Fasting State Research Articles

ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms

In brown adipose tissue (BAT), short-term cold exposure induces the activating transcription factor 4 (ATF4), and its downstream target fibroblast growth factor 21 (FGF21). Induction of ATF4 in BAT in response to mitochondrial stress is required for thermoregulation, partially by increasing FGF21 expression. In the present study, we tested the hypothesis that Atf4 and Fgf21 induction in BAT are both required for BAT thermogenesis under physiological stress by generating mice selectively lacking either Atf4 (ATF4 BKO) or Fgf21 (FGF21 BKO) in UCP1-expressing adipocytes. After 3 days of cold exposure, core body temperature was significantly reduced in ad-libitum-fed ATF4 BKO mice, which correlated with Fgf21 downregulation in brown and beige adipocytes, and impaired browning of white adipose tissue. Conversely, despite having reduced browning, FGF21 BKO mice had preserved core body temperature after cold exposure. Mechanistically, ATF4, but not FGF21, regulates amino acid import and metabolism in response to cold, likely contributing to BAT thermogenic capacity under ad libitum-fed conditions. Importantly, under fasting conditions, both ATF4 and FGF21 were required for thermogenesis in cold-exposed mice. Thus, ATF4 regulates BAT thermogenesis under fed conditions likely in a FGF21-independent manner, in part via increased amino acid uptake and metabolism.

Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes in sex-dependent and sex-independent manners.

Metformin has attracted increasing interest for its potential benefits in extending healthspan and longevity. This study examined the effects of early-life metformin treatment on the development and metabolism of C57BL/6J (B6) mice, with metformin administered to juvenile mice from 15 to 56days of age. Metformin treatment led to decreased body weight in both sexes (P < 0.05, t-test). At 9weeks of age, mice were euthanized and organ weights were recorded. The relative weight of retroperitoneal fat was decreased in females, while relative weights of perigonadal and retroperitoneal fat were decreased, and relative liver weight was increased in males (P < 0.05, t-test). Glucose and insulin tolerance tests (GTT and ITT) were conducted at the age of 7weeks. ANOVA revealed a significant impairment in insulin sensitivity by the treatment, and a significantly interactive effect on glucose tolerance between sex and treatment, underscoring a disparity in GTT between sexes in response to the treatment. Metformin treatment reduced circulating insulin levels in fasting and non-fasting conditions for male mice, with no significant alterations observed in female mice. qRT-PCR analysis of glucose metabolism-related genes (Akt2, Glut2, Glut4, Irs1, Nrip1, Pi3k, Pi3kca, Pkca) in the liver and skeletal muscle reveals metformin-induced sex- and organ-specific effects on gene expression. Comparison with previous studies in heterogeneous UM-HET3 mice receiving the same treatment suggests that genetic differences may contribute to variability in the effects of metformin treatment on development and metabolism. These findings indicate that early-life metformin treatment affects development and metabolism in both sex- and genetics-dependent manners.

Inhibition of resurgent Na+ currents by rufinamide

Na+ channels are essential for the genesis of action potentials in most neurons. After opening by membrane depolarization, Na+ channels enter a series of inactivated states (e.g. the fast, intermediate, and slow inactivated states; or If, Ii, and Is). The inactivated Na+ channel may recover via the open state upon membrane repolarization, giving rise to “resurgent” Na+ currents which could be critical for densely repetitive or burst discharges. We incubated CHO–K1 cells transfected with human NaV1.7 cDNA and measured resurgent currents with whole-cell patch recordings. We found Ii is the major inactivated state responsible for the genesis of resurgent currents. Rufinamide, in therapeutic concentrations, could selectively bind to Ii to slow the recovery process and dose-dependently inhibit resurgent currents. The other Na+ channel-inhibiting antiseizure medications (ASM), such as phenytoin and lacosamide (selectively binds to If and Is, separately), fail to show a similar inhibitory effect in clinically relevant concentrations. Resurgent currents are decreased with lengthening of the prepulse, presumably because of redistribution of the channel from Ii to If. Rufinamide could accentuate the decrease to mimic a use-dependent inhibitory effect. The molecular action of slowing of recovery from inactivation by binding to Ii also explains the highly correlative inhibitory effect of rufinamide on both transient and resurgent Na+ currents. The modest but correlative inhibition of both currents may make a novel synergistic effect and thus strong-enough suppression of pathological repetitive and especially burst discharges. Rufinamide may thus have a unique spectrum of therapeutic applications for disorders with excessive neural excitabilities.

