A 72-h sedated porcine model of traumatic spinal cord injury.

Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

Diffusional kurtosis imaging as a possible prognostic marker of cervical incomplete spinal cord injury outcome: a prospective pilot study.

BACKGROUND: Spinal cord injury (SCI) is associated with substantial chronic morbidity and mortality. Routine imaging techniques such as T1- and T2-weighted magnetic resonance imaging (MRI) are not effective in predicting neurological deficiency grade or outcome. Diffusional kurtosis imaging (DKI) is an MR imaging technique that provides microstructural information about biological tissue. There are no longitudinal prospective studies assessing DKI metrics in acute traumatic SCI. Therefore, the purpose of this study was to establish a DKI protocol for acute SCI and correlate the DKI metrics to the functional neurological outcome of the patients. METHODS: Eight consecutive SCI patients referred to our institution with cervical SCI were included in the study. An acute diagnostic MRI scan was supplemented with a novel fast, mean kurtosis DKI protocol, which describes the average deviation from Gaussian diffusional along nine different directions. Mean kurtosis values were measured at the injury site and normalized to the mean kurtosis values of a non-injured site. At discharge form specialized rehabilitation, patients were evaluated using the Spinal Cord Independence Measure-III (SCIM-III). The DKI metrics and SCIM-III were analysed using Spearman's rank correlation. RESULTS: This pilot study found a significant correlation between decreasing mean kurtosis values at the injury site of the spinal cord and higher grade of disability measured by the SCIM-III (p = 0.002). CONCLUSION: This pilot study found that DKI may be a valuable tool as a prognostic marker in the acute phase of SCI.

Vagus Nerve Cross-Sectional Area in Patients With Parkinson's Disease-An Ultrasound Case-Control Study.

Background: Vagal parasympathetic neurons are prone to degeneration in Parkinson's disease (PD). High-resolution ultrasound can precisely estimate the cross-sectional (CSA) area of peripheral nerves. Here, we tested the hypothesis that vagus CSA is reduced in PD. Methods: We included 56 healthy controls (HCs) and 63 patients with PD. Using a high-end ultrasound system equipped with a high-frequency transducer, five images were obtained of each nerve. The hypoechoic neuronal tissue was delineated offline with dedicated software and the CSA extracted. Results: In the initial PD vs. HC comparison, no statistically significant differences were observed in mean left vagus CSA (HC: 1.97 mm2, PD: 1.89 mm2, P = 0.36) nor in mean right vagus CSA (HC: 2.37 mm2, PD: 2.23 mm2, P = 0.17). The right vagus CSA was significantly larger than the left vagus CSA in both groups (P < 0.0001). Females were overrepresented in the HC group and presented with generally smaller vagus CSAs. Consequently, sex-adjusted CSA was significantly smaller for the right vagus nerve of the PD group (P = 0.041), but not for the left. Conclusion: A small but significant reduction in sex-adjusted right vagus CSA was observed in patients with PD. The left vagus CSA was not significantly reduced in patients with PD. Ultrasound may not be a suitable method to detecting vagal axonal loss in individual patients.

Fatal 3-Nitropropionic Acid Poisoning after Consuming Coconut Water.

We describe the fatal course of a patient with initial symptoms of vomiting and nausea who developed symptoms of dystonia, encephalopathy, and coma. The cause of death was poisoning with 3-nitropropionic acid from coconut water spoiled with the fungus Arthrinium saccharicola. We present the clinical findings and forensic analysis.

[Assessment of the prognosis in patients who remain comatose after resuscitation from cardiac arrest]. / Vurdering af prognose hos patienter med manglende opvågning efter hjertestop

In Denmark there are around 3,500 unexpected cardiac arrests (CA) out of hospital each year. There is an unknown number of CA in hospitals. The survival rate after CA outside a hospital in Denmark is 10% after 30 days. There are varying data for the neurological outcome in this group of patients. The purpose of this work is to disseminate new knowledge and to help standardizing the treatment in the group of patients who remain comatose after being resuscitated from CA. Assessment of the prognosis for a patient in this group can be made after 72 hours and a multi-modal approach to the patient is required.

Comparison of insulin responses in experiments using pooled mice islets versus islets from individual animals in the study of diabetes.

