bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure, distribution and taxonomic significance of leaf and petiole anatomical characters in five species of Terminalia (L.) (Combretaceae: Magnoliopsida)
Authors: Akinsulire Opeyemi Philips , Oladipo Olaniran Temitope , Akinloye Akinwumi Johnson , Illoh Herbert Chukwuma
Published: June 2019

This paper presents a synthesis of a comparative leaf anatomy (lamina and petiole) of five species of the genus Terminalia found in southwest Nigeria. Collections of plants were made from different locations in Southwest Nigeria as the geographic locations of the sites of collection were also geo-referenced with a GPS device. The samples were identified at the Herbarium of Botany Department, Obafemi Awolowo University (Ife), Nigeria, and were subjected to anatomical examinations. Quantitative data were subjected to statistical analysis and the characters vary significantly (P = 0.05). Anatomical characters which separate the taxa include petiole outline, epidermal features, vascular pattern, occurence of cortical and pericyclic fibres, presence/absence of, and types of trichomes etc, all found to be useful in identification of different species. The variations in the anatomical traits could be effectively used in taxonomic delimitation of the species and are helpful characters in determining the complexes in the genus such as adaptation of the species to xeric environments. The presence of 2-3 layers of palisade mesophyll cells in Terminalia mantaly, which is an adaptation of the species to drought, is diagnostic for the species. It is suggested that a comprehensive consideration of leaf lamina and petiole anatomy should be used as basis of taxonomy.
Assessment of well water pollution by sewage contaminants: A case study of Akure South, Ondo State, Nigeria
Authors: Owoeye Josiah Abolade , Akinneye Joseph Onaolapo
Published: June 2019

This study investigated the extent of well water contamination in dry and rainy seasons through infiltration of coliform bacteria from sewage pits in their proximity in Akure. Total and Faecal coliform counts of twenty household wells were investigated between the months of March and July with respect to proximity of wells to sewage pits, orientation of wells to sewage pits, and other well characteristics. All wells studied were assessed to be vulnerable to contamination with observable differences in characteristics, physicochemical parameters, total coliform counts and faecal coliform counts. Asides pH which was higher in the dry season, all other parameters had lower values in the dry season. At an average distance of 17.6 m from the sewage pits, all well water sampled had greater coliform counts than the WHO recommended level for drinking water (< 1 cfu/mL). Correlations between coliform counts of water samples and the distances of the wells to sewage pits was positive and not significant for both total and faecal coliform in dry season, while it was negative and significant for both total and faecal coliform in the rainy season. Topography, and distance between wells and sewage pits were prominent factors responsible for well water contamination. Amounts of coliforms found in wells were significantly affected by seasonal variation. It is thus suggested that wells be sited up-gradient and at safer distances away from sanitary systems in the ultimate bid to reduce groundwater pollution and the occurrence of water borne diseases.
La crítica de Hegel a la concepción de “alma bella” y su vinculación con los personajes de las obras de Goethe
Authors: Alfaro Carlos Víctor
Published: June 2019

Hegel menciona al protagonista de Las Desventuras del joven Werther como un caso ejemplar de su particular concepción de “alma bella”. El filósofo alemán no incluye explícitamente a la protagonista de Confesiones de un alma bella. La omisión resulta curiosa porque la última obra mencionada también es una novela de Goethe. El objetivo del presente artículo es la dilucidación de la elección realizada por Hegel.
Integrated impact assessment method for the water transfer project on regional development
Authors: Xiao Zhangling , Liang Zhongmin , Li Binquan , Hu Yiming , Wang Jun
Published: June 2019

Water transfer projects in China have become a popular research topic in recent years. This study develops a method for evaluating the comprehensive impacts of water transfer projects on regional development. In the qualitative assessment, the comprehensive index method is employed, and an evaluation index system is established from economic, social and environmental perspectives. In this approach, the weights are determined by the analytic hierarchy process (AHP) and the entropy combined method. In the quantitative assessment, the sharing coefficient method is used. The procedure is applied to the water transfer project from the Yangtze River to the Taihu Lake. The qualitative results indicate that the conclusion of the water transfer project had a ‘large positive impact’ in 2016. In the quantitative assessment, the comprehensive benefit of increasing water supply via the project was 1.87 billion CNY in 2016. In addition, the integrated impact assessment method can be implemented at the seasonal scale to produce refined results. These results show that the proposed method can provide technical support for project operation and policy formulation.
Treatment of poultry slaughterhouse wastewater using a down-flow expanded granular bed reactor
Authors: Njoya M. , Basitere M. , Ntwampe S. K. O.
Published: June 2019

This study evaluated the performance of a novel high rate anaerobic bioreactor system for the treatment of poultry slaughterhouse wastewater (PSW). The new system consisted of a granule-based technology operated in a down-flow configuration, with the assistance of medium-sized pumice stones used as packing materials for the retention of the anaerobic granules, to avoid challenges associated with the use of the three-phase separator of up-flow systems and the washout of the anaerobic biomass. Furthermore, a recycling stream was applied to the system to improve the mixing inside the Down-flow Expanded Granular Bed Reactor (DEGBR), i.e. the influent distribution to the granular biomass, and the implementation of intermittent fluidization when required to alleviate the effects of pressure drop in such systems. The DEGBR was operated under mesophilic conditions (30–35 °C) and achieved total chemical oxygen demand (tCOD), five-day biological oxygen demand and total suspended solids average removal percentages >95%, and a fats, oils and grease average removal percentage of 93.67% ± 4.51, for an organic loading rate varying between 1.1 to 38.9 gCOD/L.day.
FECUNDITY STUDIES OF ANDROGRAPHIS PANICULATA ON DROSOPHILA MELANOGASTER
Authors: Sahabudeen Sheik Mohideen , Nag Hindol , Madhavan Suneeti , Chatterjee Abhinav , Dan Pallavi , Bhattacharya Mahasweta , Nawaz Zail Ali
Published: June 2019