Changes in Isoleucine, Sarcosine, and Dimethylglycine During OGTT as Risk Factors for Diabetes.

Current metabolomics studies in diabetes have focused on the fasting state, while only a few have addressed the satiated state. We combined the oral glucose tolerance test (OGTT) and metabolomics to examine metabolite-level changes in populations with different glucose tolerance statuses and to evaluate the potential risk of these changes for diabetes. We grouped participants into those with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and newly diagnosed type 2 diabetes (NDM). During the OGTT, serum was collected at 0, 30, 60, 120, and 180 minutes. We evaluated the changes in metabolite levels during the OGTT and compared metabolic profiles among the 3 groups. The relationship between metabolite levels during the OGTT and risk of diabetes and prediabetes was analyzed using a generalized estimating equation (GEE). The regression results were adjusted for sex, body mass index, fasting insulin levels, heart rate, smoking status, and blood pressure. Glucose intake altered metabolic profile and induced an increase in glycolytic intermediates and a decrease in amino acids, glycerol, ketone bodies, and triglycerides. Isoleucine levels differed between the NGT and NDM groups and between the NGT and IGR groups. Changes in sarcosine levels during the OGTT in the diabetes groups were opposite to those in glycine levels. GEE analysis revealed that during OGTT, isoleucine, sarcosine, and acetic acid levels were associated with NDM risks, and isoleucine and acetate levels with IGR risks. Metabolic profiles differ after glucose induction in individuals with different glucose tolerance statuses. Changes in metabolite levels during OGTT are potential risk factors for diabetes development.

Surface fluorinated graphite suppressing the lithium dendrite formation for fast chargeable lithium ion batteries

Developing lithium-ion batteries with high power and fast charging features has been highlighted as an essential research area to address growing energy demands for portable electronics and long-range electric vehicles. The commercial graphite anode has been recognized as a competent material owing to its benefits, including a long cycle life, high columbic efficiency, and low volume expansion. However, the intrinsic features of their intercalation kinetics render them highly susceptible to lithium deposition, resulting in poor cycle stability at fast charging conditions. In this study, we propose a simple thermal fluorine treatment of flake-type graphite to produce fluorine-doped-flake graphite. We observed the fluorine treatment improves the Li+ ion intercalation kinetics and reduces the lithium deposition and dendrite growth upon fast charging conditions. As a result, enhanced lithiation behavior was observed, with a high specific capacity of 348.3 mAh g−1 and a good rate capability of 66 % at 2C-rate in half-cell conditions. Furthermore, a full cell demonstrated outstanding cycle stability with 83.5 % capacity retention at 2C even after 950 cycles. Our findings emphasize that fluorine doping in graphite could be a straightforward and practical approach to mitigate Li deposition issues and enhance the fast charge kinetics of graphite-based commercial Li-ion batteries.

