Threshold of hyperglycaemia associated with mortality in critically ill patients: a multicentre, prospective, observational study using continuous glucose monitoring.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.

Glycaemic outcomes in hospital with IDegAsp versus BIAsp30 premixed insulins.

BACKGROUND AND AIMS: IDegAsp (Ryzodeg 70/30), a unique premixed formulation of long-acting insulin degludec and rapid-acting insulin aspart, is increasing in use. Management of IDegAsp during hospitalisation is challenging because of degludec's ultra-long duration of action. We investigated inpatient glycaemia in patients treated with IDegAsp compared to biphasic insulin aspart (BIAsp30; Novomix30). METHODS: We performed a retrospective observational study at two hospitals assessing inpatients with type 2 diabetes treated with IDegAsp or BIAsp30 prior to and during hospital admission. Standard inpatient glycaemic outcomes were analysed based on capillary blood glucose (BG) measurements. RESULTS: We assessed 88 individuals treated with IDegAsp and 88 HbA1c-matched individuals treated with BIAsp30. Patient characteristics, including insulin dose at admission, were well matched, but the IDegAsp group had less frequent twice-daily insulin dosing than the BIAsp30 group (49% vs 87%, P < 0.001). Patient-days with BG <4 mmol/L were not different (10.6% vs 9.9%, P = 0.7); however, the IDegAsp group had a higher patient-day mean BG (10.4 (SD 3.4) vs 10.0 (3.4) mmol/L, P < 0.001), and more patient-days with mean BG >10 mmol/L (48% vs 38%, P < 0.001) compared to the BIAsp30 group. Glucose was higher in the IDegAsp group in the evening (4 PM to midnight) (11.6 (SD 4.0) vs 10.9 (4.6) mmol/L, P = 0.004), but not different at other times during the day. CONCLUSIONS: Inpatients treated with IDegAsp compared to BIAsp30 had similar hypoglycaemia incidence, but higher hyperglycaemia incidence, potentially related to less frequent twice-daily dosing. With the increasing use of IDegAsp in the community, development of hospital management guidelines for this insulin formulation is needed.

Elevated glucose promotes MMP13 and ADAMTS5 production by osteoarthritic chondrocytes under oxygenated but not hypoxic conditions.

Type 2 diabetes is linked with increased incidence and severity of osteoarthritis. The purpose of this study was to determine the effect of extracellular glucose within the normal blood glucose and hyperglycemic range on catabolic enzyme production by chondrocytes isolated from osteoarthritic (OA) and macroscopically normal (MN) human cartilage under oxygenated (18.9% oxygen) and hypoxic (1% oxygen) conditions. OA and MN chondrocytes were maintained in 4, 6, 8, or 10 mM glucose for 24 h. Glucose consumption, GLUT1 glucose transporter levels, MMP13 and ADAMTS5 production, and levels of RUNX2, a transcriptional regulator of MMP13, ADAMTS5, and GLUT1, were assessed by enzyme-linked assays, RT-qPCR and/or western blot. Under oxygenated conditions, glucose consumption and GLUT1 protein levels were higher in OA but not MN chondrocytes in 10 mM glucose compared to 4 mM. Both RNA and protein levels of MMP13 and ADAMTS5 were also higher in OA but not MN chondrocytes in 10 mM compared to 4 mM glucose under oxygenated conditions. Expression of RUNX2 was overall lower in MN than OA chondrocytes and there was no consistent effect of extracellular glucose concentration on RUNX2 levels in MN chondrocytes. However, protein (but not RNA) levels of RUNX2 were elevated in OA chondrocytes maintained in 10 mM versus 4 mM glucose under oxygenated conditions. In contrast, neither RUNX2 levels or MMP13 or ADAMTS5 expression were increased in OA chondrocytes maintained in 10 mM compared to 4 mM glucose in hypoxia. Elevated extracellular glucose leads to increased glucose consumption and increased RUNX2 protein levels, promoting production of MMP13 and ADAMTS5 by OA chondrocytes in oxygenated but not hypoxic conditions. These findings suggest that hyperglycaemia may exacerbate chondrocyte-mediated cartilage catabolism in the oxygenated superficial zone of cartilage in vivo in patients with undertreated type 2 diabetes, contributing to increased OA severity.

Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities.

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments.

Effects of apical periodontitis treatment on hyperglycaemia in diabetes: A prospective cohort study.