Objective: Andrographis paniculata is widely used in Asia for various medicinal purposes. The plant has a major bioactive chemical constituent Andrographolide, which exhibits various essential pharmacological properties. Recently, to enhance immunity against viral fevers especially dengue viral fever during monsoon season, Tamil Nadu state government has advised rural health centres to provide a tea or kashayam made from a mixture containing this plant leaf along with selected plant roots and leaves. However, there is concern among the general public population that this plant extract may have a negative impact on potency. This study is being done to investigate the toxic effects of Andrographis paniculata on fecundity and physiological properties of Drosophila melanogaster.

Methods: The flies were treated and mated in pure and mixed form of Andrographis paniculata separately.

Results: The results were obtained in the form of egg count, which was compared to control and the conclusion was obtained that Andrographis paniculata might affect the fecundity and at the same time, it was observed that the developmental span from an egg to an adult fly increased upon treatment in successive generations. More importantly, the effect of pure form plant on the fecundity was found to be significant, while that of the mixed form was not. On mating a treated male with an untreated female and an untreated male with a treated female when the treatment is being discontinued, it can be very well seen that there is no effect on the fecundity of the flies.

Conclusion: Since the continuity of the treatment played a major role on the effect of fecundity, highlighting the importance of the period of treatment and the exposure time of the compound on the fly system, therefore this research suggests that the conception of tea or kashayam extracted from mixed plant content could not have the same effect as the similar concentration of pure Andrographis paniculata and it does not have any acute effect on the fecundity when being consumed over a short period of time in Drosophila melanogaster model.
IN VIVO ACUTE AND SUB-ACUTE TOXICITY STUDY OF ROOT EXTRACT OF CARISSA SPINARUM LINN. IN SWISS ALBINO MICE
Authors: GEBREHIWOT SIBHATU
Published: June 2019

Objective: The objective of the present research work had been done to evaluate the toxicity of crude extract of Carissa spinarum in Swiss albino mice.

Methods: In studying the toxicity, the Organization for Economic Cooperation and Development (OECD) guidelines were used. Experimental animals (mice), five mice in each, were grouped into four groups; three experimental groups and one negative control. In studying the acute toxicity, 2000, 3000 up to 5000 mg/kg crude plant extract was given orally using standard intragastric oral gavages. For acute toxicity, a single dose was given and gross behavioral changes were recorded. In sub-acute oral toxicity test, Carissa spinarum crude extract was given to the mice by standard intragastric oral gavages at doses of 500, 750 and 1000 mg/kg body weight of hydro-methanolic extract and 200, 600 and 1000 mg/kg of body weight of chloroform extract in every single to 28 d and various hematological and physical parameters were recorded.

Results: In acute toxicity, the given dose of the plant extract did not produce significant physical and behavior changes up to the dose of 5000 mg/kg extracts. In addition, no death was occurred in the given doses. In sub-acute toxicity studies of the hydro-methanolic and chloroform extracts, there was no recorded significant change (p>0.05) of hematological and physical parameters in the treated groups when compared to the control groups.

Conclusion: from the present study it was revealed that the crude extract of the plant did not produce any significant toxicological effect in the experimental animals and this supports the use of the plant in folk medicines.
EFFECTS OF ALPHA-MANGOSTIN AND CITRONELLA OIL AGAINST ACNE CAUSING BACTERIA
Authors: TANNGOEN PIANGPETCH , Lamlertthon Supaporn , Tiyaboonchai Waree
Published: June 2019

Objective: This study assessed the effects of alpha-mangostin (AM) and citronella oil (CO) working alone or in combination against Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus).

Methods: The screening for antibacterial activity of AM and CO against P. acnes and S. aureus was carried out using the disk diffusion method. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these two substances were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICI) of a combination of AM and CO were obtained by checkerboard dilution assay.

Results: The results showed that alpha-mangostin and citronella oil do indeed fight against P. acnes and S. aureus. The MICs and MBCs of AM against P. acnes and S. aureus were the same at 6.25 and 50 µg/ml, respectively. Both the MIC and the MBC of CO against P. acnes were 27.81µg/ml. The MIC and the MBC of CO against S. aureus were 112.13 and 224.25 µg/ml, respectively. The FICI of a combination of AM and CO against P. acnes and S. aureus were 2.00, indicating indifferent interaction with no additional inhibitory effect.

Conclusion: AM and CO are very effective against P. acnes and S. aureus, nevertheless their effect when used together was indifferent from using alone. Further research may find that either or both of these substances combined with yet a different natural agent could provide synergy againstP. acnes and S. aureus.
DIALYSIS PRACTICE PATTERN IN PATIENTS UNDERGOING HEMODIALYSIS IN A TERTIARY AND A PRIVATE HOSPITAL
Authors: Nerurkar Dhanisha Pramod , Oommen Janet Mary , Sajith Manjusha , Jawale Sunil , Ambike S M
Published: June 2019

Objective: To evaluate the dialysis practice pattern in chronic kidney disease patients undergoing hemodialysis in a tertiary and a private hospital

Methods: A prospective observational study of six months duration was carried out in 158 CKD patients on hemodialysis for a minimum period of one month. Data such as socio-demographic, clinical characteristics and dialysis practice details were captured from the patient’s medical records into the pre-designed Patient Proforma. The collected data were analysed.