Low-cost MPPT for triple-junction solar cells used in nanosatellites: A comparative study between P&O and INC algorithms

This paper presents a study of solar panels composed of triple-junction solar cells used in CubeSats; in particular, it focuses on optimizing the power supplied by these panels using the maximum power point tracking technique (MPPT). Optimizing this power is a challenge that is not easily overcome, due to the constraints associated with CubeSats applications, especially in terms of weight, area, budget, as well as the low power generated by these panels which do not exceed 2.4 W at the maximum power point. For all these considerations, both P&O and INC techniques were chosen, since P&O is relatively easy to implement and does not require complex equipment, while INC is known for its high tracking accuracy in difficult environments under fast changing solar conditions, plus the low cost characterizing both techniques, which makes them suitable for CubeSats applications. To select the most appropriate technique for CubeSats applications, a comparative study between both P&O and INC algorithms is performed theoretically using a MATLAB/SIMULINK simulation, followed by a hardware implementation to transfer ideas from theory to practice for realizing the CubeSats power system electronic board since the present study is carried out in the context of a CubeSat application, it focuses on the nanosatellite power system, making it distinct compared to ordinary photovoltaic systems, which have been widely used and studied in previous research in the field of photovoltaics.

Maternal Serum Polyols and Its Link to Gestational Diabetes Mellitus: A Population-Based Nested Case-Control Study.

Sugar alcohols (also called polyols) are regarded as a "healthy" sugar substitute. One of the possible reasons for their safe use in pregnant women is their natural origin and the presence of polyols in maternal and fetal samples during normal human gestation. But little is known about the association between circulating sugar alcohols levels and maternal metabolic disorders during pregnancy. We aimed to detect the concentration of the polyols in participants with and without gestational diabetes mellitus (GDM), and to investigate the association between maternal serum levels of polyols and GDM, as well as newborn outcomes. A nested population-based case-control study was conducted in 109 women with and without GDM. Maternal concentrations of serum erythritol, sorbitol, and xylitol in the fasting state were quantified using a time of flight mass spectrometry system. In women with GDM, serum concentrations of erythritol and sorbitol were higher, but serum concentrations of xylitol were lower than those in women without GDM. Per 1-SD increment of Box-Cox-transformed concentrations of erythritol and sorbitol were associated with the increased odds of GDM by 43% and 155% (95% CI 1.07-1.92 and 95% CI 1.77-3.69), while decreased odds were found for xylitol by 25% (95% CI 0.57-1.00). Additionally, per 1-SD increase of Box-Cox-transformed concentrations of serum sorbitol was associated with a 52% increased odds of large for gestational age newborns controlling for possible confounders (95% CI 1.00-2.30). Maternal circulating sugar alcohols levels during pregnancy were significantly associated with GDM. These findings provide the potential roles of polyols on maternal metabolic health during pregnancy.

Examining the Effects of Communication Features of Educational Robots on Students’ Cognitive Load, Attitudes, and Learning Performance

Educational robots represent a unique form of teacher presence. Exploring how the communication features of robot instructors affect student learning experience could contribute to the advancement of educational robots. This study examined the impact of speech rate, voice type, and emotional tone of robots on students’ cognitive load, attitudes toward robot-assisted teaching, and learning performance. We recruited 477 Chinese primary school students assigned to either the speech rate, voice type, or emotional tone experiment. The results indicate that speech rate significantly influenced students’ cognitive load, with the medium speed condition resulting in higher germane load compared to both fast and slow speed conditions. Moreover, students had a lower preference for adult male voices over adult female, boy, or girl voices. However, voice type did not significantly impact attitudes toward robot-assisted teaching or learning outcomes. Emotional tone did not affect students’ cognitive load, attitudes, or learning performance. These findings provide valuable insights for instructors and designers when configuring the communication features of educational robots in classroom environments. Additionally, students generally prioritized the intelligence of the robot over its communication features, and they did not perceive the teaching content as difficult in all experiments. This study has methodological and practical significance.

