Search results for: subcutaneous insulin injection
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1290

Search results for: subcutaneous insulin injection

1110 Automatic Slider Design in Injection Moldings

Authors: Alan C. Lin, Tran Anh Son

Abstract:

This study proposes an approach to determine the undercut regions and their releasing directions for slider design of complex parts represented by the file format of STL (STereoLithography). In order to delineate the border of undercut regions, orthogonal cutting planes are firstly employed to automatically find the inner loops of a part model. To discover the facets belonging to undercut regions, attributes are then assigned to the facets of the part model based on the topological relationship of adjacent facets of each inner loop. After that, the undercut regions are separated from other facets in the model. Through the recognized facets of the undercut regions, the concept of 'visibility map (V-map)' is further applied to determine feasible releasing directions for each of the undercut regions. The undercut regions having the same releasing direction are finally grouped to form a slider in the injection mold.

Keywords: solid model, STL data, injection mold design, visibility map

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1109 Visualization of Flow Behaviour in Micro-Cavities during Micro Injection Moulding

Authors: Reza Gheisari, Paulo J. Bartolo, Nicholas Goddard

Abstract:

Polymeric micro-cantilevers (Cs) are rapidly becoming popular for MEMS applications such as chemo- and bio-sensing as well as purely electromechanical applications such as microrelays. Polymer materials present suitable physical and chemical properties combined with low-cost mass production. Hence, micro-cantilevers made of polymers indicate much more biocompatibility and adaptability of rapid prototyping along with mechanical properties. This research studies the effects of three process and one size factors on the filling behaviour in micro cavity, and the role of each in the replication of micro parts using different polymer materials i.e. polypropylene (PP) SABIC 56M10 and acrylonitrile butadiene styrene (ABS) Magnum 8434. In particular, the following factors are considered: barrel temperature, mould temperature, injection speed and the thickness of micro features. The study revealed that the barrel temperature and the injection speed are the key factors affecting the flow length of micro features replicated in PP and ABS. For both materials, an increase of feature sizes improves the melt flow. However, the melt fill of micro features does not increase linearly with the increase of their thickness.

Keywords: flow length, micro cantilevers, micro injection moulding, microfabrication

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1108 Part Performance Improvement through Design Optimisation of Cooling Channels in the Injection Moulding Process

Authors: M. A. Alhubail, A. I. Alateyah, D. Alenezi, B. Aldousiri

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In this study conformal cooling channel (CCC) was employed to dissipate heat of, Polypropylene (PP) parts injected into the Stereolithography (SLA) insert to form tensile and flexural test specimens. The direct metal laser sintering (DMLS) process was used to fabricate a mould with optimised CCC, while optimum parameters of injection moulding were obtained using Optimal-D. The obtained results show that optimisation of the cooling channel layout using a DMLS mould has significantly shortened cycle time without sacrificing the part’s mechanical properties. By applying conformal cooling channels, the cooling time phase was reduced by 20 seconds, and also defected parts were eliminated.

Keywords: optimum parameters, injection moulding, conformal cooling channels, cycle time

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1107 The Effect of Vitamin D Supplements and Aerobic Exercise on Hunger and Serum Insulin Levels in Adolescents With Metabolic Syndrome

Authors: Vahab Behmanesh

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Metabolic syndrome is defined as having at least three of the five metabolic risk factors, including abdominal obesity, high blood pressure, high triglycerides, low HDL, and insulin resistance. Lifestyle changes towards reducing physical activity, unhealthy eating habits Especially the high-fat and high-carbohydrate diet is directly related to metabolic syndrome, and due to the epidemic of overweight and sedentary life, metabolic syndrome is a serious problem worldwide. On the other hand, vitamin D deficiency is considered as one of the most common problems in the world, which is related to the dysfunction of beta cells and insulin resistance, and therefore, vitamin D deficiency is considered as a factor in the occurrence of metabolic syndrome. 40 subjects (age: 16.12 ± 4.4 years and body mass index 25.61 ± 4.4 kg/m2) were randomly assigned to groups of aerobic exercise and placebo, aerobic exercise and vitamin D and placebo (no exercise) were divided. Vitamin D was taken at a dose of 50,000 units per week in a double-blind format for eight weeks, and the daily aerobic exercise program was performed for 50 to 60 minutes, three doses per week, with an intensity of 50-60% of the maximum heart rate. From one-way analysis of variance, Factorial variance analysis (2x2) repeated measurement and correlated t-test were used for data analysis. Aerobic exercise and vitamin D intake reduced all metabolic risk indicators and blood insulin (P < 0.05). However, the subjective feeling of hunger did not change significantly (P < 0.05). Regarding waist circumference and blood glucose, the effect of exercise combined with vitamin D consumption was greater than the corresponding effect in the vitamin D group (P < 0.05). Aerobic exercises and vitamin D intake are safe and effective for improving cardiometabolic health, Imam adds vitamin D to the exercise program has more benefits for weight and blood sugar control, which suggests prescribing it for patients with metabolic syndrome.

Keywords: vitamin D, aerobic exercise, metabolic control, adolescents

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1106 Pressure Regulator Optimization in LPG Fuel Injection Systems

Authors: M. Akif Ceviz, Alirıza Kaleli, Erdoğan Güner

Abstract:

LPG pressure regulator is a device which is used to change the phase of LPG from liquid to gas by decreasing the pressure. During the phase change, it is necessary to supply the latent heat of LPG to prevent excessive low temperature. Engine coolant is circulated in the pressure regulator for this purpose. Therefore, pressure regulator is a type of heat exchanger that should be designed for different engine operating conditions. The design of the regulator should ensure that the flow of LPG is in gaseous phase to the injectors during the engine steady state and transient operating conditions. The pressure regulators in the LPG gaseous injection systems currently used can easily change the phase of LPG, however, there is no any control on the LPG temperature in conventional LPG injection systems. It is possible to increase temperature excessively. In this study, a control unit has been tested to keep the LPG temperature in a band. Result of the study showed that the engine performance characteristics can be increased by using the system.