AIM: This prospective cohort study was undertaken to evaluate the success rate of root canal treatment (RCT) in type 2 diabetes mellitus (T2DM) patients with targeted level and unachieved targeted level of glycaemic control as well as the impact of RCT on the glucose blood level in T2DM patients. METHODOLOGY: Patients needing RCT were divided into three groups: these without T2DM, that is, the control group (CG), those with targeted level of glycated haemoglobin HbA1c < 7% (TL A1c) and the third ones with unachieved targeted level (UTL A1c), that is, with HbA1c ≥ 7%. Before RCT, HbA1c and the periapical index (PAI) score were assessed, as well as 1 year later. RESULTS: Our results showed less favourable treatment results of RCT such as a reduction of radiographic lesions in T2DM patients, particularly in subjects with UTL A1c. The intergroup analysis of PAI score at the 12-month follow-up revealed a significant difference in TL A1C (p = .022) and CG (p = .001) with respect to UTL A1c. Total number of healed teeth (PAI≤2) at the 12-month after RCT in UTL A1c was significantly lower in comparison to CG (p = .008). Contrariwise, RCT may improve the glycaemic control in diabetic patients with UTL A1c after 12 months of posttreatment. Regression analysis showed that UTL A1c patients were more likely to have AP persistence after endodontic treatment (OR = 4.788; CI: 1.157-19.816; p = .031). CONCLUSIONS: T2DM retards the AP healing and conversely AP contributes to increasing the inflammatory burden in T2DM. RCT reduces the cumulative inflammatory burden in T2DM and thus may contribute to improvement of glycaemic control particularly in patients with UTL A1c.

Chronic hyperglycemia and intracranial meningiomas.

Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers, transcriptome and epigenetic landscape has revealed that benign meningiomas significantly differ in their glucose metabolism compared to aggressive lesions. However, a correlation between the systemic glucose metabolism and the metabolism of the tumor hasn't yet been found. We hypothesized that chronic levels of glycaemia (approximated with glycated hemoglobin (HbA1c)) are different in patients with aggressive and benign meningiomas. The study encompassed 71 patients with de novo intracranial meningiomas, operated on in three European hospitals, two in Croatia and one in Spain. Our results show that patients with WHO grade 2 meningiomas had significantly higher HbA1c values compared to patients with grade 1 lesions (P = 0.0290). We also found a significant number of patients (19/71; 26.7%) being hyperglycemic, harboring all the risks that such a condition entails. Finally, we found a significant correlation between our patients' age and their preoperative HbA1c levels (P = 0.0008, ρ(rho) = 0.388), suggesting that older meningioma patients are at a higher risk of having their glycaemia severely dysregulated. These findings are especially important considering the current routine and wide-spread use of corticosteroids as anti-edematous treatment. Further research in this area could lead to better understanding of meningiomas and have immediate clinical impact.

Preventing alpelisib-related hyperglycaemia in HR+/HER2-/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trial.

Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2-/PIK3CA-mutated advanced breast cancer (ABC). Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2-/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose <100 mg/dL [<5.6 mmol/L] and HbA1c <5.7%), and cohort B, prediabetes (fasting plasma glucose 100-140 mg/dL [5.6-7.8 mmol/L] and/or haemoglobin A1C [HbA1c] 5.7-6.4%). Participants were at least 18 years old, with Eastern Cooperative Oncology Group performance status of 0-1, and up to two prior lines of endocrine therapy (ET) for ABC. Alpelisib plus ET were administered in 28-day cycles after initiation of prophylactic metformin plus ET. Primary endpoint was the incidence of grade 3-4 hyperglycaemia over the first 8 weeks. Secondary endpoints included safety, progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). The primary objective for cohort A and B is met with ≤7 (14.6%) and ≤4 (20%) patients with grade 3-4 hyperglycaemia over the first 8 weeks, respectively. Findings: 233 patients were screened, and 68 (20.2%) patients were enrolled in cohorts A (n = 48) and B (n = 20). Median follow-up was 7.8 months (IQR 1.4-19.6). Over the first 8 weeks, one (2.1%) of 48 patients in cohort A (95% CI: 0.5-11.1; P < 0.0001), and three (15.0%) of 20 patients in cohort B (95% CI: 5.6-37.8; P = 0.016) had grade 3-4 hyperglycaemia. Serious treatment-related adverse events occurred in seven patients (10.3%). The most common were rash (two [2.9%]), vomiting (two [2.9%]), and diarrhoea (two [2.9%]). Discontinuation of alpelisib caused by AEs was reported in nine patients (13.2%), none caused by hyperglycaemia. At data cutoff (15 June, 2022), no treatment-related deaths were observed. In the full analysis set, median PFS was 7.3 months (95% CI: 5.9-not reached), ORR was 20.6% (95% CI: 11.7-32.1%), and CBR was 52.9% (95% CI: 40.4-65.2). Interpretation: In HR+/HER2-/PIK3CA-mutated ABC, prophylactic metformin before alpelisib plus endocrine treatment has low incidence and severity of alpelicib-induced hyperglycaemia. Funding: Novartis Pharmaceuticals.

