Serum miR-122 levels correlate with diabetic retinopathy

Clinical and Experimental Medicine - Diabetic retinopathy is the most severe ocular complication of diabetes and may lead to visual disability and blindness. Proliferative diabetic retinopathy...     

Pfeiffer syndrome: oral healthcare management and description of new dental findings in a craniosynostosis

Pfeiffer syndrome is a rare fibroblast growth factor receptor‐related craniosynostosis with variable clinical presentations. We describe new dental findings of hypodontia, microdontia, dilacerations, and radicular dentin dysplasia in a 19‐year‐old girl, and discuss the oral health management.     

Exploring the Role of Peer Advice in Self-Regulated Learning: Metacognitive,Social, and Environmental Factors

This Conversation Starters article presents a selected research abstract from the 2016 Association of American Medical Colleges Northeast Region Group on Educational Affairs annual spring meeting. The abstract is paired with the integrative commentary of three experts who shared their thoughts stimulated by the pilot study. These thoughts explore the metacognitive, social, and environmental mechanisms whereby advice plays a role in self-regulated learning.     

Effect of tetrahydrocannabinols on 3H-acetylcholine biosynthesis in various rat brain slices.

The effects of delta8- and delta9-tetrahydrocannabinol on the biosynthesis of 3H-acetylcholine (ACh) from 3H-choline in cortical, hypothalamic and striatal rat brain slices were examined. The two cannabinols were found to inhibit the synthesis of 3H-ACh in the three brain regions. Treatment with cannabidiol did not alter ACh synthesis. Delta8-tetrahydrocannabinol was approximately twice as effective as the delta9-isomer. This effect was not associated with alterations in striatal and cortical choline acetyltransferase or with an impaired high-affinity uptake system for choline in the striatum. Treatment with delta8- and delta9-cannabinols, likewise, did not change striatal choline and ACh levels. Antagonism of the ACh biosynthesis inhibition occurred when slices from treated animals were incubated in depolarizing concentration of K+ ion. These results suggest that the inhibition of ACh synthesis observed in tetrahydrocannabinol-treated rats may be related to interference with the propagated action potential or with the depolarization process in cholinergic neurons.     

The GLP-1 Receptor Agonist Liraglutide Increases Myocardial Glucose Oxidation Rates via Indirect Mechanisms and Mitigates Experimental Diabetic Cardiomyopathy

BackgroundType 2 diabetes (T2D) increases risk for cardiovascular disease. Of interest, liraglutide, a therapy for T2D that activates the glucagon-like peptide-1 receptor to augment insulin secretion, reduces cardiovascular-related death in people with T2D, though it remains unknown how liraglutide produces these actions. Notably, the glucagon-like peptide-1 receptor is not expressed in ventricular cardiac myocytes, making it likely that ventricular myocardium-independent actions are involved. We hypothesized that augmented insulin secretion may explain how liraglutide indirectly mediates cardioprotection, which thereby increases myocardial glucose oxidation.MethodsC57BL/6J male mice were fed either a low-fat diet (lean) or were subjected to experimental T2D and treated with either saline or liraglutide 3× over a 24-hour period. Mice were subsequently euthanized and had their hearts perfused in the working mode to assess energy metabolism. A separate cohort of mice with T2D were treated with either vehicle control or liraglutide for 2 weeks for the assessment of cardiac function via ultrasound echocardiography.ResultsTreatment of lean mice with liraglutide increased myocardial glucose oxidation without affecting glycolysis. Conversely, direct treatment of the isolated working heart with liraglutide had no effect on glucose oxidation. These findings were recapitulated in mice with T2D and associated with increased circulating insulin levels. Furthermore, liraglutide treatment alleviated diastolic dysfunction in mice with T2D, which was associated with enhanced pyruvate dehydrogenase activity, the rate-limiting enzyme of glucose oxidation.ConclusionsOur data demonstrate that liraglutide augments myocardial glucose oxidation via indirect mechanisms, which may contribute to how liraglutide improves cardiovascular outcomes in people with T2D.     