The effect of background information and motion speed on the performance of TTC estimation

BackgroundIn previous studies, most research on motion perception have been conducted under background-free condition when the stimulus moved in a plane parallel to the observer. In real-life situations, people’s perception of the motion state of objects is usually done under different visual noise. Based on the occlusion paradigm, this study aimed to investigate whether different background information and motion speed affect the trend and accuracy of time-to-collision (TTC) estimation when stimuli move in a plane parallel to the observer.MethodsThirty five college students (mean age = 20.94, SD = 2.95, range = 18-28 years) participated in experiment 1, and used a 2 (background orientation: horizontal, vertical) × 3 (motion speed: slow, medium, fast) design to explore the effect of different line segment orientations and motion speed on TTC estimation performance; 36 college students (mean age = 20.81, SD = 2.82, range = 18-28 years) participated in experiment 2, and used a 2 (background dimension: two-dimensional background, three-dimensional background) × 3 (motion speed: slow, medium, fast) design to explore the effect of different background dimensions and motion speed on the performance of TTC estimation. The data were analyzed using SPSS 25.0.ResultsThe results revealed that: (1) The TTC was underestimated for the slow speed condition and overestimated for the medium and fast speed conditions. (2) The highest accuracy of TTC estimation was obtained for the fast condition. (3) The TTC were overestimated for the vertical background condition and underestimated for the horizontal background condition. (4) Compared to the two-dimensional background, the TTC was overestimated in the three-dimensional background.ConclusionsObject motion speed affected the TTC estimation performance, and different background information affected the TTC estimation performance when the object moved in a plane parallel to the observer. Meanwhile, the impact of background orientation and motion speed showed significant interactions.

Low-Temperature Molten Salt Electrochemical CO2 Upcycling for Advanced Energy Materials.

One strategy for addressing the climate crisis caused by CO2 emissions is to efficiently convert CO2 to advanced materials suited for green and clean energy technology applications. Porous carbon is widely used as an advanced energy storage material because of its enhanced energy storage capabilities as an anode. Herein, we report electrochemical CO2 upcycling to solid carbon with a controlled microstructure and porosity in a ternary molten carbonate melt at 450 °C. Controlling the electrochemical parameters (voltage, temperature, cathode material) enabled the conversion of CO2 to porous carbon with a tunable morphology and porosity for the first time at such a low temperature. Additionally, a well-controlled morphology and porosity are beneficial for reversible energy storage. In fact, these carbon materials delivered high specific capacity, stable cycling performances, and exceptional rate capability even under extremely fast charging conditions when integrated as an anode in lithium-ion batteries (LIBs). The present approach not only demonstrated efficient upcycling of CO2 into porous carbon suitable for enhanced energy storage but can also contribute to a clean and green energy technology that can reduce carbon emissions to achieve sustainable energy goals.

Pharmacokinetics and Bioequivalence of Apremilast Tablets in Chinese Healthy Subjects Under Fasting and Postprandial States.

This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application. A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (Cmax), the areas under the plasma concentration-time curve (AUC0-t, AUC0-∞), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated. Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09-103.44% for Cmax, 94.05-103.51% for AUC0-t, and 94.56-103.86% for AUC0-∞ under fasting conditions, and 99.18-112.48% for Cmax, 98.79-106.02% for AUC0-t, and 98.95-105.89% for AUC0-∞ under postprandial conditions, all of which were within the bioequivalence range of 80.00-125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study. The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated. chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).

Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry.

Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the migratory motor complex. It is understudied at least in part due to the lack of commercially available immunoassays. A multiplexed liquid chromatography mass spectrometry (LC-MS/MS) method was optimised to measure motilin, insulin, C-peptide, GIP (1-42) and GIP (3-42). Corresponding active ghrelin concentrations were determined by immunoassay. Ten healthy volunteers with no prior history of gastroenterological or endocrine condition attended after overnight fast and had blood samples taken every 15 minutes for 4 hours whilst continuing to fast, and then further sampling for 2 hours following a liquid mixed meal. Hunger scores were taken at each time point using a visual analogue scale. Normal bowel habit was confirmed by 1 week stool diary. Motilin levels fluctuated in the fasting state with an average period between peaks of 109.5 mins (SD:30.0), but with no evidence of a relationship with either ghrelin levels or hunger scores. The mixed meal interrupted cyclical motilin fluctuations, increased concentrations of motilin, insulin, C-peptide, GIP(1-42) and GIP(3-42), and suppressed ghrelin levels. This study highlights the utility of LC-MS/MS for parallel measurement of motilin alongside other peptide hormones, and supports previous reports of the cyclical nature of motilin levels in the fasting state and interruption with feeding. This analytical method has utility for further clinical studies into motilin and gut hormone physiology in human volunteers.

