Intracellular signals involved in glucose control

Many proteins are involved in glucose control. The first step for glucose uptake is insulin receptor-binding. Stimulation of the insulin receptor results in rapid autophosphorylation and conformational changes in the beta chain and the subsequent phosphorylation of the insulin receptor substrate. This results in the docking of several SH2 domain proteins, including PI 3-kinase and other adapters. The final event is glucose transporter (GLUT) translocation to the cell surface. GLUT is in the cytosol but after insulin stimulation, several proteins are activated either in the GLUT vesicles or in the inner membrane. The role of the cytoskeleton is not well known, but it apparently participates in membrane fusion and vesicle mobilization. After glucose uptake, several hexokines metabolize the glucose to generate energy, convert the glucose in glycogen and store it. Type 2 diabetes is characterized by high glucose levels and insulin resistance. The insulin receptor is diminished on the cell surface membrane, tyrosine phosphorylation is decreased, serine and threonine phosphorylation is augmented. Apparently, the main problem with GLUT protein is in its translocation to the cell surface. At present, we know the role of many proteins involved in glucose control. However, we do not understand the significance of insulin resistance at the molecular level with type 2 diabetes.     

Kindling-like convulsive activities in the isolated ileum of the guinea pig. I. Electrical stimulation

A kindling-like convulsive activity model produced by subthreshold, iterative electrical stimulation of the isolated male guinea pig ileum is described. In this model, the mechanical activity of the longitudinal muscular fibers of the ileum was systematically quantified in terms of the basic frequency, tonus, amplitude, and transient amplitude increments (A, n spikes/20 min) of "normal" contractions and presence of high-amplitude, paroxysmal, "epileptiform" contractures (B, n spikes/20 min). Changes in these parameters were statistically compared through consecutive stages of the same stimulated male ileum (I = initial activation, II = initial inhibition. IIIA = late activation, and IV = late inhibition) and equivalent stages of stimulated female and nonstimulated male ilea where "kindling-like" activities were only occasionally observed. Basic tonus, amplitude, and number of A spikes showed significant changes through consecutive stimulated male ileum "kindling" stages: increased from baseline to stage I, decreased from I to II, increased from II to III and from III to IIIA, and decreased from IIIA to IV. The number of B spikes significantly increased from II to III, III to IIIA, and IIIA to IV. No significant changes in baseline frequency were found through all stages nor in tonus, amplitude, A and B spikes between stage IV and the self-sustained activity observed 120 min after stimulation. In addition, there were significant correlations between B spikes vs. basic tonus and amplitude and A spikes when the stimulated male ileum shifted from stage II to IIIA (positive correlations) and from IIIA to IV (negative correlations). Basic tonus during stage I, basic amplitude during IIIA, A spikes during self-sustained activity and B spikes during III, IIIA, IV, and self-sustained activity were in the stimulated male ileum larger than those in both the stimulated female and the nonstimulated male ilea. Tonus and A spikes during III and IIIA in the stimulated male ileum were larger than in the nonstimulated, whereas tonus during IV and self-sustaining activity and amplitude during II in the stimulated male ileum were smaller than in the female stimulated ileum.     

Valoración de parámetros clínicos y analíticos preoperatorios en apendicitis aguda complicada. Score para predecir apendicitis complicada

BackgroundTo analyze whether clinical and analytical parameters differ according to histopathology in cases of acute appendicitis (AA).MethodsThis is a retrospective, observational study including patients (>14 years of age) admitted for suspicion of AA from 1 April 2014 to 31 July 2016. Histopathology was divided into complicated (including perforated and gangrenous AA) and uncomplicated appendicitis (phlegmonous). Sex, age, temperature of patients on admission to the Emergency Department, symptom duration, preoperative white blood cell (WBC) count, neutrophil percentage, mean platelet volume (MPV), platelet distribution width (PDW), C-reactive protein (CRP) and hospital stay were compared in the two groups.ResultsThree hundred and thirty-five patients were analyzed, and 284 were included. Appendicitis was uncomplicated in 194 (68.3%) and complicated in 90 (31.7%). Age, symptom duration, neutrophil percentage, CRP and hospital stay were higher in the complicated AA group (P < .05). The mean differences between uncomplicated and complicated AA were: age 13.2 years (95% CI: 8.2-18.2), symptom duration 14.1 hours (95% CI: 6.3-21.9), neutrophil percentage 5.0% (95% CI: 3.2-6.8), CRP 73.6 mg/l (95% CI: 50.0-97.2) and hospital stay 2.2 days (95% CI: 1.4-3.0), with p<0.05 for all these variables. A model based on the preoperative parameters (age, symptom duration, neutrophil percentage and CRP) was calculated to predict the likelihood of complicated AA. The receiver operating characteristic (ROC) of the model had an area under the curve of 0.80 (95% CI 0.75-0.85).ConclusionThis model is able to diagnose complicated AA without the need for imaging techniques, although it must be validated with prospective analysis.     