Results: Majority of respondents were male (67.09%), more than 60 y of age (32.28 %), married (89.24%). Hypertension (26.51%, 17.33%) was found to be the leading cause of CKD in a tertiary and private hospital. In the tertiary hospital, 78.31% of patients were undergoing twice-weekly hemodialysis, whereas in the private hospital thrice weekly (50.67%) hemodialysis was common. About 51.81% of patients in the tertiary and 58.67% in the private hospital was undergoing hemodialysis for 1-5 y with Arterio-Venous Fistula (59.04%, 94.67%) as the permanent vascular access (P<0.001).

Conclusion: This study shows that hypertension was the leading cause of CKD in both hospitals. In the tertiary hospital twice weekly hemodialysis with arteriovenous fistula (AVF) and Permanent Catheter (IJV), were both preferred as the permanent vascular access. Whereas in the private hospital majority were undergoing thrice weekly hemodialysis and AVF was highly preferred.
Observation on a fire whirl in a vertical shaft using high-speed camera and associated correlation derived
Authors: Hung Hing , Han Shousuo , Chow Wan , Chow Cheuk
Published: June 2019

The fire whirl generated by burning a pool fire in a vertical shaft with a single corner gap of appropriate width was studied using a high-speed camera. A 7 cm diameter pool propanol fire with heat release rate 1.6 kW in free space was burnt inside a 145 cm tall vertical shaft model with gap widths lying between 2 cm and 16 cm. The flame height was between 0.25 m and 0.85 m for different gap widths. Photographs taken using a high-speed camera at critical times of swirling motion development were used to compare with those taken using a normal camera. From the experimental observations on flame swirling by a high-speed camera, stages for generating the fire whirl were identified much more accurately. Two flame vortex tubes moving over the horizontal burning surface of the liquid pool were observed. Based on these observations a set of more detailed schematic diagrams on the swirling motion was constructed. From the observed flame heights under different gap widths and using three assumptions on the variation of air entrainment velocity with height, an empirical expression relating the burning rate with flame height and the corner gap width was derived from the observation with high-speed camera. The correlation expression of the burning rate of the pool fire obtained would be useful in fire safety design in vertical shafts of tall buildings.
Experimental study on the smoke temperature distribution alongside the lining in tunnel fires
Authors: Wang Feng , Wang Yu , Huang Yubing , Yan Qixiang
Published: June 2019

Tunnel fire temperature is a key factor for tunnel structural safety and evacuation. This study aimed to investigate the smoke temperature distribution alongside the lining across the section and effects of pool sizes and fuels on it through a series of small-scale experiments. The results showed the heat release rates of diesel were significantly lower than gasoline?s when they had the same pool size and volume. Nevertheless, the duration of diesel combustion increased obviously. As a result, the maximum smoke temperature under the ceiling for gasoline was significantly higher than diesel?s. The results were subsequently adopted to compare with other test results and illustrated a similar result. The initial temperature rising rates for gasoline pool fires were shown to agree well with the standardized temperature curves, but they were significantly lower for diesel pool fires. Two exponential correlations on vertical temperature distribution were provided, respectively, for gasoline and diesel fires. These findings are expected to be useful for the design of the thermal boundary on the lining in tunnel fires.
Modeling of the hourly horizontal solar diffuse radiation in Sanliurfa, Turkey
Authors: Beyazit Nesrin , Unal Fatih , Bulut Husamettin
Published: June 2019

Horizontal diffuse solar radiation has been calculated over various models by using the total radiation data obtained from the horizontal surface due to reasons such as lack of adequate measurements and expensive measuring instruments. In this study, the measurements were calculated using the obtained data between the years 2009 and 2016 from solar radiation measurement system with solar tracking system, which belongs to the Department of Mechanical Engineering, Sanliurfa Harran University, Turkey. Three horizontal solar diffuse radiation models have been proposed by using the relationship between the diffuse radiation ratio and the clarity index obtained by eight years? data. Horizontal solar diffuse radiation values were calculated and compared with the measurement data for Sanliurfa by using 15 models of diffuse radiation given in the literature and the results obtained from the models. The statistical errors of the proposed models and 15 different diffusive radiation models were calculated. As diffuse radiation varies with time, it is determined that modelling of Model 1 and Model 2 obtained from Sanliurfa data gives better results in terms of clarity index constraints. Furthermore, although the desired success cannot be achieved with Model 2 in terms of tstat, it has been determined that the relevant model provides better results than many models when compared to statistical errors. With the improvements to be made on Model 2, a local estimation model is thought to give better results.
Kinin B1 Receptor Acts in Adipose Tissue to Control Fat Distribution in a Cell-Nonautonomous Manner
Authors: Sales Vicencia M. , Gonçalves-Zillo Thais , Castoldi Angela , Burgos Marina , Branquinho Jessica , Batista Carolina , Oliveira Valeria , Silva Elton , Castro Charlles H.M. , Câmara Niels , Mori Marcelo A. , Pesquero João Bosco
Published: June 2019