Corrosion Resistance, Composition, and Stratification of Passive Films: Ni-22Cr and Ni-22Cr-6Mo Alloys Passivated and Exposure Aged in Acidic Chloride Solutions

Ni-Cr based super-alloys have exceptional corrosion resistance, which is further improved with Mo alloying. The correlation between passive layer performance and composition was studied to gain a deeper mechanistic understanding of the role of Mo by comparing the behavior of Ni-22Cr to Ni-22Cr-6Mo (wt%) alloys. The passive layers were formed using galvanostatic holds to create fast and slow growth conditions using high and low current densities. A potentiostatic hold was added to initiate exposure aging. The passive film was characterized using electrochemical impedance spectroscopy (EIS), linear sweep voltammetry (LSV), atomic emission spectro-electrochemistry (AESEC), and X-ray photoelectron spectroscopy (XPS). Combined electrochemical and XPS characterization offered insight in cation concentrations and stratification, bonding states (oxide, hydroxide), and their modulation as a function of electrochemical conditions and performance. Most importantly: (i) Mo addition enhanced Cr(III) bound in oxide, (ii) fast growth conditions resulted in less corrosion resistant films, and (iii) exposure aging increased Cr-enrichment and reduced stratification of Mo-cations. The correlation between passive film performance and Cr, Ni, and Mo oxidation states, bonding, oxide-hydroxide contributions, and stratification is discussed. Generally accepted correlations, such as Cr-cation concentration and performance of the passive layer, have to be reexamined in order to account for the complex chemical make-up of the passive layer.

To Compare Blood Glucose Estimation Using the GOD-PAP Technique with the Hexokinase Method

Glucose is the major source of energy for all the processes working within the human body and hence it's the major carbohydrate required. During starvation or fasting, its concentration in blood is maintained by glycogenolysis and gluconeogenesis otherwise, a routine diet is sufficient for this task. Routine methods like glucose-oxidase coupled dehydrogenase are most commonly used on semiautomatic instruments with mono reagent. Hexokinase is the definite method to measure glucose concentration during different fed and fasting states but it requires an automated instrument and specific reagent which comparatively affects its cost. Objective: To compare the GOD-PAP and Hexokinase methods for blood glucose estimation. Methodology: This study was conducted in the Chemical pathology lab and Diabetic clinic of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan from June to December 2023. 110 samples were obtained. Both genders with hyperglycemia and normoglycemia were selected. Hemolyzed, lipemic, icteric specimens and blood samples with low glucose &lt;50 mg/dl were excluded. Results: 110 patient specimens were analyzed on both fully automated and semi-automatic instruments for method comparison. Precision determined by replication study in which Random Error was (RE) &lt; Total Allowable Error (TAE). The mean value determined by the Hexokinase method was 106.34 while by GODAP it gave 100.29. There was a negative bias of -6.14. The linear regression analysis was performed for comparison of methods. The line of best fit was obtained. Linear correlation between the two methods was documented by calculating the correlation coefficient. The accuracy of the test method was measured by conducting a "Recovery study" on the specimen sera. The proportional error was less than the total allowable error. The P-value was found to be 0.000. Conclusion: Our study concluded that the estimation of glucose using the GOD-PAP (glucose oxidase-peroxidase) technique gave acceptable results when compared with the Hexokinase reference method. So, the validated method can be used in small and medium workload laboratories for cost-effective reliable blood glucose test results.