Keywords: temperature, pressure regulator, LPG, PID

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1105 Fatty Acid Translocase (Cd36), Energy Substrate Utilization, and Insulin Signaling in Brown Adipose Tissue in Spontaneously Hypertensive Rats

Authors: Michal Pravenec, Miroslava Simakova, Jan Silhavy

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Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Recently, using systems genetics approach in the BAT from BXH/HXB recombinant inbred strains, derived from the SHR (spontaneously hypertensive rat) and BN (Brown Norway) progenitors, we identified Cd36 (fatty acid translocase) as the hub gene of co-expression module associated with BAT relative weight and function. An important aspect of BAT biology is to better understand the mechanisms regulating the uptake and utilization of fatty acids and glucose. Accordingly, BAT function in the SHR that harbors mutant nonfunctional Cd36 variant (hereafter referred to as SHR-Cd36⁻/⁻) was compared with SHR transgenic line expressing wild type Cd36 under control of a universal promoter (hereafter referred to as SHR-Cd36⁺/⁺). BAT was incubated in media containing insulin and 14C-U-glucose alone or 14C-U-glucose together with palmitate. Incorporation of glucose into BAT lipids was significantly higher in SHR-Cd36⁺/⁺ versus SHR-Cd36⁻/⁻ rats when incubation media contained glucose alone (SHR-Cd36⁻/⁻ 591 ± 75 vs. SHR-Cd36⁺/⁺ 1036 ± 135 nmol/gl./2h; P < 0.005). Adding palmitate into incubation media had no effect in SHR-Cd36⁻/⁻ rats but significantly reduced glucose incorporation into BAT lipids in SHR-Cd36⁺/⁺ (SHR-Cd36⁻/⁻ 543 ± 55 vs. SHR-Cd36⁺/⁺ 766 ± 75 nmol/gl./2h; P < 0.05 denotes significant Cd36 x palmitate interaction determined by two-way ANOVA). This Cd36-dependent reduced glucose uptake in SHR-Cd36⁺/⁺ BAT was likely secondary to increased palmitate incorporation and utilization due to the presence of wild type Cd36 fatty acid translocase in transgenic rats. This possibility is supported by increased incorporation of 14C-U-palmitate into BAT lipids in the presence of both palmitate and glucose in incubation media (palmitate alone: SHR-Cd36⁻/⁻ 870 ± 21 vs. SHR-Cd36⁺/⁺ 899 ± 42; glucose+palmitate: SHR-Cd36⁻/⁻ 899 ± 47 vs. SHR-Cd36⁺/⁺ 1460 ± 111 nmol/palm./2h; P < 0.05 denotes significant Cd36 x glucose interaction determined by two-way ANOVA). It is possible that addition of glucose into the incubation media increased palmitate incorporation into BAT lipids in SHR-Cd36⁺/⁺ rats because of glucose availability for glycerol phosphate production and increased triglyceride synthesis. These changes in glucose and palmitate incorporation into BAT lipids were associated with significant differential expression of Irs1, Irs2, Slc2a4 and Foxo1 genes involved in insulin signaling and glucose metabolism only in SHR-Cd36⁺/⁺ rats which suggests Cd36-dependent effects on insulin action. In conclusion, these results provide compelling evidence that Cd36 plays an important role in BAT insulin signaling and energy substrate utilization.

Keywords: brown adipose tissue, Cd36, energy substrate utilization, insulin signaling, spontaneously hypertensive rat

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1104 A Comparison of Direct Water Injection with Membrane Humidifier for Proton Exchange Membrane Fuel Cells Humification

Authors: Flavien Marteau, Pedro Affonso Nóbrega, Pascal Biwole, Nicolas Autrusson, Iona De Bievre, Christian Beauger

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Effective water management is essential for the optimal performance of fuel cells. For this reason, many vehicle systems use a membrane humidifier, a passive device that humidifies the air before the cathode inlet. Although they offer good performance, humidifiers are voluminous, costly, and fragile, hence the desire to find an alternative. Direct water injection could be an option, although this method lacks maturity. It consists of injecting liquid water as a spray in the dry heated air coming out from the compressor. This work focuses on the evaluation of direct water injection and its performance compared to the membrane humidifier selected as a reference. Two architectures were experimentally tested to humidify an industrial 2 kW short stack made up of 20 cells of 150 cm² each. For the reference architecture, the inlet air is humidified with a commercial membrane humidifier. For the direct water injection architecture, a pneumatic nozzle was selected to generate a fine spray in the air flow with a Sauter mean diameter of about 20 μm. Initial performance was compared over the entire range of current based on polarisation curves. Then, the influence of various parameters impacting water management was studied, such as the temperature, the gas stoichiometry, and the water injection flow rate. The experimental results obtained confirm the possibility of humidifying the fuel cell using direct water injection. This study, however shows the limits of this humidification method, the mean cell voltage being significantly lower in some operating conditions with direct water injection than with the membrane humidifier. The voltage drop reaches 30 mV per cell (4 %) at 1 A/cm² (1,8 bara, 80 °C) and increases in more demanding humidification conditions. It is noteworthy that the heat of compression available is not enough to evaporate all the injected liquid water in the case of DWI, resulting in a mix of liquid and vapour water entering the fuel cell, whereas only vapour is present with the humidifier. Variation of the injection flow rate shows that part of the injected water is useless for humidification and seems to cross channels without reaching the membrane. The stack was successfully humidified thanks to direct water injection. Nevertheless, our work shows that its implementation requires substantial adaptations and may reduce the fuel cell stack performance when compared to conventional membrane humidifiers, but opportunities for optimisation have been identified.

Keywords: cathode humidification, direct water injection, membrane humidifier, proton exchange membrane fuel cell

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1103 Liraglutide Augments Extra Body Weight Loss after Sleeve Gastrectomy without Change in Intrahepatic and Intra-Pancreatic Fat in Obese Individuals: Randomized, Controlled Study

Authors: Ashu Rastogi, Uttam Thakur, Jimmy Pathak, Rajesh Gupta, Anil Bhansali

Abstract:

Introduction: Liraglutide is known to induce weight loss and metabolic benefits in obese individuals. However, its effect after sleeve gastrectomy are not known. Methods: People with obesity (BMI>27.5 kg/m2) underwent LSG. Subsequently, participants were randomized to receive either 0.6mg liraglutide subcutaneously daily from 6 week post to be continued till 24 week (L-L group) or placebo (L-P group). Patients were assessed before surgery (baseline) and 6 weeks, 12weeks, 18weeks and 24weeks after surgery for height, weight, waist and hip circumference, BMI, body fat percentage, HbA1c, fasting C-peptide, fasting insulin, HOMA-IR, HOMA-β, GLP-1 levels (after standard OGTT). MRI abdomen was performed prior to surgery and at 24weeks post operatively for the estimation of intrapancreatic and intrahepatic fat content. Outcome measures: Primary outcomes were changes in metabolic variables of fasting and stimulated GLP-1 levels, insulin, c-peptide, plasma glucose levels. Secondary variables were indices of insulin resistance HOMA-IR, Matsuda index; and pancreatic and hepatic steatosis. Results: Thirty-eight patients undergoing LSG were screened and 29 participants were enrolled. Two patients withdrew consent and one patient died of acute coronary event. 26 patients were randomized and data analysed. Median BMI was 40.73±3.66 and 46.25±6.51; EBW of 49.225±11.14 and 651.48±4.85 in the L-P and L-L group, respectively. Baseline FPG was 132±51.48, 125±39.68; fasting insulin 21.5±13.99, 13.15±9.20, fasting GLP-1 2.4± .37, 2.4± .32, AUC GLP-1 340.78± 44 and 332.32 ± 44.1, HOMA-IR 7.0±4.2 and 4.42±4.5 in the L-P and L-L group, respectively. EBW loss was 47± 13.20 and 65.59± 24.20 (p<0.05) in the placebo versus liraglutide group. However, we did not observe inter-group difference in metabolic parameters between the groups in spite of significant intra-group changes after 6 months of LSG. Intra-pancreatic fat prior to surgery was 3.21±1.7 and 2.2±0.9 (p=0.38) that decreased to 2.14±1.8 and 1.06±0.8 (p=0.25) at 6 months in L-P and L-L group, respectively. Similarly, intra-pancreatic fat was 1.97±0.27 and 1.88±0.36 (p=0.361) at baseline that decreased to 1.14±0.44 and 1.36±0.47 (p=0.465) at 6 months in L-P and L-L group, respectively. Conclusion: Liraglutide augments extra body weight loss after sleeve gastrectomy. A decrease in intra-pancreatic and intra-hepatic fat is noticed after bariatric surgery without additive benefit of liraglutide administration.

Keywords: sleeve gastrectomy, liraglutide, intra-pancreatic fat, insulin

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1102 Depth of Penetration and Nature of Interferential Current in Cutaneous, Subcutaneous and Muscle Tissues

Authors: A. Beatti, L. Chipchase, A. Rayner, T. Souvlis

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The aims of this study were to investigate the depth of interferential current (IFC) penetration through soft tissue and to investigate the area over which IFC spreads during clinical application. Premodulated IFC and ‘true’ IFC at beat frequencies of 4, 40 and 90Hz were applied via four electrodes to the distal medial thigh of 15 healthy subjects. The current was measured via three Teflon coated fine needle electrodes that were inserted into the superficial layer of skin, then into the subcutaneous tissue (≈1 cm deep) and then into muscle tissue (≈2 cm deep). The needle electrodes were placed in the middle of the four IFC electrodes, between two channels and outside the four electrodes. Readings were taken at each tissue depth from each electrode during each treatment frequency then digitized and stored for analysis. All voltages were greater at all depths and locations than baseline (p < 0.01) and voltages decreased with depth (P=0.039). Lower voltages of all currents were recorded in the middle of the four electrodes with the highest voltage being recorded outside the four electrodes in all depths (P=0.000).For each frequency of ‘true’ IFC, the voltage was higher in the superficial layer outside the electrodes (P ≤ 0.01).Premodulated had higher voltages along the line of one circuit (P ≤ 0.01). Clinically, IFC appears to pass through skin layers to depth and is more efficient than premodulated IFC when targeting muscle tissue.

Keywords: electrotherapy, interferential current, interferential therapy, medium frequency current

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1101 Palliative Orthovoltage Radiotherapy and Subcutaneous Infusion of Carboplatin for Treatment of Appendicular Osteosarcoma in Dogs

Authors: Kathryn L. Duncan, Charles A. Kuntz, Alessandra C. Santamaria, James O. Simcock

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Access to megavoltage radiation therapy for small animals is limited in many locations around the world. This can preclude the use of palliative radiation therapy for the treatment of appendicular osteosarcoma in dogs. The objective of this study was to retrospectively assess the adverse effects and survival times of dogs with appendicular osteosarcoma that were treated with hypofractionated orthovoltage radiation therapy and adjunctive carboplatin chemotherapy administered via a single subcutaneous infusion. Medical records were reviewed retrospectively to identify client-owned dogs with spontaneously occurring appendicular osteosarcoma that was treated with palliative orthovoltage radiation therapy and a single subcutaneous infusion of carboplatin. Data recorded included signalment, tumour location, results of diagnostic imaging, haematologic and serum biochemical analyses, adverse effects of radiation therapy and chemotherapy, and survival times. Kaplan-Meier survival analysis was performed, and log-rank analysis was used to determine the impact of specific patient variables on survival time. Twenty-three dogs were identified that met the inclusion criteria. Median survival time for dogs was 182 days. Eleven dogs had adverse haematologic effects, 3 had adverse gastrointestinal effects, 6 had adverse effects at the radiation site and 7 developed infections at the carboplatin infusion site. No statistically significant differences were identified in survival times based on sex, tumour location, development of infection, or pretreatment serum alkaline phosphatase. Median survival time and incidence of adverse effects were comparable to those previously reported in dogs undergoing palliative radiation therapy with megavoltage or cobalt radiation sources and conventional intravenous carboplatin chemotherapy. The use of orthovoltage palliative radiation therapy may be a reasonable alternative to megavoltage radiation in locations where access is limited.