The kinin B1 receptor (B1R) plays a role in inflammatory and metabolic processes. B1R deletion (B1−/−) protects mice from diet-induced obesity and improves insulin and leptin sensitivity. In contrast, genetic reconstitution of B1R exclusively in adipose tissue reverses the lean phenotype of B1−/− mice. To study the cell-nonautonomous nature of these effects, we transplanted epididymal white adipose tissue (eWAT) from wild-type donors (B1+/+) into B1−/− mice (B1+/+→B1−/−) and compared them with autologous controls (B1+/+→B1+/+ or B1−/−→B1−/−). We then fed these mice a high-fat diet for 16 weeks and investigated their metabolic phenotypes. B1+/+→B1−/− mice became obese but not glucose intolerant or insulin resistant, unlike B1−/−→B1−/− mice. Moreover, the endogenous adipose tissue of B1+/+→B1−/− mice exhibited higher expression of adipocyte markers (e.g., Fabp4 and Adipoq) and changes in the immune cell pool. These mice also developed fatty liver. Wild-type eWAT transplanted into B1−/− mice normalized circulating insulin, leptin, and epidermal growth factor levels. In conclusion, we demonstrated that B1R in adipose tissue controls the response to diet-induced obesity by promoting adipose tissue expansion and hepatic lipid accumulation in cell-nonautonomous manners.
1002-P: Sacubitril/Valsartan Increases Postprandial Glucagon-Like Peptide-1 Concentrations and Has Synergistic Effects when Combined with Sitagliptin
Authors: WEWER ALBRECHTSEN NICOLAI JACOB , MARK PETER DALL , HANSEN LASSE H. , ANDERSEN ULRIK ØRSØ , HARTMANN BOLETTE , CARR RICHARD D. , GUSTAFSSON FINN , DEACON CAROLYN F. , HOLST JENS J. , GØTZE JENS PETER , PLOMGAARD PETER
Published: June 2019

Diabetes is an independent risk factor for heart failure. Treatment with a neprilysin inhibitor-angiotensin receptor blocker (sacubitril/valsartan) was demonstrated to improve glycemia and reduce time to initiation of insulin therapy but the underlying mechanism(s) are unknown. We hypothesized that sacubitril/valsartan attenuates neprilysin-dependent degradation of GLP-1, and that combined inhibition of the other enzyme cleaving intact GLP-1, dipeptidyl peptidase 4 (DPP-4), would have synergistic effects on levels of intact GLP-1. In two open-labeled clinical trials, a total of 16 healthy men received a standardized meal (34% carbohydrates, 45% fat, 21% protein) combined with a prior single dose of sacubitril (194mg)/valsartan(206mg), sitagliptin (2x100mg), sacubitril(194mg)/valsartan(206mg) and sitagliptin (2x100mg), or control. Sacubitril/valsartan increased postprandial plasma concentrations of total GLP-1 by 67% and had synergistic effects on intact GLP-1 when combined with sitagliptin. Concentrations of glucose, insulin, and GIP were not significantly changed upon sacubitril/valsartan treatment. Sacubitril/valsartan synergistically protects intact GLP-1 when combined with a DPP-4 inhibitor pointing to a therapeutic potential for the combination in patients with cardiovascular disease and diabetes.

Disclosure

N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp. P.D. Mark: None. L.H. Hansen: None. U.Ø. Andersen: None. B. Hartmann: None. R.D. Carr: Employee; Self; Merck & Co., Inc. Speaker's Bureau; Spouse/Partner; Eli Lilly and Company, Merck & Co., Inc. F. Gustafsson: Advisory Panel; Self; Abbott, Corvia Medical, Inc. Consultant; Self; Bayer AG. Employee; Spouse/Partner; Novo Nordisk A/S. Research Support; Self; Novo Nordisk Foundation. Speaker's Bureau; Self; Novartis AG, Novo Nordisk A/S. C.F. Deacon: Employee; Spouse/Partner; Merck Sharp & Dohme Corp. Stock/Shareholder; Spouse/Partner; Merck & Co., Inc. Other Relationship; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. J.P. Gøtze: None. P. Plomgaard: None.

Funding

Rigshopitalet
1005-P: Efficacy and Safety of Evogliptin in a Brazilian T2DM Population—A Bridging Study
Authors: FORTI ADRIANA C. , FELÍCIO JOÃO SOARES , RUSSO LUIS AUGUSTO , BORGES JOAO LINDOLFO , CHACRA ANTONIO R. , SALLES JOAO EDUARDO , CERCATO CINTIA
Published: June 2019

Ethnicity is a known factor for DPP-4 inhibitors (DPP-4i)response in type 2 diabetes mellitus (T2DM). A bridging study was conducted to confirm the approved dosage of Evogliptin (EVO), in Korea (once daily 5mg) and the safety for the Brazilian population. In this randomized, double-blind, double-dummy, parallel trial, 146 T2DM patients (male: 50.7%; age: 51.5 ± 10.2 years; time from T2DM diagnosis: 1.7 ± 3.5 years; baseline HbA1c: 8.9 ± 0.9%) with inadequate glycemic control on diet and exercise were randomly assigned to a 12-week once daily treatment with EVO 2,5 mg, EVO 5 mg, EVO 10 mg or sitagliptin (SITA) 100 mg.T2DM patients aged 20 to 75 years, with 7.5% ≤ HbA1c ≤ 10.5% at screening, and who have not been on any hypoglycemic agent within 12 weeks prior to screening were eligible for the study. Subjects with fasting plasma glucose ≥ 300 mg/dL at screening in the presence of severe signs/symptoms of T2DM were excluded. Sample size was estimated to identify a clinically relevant HbA1c mean reduction ≥ 0,5% within each treatment group. Change from baseline to Week 12 (mean; 90% CI) in HbA1c (%) and, fasting plasma glucose levels (mg/dL) was calculated. Treatment effects on HbA1c and fasting glucose levels adjusted by baseline HbA1c, fasting plasma glucose and BMI were also estimated. The results confirmed the clinical benefit of a daily EVO 5,0 mg regimen in the Brazilian population.