Bioavailability comparison study of two benzathine benzylpenicillin 1,200,000 IU intramuscular formulations in healthy male participants under fast state

Introduction: Benzathine benzylpenicillin G is a drug present in the list of essential medicines of the World Health Organization and largely used in Brazil, where this antibiotic is used for treating pneumonias, pharyngitis, syphilis, and other infections caused by Gram-positive bacteria, being one of the most prescribed antibiotics of the public healthcare system. Objective: The objective of this study was to evaluate the relative bioavailability of two formulations of benzathine benzylpenicillin (Benzetacil®) 1,200,000 IU, both manufactured by Eurofarma Laboratórios S/A, by comparison of plasma levels of both drugs administered intra-muscularly, evaluating the pharmacokinetic parameters: Cmax and AUC0-t, being t=672 h. Methods: A randomized, parallel, open-label study with one treatment and one period in 168 healthy male volunteers. Subjects received the test or reference formulations by intramuscular injection. A total of 20 blood samples were collected after administration for plasmatic quantification of the drug by LC-MS/MS along 672 h. Results: Both formulations were considered well tolerated, and no serious adverse event was reported during the trial. Cmax and AUC0-t were compared: the rate between test and reference formulations for Cmax was 97.75% with confidence interval (CI) (86.34–110.67%) and power 90.55%. The rate between test and reference formulations for AUC0-t was 91.15% CI (85.29–97.42%) and power of 99.99%. The rate between test and reference formulations for AUC0-inf was 87.98% with CI (81.29–95.23%) and power of 99.85%. Conclusion: Reference and test formulations were shown to be statistically bioequivalents according to their rate and extension of absorption, based on ANVISA criteria.

Serum Levels of Selected Cytokines and Chemokines and IgG4 in Children With Recurrent Respiratory Tract Infections.

Background: Respiratory tract infections are a common health problem. Cytokines/chemokines play a critical role in the regulation of the immune system. Their defective production may predispose to recurrent respiratory tract infections (RRIs), and an excessive immune response may lead to chronic inflammation and cause damage to the respiratory tract. Another biomarker of respiratory infections may be immunoglobulin-IgG4. Its meaning has still been little explored. We wanted to assess the suitability of the levels of biomarkers tested: interleukin (IL)-17A, IL-18, IL-23, normal T cells expressed and secreted (RANTES), and induced protein (IP)-10, as well as immunoglobilun G4 (IgG4) to predict recurrent infections. Methods: The study group (SG) included a total of 130 children (68 girls, 62 boys) between 3 and 17 years of age with RRI. The control group (CG) included 86 healthy children with no symptoms of inflammatory or allergic diseases (44 girls and 42 boys) of the same age. Blood samples were collected in fasting state and then serum samples were frozen and stored until biomarker assay. Results: Serum RANTES, IL-18, IL-23, and IgG4 concentration were higher in all children with recurrent infections vs. those in the CG (p < 0001). Serum levels of IL-17A and IP-10 were also significantly higher in the SG than in the CG, but only in the youngest children. Among the six serum markers, RANTES demonstrated the highest area under the receiver operating characteristic curve (area under curve) value (0.998, 95% confidence interval [CI]: 0.98-1.0, p < 0.001) for the diagnosis of RRIs, followed by IL-23 (0.99, 95% CI 0.966-0,999, p < 0.001) and IL-18 (0.957, 95% CI 0.921-0.980, p < 0.001). Conclusions: RANTES, IL-23, and IL-18 could be strong predictors of respiratory infections recurrence in children.

Duodenal-Jejunal Bypass Restores Sweet Taste Receptor-Mediated Glucose Sensing and Absorption in Diabetic Rats.