Keywords: radiotherapy, veterinary oncology, chemotherapy, osteosarcoma

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1100 Associations between Surrogate Insulin Resistance Indices and the Risk of Metabolic Syndrome in Children

Authors: Mustafa M. Donma, Orkide Donma

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A well-defined insulin resistance (IR) is one of the requirements for the good understanding and evaluation of metabolic syndrome (MetS). However, underlying causes for the development of IR are not clear. Endothelial dysfunction also participates in the pathogenesis of this disease. IR indices are being determined in various obesity groups and also in diagnosing MetS. Components of MetS have been well established and used in adult studies. However, there are some ambiguities particularly in the field of pediatrics. The aims of this study were to compare the performance of fasting blood glucose (FBG), one of MetS components, with some other IR indices and check whether FBG may be replaced by some other parameter or ratio for a better evaluation of pediatric MetS. Five-hundred and forty-nine children were involved in the study. Five groups were constituted. Groups 109, 40, 100, 166, 110, 24 children were included in normal-body mass index (N-BMI), overweight (OW), obese (OB), morbid obese (MO), MetS with two components (MetS2) and MetS with three components (MetS3) groups, respectively. Age and sex-adjusted BMI percentiles tabulated by World Health Organization were used for the classification of obesity groups. MetS components were determined. Aside from one of the MetS components-FBG, eight measures of IR [homeostatic model assessment of IR (HOMA-IR), homeostatic model assessment of beta cell function (HOMA-%β), alanine transaminase-to-aspartate transaminase ratio (ALT/AST), alanine transaminase (ALT), insulin (INS), insulin-to-FBG ratio (INS/FBG), the product of fasting triglyceride and glucose (TyG) index, McAuley index] were evaluated. Statistical analyses were performed. A p value less than 0.05 was accepted as the statistically significance degree. Mean values for BMI of the groups were 15.7 kg/m2, 21.0 kg/m2, 24.7 kg/m2, 27.1 kg/m2, 28.7 kg/m2, 30.4 kg/m2 for N-BMI, OW, OB, MO, MetS2, MetS3, respectively. Differences between the groups were significant (p < 0.001). The only exception was MetS2-MetS3 couple, in spite of an increase detected in MetS3 group. Waist-to-hip circumference ratios significantly differed only for N-BMI vs, OB, MO, MetS2; OW vs MO; OB vs MO, MetS2 couples. ALT and ALT/AST did not differ significantly among MO-MetS2-MetS3. HOMA-%β differed only between MO and MetS2. INS/FBG, McAuley index and TyG were not significant between MetS2 and MetS3. HOMA-IR and FBG were not significant between MO and MetS2. INS was the only parameter, which showed statistically significant differences between MO-MetS2, MO-MetS3, and MetS2-MetS3. In conclusion, these findings have suggested that FBG presently considered as one of the five MetS components, may be replaced by INS during the evaluation of pediatric morbid obesity and MetS.

Keywords: children, insulin resistance indices, metabolic syndrome, obesity

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1099 Mutational Analysis of DNase I Gene in Diabetic Patients

Authors: Hateem Zafar Kayani, Nageen Hussain

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The main aim is to analyze the mutations of DNASE I gene in diabetic patients. A total of 120 diabetes patients and 120 controls were sampled. The total number of male diabetic patients included in the study was 79 (66%) while female patients were 41 (34%) in number. Exon 8 of the DNASE I gene was amplified by using thermo cycler. The possible band of interest was located at 165 base pairs. Two samples showed similar missense mutations at 127th position of exon 8 which replaced amino acid Arginine (Arg) to Glutamine (Gln). All controls showed no mutations. The association of diabetes with different levels of blood pressure and body mass index (BMI) were found to be significant.

Keywords: deoxyribonuclease I, polymerase chain reaction, insulin-dependent diabetes mellitus, non-insulin dependent diabetes mellitus

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1098 A Comparative Study on the Hypoglycemic Effects of Hydroalcoholic Extracts from Silybum marianum, Camellia sinensis (Green Tea), and Urtica dioica Plants in Diabetic Rats

Authors: Sogand Moshfeghi, Alireza Biglari

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Diabetes is an endocrine disorder that is commonly treated with insulin. However, long-term usage of insulin and hypoglycemic chemical drugs can result in various side effects. Therefore, it is crucial to explore effective compounds with minimal side effects for diabetes treatment. This study aimed to compare the hypoglycemic effects of hydroalcoholic extracts derived from Silybum marianum, Camellia sinensis (green tea), and Urtica dioica plants. Male Wistar rats were allocated to 5 groups. Group 1 received normal Salin. Other groups were diabetic (induced by Streptozotocin 65 mg/kg Ip), group 2 received normal Salin (Ip, qod. 21 days). Group 3 received Silybum Marianum L, hydroalcoholic extract (100 mg/kg, ip.qod, 21 days). Group 4 received Camellia sinesis L, hydroalcoholic extract (100mg/kg,ip,qod,21 days), and group 5 received Urtica dioica L. hydroalcoholic extract (100mg/kg, ip,qod,21 days). Blood samples were collected at 14 and 21 days after the initial injection to evaluate the blood glucose levels. On the fourteenth day, the blood glucose levels for the diabetic groups were as follows: Group 2: 424.7±34.5, Group 3: 390.7±10.5, Group 4: 350.4±16.9, and Group 5: 340±20.5. On the 21st day, the respective blood glucose levels were: Group 2: 432±5.0, Group 3: 410.16±5.0, Group 4: 264.3±17.5, and Group 5: 270.7±24.5. Statistical analysis using the Tukey Anova test indicated that on the fourteenth day, both the green tea and Urtica groups exhibited significant hypoglycemic effects. Furthermore, on the 21st day, Urtica dioica extract demonstrated comparable effects to Camellia Sinensis extract, while Silybum Marianum extract did not significantly lower blood glucose levels compared to the diabetic group. In conclusion, the hydroalcoholic extracts from Camellia sinensis and Urtica dioica plants exhibited promising hypoglycemic effects in diabetic rats. These findings provide valuable insights into the potential use of natural plant extracts as alternative or complementary treatments for diabetes, warranting further investigation to harness their therapeutic benefit effectively.

Keywords: Camellia sinesis, glucose, Silybum marianum, Urtica dioica

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1097 Modelling Optimal Control of Diabetes in the Workplace

