Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease:2020 Practice Guidance by the American Association for the Study of Liver Diseases

An overview of the current understanding of bleeding and thrombosis in cirrhosis. An evidence-based justification for bleeding risk assessment in patients with cirrhosis prior to invasive procedures, including current concepts in preprocedural testing and laboratory analysis and their role in predicting bleeding complications. An outline of established and recently identified risk factors for venous thrombosis in the portal and hepatic venous systems in both patients with and without cirrhosis along with thrombophilia testing recommendations

Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

Diabetes in Danish Bank Voles (M. glareolus): Survivorship, Influence on Weight, and Evaluation of Polydipsia as a Screening Tool for Hyperglycaemia

BACKGROUND: Previous studies have concluded that the development of polydipsia (PD, a daily water intake ≥ 21 ml) among captive Danish bank voles, is associated with the development of a type 1 diabetes (T1D), based on findings of hyperglycaemia, glucosuria, ketonuria/-emia, lipemia, destroyed beta cells, and presence of autoantibodies against GAD65, IA-2, and insulin. AIM AND METHODS: We retrospectively analysed data from two separate colonies of Danish bank voles in order to 1) estimate survivorship after onset of PD, 2) evaluate whether the weight of PD voles differed from non-PD voles, and, 3), evaluate a state of PD as a practical and non-invasive tool to screen for voles with a high probability of hypeglycaemia. In addition, we discuss regional differences related to the development of diabetes in Scandinavian bank voles and the relevance of the Ljungan virus as proposed etiological agent. RESULTS: We found that median survival after onset of PD is at least 91 days (lower/upper quartiles = 57/134 days) with a maximum recording of at least 404 days survivorship. The development of PD did not influence the weight of Danish bank voles. The measures of accuracy when using PD as predictor of hyperglycaemia, i.e. sensitivity, specificity, positive predictive value, and negative predictive value, equalled 69%, 97%, 89%, and 89%, respectively. CONCLUSION: The relatively long survival of Danish PD bank voles suggests potentials for this model in future studies of the long-term complications of diabetes, of which some observations are mentioned. Data also indicates that diabetes in Danish bank is not associated with a higher body weight. Finally, the method of using measurements of daily water intake to screen for voles with a high probability of hyperglycaemia constitutes a considerable refinement when compared to the usual, invasive, methods

Structure-Activity Relationships and Therapeutic Potentials of 5-HT7 Receptor Ligands: An Update

Serotonin 5-HT7 receptor (5-HT7R) has been the subject of intense research efforts because of its presence in brain areas such as the hippocampus, hypothalamus, and cortex. Preclinical data link the 5-HT7R to a variety of central nervous system processes including the regulation of circadian rhythms, mood, cognition, pain processing, and mechanisms of addiction. 5-HT7R blockade has antidepressant effects and may ameliorate cognitive deficits associated with schizophrenia. 5-HT7R has been recently shown to modulate neuronal morphology, excitability, and plasticity, thus contributing to shape brain networks during development and to remodel neuronal wiring in the mature brain. Therefore, the activation of 5-HT7R has been proposed as a therapeutic approach for neurodevelopmental and neuropsychiatric disorders associated with abnormal neuronal connectivity. This Perspective celebrates the silver jubilee of the discovery of 5-HT7R by providing a survey of recent studies on the medicinal chemistry of 5-HT7R ligands and on the neuropharmacology of 5-HT7R

Solid Lipid Nanoparticles Loading Idebenone Ester with Pyroglutamic Acid: In Vitro Antioxidant Activity and In Vivo Topical Efficacy

Idebenone (IDE), a strong antioxidant widely investigated for the treatment of neurodegenerative diseases and skin disorders, shows low oral and topical bioavailability due to its unfavorable physico-chemical properties. In this work, to improve IDE topical effectiveness, we explored a two-steps approach: (1) we synthesized an IDE ester (IDEPCA) with pyroglutamic acid, a molecule whose hydrating effects are well known; (2) we loaded IDEPCA into solid lipid nanocarriers (SLN). We evaluated in vitro antioxidant and anti-glycation activity and in vivo hydrating effects after topical application in human volunteers from gel vehicles of IDEPCA SLN in comparison to IDE SLN. All SLN showed good technological properties (mean particle size < 25 nm, polydispersity index < 0.300, good stability). The oxygen radical absorbance capacity assay showed that IDEPCA SLN and IDE SLN had similar antioxidant activity while IDEPCA SLN were more effective in the in vitro NO scavenging assay. Both IDEPCA and IDE SLN showed the same effectiveness in inhibiting the formation of advanced glycation end products. In vivo experiments pointed out a better hydrating effect of IDEPCA SLN in comparison to IDE SLN. These results suggest that the investigated approach could be a promising strategy to obtain topical formulations with increased hydrating effects