Vitamin D status of pregnant women with obesity in the United Kingdom and its association with pregnancy outcomes: a secondary analysis of the UPBEAT study.

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI≥30kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17±1 weeks' gestation were assessed using multivariable linear regression and reported as percent differences in serum hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67% had 25(OH)D <50nmol/L and 26% had concentrations <25nmol/L. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = -33; 95%CI: -39 to -27), Asian (% difference= -43; 95%CI: -51 to -35) and other non-White (% difference= -26; 95%CI: -35 to -14) ethnicity compared to women of White ethnicity (n=1086; P<0.001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D <25nmol/L compared to ≥50nmol/L (OR=1.58; 95%CI: 1.09 to 2.31), but the magnitude of effect estimates was attenuated in the multivariable model (OR=1.33; 95%CI: 0.88 to 2.00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth, or SGA or LGA delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.

Diabetes Fever.

While diabetes manifests multiple clinical presentations, complications and comorbidities, most modern discourse focuses on the cardiovascular aspects of the syndrome. In this communication, we explore the vast spectrum of fever and diabetes. We highlight the bidirectional interactions between febrile illness and diabetes, as well as drug-drug interactions. These multifaceted connections must be understood by all health care professionals who manage diabetes and/or fever.

Maladaptive response following glucose overload in GLUT4-overexpressing H9C2 cardiomyoblasts.

BACKGROUND: Glucose overload drives diabetic cardiomyopathy by affecting the tricarboxylic acid pathway. However, it is still unknown how cells could overcome massive chronic glucose influx on cellular and structural level. METHODS/MATERIALS: Expression profiles of hyperglycemic, glucose transporter-4 (GLUT4) overexpressing H9C2 (KE2) cardiomyoblasts loaded with 30 mM glucose (KE230L) and wild type (WT) cardiomyoblasts loaded with 30 mM glucose (WT30L) were compared using proteomics, real-time polymerase quantitative chain reaction analysis, or Western blotting, and immunocytochemistry. RESULTS: The findings suggest that hyperglycemic insulin-sensitive cells at the onset of diabetic cardiomyopathy present complex changes in levels of structural cell-related proteins like tissue inhibitor of metalloproteases-1 (1.3 fold), intercellular adhesion molecule 1 (1.8 fold), type-IV-collagen (3.2 fold), chaperones (Glucose-Regulated Protein 78: 1.8 fold), autophagy (Autophagosome Proteins LC3A, LC3B: 1.3 fold), and in unfolded protein response (UPR; activating transcription factor 6α expression: 2.3 fold and processing: 2.4 fold). Increased f-actin levels were detectable with glucose overload by immnocytochemistry. Effects on energy balance (1.6 fold), sirtuin expression profile (Sirtuin 1: 0.7 fold, sirtuin 3: 1.9 fold, and sirtuin 6: 4.2 fold), and antioxidant enzymes (Catalase: 0.8 fold and Superoxide dismutase 2: 1.5 fold) were detected. CONCLUSION: In conclusion, these findings implicate induction of chronic cell distress by sustained glucose accumulation with a non-compensatory repair reaction not preventing final cell death. This might explain the chronic long lasting pathogenesis observed in developing heart failure in diabetes mellitus.

Antioxidant, Anti-Diabetic, and Anti-Inflammation Activity of Garcinia livingstonei Aqueous Leaf Extract: A Preliminary Study.

Diabetes mellitus (DM) is the second leading cause of mortality globally. The increased concern for DM is due to the underlying complications accompanying hyperglycaemia, associated with oxidative stress and consequent inflammation. The investigation of safe and effective treatments for DM is necessary. In the present study, the cytotoxicity, phytochemical analysis, antioxidant capacity, anti-inflammatory, and antidiabetic effects in an aqueous extract of Garcinia livingstonei leaves were assessed. All tested extract concentrations showed no toxicity against C3A hepatocytes. Several phenolic compounds were identified using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). The total polyphenol content was 100.9741 mg GAE/g, 16.7712 mg CE/g flavanols, and 2.3548 mg QE/g flavonols. The antioxidant capacity values were 253.4268 mg AAE/g, 192.232 mg TE/g, and 167.8724 mg TE/g for ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and 2,2-diphenyl-1-pycrylhydrazyl (DPPH), respectively. The plant extract significantly (p < 0.05) demonstrated anti-inflammatory and hypoglycaemic effects in a dose-dependent manner, with the α-glucosidase inhibition of the extract being higher (p < 0.05) than in the standard conventional drug (acarbose). The findings of this study revealed the potential of the constituents of G. livingstonei aqueous leaf extract in DM treatment. Further studies on the preparation and mechanisms of action of the plant in DM treatment are recommended.