Authors: Eunice Christabel Chukwu

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Introduction: Diabetes is a chronic medical condition which is characterized by high levels of glucose in the blood and urine; it is usually diagnosed by means of a glucose tolerance test (GTT). Diabetes can cause a range of health problems if left unmanaged, as it can lead to serious complications. It is essential to manage the condition effectively, particularly in the workplace where the impact on work productivity can be significant. This paper discusses the modelling of optimal control of diabetes in the workplace using a control theory approach. Background: Diabetes mellitus is a condition caused by too much glucose in the blood. Insulin, a hormone produced by the pancreas, controls the blood sugar level by regulating the production and storage of glucose. In diabetes, there may be a decrease in the body’s ability to respond to insulin or a decrease in insulin produced by the pancreas which will lead to abnormalities in the metabolism of carbohydrates, proteins, and fats. In addition to the health implications, the condition can also have a significant impact on work productivity, as employees with uncontrolled diabetes are at risk of absenteeism, reduced performance, and increased healthcare costs. While several interventions are available to manage diabetes, the most effective approach is to control blood glucose levels through a combination of lifestyle modifications and medication. Methodology: The control theory approach involves modelling the dynamics of the system and designing a controller that can regulate the system to achieve optimal performance. In the case of diabetes, the system dynamics can be modelled using a mathematical model that describes the relationship between insulin, glucose, and other variables. The controller can then be designed to regulate the glucose levels to maintain them within a healthy range. Results: The modelling of optimal control of diabetes in the workplace using a control theory approach has shown promising results. The model has been able to predict the optimal dose of insulin required to maintain glucose levels within a healthy range, taking into account the individual’s lifestyle, medication regimen, and other relevant factors. The approach has also been used to design interventions that can improve diabetes management in the workplace, such as regular glucose monitoring and education programs. Conclusion: The modelling of optimal control of diabetes in the workplace using a control theory approach has significant potential to improve diabetes management and work productivity. By using a mathematical model and a controller to regulate glucose levels, the approach can help individuals with diabetes to achieve optimal health outcomes while minimizing the impact of the condition on their work performance. Further research is needed to validate the model and develop interventions that can be implemented in the workplace.

Keywords: mathematical model, blood, insulin, pancreas, model, glucose

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1096 Study on Inverse Solution from Remote Displacements to Reservoir Process during Flow Injection

Authors: Sumei Cai, Hong Li

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Either during water or gas injection into reservoir, in order to understand the areal flow pressure distribution underground, associated bounding deformation is prevalently monitored by ground or downhole tiltmeters. In this paper, an inverse solution to elastic response of far field displacements induced by reservoir pressure change due to flow injection was studied. Furthermore, the fundamental theory on inverse solution to elastic problem as well as its spatial smoothing approach is presented. Taking advantage of source code development based on Boundary Element Method, numerical analysis on the monitoring data of ground surface displacements to further understand the behavior of reservoir process was developed. Numerical examples were also conducted to verify the effectiveness.

Keywords: remote displacement, inverse problem, boundary element method, BEM, reservoir process

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1095 Study of the Late Phase of Core Degradation during Reflooding by Safety Injection System for VVER1000 with ASTECv2 Computer Code

Authors: Antoaneta Stefanova, Rositsa Gencheva, Pavlin Groudev

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This paper presents the modeling approach in SBO sequence for VVER 1000 reactors and describes the reactor core behavior at late in-vessel phase in case of late reflooding by HPIS and gives preliminary results for the ASTECv2 validation. The work is focused on investigation of plant behavior during total loss of power and the operator actions. The main goal of these analyses is to assess the phenomena arising during the Station blackout (SBO) followed by primary side high pressure injection system (HPIS) reflooding of already damaged reactor core at very late ‘in-vessel’ phase. The purpose of the analysis is to define how the later HPIS switching on can delay the time of vessel failure or possibly avoid vessel failure. For this purpose has been simulated an SBO scenario with injection of cold water by a high pressure pump (HPP) in cold leg at different stages of core degradation. The times for HPP injection were chosen based on previously performed investigations.

Keywords: VVER, operator action validation, reflooding of overheated reactor core, ASTEC computer code

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1094 Gas Injection Transport Mechanism for Shale Oil Recovery

Authors: Chinedu Ejike

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The United States is now energy self-sufficient due to the production of shale oil reserves. With more than half of it being tapped daily in the United States, these unconventional reserves are massive and provide immense potential for future energy demands. Drilling horizontal wells and fracking are the primary methods for developing these reserves. Regrettably, recovery efficiency is rarely greater than 10%. As a result, optimizing recuperation offers a significant benefit. Huff and puff gas flooding and cyclic gas injection have all been demonstrated to be more successful than tapping the remaining oil in place. Methane, nitrogen, and carbon (IV) oxide, among other high-pressure gases, can be injected. Operators use Darcy's law to assess a reservoir's productive capacity, but they are unaware that the law may not apply to shale oil reserves. This is due to the fact that, unlike pressure differences alone, diffusion, concentration, and gas selection all play a role in the flow of gas injected into the wellbore. The reservoir drainage and oil sweep efficiency rates are determined by the transport method. This research assesses the parameters that influence the gas injection transport mechanism. Understanding the process causing these factors could accelerate recovery by two to three times, according to peer-reviewed studies and effective field testing.

Keywords: enhanced oil recovery, gas injection, shale oil, transport mechanism, unconventional reserve

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1093 Women’s Perceptions of DMPA-SC Self-Injection in Malawi

Authors: Mandayachepa C. Nyando, Lauren Suchman, Innocencia Mtalimanja, Address Malata, Tamanda Jumbe, Martha Kamanga, Peter Waiswa

Abstract:

Background: Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is a new innovation in contraceptive methods that allow users to inject themselves with a hormonal contraceptive in their own homes. Self-injection (SI) of DMPA-SC has the potential to improve the accessibility of family planning to women who want it and who are capable of injecting themselves. Malawi started implementing this new innovation in 2018. SI was incorporated into the DMPA-SC delivery strategy from its outset. Methodology: This study involved two districts in Malawi where DMPA-SC SI was rolled out: Mulanje and Ntchisi. We used a qualitative cross-sectional study design where 60 in-depth interviews were conducted with women of reproductive age group stratified as 15-45 age band. These included women who were SI users, non-users, and any woman who was on any contraceptive methods. The women participants were tape-recorded, and data were transcribed and then analysed using Dedoose software, where themes were categorised into mother and child themes. Results: Women perceived DMPA SC SI as uniquely private, convenient, and less painful when self-injected. In terms of privacy, women in Mulanje and Ntchisi especially appreciated that self-injecting allowed them to use covertly from partners. Some men do not allow their spouses to use modern contraceptive methods; hence women prefer to use them covertly. “… but I first reach out to men because the strongest power is answered by men (MJ015).” In addition, women reported that SI offers privacy from family/community and less contact with healthcare providers. These aspects of privacy were especially valued in areas where there is a high degree of mistrust around family planning and among those who feel judged or antagonized purchasing contraception, such as young unmarried women. Women also valued the convenience SI provided in terms of their ability to save time by injecting themselves at home rather than visiting a healthcare provider and having more reliable access to contraception, particularly in the face of stockouts. SI allows for stocking up on doses to accommodate shifting work schedules in case of future stockouts or hard times, such as the period of COVID-19, where there was a limitation in the movement of the people. Conclusion: Our findings suggest that SI may meet the needs of many women in Malawi as long as the barriers are eliminated. The barriers women mentioned include fear of self-inject and proper storage of the DMPA SC SI, and these barriers can be eliminated by proper training. The findings also set the scene for policy revision and direction at a national level and integrate the approach with national family planning strategies in Malawi. Findings provide insights that may guide future implementation strategies, strengthen non-clinic family planning access programs and stimulate continued research.