Disclosure

A.C. Forti: None. J.S. Felício: None. L.A. Russo: None. J. Borges: None. A.R. Chacra: None. J.E. Salles: Board Member; Spouse/Partner; AstraZeneca, Merck & Co., Inc., Novo Nordisk A/S. Other Relationship; Spouse/Partner; Eurofarma Laboratórios S.A. C. Cercato: Board Member; Self; Novo Nordisk Inc. Research Support; Self; Eurofarma, Novo Nordisk Inc.

Funding

Eurofarma Laboratórios S.A.
1007-P: Incretin Therapy with DPP-4-I and GLP1-RA for the Hospital Management of Elderly Adults with Type 2 Diabetes
Authors: FAYFMAN MAYA , ANZOLA ISABEL , URRUTIA MARIA A. , PASQUEL FRANCISCO J. , GALINDO RODOLFO J. , CARDONA SAUMETH , WANG HEQIONG , UMPIERREZ GUILLERMO E.
Published: June 2019

Management of hospitalized older adults (> 65 years) with T2D is challenging and associated with increased risk of hypoglycemia. Incretin-based therapy with DPP-4i and GLP-1RA have been shown to be safe and efficacious in hospitalized patients with mild-moderate hyperglycemia. We performed a post hoc pooled analysis of 4 randomized controlled trials comparing DPP-4i and GLP-1RA alone or in combination with basal insulin to basal-bolus regimen in older adults in non-ICU settings. The primary endpoint was percentage of BG readings within target range (70-180 mg/dL). Secondary endpoints included mean hospital BG, hypoglycemia and a composite of hospital complications.

Among a total of 192 elderly patients, 88 (45.8%) received basal+bolus, 52 (27%) incretin+basal, and 52 (27%) incretin therapy alone. All treatment groups had improvement in glycemic control with no differences in % BG between 70-180 mg/dL or in the mean daily BG, or hospital complications between groups (Table). Patients treated with basal+bolus insulin had the highest rate of hypoglycemia. No differences were found on % of BG readings within range of 70-180 mg/dl (primary outcome) for patients with randomization BG ≤ 200 mg/dL or BG > 200 mg/dl.

In summary, incretin therapy is safe and associated with similar glycemic control and lower rates of hypoglycemia compared to basal+bolus regimen among elderly hospitalized adults with T2D.

Disclosure

M. Fayfman: None. I. Anzola: None. M.A. Urrutia: None. F.J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. R.J. Galindo: Advisory Panel; Self; Abbott, Novo Nordisk Inc., Sanofi US. Research Support; Self; Novo Nordisk Inc. S. Cardona: None. H. Wang: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US.
101-LB: Real-Time Monitoring of Cholesterol Levels Using a Microfluidic Device
Authors: BHUSHAN ABHINAV , KARNIK SONALI J.
Published: June 2019

The lack of point-of-care (POC) devices that continuously monitor health is an unmet need. The challenge is not just to create POC devices, but to also go beyond the single time point or discrete measurements. For instance, in a critical in-patient setting, the need to monitor patients’ biochemical signals is important; discrete POC devices are not effective and increase clinical burden. For example, continuous glucose monitors have made it easier for patients to track glucose levels, there are currently no other similar devices either in POC or in an in-patient setting. We had previously reported results in which we carried out, in real-time, continuous measurement of albumin from hepatocytes as a marker of liver function. These measurements were carried out at high sensitivity (∼fg) and temporal resolution (<20s) (10.1007/s10544-017-0244-6). In this abstract, we now report novel POC devices that utilize smart chemistry to carry out continuous, real-time measurement of cholesterol using a tiny sample volume (∼1ul) and achieving detection limit surpassing the conventional assays. The response of hepatocytes to simvastatin was accurately measured by the device, again in real-time. Since the devices are easily customizable, by simply changing the enzymes used in the reactions, we can measure glucose, lactate, and urea. These devices can be groundbreaking in personalized tracking of metabolic health in a POC setting as well as for in-patient situation to assess treatments of ongoing interventions without increasing clinical burden.

Disclosure

A. Bhushan: None. S.J. Karnik: None.

Funding

National Institutes of Health (DK095984)
1015-P: Effects of the Oral, Small Molecule GLP-1R Agonist TTP273 on Patients with Stage 2 Hypertension: Results from a Post Hoc Analysis of the Phase 2 Logra Study
Authors: VALCARCE CARMEN , DUNN IMOGENE , FREEMAN JENNIFER L.R.
Published: June 2019

TTP273, an oral, non-peptide GLP-1R agonist showed significant placebo-subtracted reductions in A1c of 0.9 and 0.7% when dosed at 150mg QPM or BID, respectively, in LOGRA, a 12-week, phase 2, double-blind, placebo-controlled randomized study [Diabetes 2017 Jun; 66 (S 1) A326]. In addition, less nausea was observed in the active groups than in the placebo group and the only incidence of vomiting occurred in the placebo group.

A post hoc analysis of patients from the LOGRA study with Stage 2 hypertension that completed 12 weeks of dosing revealed a subgroup with a nominally statistically significant reduction in systolic blood pressure (SBP). Entry criteria allowed patients on standard of care treatment for hypertension, but excluded patients with persistent, uncontrolled hypertension at screening (SBP ≥ 160mmHg and/or diastolic blood pressure (DBP) ≥ 90mmHg). Approximately 25% of the patients that completed the study were considered to have Stage 2 hypertension at baseline (defined by SBP ≥ 140mmHg or DBP ≥90mmHg) and around 75% of those patients received 1 or more concomitant medications to treat hypertension.