Sex differences in muscarinic receptor binding after chronic ethanol administration in the rat

Male and female rats were administered ethanol (5% v/v) in a liquid diet for 18 weeks. Pair-fed control animals were fed the same diet except that dextrose was substituted isocalorically for ethanol. Normal controls received a commercial laboratory chow for the same duration. Results showed that, in females, chronic ingestion of an ethanol liquid diet significantly increased the number of muscarinic receptor binding sites compared to both control groups. In contrast, for males, there was no significant difference in the mean number of binding sites among the treatment groups. Furthermore, the mean maximum number of binding sites for males and females varied across brain areas. Males had a significantly greater number of receptor binding sites than females in the striatum, while females had a greater number in the cortex. It was suggested that the geuder differences observed in the present study could be mediated by hormonal effects on central muscarinic functioning.     

Acute in vivo exposure to ethylcholine aziridinium (AF64A) depresses the secretion of quanta from motor nerve terminals

Quantal release of acetylcholine was evaluated for soleus nerve-muscle preparations removed from mice treated with the cholinergic neurotoxin AF64A. Treatment with two and three times the LD50 (i.p.) of AF64A caused a marked reduction of the frequency of miniature end-plate potentials (mepps) and the amplitude of end-plate potentials (epps). Since the amplitude of mepps was not altered, the reduction of epps was not due to reduction in the number of molecules of acetylcholine (ACh) per quantum or the end-plate sensitivity to ACh, but to a reduction of the number of quanta released in response to a nerve action potential. While this effect was not reversed when preparations were washed for 3 h, exposure to the potassium channel blocker, 3,4-diaminopyridine returned the mean quantal content of epps to normal. These data further support a presynaptic site of action for AF64A, and suggest that it may acutely disrupt the ionic processes underlying transmitter release.     

Path analysis of psychopharmacological data: catecholamine breakdown in man

This article applies path analysis to the problem of characterizing metabolic alterations in catecholamine systems when only static or single measures of precursor and products are available. In this article, simulated data from kinetic models of norepinephrine metabolism were examined using path analysis. The method of path analysis, which is based on correlations between compartments and not actual flow, correctly identified operative and nonoperative metabolic pathways in simulated models. In addition, actual data from normal subjects as to the 24-hour urinary values for norepinephrine, normetanephrine, vanillylmandelic acid, and 3-methoxy-4-hydroxyphenylglycol were analyzed using path analysis. It was found that metabolic routes that are known to be incomplete did not fit these data, whereas the known metabolic pathways for norepinephrine were correctly identified using path analysis. These results suggest that path analysis may provide a useful tool in identifying normal and abnormal catecholamine metabolic pathways in experimental situations where only single values of precursor and products are available.     

Stimulation of cell membrane sodium transport activity by lithium: possible relationship to therapeutic action

Because lithium is extruded from cells by means of coupled exchange for external sodium (Na+-Li+ countertransport), we hypothesized that clinical treatment with this agent could lead to significant augmentation of net cellular sodium influx. We therefore directly measured sodium influx in vitro using erythrocytes (RBCs) from 27 depressed bipolar patients. When cells were loaded with sufficient lithium to maximally stimulate Na+-Li+ countertransport activity (5.1 mmoles/1 RBCs), there was a significant 44% increase in mean sodium influx. To approximate clinical conditions more closely, we also studied sodium influx in a subset of eight subjects after loading cells with 0, 0.40, 0.66, and 1.55 mmoles lithium/1 RBCs. Over this range of lithium concentrations, sodium influx increased progressively. In separate experiments, we found that RBC sodium content measured in eight subjects did not change significantly during a 4-week course of lithium treatment. Thus, excess cellular sodium during such treatment may be extruded by increased activity of the membrane Na+-K+ pump, which has electrogenic properties and thereby could augment the membrane potential. In the nervous system, such an effect could stabilize cell membranes electrophysiologically, and possibly affect processes, such as behavioral sensitization or kindling, proposed to have a role in the development of recurrent affective disorders.