Keywords: family planning, Malawi, Sayana press, self-injection

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1092 Gas Lift Optimization Using Smart Gas Lift Valve

Authors: Mohamed A. G. H. Abdalsadig, Amir Nourian, G. G. Nasr, M. Babaie

Abstract:

Gas lift is one of the most common forms of artificial lift, particularly for offshore wells because of its relative down hole simplicity, flexibility, reliability, and ability to operate over a large range of rates and occupy very little space at the well head. Presently, petroleum industry is investing in exploration and development fields in offshore locations where oil and gas wells are being drilled thousands of feet below the ocean in high pressure and temperature conditions. Therefore, gas-lifted oil wells are capable of failure through gas lift valves which are considered as the heart of the gas lift system for controlling the amount of the gas inside the tubing string. The gas injection rate through gas lift valve must be controlled to be sufficient to obtain and maintain critical flow, also, gas lift valves must be designed not only to allow gas passage through it and prevent oil passage, but also for gas injection into wells to be started and stopped when needed. In this paper, smart gas lift valve has been used to investigate the effect of the valve port size, depth of injection and vertical lift performance on well productivity; all these aspects have been investigated using PROSPER simulator program coupled with experimental data. The results show that by using smart gas lift valve, the gas injection rate can be controlled which leads to improved flow performance.

Keywords: Effect of gas lift valve port size, effect water cut, vertical flow performance

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1091 Numerical Analysis of CO₂ Storage as Clathrates in Depleted Natural Gas Hydrate Formation

Authors: Sheraz Ahmad, Li Yiming, Li XiangFang, Xia Wei, Zeen Chen

Abstract:

Holding CO₂ at massive scale in the enclathrated solid matter called hydrate can be perceived as one of the most reliable methods for CO₂ sequestration to take greenhouse gases emission control measures and global warming preventive actions. In this study, a dynamically coupled mass and heat transfer mathematical model is developed which elaborates the unsteady behavior of CO₂ flowing into a porous medium and converting itself into hydrates. The combined numerical model solution by implicit finite difference method is explained and through coupling the mass, momentum and heat conservation relations, an integrated model can be established to analyze the CO₂ hydrate growth within P-T equilibrium conditions. CO₂ phase transition, effect of hydrate nucleation by exothermic heat release and variations of thermo-physical properties has been studied during hydrate nucleation. The results illustrate that formation pressure distribution becomes stable at the early stage of hydrate nucleation process and always remains stable afterward, but formation temperature is unable to keep stable and varies during CO₂ injection and hydrate nucleation process. Initially, the temperature drops due to cold high-pressure CO₂ injection since when the massive hydrate growth triggers and temperature increases under the influence of exothermic heat evolution. Intermittently, it surpasses the initial formation temperature before CO₂ injection initiates. The hydrate growth rate increases by increasing injection pressure in the long formation and it also expands overall hydrate covered length in the same induction period. The results also show that the injection pressure conditions and hydrate growth rate affect other parameters like CO₂ velocity, CO₂ permeability, CO₂ density, CO₂ and H₂O saturation inside the porous medium. In order to enhance the hydrate growth rate and expand hydrate covered length, the injection temperature is reduced, but it did not give satisfactory outcomes. Hence, CO₂ injection in vacated natural gas hydrate porous sediment may form hydrate under low temperature and high-pressure conditions, but it seems very challenging on a huge scale in lengthy formations.

Keywords: CO₂ hydrates, CO₂ injection, CO₂ Phase transition, CO₂ sequestration

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1090 Application of Mesenchymal Stem Cells in Diabetic Therapy

Authors: K. J. Keerthi, Vasundhara Kamineni, A. Ravi Shanker, T. Rammurthy, A. Vijaya Lakshmi, Q. Hasan

Abstract:

Pancreatic β-cells are the predominant insulin-producing cell types within the Islets of Langerhans and insulin is the primary hormone which regulates carbohydrate and fat metabolism. Apoptosis of β-cells or insufficient insulin production leads to Diabetes Mellitus (DM). Current therapy for diabetes includes either medical management or insulin replacement and regular monitoring. Replacement of β- cells is an attractive treatment option for both Type-1 and Type-2 DM in view of the recent paper which indicates that β-cells apoptosis is the common underlying cause for both the Types of DM. With the development of Edmonton protocol, pancreatic β-cells allo-transplantation became possible, but this is still not considered as standard of care due to subsequent requirement of lifelong immunosuppression and the scarcity of suitable healthy organs to retrieve pancreatic β-cell. Fetal pancreatic cells from abortuses were developed as a possible therapeutic option for Diabetes, however, this posed several ethical issues. Hence, in the present study Mesenchymal stem cells (MSCs) were differentiated into insulin producing cells which were isolated from Human Umbilical cord (HUC) tissue. MSCs have already made their mark in the growing field of regenerative medicine, and their therapeutic worth has already been validated for a number of conditions. HUC samples were collected with prior informed consent as approved by the Institutional ethical committee. HUC (n=26) were processed using a combination of both mechanical and enzymatic (collagenase-II, 100 U/ml, Gibco ) methods to obtain MSCs which were cultured in-vitro in L-DMEM (Low glucose Dulbecco's Modified Eagle's Medium, Sigma, 4.5 mM glucose/L), 10% FBS in 5% CO2 incubator at 37°C. After reaching 80-90% confluency, MSCs were characterized with Flowcytometry and Immunocytochemistry for specific cell surface antigens. Cells expressed CD90+, CD73+, CD105+, CD34-, CD45-, HLA-DR-/Low and Vimentin+. These cells were differentiated to β-cells by using H-DMEM (High glucose Dulbecco's Modified Eagle's Medium,25 mM glucose/L, Gibco), β-Mercaptoethanol (0.1mM, Hi-Media), basic Fibroblast growth factor (10 µg /L,Gibco), and Nicotinamide (10 mmol/L, Hi-Media). Pancreatic β-cells were confirmed by positive Dithizone staining and were found to be functionally active as they released 8 IU/ml insulin on glucose stimulation. Isolating MSCs from usually discarded, abundantly available HUC tissue, expanding and differentiating to β-cells may be the most feasible cell therapy option for the millions of people suffering from DM globally.