An effective insulin infusion protocol for severe traumatic brain injury patients: A retrospective observational study.

PURPOSE: Severe traumatic brain injury (sTBI) patients often experience stress hyperglycaemia, which can lead to negative outcomes. This study aims to introduce an effective insulin infusion protocol specifically designed for sTBI patients. METHODS: Data was collected from all sTBI patients during two periods: 1 October 2019 to 30 April 2020, and 1 June 2020 to 31 December 2020. In May 2020, a new insulin infusion protocol was implemented. Blood glucose management, infection, coagulation, and prognosis were compared in these two periods. RESULT: 195 patients were included, with 106 using the new protocol. The proportion of hyperglycaemia decreased from 40.04% to 26.91% (P<0.05), and the proportion of on-target blood glucose levels increased from 35.69% to 38.98% (P<0.05). Average blood glucose levels decreased from 9.98±2.79mmol/L to 8.96±2.82mmol/L (P<0.05). There was no substantial increase in hypoglycaemia, which remained controlled below 1%. The new protocol positively influenced glucose concentration and dispersion trends. There were no significant differences in catheter-related infections, antibiotic use, mechanical ventilation (MV) duration, length of stay in ICU, Glasgow Outcome Scale (GOS), or mortality. However, the conventional protocol group had a higher coagulation tendency (R-value of thromboelastography 4.80±1.35min vs. 5.52±1.87min, P<0.05), with no difference in deep vein thrombosis (DVT) incidence. CONCLUSION: Our findings suggest that a customized insulin infusion process for sTBI patients can effectively manage blood glucose. While there is no significant improvement in infection control or prognosis, it may have a positive impact on coagulation without affecting the occurrence of DVT.

Ward monitoring 4.0: real-time metabolic insights from continuous glucose monitoring into perioperative organ dysfunction.

The now-routine clinical deployment of continuous glucose monitoring has demonstrated benefit in real-world settings. We make the case that continuous glucose monitoring can help re-examine, at scale, the role that (stress) hyperglycaemia plays in fuelling organ dysfunction after tissue trauma. Provided robust perioperative data do emerge, well-established continuous glucose monitoring technology could soon help transform the perioperative landscape.

Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis-A Translational Narrative Review.

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood-brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI.

Prevalence of Non-diabetic Hyperglycemia in Young Adults and Its Impact on Periodontal Health.

Background Non-diabetic hyperglycemia is a transitional phase of hyperglycemia that poses a hidden risk for the development of diabetes mellitus and related complications, including periodontal destruction. The current study sought to determine the prevalence of non-diabetic hyperglycemia in young adults and any possible links to periodontal health. Methods A total of 400 participants in this cross-sectional study were evaluated for non-diabetic hyperglycemia between the ages of 18 and 35 years. Group I consisted of non-diabetic hyperglycemic participants. Group II comprised an equal number of matched, healthy subjects. The groups' hyperglycemic and clinical periodontal characteristics were contrasted. Using a one-sample t-test and logistic regression analysis, the acquired data were subjected to statistical analysis. Results The prevalence of non-diabetic hyperglycemia was 19%, with men (13%) having a higher prevalence than women (6%). The mean fasting plasma glucose and hemoglobin A1c (HbA1c) levels were 114.47 ± 6.40 mg/dL and 6.10 ± 0.21%, respectively, for group I, and 85.72 ± 7.24 mg/dL and 4.38 ± 0.70% for group II. When compared to healthy controls, all periodontal parameters, including plaque index, gingival index, bleeding on probing, probing depth, and clinical attachment loss, were significantly higher in group I non-diabetic hyperglycemic patients. The regression analysis revealed statistically significant links between hyperglycemic and periodontal parameters. Conclusion The prevalence of non-diabetic hyperglycemia among young adults is a serious concern similar to that of older adults with the risk for periodontal diseases. Non-diabetic hyperglycemic considerations in young adults should be emphasized in dental and medical clinics to reduce the risk of developing diabetes mellitus and to avoid irreversible periodontal tissue damage.