Among treatment groups, characteristics were relatively well balanced with an approximately equal number of patients enrolled per treatment group with similar baseline values for SBP/DBP and pulse rate among treatment groups (mean baseline values of 147/85 mmHg and 73 bpm). The post hoc analysis demonstrated a mean decrease from baseline in SBP of 17 in the 150mg QPM arm (n=9) (p < 0.05 vs. placebo), 12 in the 150mg BID TTP273 arm (n=10) and of 6 mmHg in the placebo arm (n=8), respectively. No significant changes in DBP or pulse rate were observed with either active group compared to placebo.

Results from this post hoc analysis suggest that TTP273 could provide an additional benefit of reducing SBP, in line with other GLP-1R agonists. Unlike other GLP-1R agonists, these effects occurred without the side effects of nausea and vomiting.

Disclosure

C. Valcarce: Employee; Self; vTv Therapeutics. I. Dunn: None. J.L.R. Freeman: Employee; Self; vTv Therapeutics. Stock/Shareholder; Spouse/Partner; vTv Therapeutics.
1018-P: Comparison of Short- and Long-Acting Glucagon-Like Peptide-1 Receptor Agonist Effects on Postprandial Glucose and Lipid Excursion via Gastric Emptying
Authors: KUWATA HITOSHI , YABE DAISUKE , HAMAMOTO YOSHIYUKI , KUROSE TAKESHI , SEINO YUTAKA
Published: June 2019

Background: It has been suggested that short- and long-acting glucagon-like peptide 1 receptor agonists (GLP-1RAs) exert different actions on gastric emptying rate (GE). However, the alterations in gastric emptying and their contributions to postprandial glucose and lipid excursions have not been fully evaluated.

Methods: A 3-arm non-randomized trial was conducted in Japanese patients with type 2 diabetes. Meal tolerance test was performed before and 12 weeks after initiation of treatment by short-acting GLP-1RA (Lixisenatide (X)) or long-acting GLP-1RA [Liraglutide (R) or Dulaglutide(D)]. Plasma glucose, ApoB48, insulin and gastric emptying (13C breath test) were measured after taking a solid test meal. Data were presented as average±SD and evaluated using student’s or paired t-test. p<0.05 was considered significant.

Results: 18 patients were enrolled [X: n=7; age(year) 45.6±2.3; duration(year) 4.6±5.0; ΔCPR(glucagon stimulation test (mg/dl) 3.2±1.4, R: n=6; age 49.0±11.4; duration 8.2±9.2; ΔCPR 3.1±0.5, D; n=5; age 51.8±7.6; duration 4.6±3.8; ΔCPR 2.7±1.3)]. After 12 weeks administration, HbA1c was significantly improved in all groups [HbA1c (%), X: 8.2±1.6 to 6.3±0.4, L: 9.0±0.8 to 6.6±1.1, D: 8.6±0.9 to 6.6±0.3]. GE was delayed only in X [T1/2(min), X: 26.4±6.5 to 64.4±34.4, L: 33.5±15.5 to 29.1±9.2, and D: 26.3±3.8 to 31.1±9.7]. Postprandial insulin and ApoB48 secretion was significantly decreased only in X [IRI-AUC0-240(uIU/dlxmin), X: 11724.0±5582.0 to 6248.2±3718.7, L: 8206.7±3075.4 to 9905.0±3450.3, D: 9832.8±5087.3 to 10640.6±4195.1 and ApoB48-iAUC0-240(ug/mlxmin), X: 513.2±394.4 to -83.7±242.6; L: 745.1±352.4 to 534.1±193.4; and D: 983.5±239.0 to 568.2±374.4].

Conclusion: These results indicate that short-acting agents improve postprandial glycemic and lipidemic metabolism through delaying GE; long-acting agents improve glycemic control through enhanced insulin secretion.

Disclosure

H. Kuwata: Research Support; Self; Eli Lilly and Company. D. Yabe: Advisory Panel; Self; Abbott. Research Support; Self; Astellas Pharma Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Hamamoto: Speaker's Bureau; Self; Novo Nordisk A/S. T. Kurose: Consultant; Self; Taisho Pharmaceutical Co., Ltd. Speaker's Bureau; Self; FujiFilm Pharma, Ono Pharmaceutical Co., Ltd. Y. Seino: Research Support; Self; Arkray, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation.
1024-P: Effect of Tirzepatide, a Dual GIP and GLP-1 Receptor Agonist, on Glycemic Control and Body Weight in Japanese Patients with T2DM
Authors: OHWAKI KENJI , FURIHATA KENICHI , MIMURA HANAKA , OURA TOMONORI , IMAOKA TAKESHI
Published: June 2019

Tirzepatide (TZP), a novel dual GIP and GLP-1 receptor agonist (RA), has shown superior glycemic control and weight loss compared to a selective GLP-1 RA. A Phase 1, double-blind, placebo-controlled, randomized, parallel-dose group, 8-week multiple ascending dose study investigated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TZP administered QW in 48 Japanese patients with T2DM. This study consisted of 1 fixed dose (5 mg) and 2 dose titration (2.5-2.5-5-5-10-10-10-10 mg and 5 5 10 10 10 10 15 15 mg) cohorts of TZP. With TZP, there were marked reductions from baseline to Week 8 in fasting serum glucose, HbA1c, and body weight. The half-life of plasma TZP concentration was approximately 5 days and supports QW dosing regimen. All doses of TZP were well tolerated. The most frequently reported treatment-emergent adverse events (AEs) were decreased appetite and gastrointestinal AEs (constipation, diarrhea, abdominal discomfort, abdominal distension, vomiting, and nausea). These AEs were generally dose dependent and mild in severity. The safety, tolerability, PK, and PD profiles of TZP in this study appeared comparable to other Phase 1 and 2 studies in non-Japanese patients with T2DM. The data support Phase 3 development of TZP for QW dosing in Japanese patients with T2DM.

