GLINT: GlucoCEST in neoplastic tumors at 3 T—clinical results of GlucoCEST in gliomas

Objective Clinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein. Materials and methods Motion and field inhomogeneity corrected T1ρ‐based DGE (DGE⍴) images were acquired before, during and after a d-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood–brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T. Results In high-grade gliomas with BBB leakage, d-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor. Conclusion First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.

Effect of Shenfu Injection on Reperfusion Injury in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Segment Elevation Myocardial Infarction: A Pilot Randomized Clinical Trial

Background: Shenfu injection is a traditional Chinese medicine formulation that alleviates ischemia-reperfusion injury through multiple pharmacologic effects. However, no data are available regarding its efficacy in patients with myocardial infarction. We aimed to examine the effects of Shenfu injection on infarct size in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods: From April 2016 to February 2018, 40 patients with first-time anterior STEMI undergoing primary PCI within 6 h of symptom onset were randomized 1:1 to intravenous Shenfu injection (80 ml Shenfu injection + 70 ml 5% glucose injection) or placebo (150 ml 5% glucose injection) before reperfusion. Treatment started before PCI and maintained for 5 days after PCI. The primary end point was infarct size assessed by CK-MB area under the curve (AUC) over 72 h and cardiac magnetic resonance (CMR) imaging 4 ± 1 days after PCI.Results: Infarct size by area under the curve for CK-MB over 72 h did not differ between the Shenfu injection and placebo groups (5602.5 [3539.4–7526.4] vs. 6403.2 [2234.4–8340.6] ng·h/ml, P = 0.82). Among 32 patients who underwent CMR Imaging, a nominal reduction in infarct size was observed in the Shenfu injection group compared with the placebo group (23.9 [15.2–28.5] % vs. 27 [21.9–31.9] %, P = 0.42). After excluding patients with no or minimal infarct, there was a trend toward reduction in infarct size in the Shenfu injection group (24.1 [20.3–29.3] % vs. 29.1 [24.5–32] %, P = 0.18). Incidence of adverse events was similar between the groups.Conclusions: This pilot study showed that the use of Shenfu injection was safe but did not reduce infarct size by CMR Imaging and CK-MB release kinetics in reperfused patients with STEMI. Larger studies (confining to patients with extensive infarct size) to evaluate the efficacy of Shenfu injection on reperfusion injury are warranted.Clinical Trail Registration:clinicaltrials.gov, identifier: NCT02709798.

Glucose inhibits haemostasis and accelerates diet-induced hyperlipidaemia in zebrafish larvae

Hyperglycaemia damages the microvasculature in part through the reduced recruitment of immune cells and interference with platelet signalling, leading to poor wound healing and accelerated lipid deposition in mammals. We investigated the utility of zebrafish larvae to model the effect of exogenous glucose on neutrophil and macrophage recruitment to a tail wound, wound-induced haemostasis, and chicken egg yolk feed challenge-induced hyperlipidaemia by supplementing larvae with exogenous glucose by immersion or injection. Neither method of glucose supplementation affected the recruitment of neutrophils and macrophages following tail transection. Glucose injection reduced thrombocyte retention and fibrin plug formation while only thrombocyte retention was reduced by glucose immersion following tail transection. We observed accelerated lipid accumulation in glucose-injected larvae challenged with high fat chicken egg yolk feeding. Our study identifies conserved and divergent effects of high glucose on inflammation, haemostasis, and hyperlipidaemia in zebrafish larvae compared to mammals.

Common causes and treatment of hypoglycemia in older patients with diabetes at Thanh Nhan hospital

Objectives: To determine common causes and treatment of hypoglycemia in oler patients with diabetes at Thanh Nhan hospital. Methods: A cross-sectional study on 1215 diabetic patients treated at Thanh Nhan Hospital from November 2018 to May 2019. Subjects were interviewed according to a uniform medical record. Hypoglycemia was diagnosed according to the ADA 2018 criteria: blood glucose ≤ 3.9 mmol/l. Results: the most common cause of hypoglycemia was a reduced diet (49.6%); eating late (24.1%); skipping meals (9.3%); overdose, wrong insulin regimen due to patients (7.4%); overdose and wrong insulin regimen by doctor (4.2%). The proportion of patients receiving intravenous hypertonic glucose injection/infusion was 7.7%; eating foods containing glucose was 63.1%; eating foods containing carbonhydrat was 29.2%. The majority of patients with symptoms of hypoglycemia lasting within 15 minutes accounted for 56.3%, the number of patients with hypoglycemia lasting more than 60 minutes accounted for 0.9%. Conclusions: The common cause of hypoglycemia in the study subjects was mainly related to the patient's diet. The treatment of the patient's hypoglycemia was not completely correct. Therefore, medical staff should have measures to advise and educate about the causes as well as how to manage hypoglycemia for this subject regularly