Isolated islets of Langerhans have been widely used to clarify the beta-cell function and insulin secretion in normal and diabetic states. Most of these studies have applied a pooled-islet design using isolated islets from a number of animals. However, to our knowledge, no previous studies have explored the consequences of using the pooled-islet design. From a statistical point, it may be preferable to use a design with islets from only one animal at a time under different experimental conditions and subsequently to repeat the experiments with islets from other animals. The present study compares these 2 designs in terms of their insulin response to glucose and arginine. We found higher insulin responses to glucose and arginine in pooled islets than in islets from individual animals, but differences between different stimuli were comparable between the 2 designs. However, the SEs on these differences are much smaller in the design with pooled islets than in the separate-islet design, and, consequently, corresponding P values will be much smaller. The statistical analysis of the design with islet separated per animal can explain this discrepancy because it identifies a non-ignorable random variation between animals compared with the variation within animals. In statistical terms, this implies a positive correlation between islets from the same animal. Ignoring this fact in the design with pooled islets overestimates the degrees of freedom and hence underestimates the SEs on the mean responses. This will in turn produce too small P values when using statistical tests to compare mean responses to different stimuli.

Comparison of a high saturated fat diet with a high carbohydrate diet during pregnancy and lactation: effects on insulin sensitivity in offspring of rats.

Insulin resistance plays a critical role in metabolic syndrome and is influenced by the amount and saturation of dietary fat. Both prenatal over and under nutrition can program susceptibility to insulin resistance. The aim of the study was to explore the impact of dietary fat given to mothers during gestation on the insulin sensitivity of the offspring. Female Wistar rats were fed with diets rich in carbohydrate (CHO) or saturated fat (SAFA) during pregnancy. The male offspring was split into 5 subgroups: groups 1 (control) and 3 continued on CHO or SAFA after birth, respectively. Group 2 with mothers on CHO continued on the CHO diet during the nursing period and changed to SAFA postweaning. Group 4 with mothers on SAFA continued on SAFA during the weaning period and changed to CHO postweaning. For group 5 the offspring of mothers given SAFA diet was changed to nursing mothers on CHO diet immediately after birth and continued on the same diet postweaning. At the age of 16 weeks, a euglycemic hyperinsulinemic clamp was performed. The glucose infusion rate was lowered in the groups receiving the SAFA diet (group 2, 24.7 +/- 2.0 mg/kg per minute; group 3, 22.0 +/- 1.9 mg/kg per minute; P < .05) compared with group 1 (32.2 +/- 2.3 mg/kg per minute). We did not detect any alterations in the rate of glucose disappearance during the clamp for any of the groups compared with group 1. A diet high in SAFA given to mothers during gestation and/or the weaning period does not seem to have deleterious effects on the insulin sensitivity in the offspring.

Preventive effects of a soy-based diet supplemented with stevioside on the development of the metabolic syndrome and type 2 diabetes in Zucker diabetic fatty rats.

The world witnesses an explosive increase in diabetes, demanding intensified prevention and treatment not least for the low-income population. The plant, Stevia rebaudiana Bertoni, has been used for the treatment of diabetes in traditional medicine. We have previously demonstrated that stevioside, a diterpene glycoside isolated from the plant Stevia rebaudiana Bertoni, possesses insulinotropic, glucagonostatic, antihyperglycemic, and blood pressure-lowering effects in animal studies. We have also found that a dietary supplement, Abalon, of soy protein, isoflavones, and cotyledon fiber has beneficial effects on cardiovascular risk markers in type 2 diabetes. The aim of this study was to investigate if the combination of stevioside and a dietary supplement of soy protein possesses beneficial qualities in the treatment of type 2 diabetes and the metabolic syndrome. We randomized male Zucker diabetic fatty rats into 4 groups and fed them the different test diets for 10 weeks: (A) standard carbohydrate-rich laboratory diet (chow), (B) chow+stevioside (0.03 g/kg body weight [BW] per day), (C) 50% soy (Abalon)+50% chow (adjusted for vitamins and minerals), and (D) 50% soy (Abalon)+50% chow+stevioside 0.03 g/kg BW per day. We measured plasma glucose, blood pressure, weight, and food intake once weekly. The animals were equipped with an intra-arterial catheter, and at week 10, the conscious rats underwent an intra-arterial glucose tolerance test (2.0 g/kg BW). Stevioside exerts beneficial effects in type 2 diabetic Zucker diabetic fatty rats, that is, lowers blood glucose (area under the glucose curve [AUC(30min)]: group A vs B, a 19% reduction; and group C vs D, a 12% reduction; P<.001). We did not detect any effect on insulin or glucagon responses. After 2 weeks of treatment, a decrease in the systolic blood pressure was observed in the stevioside-treated groups (P<.01). Abalon had beneficial effects on cardiovascular risk markers, that is, (1) lowers total cholesterol (P<.01), (2) reduces triglycerides (P=.01), and (3) reduces free fatty acids (P<.001). The combination of stevioside and soy supplementation appears to possess the potential as effective treatment of a number of the characteristic features of the metabolic syndrome, that is, hyperglycemia, hypertension, and dyslipidemia. A long-term human study of the concept in type 2 diabetic subjects is needed to verify these promising results in animal diabetes.