Disclosure

K. Ohwaki: Employee; Self; Eli Lilly and Company. K. Furihata: None. H. Mimura: Employee; Self; Eli Lilly and Company. T. Oura: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. T. Imaoka: Employee; Self; Eli Lilly and Company.
1038-P: Results of Interim Analysis of a Randomized Crossover Study in Type 1 Diabetes (T1D) of a Dual-Hormone Closed-Loop System with Xerisol™ Glucagon vs. Insulin-Only Closed-Loop System vs. a Predictive Low Glucose Suspend System
Authors: WILSON LEAH M. , JACOBS PETER G. , RESALAT NAVID , REDDY RAVI , YOUSSEF JOSEPH EL , BRANIGAN DEBORAH , LEITSCHUH JOSEPH A. , SENF BRIAN , GABO VIRGINIA , CASTLE JESSICA R.
Published: June 2019

Dual-hormone systems show promise to reduce hypoglycemia, but require a stable liquid glucagon formulation. XeriSol™ glucagon is a shelf-stable glucagon product for this use. Nineteen subjects with T1D are completing a single-center three-day outpatient study comparing control modes of the Oregon Artificial Pancreas system: 1) dual hormone (DH) closed-loop with Novolog™ insulin and XeriSol™ glucagon, 2) insulin-only single hormone (SH) closed-loop, 3) insulin-only predictive low glucose suspend system (PLGS). In clinic aerobic exercise (45 minutes at 60% VO2max) and home exercise was completed with each arm. SH and DH used automated exercise detection to adaptively dose insulin/glucagon for predicted hypoglycemia and tailored mealtime dosing based on past meal responses with an adaptive algorithm. An interim analysis after 7 subjects was completed for safety. The primary outcome measures are % time 70-180 mg/dL and % time <70 mg/dL for the 3-day study and the 4-hour period from start of exercise until the next meal. From start of exercise until the next meal, DH showed a clinically meaningful reduction of time in hypoglycemia compared with PLGS and SH. For the entire study, DH showed a clinically meaningful lower time <70mg/dL. No serious events or unexpected side effects occurred.

Disclosure

L.M. Wilson: None. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies. N. Resalat: None. R. Reddy: None. J. El Youssef: None. D. Branigan: None. J.A. Leitschuh: Other Relationship; Self; AgaMatrix. B. Senf: None. V. Gabo: None. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc., Zealand Pharma A/S. Consultant; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc.

Funding

JDRF
1044-P: Insulin Intensification with a 24-Hour Wearable Insulin Delivery Device in Patients Inadequately Controlled with Basal Insulin Therapy
Authors: ZEIDAN TRISHA , NIKKEL CARLA C. , DZIENGELEWSKI ELIZABETH A.
Published: June 2019

A stepwise approach for the addition of prandial insulin is recommended when intensification from basal to basal-bolus therapy is required. Rationale for this approach includes patient resistance to multiple daily injections and a stepwise approach has been associated with lower rates of hypoglycemia. Unfortunately, evidence suggests within a year of initiating prandial insulin, up to 75% of patients require full basal-bolus therapy. This results in the ongoing need to address the same barriers that initially delayed intensification to full basal-bolus therapy. In light of these considerations, insulin delivery options that simplify basal-bolus therapy while offering clinical benefit without increased safety risk may be an attractive option. This study retrospectively evaluated the use of a wearable basal-bolus insulin delivery device (V-Go) in 73 patients with type 2 diabetes inadequately controlled with basal insulin. Change in A1C, insulin basal and total daily doses (TDD) and prevalence of hypoglycemia were analyzed. Mean ± SD characteristics at baseline included duration of diabetes 12 ± 7 years, A1C 9.6 ± 1.5%, basal TDD 52 ± 34 u/day (range 10 to 170), and basal TDD 0.53 ± 0.35 u/kg. Concomitant anti-hyperglycemic agents were prescribed in 93% of patients. After a mean of 5 months of V-Go use, mean ± SD reductions in A1C (-1.3 ± 1.5%; p<0.0001) and basal TDD (-22 ± 30 u/day; p<0.0001 and -0.24 ± 0.31 u/kg; p<0.0001) were observed. Compared to baseline, TDD was similar on V-Go, 52 ± 18 u/day; p=0.946, however, insulin dose was redistributed to incorporate prandial coverage (22 ± 9 u/day) and basal coverage (30 ± 13 u/day). With V-Go use, severe hypoglycemia was reduced from 10% at baseline to 3% and fewer concomitant agents were prescribed. Intensification from basal insulin to basal-bolus therapy with V-Go was effective and resulted in a lower prevalence of hypoglycemia.