Psychiatric aspects of parathyroid disease

Parathyroid diseases can present with psychiatric symptoms and can be recognized through determinations of serum electrolytes, especially the calcium level. Psychiatric evaluations should include a serum calcium concentration test, which is also essential in reassessment of patients poorly responsive to mental illness treatment. A magnesium and a phosphate assay may also be diagnostically helpful. Abnormality of divalent cation levels may provide evidence for consideration of, or ruling out, parathyroid disorders. Determinations of parathyroid hormone are performed if clinically indicated, and if abnormal divalent cation quantifications are confirmed. If parathyroid disease is identified, corrective endocrine therapies may diminish or even cure psychiatric aspects of parathyroid pathology. Failure to recognize a parathyroid disorder leaves an endocrine-induced mental dysfunction without proper treatment.     

Membrane events related to transmitter release in mouse motor nerve terminals captured by ultrarapid cryofixation

Summary The sequence of structural changes occurring in the presynaptic membrane during transmitter release was studied at the mouse neuromuscular junction using the combined quick-freezing and cryosubstitution techniques. The mouse levator auris longus (LAL) muscle was stimulated by two means: either, chemically, by soaking 5 min before freezing in a physiological solution containing 25mm potassium chloride or, electrically, by applying, 10 ms before freezing, a single supramaximal stimulus to the nerve-muscle preparation treated with 50 M 3,4-diaminopyridine (3,4-DAP) and 100 M (+)tubocurarine. In both cases, the preparations were maintained at approximately 5 °C, 5 min prior to freezing, in order to prolong nerve membrane changes. In most experiments, tannic acid (0.1%) was added to the substitution medium for better preservation of membranes. The different steps of warming in the substitution medium were strictly controlled from –90 °C to 4 °C. When fixed under chemical stimulation, the presynaptic membrane appeared very sinuous and synaptic vesicles were seen apposed to specialized sites facing subjunctional folds. When submitted to a single electrical stimulus, after treatment with 3,4-diaminopyridine, features of synaptic vesicle fusion were observed at these specialized sites which appear similar by their morphology, their macromolecular organization (already described) and their functional changes to active zones of the frog neuromuscular junction. Other images suggested that with 3,4-diaminopyridine which causes a pronounced and long-lasting release of transmitter, some vesicles collapse after exocytosis instead of being locally reformed by endocytosis.     

Spatiotemporal profile of synaptic activation produced by the electrical and visual stimulation of retinal inputs to the optic tectum: a current source density analysis in the pigeon (Columba livia)

The optic tectum of the pigeon is a highly organized, multilayered structure that receives a massive polystratified afference of at least five different populations of retinal ganglion cells and gives rise to various anatomically segregated efferent systems. The synaptic organization of retino-tectal circuitry is, at present, mostly unknown. To investigate the spatiotemporal profile of synaptic activation produced by differential (electrical and visual) stimulation of the retinal inputs, we performed a high-spatial-resolution current source density analysis in the optic tectum of the anaesthetized pigeon. Electrical stimuli consisted of brief pulses of different durations applied to the optic nerve head, while visual stimuli consisted of light flashes of different intensities. Electrical stimulation generated sinks confined to retinorecipient layers. The temporal structure, spatial location and thresholds of these sinks indicated that they are all due to primary tectal synapses of retinal fibers with different conduction velocities. Sinks evoked by the fastest retinal axons were more superficially located than sinks produced by slower retinal fibers. Visual stimulation, on the other hand, resulted in a more complex pattern of current sinks, with various sinks located in the retinorecipient layers and also well below. Visual stimulation induced action potentials at superficial as well as deep tectal levels. We conclude that electrical stimulation activates most of the populations of ganglion cells as well as their primary tectal synapses, but is unable to elicit a significant activation of secondary tectal synapses. Visual stimulation, on the contrary, activates just some of the incoming retinal populations, but in a way that produces noticeable secondary activation of intratectal circuits. Laminar segregation of retinally evoked tectal activity, as reported here, has also been found in other vertebrates. Similarities and differences with previous studies are discussed.     

Progressive acquired lymphangioma: report of a case and review of the literature

We present 2-year-old patient with a allopecia lesions in scalp, and clinique diagnostic of Cutis Aplasia. The anatomopathologic study have diagnosed the lesions as Acquired Progressive Lymphangioma (APL). Is a rare vascular tumour that has a tendency to appear in childhood an to progress slowly over the years. It could present as a solitary erythematous macule or plaque and a simple excision is usually curative. Our patient is the youngest reported in the literature.     

Axillary hibernoma: an unusual soft tissue tumor

Hibernomas are rare soft tissue tumors of brown fat differentiation. A case of a large axillary hibernoma, along with a review of its pathology, is presented. This tumor matches the largest hibernoma in the literature and is the largest in an axillary site.