Aim: The aim of the study is to identify the regulatory role of intestinal sweet taste receptors (STRs) and glucose transporters (SGLT1, GLUT2) and gut peptide secretion in duodenal-jejunal bypass (DJB)-ameliorated glycemic control in Type 2 diabetes. Materials and Methods: DJB and sham surgeries were performed in streptozotocin-induced diabetic male rats. The blood GLP-1 and GLP-2 levels were evaluated under feeding and fasting conditions. The expression of STRs (T1R2, T1R3), sweet taste signaling effector (Gα-gustducin), SGLT1, and GLUT2 was detected in the intestinal alimentary limb (A limb), biliopancreatic limb (BP limb), and common limb (C limb). The effects of STR inhibition on glucose control were measured with lactisole. Results: Glucose tolerance was improved in DJB-operated rats compared with the sham group, similar to that of normal control rats, without significant differences in food intake and body weight. The plasma GLP-1 levels of DJB rats were increased under diet-fed condition, and GLP-2 levels were increased after fasting. The villus height and crypt depth were significantly increased in the A limb of DJB-operated rats. In addition, GLP-1 expression was restored in enterocytes. The expression of T1R2, Gα-gustducin, and SGLT1 was elevated in the A limb after DJB, while GLUT2 was downregulated in the A, BP, and C limbs. The localization of GLUT2 was normalized in the three intestinal limbs after DJB. However, the beneficial effects of DJB on glucose control were abolished in the presence of lactisole in vivo. Conclusion: DJB ameliorates glycemic control probably by restoring STR-mediated glucose sensing and absorption with the responses of GLP-1 and GLP-2 to carbohydrate.

Ibuprofen and pseudoephedrive hydrochloride as granules for oral solution. A comparative pharmacokinetic study

Introduction: Conventional oral formulations can be difficult to swallow for patients with dysphagia, children, and the elderly. A new pharmaceutical form containing a combination of ibuprofen/pseudoephedrine designed to provide easier administration and more flexible dose adjustment while maintaining similar pharmacokinetic profile to other conventional formulations already on the market was developed. The objective of this study was to evaluate the bioequivalence of a fixed oral combination of 400 mg ibuprofen and 60 mg pseudoephedrine granules for oral solution, compared with a reference market standard formulated in soft capsules after single dose administration. Methods: An open, randomized, single dose, two-period, crossover trial was conducted. Subjects were randomly assigned to receive either 1 sachet of granules for oral solution (400 mg/60 mg – Test product), or 2 soft capsules with liquid content of SpaltGrippal® (200 mg/30 mg - Reference product) under fasting conditions. For the evaluation of bioequivalence, the 90% CI of log-transformed values were calculated for the ratios Test vs Reference for AUC(0-t) and Cmax of ibuprofen (racemic) and (1S,2S)-pseudoephedrine and then compared to the corresponding acceptance ranges. Safety and tolerability were assessed during the clinical period and one week after the last dose. Results: Bioequivalence was demonstrated for both Cmax and AUC(0-t) of pseudoephedrine, as well as for the total exposure of ibuprofen, while the Cmax of ibuprofen slightly exceeded the upper acceptance limit by approximately 6%. For both actives, Tmax was lower with the granule’s formulation. The overall safety and tolerability of the study medications were identical Conclusions: Although the bioequivalence criteria between Test and Reference product were not completely met, the new formulation of ibuprofen/pseudoephedrine granules for oral solution is able to provide a therapeutic equivalence to conventional solid forms, ensuring a more convenient administration, faster onset of analgesia for the patient without altering its total exposure.

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

Implementation of Neural Network for Classification of Diabetes Mellitus through Finger Nail Image

This study aims to obtain accuracy for classification of diabetes mellitus based on fingernail images using neural network. The data is fingernail images with fasting conditions and non-fasting conditions. In each condition, data is divided into three namely diabetes, prediabetes and normal data. Images in each data are 100 images. Methods were preprocessing, GLCM, neural network (NN) and accuracy. Preprocessing were cropping and grayscaling. GLCM were contrast, entropy, homogeneity, energy and correlation features. In NN, number of epochs used is 1000. Images in the training data is 240. The accuracy were 100% for fasting condition and 85% for non-fasting condition.