The dangerous "West Coast Swing" by hyperglycaemia and chronic stress in the mouse hippocampus: Role of kynurenine catabolism.

Growing epidemiological studies highlight a bi-directional relationship between depressive symptoms and diabetes mellitus. However, the detrimental impact of their co-existence on mental health suggests the need to treat this comorbidity as a separate entity rather than the two different pathologies. Herein, we characterized the peculiar mechanisms activated in mouse hippocampus from the concurrent development of hyperglycaemia, characterizing the different diabetes subtypes, and chronic stress, recognized as a possible factor predisposing to major depression. Our work demonstrates that kynurenine overproduction, leading to apoptosis in the hippocampus, is triggered in a different way depending on hyperglycaemia or chronic stress. Indeed, in the former, kynurenine appears produced by infiltered macrophages whereas, in the latter, peripheral kynurenine preferentially promotes resident microglia activation. In this scenario, QA, derived from kynurenine catabolism, appears a key mediator causing glutamatergic synapse dysfunction and apoptosis, thus contributing to brain atrophy. We demonstrated that the coexistence of hyperglycaemia and chronic stress worsened hippocampal damage through alternative mechanisms, such as GLUT-4 and BDNF down-expression, denoting mitochondrial dysfunction and apoptosis on one hand and evoking the compromission of neurogenesis on the other. Overall, in the degeneration of neurovascular unit, hyperglycaemia and chronic stress interacted each other as the partners of a "West Coast Swing" in which the leading role can be assumed alternatively by each partner of the dance. The comprehension of these mechanisms can open novel perspectives in the management of diabetic/depressed patients, but also in the understanding the pathogenesis of other neurodegenerative disease characterized by the compromission of hippocampal function.

Radiological and laboratory prognostic parameters for gastric dilation in rabbits (Oryctolagus cuniculus).

BACKGROUND: The aim of this study was to evaluate the radiographical and laboratory findings in pet rabbits with gastric dilation (GD) and identify prognostic parameters. METHODS: One hundred and fifty-five rabbits with GD were included for the radiographical analyses and 75 for the laboratory analyses. A vertebral stomach score (VSS) was established to determine the extension of the stomach on lateral radiographs. In addition, the caudal limit of gastric distention and the extension and position of gas accumulation in the stomach were recorded. RESULTS: The VSS was significantly higher in rabbits with GD than in healthy rabbits (p = 0.001). Extensive amounts of gas accumulation in the stomach (p = 0.001) and a ventral or central location of gas accumulation (p = 0.023) were associated with significantly increased mortality. Azotemia (51%), hyperglycaemia (44%) and hyponatraemia (37%) were the most frequent biochemical alterations in rabbits with GD. LIMITATIONS: Due to the retrospective nature of the data, the cause of GD could not be determined in all animals. CONCLUSION: Rabbits with GD and severe alterations in glucose, creatinine and sodium concentrations, ventral or central gas accumulations and a large amount of gas in the stomach had a poor prognosis.

Chemodiverse monoterpene indole alkaloids from Kopsia teoi, inhibitory potential against α-amylase, and their molecular docking studies.

Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative inquiry encompassed the isolation of phytochemical components from the bark of Kopsia teoi, followed by the assessment of their α-amylase inhibition. The phytochemical composition of the K. teoi culminated in the discovery of a pair of new indole alkaloids; which are 16-epi-deacetylakuammiline N(4)-methylene chloride (akuammiline) (1), and N(1)-methoxycarbonyl-11-methoxy-12-hydroxy-Δ14-17-kopsinine (aspidofractinine) (2), together with five known compounds i.e. kopsiloscine G (aspidofractinine) (3), akuammidine (sarpagine) (4), leuconolam (aspidosperma) (5), N-methoxycarbonyl-12-methoxy-Δ16, 17-kopsinine (aspidofractinine) (6), and kopsininate (aspidofractinine) (7). All compounds were determined via spectroscopic analyses. The in vitro evaluation against α-amylase showed good inhibitory activities for compounds 5-7 with the inhibitory concentration (IC50) values of 21.7 ± 1.2, 34.1 ± 0.1, and 30.0 ± 0.8 µM, respectively compared with the reference acarbose (IC50 = 34.4 ± 0.1 µM). The molecular docking outputs underscored the binding interactions of compounds 5-7 ranging from -8.1 to -8.8 kcal/mol with the binding sites of α-amylase. Consequently, the outcomes highlighted the anti-hyperglycemic attributes of isolates from K. teoi.