cell proteins including insulin, glutamic acid decarboxylase, and tyrosine phosphatase antigens (IA-2) are targeted by the autoimmune responses in IDD patients. Since its discovery 75 years ago, insulin has been the major player in the clinical management of hyperglycaemia in these patients. The morbidity and mortality associated with IDD derives mainly from the complications of the disease. However, routine insulin injections seldom achieve a consistent, near-normal glucose level, where multiple daily doses of the hormone involve considerable restrictions to a normal lifestyle. In terms of economics, the management of diabetes is expensive, and in the USA diabetes alone accounts for one seventh of the healthcare budget. These clinical, lifestyle and economic issues emphasize the need to investigate alternative preventative measures in IDD treatment. Recent reports suggest a pivotal role for insulin in various aspects of the immune system. In this study, insulin and B-chain were used to modulate autoimmune responses in non-obese diabetic mice, findings which have therapeutic implications in man.

  6. Insulin decreases atherosclerotic plaque burden and increases plaque stability via nitric oxide synthase in apolipoprotein E-null mice.

    Science.gov (United States)

    Mori, Yusaku; Chiang, Simon; Bendeck, Michelle P; Giacca, Adria

    2016-08-01

    It has been argued whether insulin accelerates or prevents atherosclerosis. Although results from in vitro studies have been conflicting, recent in vivo mice studies demonstrated antiatherogenic effects of insulin. Insulin is a known activator of endothelial nitric oxide synthase (NOS), leading to increased production of NO, which has potent antiatherogenic effects. We aimed to examine the role of NOS in the protective effects of insulin against atherosclerosis. Male apolipoprotein E-null mice (8 wk old) fed a high-cholesterol diet (1.25% cholesterol) were assigned to the following 12-wk treatments: control, insulin (0.05 U/day via subcutaneous pellet), N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME, via drinking water at 100 mg/l), and insulin plus l-NAME. Insulin reduced atherosclerotic plaque burden in the descending aorta by 42% compared with control (plaque area/aorta lumen area: control, 16.5 ± 1.9%; insulin, 9.6 ± 1.3%, P < 0.05). Although insulin did not decrease plaque burden in the aortic sinus, macrophage accumulation in the plaque was decreased by insulin. Furthermore, insulin increased smooth muscle actin and collagen content and decreased plaque necrosis, consistent with increased plaque stability. In addition, insulin treatment increased plasma NO levels, decreased inducible NOS staining, and tended to increase phosphorylated vasodilator-stimulated phosphoprotein staining in the plaques of the aortic sinus. All these effects of insulin were abolished by coadministration of l-NAME, whereas l-NAME alone showed no effect. Insulin also tended to increase phosphorylated endothelial NOS and total neuronal NOS staining, effects not modified by l-NAME. In conclusion, we demonstrate that insulin treatment decreases atherosclerotic plaque burden and increases plaque stability through NOS-dependent mechanisms. Copyright © 2016 the American Physiological Society.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Are switches from oral to subcutaneous methotrexate or addition of ciclosporin to methotrexate useful steps in a tight control treatment strategy for rheumatoid arthritis? A post hoc analysis of the CAMERA study.

    Science.gov (United States)

    Bakker, M F; Jacobs, J W G; Welsing, P M J; van der Werf, J H; Linn-Rasker, S P; van der Veen, M J; Lafeber, F P J G; Bijlsma, J W J

    2010-10-01

    To investigate the effects of a switch from oral methotrexate (MTX) to subcutaneous MTX (scMTX) or adding ciclosporin to oral MTX with a simultaneous reduction of the MTX dose, in case of adverse events (AE) or insufficient effect (IE) in rheumatoid arthritis (RA). The tight control treatment arm of the Computer Assisted Management in Early RA (CAMERA) trial was evaluated. The change in 28-joint Disease Activity Score (DAS28) after taking scMTX (over 1 month) or adding ciclosporin (over 3 months) was compared to the average monthly change in the preceding 3 months. Analyses were performed separately for strategy steps because of AE or IE. Of 151 patients, 57 needed the scMTX strategy step (21 because of AE, 36 because of IE) and 40 the following ciclosporin strategy step (20 and 20, respectively). The decrease in DAS28 after taking the scMTX strategy step was 0.30 points (p<0.05); no significant change in DAS28 was seen after the ciclosporin strategy step. In both strategy steps for AE or IE, quite similar observations were made. Of the patients who took the scMTX strategy step, 63% showed improvement. scMTX seems a useful treatment step after oral MTX in a tight control strategy, whereas the ciclosporin step seems ineffective.

  9. Home-based subcutaneous immunoglobulin G replacement therapy under real-life conditions in children and adults with antibody deficiency

    Directory of Open Access Journals (Sweden)

    Hoffmann F

    2010-06-01

    Full Text Available Abstract Background Subcutaneous immunoglobulin (SCIG therapy is an alternative to intravenous immunoglobulin (IVIG therapy. Methods We evaluated the efficacy and safety of the SCIG Vivaglobin® (formerly known as Beriglobin® SC under real-life conditions in a post-marketing observational study in 82 patients with primary or secondary antibody deficiencies. Health-related quality of life (HRQoL was evaluated in a subset of 30 patients previously treated with IVIG (including 11 children Results The mean serum immunoglobulin G (IgG trough level during SCIG treatment (7.5 g/L was higher than during previous IVIG treatment (6.6 g/L; p Conclusion This study confirms that therapy with Vivaglobin® at home is effective, safe, well tolerated, and improves quality of life in patients with antibody deficiency.

