Galanin expressed in the excitatory fibers attenuates synaptic strength and generalized seizures in the piriform cortex of mice

The neuropeptide galanin is considered to be an endogenous antiepileptic agent, presumably acting via inhibition of glutamate release. Previously, we have demonstrated that in mice ectopically overexpressing galanin in cortical and hippocampal neurons, particularly in granule cells and their axons, the mossy fibers, hippocampal kindling epileptogenesis is suppressed and is associated with attenuated frequency facilitation in mossy fiber-CA3 cell synapses. We hypothesized that changes in synaptic transmission might occur also in other excitatory synapses of the galanin overexpressing (GalOE) mouse, contributing to seizure suppression. Lateral olfactory tract (LOT) synapses, formed by axons of olfactory bulb (OB) mitral cells and targeting piriform cortex (PC) pyramidal cells, ectopically express galanin in GalOE mice. Using whole-cell patch-clamp recordings, we found that excitatory synaptic responses recorded in PC pyramidal cells during high frequency stimulation of the LOT were attenuated in GalOE mice as compared to wild-type controls. This effect was mimicked by bath application of galanin or its agonist galnon to wild-type slices, supporting the notion of ectopic galanin action. Since the high frequency activation induced in vitro resembles epileptic seizures in vivo, we asked whether the observed synaptic inhibition would result in altered epileptogenesis when animals were kindled via the same synapses. In male GalOE mice, we found that the latency to convulsions was prolonged, and once animals had experienced the first stage 5 seizure, generalized seizures were less sustainable. These data indicate that the PC is a possible target for epilepsy treatment by ectopically overexpressing galanin to modulate seizure activity.     

Methamphetamine laboratory-related burns in Western Australia--why the explosion?

Introduction

With increasing numbers of illicit drug users in both urban and rural communities, users and producers are becoming increasingly enterprising in their sourcing of mind altering drugs. An example of this is the ‘amateur’ production of methamphetamine in domestic dwellings. We describe the mechanism of burn seen in methamphetamine production, the pattern of clinical injury, and the difficulties in treating these patients.

Methods

A 12 month retrospective study of five patient groups presenting to our burn service with injuries following methamphetamine laboratory explosion.

Results

Out of five patient groups we have treated 9 individual patients (with one patient presenting on two different occasions) with burns following methamphetamine laboratory explosion. All patients were male and required hospital admission. The cause of the explosive injury was initially reported as barbeque or oven related, assault, or accident in all patients. Two patients (in separate events) required intubation for associated inhalation injury. Burn size varied from 1% to 40% BSA. 7 patients required surgical debridement and skin grafting. Injury type was thermal and chemical. All patients had difficult follow-up due to low levels of clinic attendance.

Conclusion

Methamphetamine laboratory explosion burns are difficult injuries from the start. Invariably the true circumstances surrounding the injury are not clear, and clinicians should be suspicious of a meth lab explosion in suspect individuals with burns plus airway injury. Patient management is complex and often requires substantial analgesic and anxiolytic medication in conjunction with clinical psychology and psychiatry as an inpatient.     

Gluteus minimus-induced femoral head deformation in dysplasia of the hip

Lateral notching of the femoral head is considered pathognomonic for spastic subluxation of the hip. Less frequently, flattening is seen with extrusion of the femoral head in nonspastic hip dysplasia. The aim of this study was to throw light on its underlying pathomechanism. On the radiographs of 297 hips with developmental dysplasia, lateral flattening of the femoral head was seen in 18 hips (6%), but notching was present in only 1. Of 7 dysplasias due to cerebral palsy, 6 showed lateral notching. The gluteus minimus was felt to be responsible for the lateral femoral head changes as the muscle counteracts lateral migration of the femoral head. Intraoperative dissection of 3 hips supported this view. 1 hip with developmental dysplasia and lateral notching was subjected to a periacetabular osteotomy. At surgery, the tendon of the gluteus minimus was found to fit tightly into the notch. Of 2 hips with spastic dysplasia, 1 presented with and the other without lateral notching. In the hip with lateral notching, the gluteus minimus had a normal appearance and it lay in the defect of the femoral head. In the hip without notching, the gluteus minimus was atrophied with signs of fatty degeneration. We therefore believe that lateral notching is a sign of hypertonicity of the gluteus minimus muscle.     