A Single-Center Clinical Study to Evaluate Shenxiong Glucose Injection Combined with Edaravone in the Treatment of Acute Large-Area Cerebral Infarction

Objectives. To investigate the clinical efficacy and safety of Shenxiong glucose injection combined with edaravone in the treatment of acute large-area cerebral infarction. Methods. 156 patients with acute large-area cerebral infarction admitted to our hospital from July 2015 to January 2017 were included in the analysis. The patients were randomly divided into experimental (78 cases) and control (78 cases) groups. Patients in the experimental group were given a 30 mg injection of edaravone in 100 ml of 0.9% sodium chloride solution by intravenous drip, twice a day within 30 minutes and a daily 200 ml injection of Shenxiong glucose by intravenous drip. Patients in the control group were given a 30 mg edaravone injection in 100 ml of 0.9% sodium chloride solution by intravenous drip, twice a day, and the drip was completed within 30 minutes. Patients in both groups were treated for 2 weeks. The levels of fibrinogen (FIB), D-dimer, interleukin 6 (IL-6), P-selectin (CD62P), and hypersensitive C-reactive protein (hs-CRP) were evaluated in the two groups of patients. Neurological disability was evaluated using the modified Rankin scale (mRS) and the neurological deficit score (National Institute of Health Stroke Scale, NIHSS). Adverse reactions to the treatments were also recorded. Results. No significant differences in age, gender, medical histories, and blood biochemical indices were observed between the two groups before treatment ( P > 0.05 ). After treatment, the levels of FIB, D-dimer, IL-6, CD62P, and hs-CRP were significantly lower following treatment and compared to the control group ( P < 0.05 ). Also, the mRS and NIHSS scores were significantly lower after treatment and compared with the control group ( P < 0.05 ). The total effective rate of the treatment in the experimental group was significantly higher compared to the control group ( P < 0.05 ). During the treatment period, no obvious adverse reactions were observed in the two groups of patients. Conclusions. In addition to the routine basic treatment of acute large-area cerebral infarction, the addition of Shenxiong glucose injection combined with edaravone injection can improve platelet aggregation and reduce inflammation by affecting P-selectin, D-dimer, and FIB. This treatment approach promotes the recovery of nerve defect function without obvious adverse reactions in patients with acute large-area cerebral infarction.

Environmental Enrichment Potentiates Glucose-Induced Anorexia in Mice

The hypothalamus controls food intake and metabolism by integrating nutrient and hormonal signals from peripheral tissues. Both central and peripheral administration of glucose leads to a reduction in food intake in rodents. Similarly, administration of the adipocyte hormone leptin or the gastrointestinal hormone xenin reduces food intake. In contrast, impairments in hypothalamic signaling of these factors cause hyperphagia and obesity in rodents and humans. Environmental factors affect behavior including feeding behavior and energy metabolism in rodents and humans. Studies have found that environmental enrichment (EE), in which mice interact with complex sensory and motor stimulation, led to a significant reduction in adiposity and resistance to diet-induced obesity in mice. This effect is independent of energy expenditure and is associated with enhanced hypothalamic signaling, but the exact mechanism is unknown. We hypothesized that EE potentiates the feeding suppressing effects of anorectic signals. To address this hypothesis, 4-week-old male C57BL/6 mice were group housed (5/cage) under standard laboratory conditions or EE conditions with free access to regular rodent chow and feeding response to glucose, leptin and xenin was examined. EE cages were supplemented with a house, running wheels, igloos, wood logs, maze and nesting materials. Four weeks after initiating EE protocol, mice were fasted for 8 h and received an intraperitoneal injection of glucose (2 mg/g b.w.) or saline just before the onset of the dark phase. Treatment assignments were reversed for the second injection so that each animal received both treatments with a washout period of 1 week. Mice were given food immediately after the injection and food intake was measured for 4 h after the injection at 0.5–1 h intervals. The same design was repeated using leptin (2.5 μg/g b.w.) and xenin (15 or 50 μg/g b.w.). Glucose injection caused a significant reduction of food intake in both control and EE mice. However, anorexic effect of glucose was more significant in EE group compared to the control group (main effect of treatment: P = 0.0016 for control and P &lt; 0.0001 for EE, two-way ANOVA). Significant reductions in food intake were observed between 0.5 and 2.5 h after glucose injection in EE mice, while no significant reduction was observed thereafter. Moreover, three-way ANOVA showed a significant interaction between housing condition and treatment (P = 0.0086). In contrast, although both leptin and xenin caused a significant reduction in food intake, there was no significant interaction between housing condition and treatment. These data suggest that environmental enrichment enhances the anorectic action of glucose without altering feeding response to leptin and xenin. It is speculated that enhanced hypothalamic glucose sensing may mediate beneficial effects of environmental enrichment on metabolism.