  10. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    studies in β cell-specific IR knockout mice, which develop peripheral insulin resistance and diabetes, most probably due to the changes in the pattern of insulin secretion (Kulkarni et al 1999). FFA also affects downstream insulin signalling molecules. It inhibits insulin activation of IRS-1-associated PI3K activity in muscle.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    O. A. Sánchez

    2009-01-01

    Full Text Available 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 of five experimental groups (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.

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

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    Full Text Available 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.

  15. Effects of insulin on renal haemodynamics and sodium handling in normal subjects

    DEFF Research Database (Denmark)

    Nørgaard, K; Jensen, T; Skøtt, P

    1991-01-01

    Diabetic patients treated with insulin injected subcutaneously are characterized by peripheral hyperinsulinaemia and an increased mass of total body exchangeable sodium. We hypothesized that this may cause, at least in part, the glomerular hyperfiltration seen in the diabetic state. Six normal...... subjects were studied on 2 days in random order. Day A: Basal state for 40 min, hyperinsulinaemic euglycaemic clamp for 1 h (insulin infusion rate 2 mU kg-1 min-1 and 50% glucose infusion) and hyperinsulinaemic euglycaemic clamp combined with volume expansion (2 1 isotonic sodium chloride) for 2 h. Day B.......01) was observed compared with basal conditions. GFR and CLi were unchanged during day B. Insulin infusion reduced renal sodium excretion. Absolute proximal tubular reabsorption was unchanged on both days. Insulin infusion without volume expansion caused a decrease of 24% in the fractional distal sodium excretion...

  16. Improved Insulin Absorption by Means of Standardized Injection Site Modulation Results in a Safer and More Efficient Prandial Insulin TreatmentA Review of the Existing Clinical Data

    Science.gov (United States)

    Raz, Itamar; Bitton, Gabriel; Klonoff, David; Nagar, Ron; Hermanns, Norbert; Haak, Thomas

    2014-01-01

    Temperature changes on the surface of the skin lead to modifications of subcutaneous microcirculation. This phenomenon is employed in a standardized way by the InsuPad device to stabilize skin conditions before injections, which is associated with enhanced prandial insulin absorption. Three programmed warming cycles to 40°C within 50 minutes are resulting in faster insulin appearance in the plasma. Early standardized meal tolerance studies indicated a substantial improvement in postprandial glucose control when the same short-acting insulin analog dose was applied using InsuPad, and a dose reduction by 20% resulted in comparable glucose excursions. Similar results were obtained when patients applied the device under real-world conditions for 1 month. The InsuPad device was also tested in a prospective, controlled, parallel 3-month real-world study with 145 well-controlled but insulin-resistant patients with type 1 or type 2 diabetes. Patients were treated to target in both treatment arms (6.2 ± 0.5% in each group), with or without the device. However, patients with InsuPad needed 28% less prandial insulin, needed 12.5% less total insulin, and had 46% less confirmed hypoglycemic events (blood glucose insulin doses may result in a safer and more efficient treatment of type 1 or type 2 diabetes. PMID:25352633

  17. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis...

  18. Downregulation of complement C3 and C3aR expression in subcutaneous adipose tissue in obese women.

    Directory of Open Access Journals (Sweden)

    Abhishek Gupta

    Full Text Available The central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women.Women (n = 140, 21-69 years, BMI 19.5-79 kg/m2 were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.Subjects were separated into groups (n = 34-36 according to obesity: normal/overweight (≤30 kg/m2, obese I (≤45 kg/m2, obese II (≤51 kg/m2, and obese III (≤80 kg/m2. Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01, with a concomitant decrease in SC/OM ratio (p<0.001. In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05-0.0001. While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05. Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively with subcutaneous C3 and C3aR expression (p<0.05-0.001 or less.The obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.

  19. Oral insulin administration and residual beta-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial. Diabète Insuline Orale group.

    Science.gov (United States)

    Chaillous, L; Lefèvre, H; Thivolet, C; Boitard, C; Lahlou, N; Atlan-Gepner, C; Bouhanick, B; Mogenet, A; Nicolino, M; Carel, J C; Lecomte, P; Maréchaud, R; Bougnères, P; Charbonnel, B; Saï, P

    2000-08-12

    Oral administration of autoantigens can slow the progression of beta-cell destruction in non-obese diabetic mice. We investigated whether oral administration of recombinant human insulin could protect residual beta-cell function in recent-onset type 1 diabetes. We enrolled 131 autoantibody-positive diabetic patients aged 7-40 years within 2 weeks of diagnosis (no ketoacidosis at diagnosis, weight loss insulin daily or placebo for 1 year, in addition to subcutaneous insulin therapy. Serum C-peptide concentrations were measured in the fasting state and after stimulation, to assess beta-cell function. Autoantibodies to beta-cell antigens were assayed. Analyses were by intention to treat. Baseline C-peptide and haemoglobin A1c concentrations were similar in the three groups. During follow-up, there were no differences between the groups assigned 2.5 mg or 7.5 mg oral insulin or placebo in subcutaneous insulin requirements, haemoglobin A1c concentrations, or measurements of fasting (mean at 12 months 0.18 [SD 0.17], 0.17 [0.17], and 0.17 [0.12] nmol/L) or stimulated C-peptide concentrations (glucagon-stimulated 0.39 [0.38], 0.37 [0.39], and 0.33 [0.24] nmol/L; meal-stimulated 0.72 [0.60], 0.49 [0.49], and 0.57 [0.51 nmol/L]. Neither age nor C-peptide concentration at entry influenced treatment effects. No differences were seen in the time-course or titres of antibodies to insulin, glutamic acid decarboxylase, or islet antigen 2. At the doses used in this trial, oral administration of insulin initiated at clinical onset of type 1 diabetes did not prevent the deterioration of beta-cell function.

  20. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    Science.gov (United States)

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696