Keywords: diabetes mellitus, human umbilical cord, mesenchymal stem cells, differentiation

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1089 Effect of Thermal Radiation on Flow, Heat, and Mass Transfer of a Nanofluid over a Stretching Horizontal Cylinder Embedded in a Porous Medium with Suction/Injection

Authors: Elsayed M. A. Elbashbeshy, T. G. Emam, M. S. El-Azab, K. M. Abdelgaber

Abstract:

The effect of thermal radiation on flow, heat and mass transfer of an incompressible viscous nanofluid over a stretching horizontal cylinder embedded in a porous medium with suction/injection is discussed numerically. The governing boundary layer equations are reduced to a system of ordinary differential equations. Mathematica has been used to solve such system after obtaining the missed initial conditions. Comparison of obtained numerical results is made with previously published results in some special cases, and found to be in a good agreement.

Keywords: laminar flow, boundary layer, stretching horizontal cylinder, thermal radiation, suction/injection, nanofluid

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1088 A Time since of Injection Model for Hepatitis C Amongst People Who Inject Drugs

Authors: Nader Al-Rashidi, David Greenhalgh

Abstract:

Mathematical modelling techniques are now being used by health organizations worldwide to help understand the likely impact that intervention strategies treatment options and combinations of these have on the prevalence and incidence of hepatitis C virus (HCV) in the people who inject drugs (PWID) population. In this poster, we develop a deterministic, compartmental mathematical model to approximate the spread of the HCV in a PWID population that has been divided into two groups by time since onset of injection. The model assumes that after injection needles adopt the most infectious state of their previous state or that of the PWID who last injected with them. Using analytical techniques, we find that the model behaviour is determined by the basic reproductive number R₀, where R₀ = 1 is a critical threshold separating two different outcomes. The disease-free equilibrium is globally stable if R₀ ≤ 1 and unstable if R₀ > 1. Additionally, we make some simulations where have confirmed that the model tends to this endemic equilibrium value with realistic parameter values giving an HCV prevalence.

Keywords: hepatitis C, people who inject drugs, HCV, PWID

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1087 Comparing the Efficacy of Minimally Supervised Home-Based and Closely Supervised Gym Based Exercise Programs on Weight Reduction and Insulin Resistance after Bariatric Surgery

Authors: Haleh Dadgostar, Sara Kaviani, Hanieh Adib, Ali Mazaherinezhad, Masoud Solaymani-Dodaran, Fahimeh Soheilipour, Abdolreza Pazouki

Abstract:

Background and Objectives: Effectiveness of various exercise protocols in weight reduction after bariatric surgery has not been sufficiently explored in the literature. We compared the effect of minimally supervised home-based and closely supervised Gym based exercise programs on weight reduction and insulin resistance after bariatric surgery. Methods: Women undergoing gastric bypass surgery were invited to participate in an exercise program and were randomly allocated into two groups. They were either offered a minimally supervised home-based (MSHB) or closely supervised Gym-based (CSGB) exercise program. The CSGB protocol constitute two sessions per week of training under ACSM guidelines. In the MSHB protocol participants received a notebook containing a list of recommended aerobic and resistance exercises, a log to record their activity and a schedule of follow up phone calls and clinic visits. Both groups received a pedometer. We measured their weight, BMI, lipid profile, FBS, and insulin level at the baseline and after 20 weeks of exercise and were compared at the end of the study. Results: A total of 80 patients completed our study (MSHB=38 and CSGB=42). The baseline comparison showed that the two groups are similar. Using the ANCOVA method of analysis the mean change in BMI (covariate: BMI at the beginning of the study) was slightly better in CSGB compared with the MSHB (between-group mean difference: 3.33 (95%CI 4.718 to 1.943, F: 22.844 p < 0.001)). Conclusion: Our results showed that both MSHB and CSGB exercise methods are somewhat equally effective in improvement of studied factors in the two groups. With considerably lower costs of Minimally Supervised Home Based exercise programs, these methods should be considered when adequate funding are not available.

Keywords: postoperative exercise, insulin resistance, bariatric surgery, morbid obesity

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1086 Xiaflex (Collagenase) Impact on the Management of Dupuytren's Disease: Making the Case for Treatment in a Public Healthcare System

Authors: Anthony Barker, Roland Jiang

Abstract:

Dupuytren’s contractures are a debilitating condition affecting the palmar fascia of the hand reducing its function. This case series looks at the minimally-invasive technique of Xiaflex injections and the outcome in a public health setting. 15 patients undertook collagenase injection (Xiaflex, C. histolyticum) injection over the period from September 2015 to May 2017 at Fairfield Hospital, NSW. Their reported outcome post injection and in follow-up was recorded as well as their satisfaction and likelihood to request the procedure in the future. Other treatment modalities include percutaneous needle aponeurotomy, limited palmar fasciotomy, and palmar fasciectomy. A literature review of cost-effectiveness was performed to compare Xiaflex suitability for waitlist reduction in a public setting given average waiting times in the public setting extend past 365 days.

Keywords: Dupuytrens Disease, xiaflex, collagenase, plastic surgery

Procedia PDF Downloads 187
1085 Specific Biomarker Level and Function Outcome Changes in Treatment of Patients with Frozen Shoulder Using Dextrose Prolotherapy Injection

Authors: Nuralam Sam, Irawan Yusuf, Irfan Idris, Endi Adnan

Abstract:

The most case in the shoulder in the the adult is the frozen shoulder. It make an uncomfortable sensation which disturbance daily activity. The studies of frozen shoulder are still limited. This study used a true experimental pre and post test design with a group design. The participant underwent dextrose prolotherapy injection in the rotator cuff, intraarticular glenohumeral joint, long head tendon biceps, and acromioclavicular joint injections with 15% dextrose, respectively, at week 2, week 4, and week 6. Participants were followed for 12 weeks. The specific biomarker MMP and TIMP, ROM, DASH score were measured at baseline, at week 6, and week 12. The data were analyzed by multivariate analysis (repeated measurement ANOVA, Paired T-Test, and Wilcoxon) to determine the effect of the intervention. The result showed a significant decrease in The Disability of the Arm, Shoulder, and Hand (DASH) score in prolo injection patients in each measurement week (p < 0.05). While the measurement of Range of Motion (ROM), each direction of shoulder motion showed a significant difference in average each week, from week 0 to week 6 (p <0.05).Dextrose prolotherapy injection results give a significant improvement in functional outcome of the shoulder joint, and ROMand did not show significant results in assessing the specific biomarker, MMP-1, and TIMP-1 in tissue repair. This study suggestion an alternative to the use of injection prolotherapy in Frozen shoulder patients, which has fewer side effects and better effectiveness than the use of corticosteroid injections.