MO747AN ASSESSMENT OF COMPLEXITY OF CARDIOVASCULAR SIGNALS USING ENTROPY IN HEMODIALYSIS SESSION AND GLUCOSE INJECTION DURING HEMODIALYSIS IN END STAGE RENAL DISEASE PATIENTS WITH AND WITHOUT DIABETES MELLITUS TYPE 2

Background and Aims Few studies have focused on the imbalance of the autonomic nervous system during hemodialysis (HD), although it seems to be an important factor for the maintenance of blood pressure. The aim of this work was to assess the impact of hemodialysis (HD) and glucose injection upon entropy of heart rate and blood pressure during HD session in end stage renal disease (ESRD) patients with and without diabetes mellitus (DM) type 2. Method 21 patients without DM (NDO), in age 54,95 +/-13,08 y.o., and 10 DM patients, in age 69,70 +/- 8,27 y.o., were studied during HD. 30 minutes after dialysis begins, 40% glucose solution was administered in the amount of 0.5g/kg body dry-weight (constant rate of 1 mL/s). The cardiovascular signals were extracted from the recordings using Portapres® system. The analysis was performed using Amplitude Aware Permutation Entropy (AAPE). The parameters of AAPE were set as d=7, A=0.5. All statistical analysis were performed on significance level α=0.05. The comparisons between groups were conducted with Mann-Whitney test with Holm corrections. The comparisons in time points were performed using Friedman test with post-hoc (Wilcoxon test with Holm corrections). The calculations of AAPE and all statistical analysis were performed with Matlab R2020a and R. Results The results are presented in table. It was found that AAPE(HR) tends to decrease during dialysis (NS) and increases only in the DM group after glucose injection (p=0.019); without difference between groups. There were no differences in AAPE of blood pressure between the groups, but hemodialysis reduces AAPE(fiSYS) in both groups (p&lt;0.001 in both DM and NDO groups) and AAPE(fiDIA) in NDO (p&lt;0.01). AAPE(TPR) is high before dialysis, and decreases during HD in both groups (p&lt;0.0001). There is no effect of glucose injection on AAPE(HR) in both groups, but AAPE(fiSYS) and AAPE(fiDIA) increase in NDO (p&lt;0.001, p&lt;0.01, p&lt;0.05 respectively); without difference between groups. AAPE(TPR) tends to increase after glucose injection (p&lt;0.05 for NDO, NS for DM). Conclusion AAPE(HR)tends to decrease during HD, and glucose injections increase AAPE(HR) in DM patients. Hemodialysis reduce, and glucose injections increase AAPE of blood pressure especially in NDO. A weaker response to hemodialysis and glucose injection in diabetic patients may be caused by impairment of the autonomic system, and may have clinical impact – may leads to faint. Glucose administration does not prevent autonomic system disorders in patients with DM.

Sequence and expression analysis of glucokinase mRNA from herbivorous Giant gourami (Osphronemus goramy)

Sari DN, Nasrullah H, Ekasari J, Suprayudi MA, Alimuddin A. 2021. Sequence and expression analysis of glucokinase mRNA from herbivorous Giant gourami (Osphronemus goramy). Biodiversitas 22: 741-750. Glucokinase (GCK) is one of the enzymes that play important roles in carbohydrate metabolism and high glucose homeostatic in fish. The information about the GCK mRNA sequence and its expression is limited in Giant gourami, one of the most important herbivorous aquaculture species in Indonesia. The present study aimed to characterize the GCK mRNA and analyze its mRNA expression and plasma glucose levels after high glucose injection in Giant gourami. We also compared its sequence variability among carnivorous and herbivorous fish. The GCK mRNA was identified using polymerase chain reaction (PCR) method from the fish liver. Its mRNA level was analyzed by real-time PCR (qPCR). Giant gourami GCK mRNA sequence was 2104 nucleotide long, encoding 478 amino acids, and shared high similarity with other fish. GCK was mainly expressed in the liver. The mRNA level of GCK was highly up-regulated after 6 hours of high glucose injection, in-line with the plasma glucose in the blood. There are no major differences observed in the GCK amino acid sequences among Giant gourami and other fish. The knowledge gained from this study could be used as a reference for further exploration of metabolic regulation in Giant gourami.