Disclosure

T. Zeidan: Advisory Panel; Self; Corcept Therapeutics. Research Support; Self; Valeritas, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Valeritas, Inc. C.C. Nikkel: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc. E.A. Dziengelewski: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc.
1046-P: Day-to-Day Variability of Insulin Requirements in Inpatients on General Wards
Authors: BOUGHTON CHARLOTTE K. , BALLY LIA , THABIT HOOD , HARTNELL SARA , HERZIG DAVID , VOGT ANDREAS , ANDEREGGEN EVELINE , RUAN YUE , WILINSKA MALGORZATA E. , EVANS MARK , WERTLI MARIA M. , COLL ANTHONY P. , STETTLER CHRISTOPH , HOVORKA ROMAN
Published: June 2019

Aim: To characterize variability of exogenous insulin requirements during fully closed-loop insulin delivery in hospitalized patients with hyperglycaemia requiring subcutaneous insulin.

Methods: We retrospectively analyzed data from randomized trials investigating fully closed-loop insulin delivery for up to 15 days in inpatients with hyperglycaemia on general wards (type 1 diabetes excluded). We calculated insulin amounts delivered by closed-loop overnight (2300-0449), during breakfast (0500-1059), lunch (1100-1659), and evening meal (1700-2249). The coefficient of variation (CV) quantified between day and between night variability of insulin requirements in inpatients using closed-loop for at least 5 days.

Results: Data from 487 days in 55 participants were analyzed [age 69(8)years, weight 100(32)kg, baseline HbA1c 8.0(2.1)%, duration of diabetes 18(13)years, duration of insulin 9(10)years, mean(SD)]; 14.5% of participants received dialysis, 29.1% enteral/parenteral nutrition and 21.8% steroids. Closed-loop directed insulin infusion rate was 1.6(0.8), 2.9(1.2), 3.1(1.4), 2.1(1.0)units/kg/h during overnight, breakfast, lunch, and evening meal periods, respectively. The CV of insulin delivery was higher between nights than between any of the daytime periods [overnight 54(21)% compared with 42(21)% at breakfast, 41(16)% lunchtime and 48(17)% dinner; p=0.001].

Conclusions: Overnight exogenous insulin requirements are more variable than daytime requirements. Particular attention needs to be paid to glucose management overnight to prevent dysglycaemia in inpatients receiving insulin therapy on general wards.

Disclosure

C.K. Boughton: None. L. Bally: None. H. Thabit: Research Support; Self; Dexcom, Inc. S. Hartnell: Advisory Panel; Self; Dexcom, Inc., JDRF. Speaker's Bureau; Self; Sanofi. D. Herzig: None. A. Vogt: None. E. Andereggen: None. Y. Ruan: None. M.E. Wilinska: None. M. Evans: Advisory Panel; Self; Dexcom, Inc., Medtronic, Roche Diabetes Care, Zucara Therapeutics Inc. Research Support; Self; MedImmune, Sanofi. Speaker's Bureau; Self; AstraZeneca. Other Relationship; Self; Abbott, Eli Lilly and Company, Novo Nordisk Inc. M.M. Wertli: None. A.P. Coll: None. C. Stettler: None. R. Hovorka: Advisory Panel; Self; Novo Nordisk A/S. Research Support; Self; Abbott, Dexcom, Inc., Medtronic. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; B. Braun Medical Inc., Medtronic.
1048-P: Insulin Pump Catheters Can Be Worn Much More Than the Recommended Three Days
Authors: ARDILOUZE JEAN-LUC , GOBEIL FERNAND , MENARD JULIE , BOVAN DANIJELA , MESSIER VIRGINIE , SAVARD MARTIN , BAILLARGEON JEAN-PATRICE , RABASA-LHORET RÉMI
Published: June 2019

Background and Objectives: Current recommendation is to change insulin pump catheters every 3 days. The rational supporting this recommendation is weak, mostly historical or anecdotical, and based on habits. Our objective was to determine catheter length of wearing under day-to-day condition.

Methods: Participants with type 1 diabetes (T1D) worn their usual catheter during 2 periods as long as glycemic control was acceptable and insertion site remained comfortable. Data are presented as means ± standard deviations. Hypoglycemia (≤ 3.5 mmol/L) and hyperglycemia (≥ 13.8 mmol/L) were recorded via self-monitoring of blood glucose or continuous glucose monitoring. Each experimental period was separated by a 1-week washout, consisting of the usual catheter management.

Results: Participants (n=22, 12 males, age: 47.1±16.2 years, BMI: 26.6±4.1 kg/m2, duration of T1D: 27.5±14.3 years, pump therapy: 8.8±6.2 years, 14 using Medtronic, 8 using Animas, usual catheter wearing: 3.5±0.5 days, insulin: 51.7±15.5 units/day, A1c: 7.4±0.8%) completed 41/44 periods (348.7 experimental days; one subject quitted, 2 catheters accidentally ripped-out). Catheters were worn 8.18±2.93 days, the shortest and the longest periods were respectively 3.81 and 15.61 days. Reasons for removal were uncontrolled glycemia despite bolusing (73%), discomfort (15%), or both (12%). Number of hypoglycemia and hyperglycemia per day were 0.18±0.17 and 0.90±0.56, respectively. No severe hypoglycemia, nor hyperglycemia ≥ 20 mmol/L or ketosis were observed over the study.

Conclusions: Catheters might be worn beyond 3 days, up to 8 days and possibly more, significantly reducing patients and financial burden. Longer-term data are required to ensure that longer catheter wearing is not associated with impact on glucose control or lipohypertrophy.

Disclosure

J. Ardilouze: None. F. Gobeil: None. J. Menard: None. D. Bovan: None. V. Messier: Other Relationship; Self; Eli Lilly and Company. M. Savard: None. J. Baillargeon: None. R. Rabasa-Lhoret: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S.

Funding

JDRF