Keywords: frozen shoulder, ROM, DASH score, prolotherapy, MMP-1, TIMP-1

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1084 Botulinum Toxin type A for Lower Limb Lengthening and Deformity Correction: A Systematic Review and Meta-analysis

Authors: Jawaher F. Alsharef, Abdullah A. Ghaddaf, Mohammed S. Alomari, Abdullah A. Al Qurashi, Ahmed S. Abdulhamid, Mohammed S. Alshehri, Majed Alosaimi

Abstract:

Botulinum toxin type A (BTX-A) is the most popular therapeutic agent for muscle relaxation and pain control. Lately, BTX-A injection received great interest as a part of multimodal pain management for lower limb lengthening and deformity correction. This systematic review aimed to determine the role of BTX-A injection in pain management for during lower limb lengthening and/or deformity correction. We searched Medline, Embase, and CENTRAL. We included randomized controlled trials (RCTs) that compared the BTX-A injection to placebo for individuals undergoing lower limb lengthening and/or deformity correction. We sought to evaluate the following outcomes: pain on visual analogue scale (VAS), range of motion parameters, average opioid consumption, and adverse events. The standardized mean difference (SMD) was used to represent continuous outcomes while risk ratio (RR) was used to represent dichotomous outcomes. A total of 4 RCTs that enrolled 257 participants (337 limbs) deemed eligible. Adjuvant BTX-A injection showed a significant reduction in post-operative pain compared to placebo (SMD=–0.28, 95% CI –0.53 to –0.04). No difference was found between BTX-A injection and placebo in terms of range of motion parameters, average opioid consumption, or adverse events after surgical limb lengthening and/or deformity correction (RR= 0.77, 95% CI –0.58 to 1.03). Conclusions: Adjuvant BTX-A injection conferred a discernible reduction in post-operative pain during surgical limb lengthening and/or deformity without increasing the risk of adverse events.

Keywords: botulinum toxin type A, limb lengthening, distraction osteogenesis, deformity correction, pain management

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1083 Mechanism of in Vitro Inhibition of Alpha-Amylase, Alpha-Glucosidase by Ethanolic Extracts of Polyalthia Longifolia, Its in Vitro Cytotoxicity on L6, Vero Cell-Lines and Influence of Glucose Uptake by Rat Hemi-Diaphragm

Authors: P. Gayathri, G. P. Jeyanthi

Abstract:

The bark of Polyalthia longifolia is used in ayurvedic system of medicine for the manangement of various ailments including diabetes mellitus. The bark of P. longifolia extracts was extracted using various polar and non-polar solvents and tested for inhibition of alpha-amylase and alpha-glucosidase among which the ethanolic extracts were found to be more potent. The ethanolic extracts of the bark were tested for the in vitro inhibition of alpha-amylase using starch as substrate and alpha-glucosidase using p-nitro phenyl alpha-D-gluco pyranoside as substrate to establish its in vitro antidiabetic effect. The mechanism of inhibition was determined by Dixon plot and Cornish-Bowden plot. The cytotoxic effect of the extract was tested on L6 and Vero cell-lines. The extract was partially purified by TLC. The individual effect of the ethanolic extract, TLC fractions and its combinatorial effect with insulin and glibenclamide on glucose uptake by rat hemi-diaphragm were studied.Results revealed that the ethanolic extracts of Polyalthia longifolia bark exhibited competitive inhibition of alpha-amylase and alpha-glucosidase. The extracts were also found not to be cytotoxic at the highest dose of 1 mg/mL. Glucose uptake study revealed that the extract alone and when combined with insulin, decreased the glucose uptake when compared to insulin control, however the purified TLC fractions exhibited significantly higher (p<0.05) glucose uptake by the rat hemi-diaphragm when compared to insulin. The study shows various possible mechanism of in vitro antidiabetic effect of the P. longifolia bark.

Keywords: alpha-amylase, alpha-glucosidase, dixon, cornish-bowden, L6 , Vero cell-lines, glucose uptake, polyalthia longifolia bark, ethanolic extract, TLC fractions

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1082 Pressure Drop Study in Moving and Stationary Beds with Lateral Gas Injection

Authors: Vinci Mojamdar, Govind S. Gupta

Abstract:

Moving beds in the presence of gas flow are widely used in metallurgical and chemical industries like blast furnaces, catalyst reforming, drying, etc. Pressure drop studies in co- and counter – current conditions have been done by a few researchers. However, to the best of authours knowledge, proper pressure drop study with lateral gas injection lacks especially in the presence of cavity and nozzle protrusion inside the packed bed. The latter study is more useful for metallurgical industries for the processes such as blast furnaces, shaft reduction and, COREX. In this experimental work, a two dimensional cold model with slot type nozzle for lateral gas injection along with the plastic beads as packing material and dry air as gas have been used. The variation of pressure drop is recorded at various horizontal and vertical directions in the presence of cavity and nozzle protrusion. The study has been performed in both moving and stationary beds. Also, the experiments have been carried out in both increasing as well as decreasing gas flow conditions. Experiments have been performed at various gas flow rates and packed bed heights. Some interesting results have been reported such as there is no pressure variation in the moving bed for both the increasing and decreasing gas flow condition that is different from the stationary bed. Pressure hysteresis loop has been observed in a stationary bed.

Keywords: lateral gas injection, moving bed, pressure drop, pressure hysteresis, stationary bed

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1081 The Beneficial Effects of Inhibition of Hepatic Adaptor Protein Phosphotyrosine Interacting with PH Domain and Leucine Zipper 2 on Glucose and Cholesterol Homeostasis

Authors: Xi Chen, King-Yip Cheng

Abstract:

Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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