Femoroacetabular impingement and the cam-effect. A MRI-based quantitative anatomical study of the femoral head-neck offset

We have observed damage to the labrum as a result of repetitive acetabular impingement in non-dysplastic hips, in which the femoral neck appears to abut against the acetabular labrum and a non-spherical femoral head to press against the labrum and adjacent cartilage. In both mechanisms anatomical variations of the proximal femur may be a factor. We have measured the orientation of the femoral neck and the offset of the head at various circumferential positions, using MRI data from volunteers with no osteoarthritic changes on standard radiographs. Compared with the control subjects, paired for gender and age, patients showed a significant reduction in mean femoral anteversion and mean head-neck offset on the anterior aspect of the neck. This was consistent with the site of symptomatic impingement in flexion and internal rotation, and with lesions of the adjacent rim. Furthermore, when stratified for gender and age, and compared with the control group, the mean femoral head-neck offset was significantly reduced in the lateral-to-anterior aspect of the neck for young men, and in the anterolateral-to-anterior aspect of the neck for older women. For patients suspected of having impingement of the rim, anatomical variations in the proximal femur should be considered as a possible cause.     

Evaluation of elbow and shoulder problems in professional baseball pitchers

When a professional athlete injures an elbow or shoulder, the uninjured joint must receive as much attention as the injured joint. Is there a relationship between injury of one joint and subsequent injury of the other joint? In the prospective study reported here, we created a database (a) to determine whether injury to one joint was more likely to result in a problem with the other joint and (b) to analyze for trends and correlations. A survey was administered to all pitchers on a professional baseball team to collect data about shoulder and elbow problems during their careers. Eighty-four pitchers (737 seasons of experience, 52 index injuries) were evaluated. Of the injured players, 27 were treated surgically. Risk for later injury was 4.6 times larger for players who had an index surgery than for those who had not. Of the players who had ulnar collateral ligament (UCL) reconstruction, 42% later sustained a shoulder injury. No player with rotator cuff surgery sustained a subsequent elbow or shoulder injury. There were significantly more upper extremity injuries with right-handed throwers. An elbow injury was more likely to result in shoulder problems, specifically after UCL reconstruction. Players who required surgery were almost 5 times more likely to have a later injury or surgery than players who did not require surgery.     

Molecular control of iron transport

The iron-regulatory hormone hepcidin is a 25-amino acid peptide that is synthesized in hepatocytes. Hepcidin binds to the cellular iron export channel ferroportin and causes its internalization and degradation and thereby decreases iron efflux from iron exporting tissues into plasma. By this mechanism, hepcidin inhibits dietary iron absorption, the efflux of recycled iron from splenic and hepatic macrophages, and the release of iron from storage in hepatocytes. Hepcidin synthesis is stimulated by plasma iron and iron stores and is inhibited by erythropoietic activity, ensuring that extracellular plasma iron concentrations and iron stores remain stable and the erythropoietic demand for iron is met. During inflammation, increased hepcidin concentrations cause iron sequestration in macrophages, resulting in hypoferremia and eventually anemia of inflammation. Hepcidin deficiency plays a central role in most iron overload disorders. The role of hepcidin abnormalities in anemias that are associated with renal disease and in resistance to erythropoietic therapies remains to be elucidated.     

A novel stop mutation in the EDNRB gene in a family with Hirschsprung’s disease associated with Multiple Sclerosis

Purpose

We identified a girl with Hirschsprung’s disease (HSCR) whose mother and grandmother had HSCR associated with multiple sclerosis (MS). The aim of this study was to outline mutations in HSCR-related genes and MS susceptibility alleles in these three individuals.

Methods

The phenotypes were reviewed based on medical records. The three subjects had rectosigmoid HSCR verified with histopathology. The mother and grandmother fulfilled the McDonald criteria for MS. DNA was isolated from EDTA-preserved blood according to standard procedures. Exome sequencing aiming mainly at analyzing HSCR associated genes as well as Sanger sequencing for confirmation was performed.

Results

All affected individuals carry a novel heterozygous nonsense mutation in the EDNRB gene (c.C397T,p.R133X,refNM_000115), changing an arginine at position 133 into a premature stop codon. None of the subjects were homozygous for the HLA risk alleles for MS.

Conclusion

We report a novel non-sense EDNRB gene mutation in a girl with HSCR and her mother and grandmother with HSCR and MS. We propose that this EDNRB gene mutation plays a role in the etiology of HSCR and also makes the subjects susceptible to MS.     

Influence of Oral Vitamin E Therapy on Micro-Inflammation and Cardiovascular Disease Markers in Chronic Hemodialysis Patients

Background. The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. Methods. 29 HD patients were randomized into two groups: 15 patients were treated orally with 400mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical – TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. Results. Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23±11.94 vs. 11.41±1.94 mIU/L, p<0.001; CRP: 5.20±3.50 vs. 3.40±3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. Conclusion. Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.