Severity assessment in mice subjected to carbon tetrachloride.

The Directive 2010/63 EU requires classifying burden and severity in all procedures using laboratory animals. This study evaluated the severity of liver fibrosis induction by intraperitoneal carbon tetrachloride (CCl4) injections in mice. 29 male C57BL/6N mice were treated three times per week for 4 weeks with an intraperitoneal injection (50 µl) of either 0.6 ml/kg body weight CCl4-vehicle solution, germ oil (vehicle-control) or handling only. Severity assessment was performed using serum analysis, behavioral tests (open field test, rotarod, burrowing and nesting behavior), fecal corticosterone metabolite (FCM) measurement, and survival. The most significant group differences were noticed in the second week of treatment when the highest AST (1463 ± 1404 vs. 123.8 ± 93 U/L, p < 0.0001) and nesting values were measured. In addition, respective animals showed lower moving distances (4622 ± 1577 vs. 6157 ± 2060 cm, p < 0.01) and velocity in the Open field, identified as main factors in principal component analysis (PCA). Overall, a 50% survival rate was observed within the treatment group, in which the open field performance was a good tracer parameter for survival. In summary, this study demonstrates the feasibility of assessing severity in mice using behavioral tests and highlight the open field test as a possible threshold parameter for risk assessment of mortality.

Epileptic seizure discharges in patients after open chamber cardiac surgery-a prospective prevalence pilot study using continuous electroencephalography.

PURPOSE: Patients undergoing cardiac surgery often develop delirium which increases the risk of postoperative morbidity and leads to a reduced quality of life. Retrospective studies show a higher incidence of delirium in patients with seizures. However, these studies do not systematically detect subclinical seizures, so the incidence of seizures after cardiac surgery remains speculative. The objective of this study is to determine the prevalence of electrographic seizures after elective open-chamber cardiac surgery. METHODS: This prospective, blinded, monocentric, observational study investigated patients scheduled for elective open-chamber valve reconstruction or replacement. Anaesthesia, surgery and postoperative treatment were standardized and not influenced by the presented observation. After surgery, all patients arrived at the ICU, and EEG monitoring started within the first hour. EEG recording was continuously performed for up to 24 h, and the results were independently analysed by two blinded EEG board-certified neurologists. RESULTS: 100 patients were included. Abnormal EEG patterns were present in 33% of patients, and 9% of all patients showed electrographic seizures. The main EEG activity at the beginning of each recording was suppressed or showed a burst-suppression pattern, and at the end of recording, all patients had an alpha/theta rhythm. An association between electrographic seizures and delirium was found (pχ2 < 0.01). CONCLUSION: This study reveals a surprisingly high incidence of abnormal EEG patterns and electrographic seizures in patients undergoing open-chamber cardiac surgery. As electrographic seizures are associated with the incidence of delirium, this finding is a relevant phenomenon in the post-cardiac surgery ICU population.

Adjustment of oral diet based on flexible endoscopic evaluation of swallowing (FEES) in acute stroke patients: a cross-sectional hospital-based registry study.

BACKGROUND: Diagnosing dysphagia in acute stroke patients is crucial, as this comorbidity determines morbidity and mortality; we therefore investigated the impact of flexible nasolaryngeal endoscopy (FEES) in acute stroke patients. METHODS: The FEES investigation as performed in acute stroke patients treated at a large university hospital, allocated as a standard procedure for all patients suspected of dysphagia. We correlated our findings with baseline data, disability status, pneumonia, duration of hospitalisation, necessity for mechanical ventilation and treatment on the intensive care unit. The study was designed as a cross-sectional hospital-based registry. RESULTS: We investigated 152 patients. The median age was 73; 94 were male. Ischemic stroke was diagnosed in 125 patients (82.2%); 27 (17.8%) suffered intracerebral haemorrhage. Oropharyngeal dysphagia was diagnosed in 72.4% of the patients, and was associated with higher stroke severity on admission (median NIHSS 11 [IQR 6-17] vs. 7 [4-12], p = .013; median mRS 5 [IQR 4-5] vs. 4 [IQR 3-5], p = .012). Short-term mortality was higher among patients diagnosed with dysphagia (7.2% vs. 0%, p = .107). FEES examinations revealed that only 30.9% of the patients had an oral diet appropriate for their swallowing abilities. A change of oral diet was associated with a better outcome at discharge (mRS; p = .006), less need of mechanical ventilation (p = .028), shorter period of hospitalisation (p = .044), and lower rates of pneumonia (p = .007) and mortality (p = .011). CONCLUSION: Due to the inability of clinical assessments to detect silent aspiration, FEES might be better suited to identify stroke patients at risk and may contribute to a better functional outcome and lower rates of pneumonia and mortality. Our findings also point to a low awareness of dysphagia, even in a specialised stroke centre. FEES in acute stroke patients helps to adjust the oral diet for the vast majority of stroke patients (69.1%) based on their swallowing abilities, potentially avoiding severe complications.

Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping.

PURPOSE: Fabry disease (FD) is an X-linked multi-organ disorder of lysosomal metabolism with cardiac disease being the leading cause of death. Identifying early FD-specific pathologies is important in the context of maximum therapeutic benefit in these stages. Therefore, the aim of this study was to investigate the value of quantitative cardiac T1 mapping as a potential disease-specific surrogate. METHODS: 16 consecutive FD patients (9 female, 7 male; median age: 54 years, IQR 17) and 16 control patients (9 female, 7 male; median age: 52 years, IQR 20) were investigated at 1.5 Tesla. Native T1 mapping was performed using a modified look locker inversion recovery sequence (MOLLI) and native T1 times were measured within the septal myocardium at the midventricular short-axis section. Also functional parameters, left ventricular morphology, presence of late-gadolinium enhancement, cTnI- and Lyso-Gb3-Levels were evaluated. RESULTS: The median native septal T1 time for FD was 889.0 ms and 950.6 ms for controls (p < 0.003). LGE and positive cTnI values (0.26 ±â€Š0.21) were present in 5 FD patients (31.25 %), and left ventricular hypertrophy (LVH) was present in 4 FD patients (25.00 %). The 4 cTnI and 8 Lyso-Gb3 positive FD patients had significantly lower native T1 values (p < 0.05, respectively p < 0.01). Assuming a T1 cut-off value of 900 ms for the identification of increased cardiac lipid deposit, 9 patients with FD (56.25 %) had pathologic values (4 patients cTnI and 8 patients Lyso-Gb3 positive). Moreover, native septal T1 showed a good negative correlation to Lyso-Gb3 (r = - 0.582; p = 0.018). CONCLUSION: A pathologic cardiac native T1 time obviously reflects cardiac involvement in the scope of FD at tissue level. In the future native T1 mapping as an imaging biomarker might allow identification of early stages of cardiac involvement in FD before morphological changes are obvious. KEY POINTS: · Native T1 values are significantly decreased in Fabry disease.. · Native T1 shows promising correlation to cardiac and Fabry-specific biomarkers.. · Native T1 mapping might have great potential for early disease detection and therapy monitoring.. CITATION FORMAT: · Roller FC, Fuest S, Meyer M et al. Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping. Fortschr Röntgenstr 2019; 191: 932 - 939.

What is the value of fibre-endoscopic evaluation of swallowing (FEES) in neurological patients? A cross-sectional hospital-based registry study.

OBJECTIVES: Fibre-endoscopic evaluation of swallowing (FEES) to detect dysphagia is gaining more and more importance as a diagnostic tool. Therefore, we have investigated the impact of FEES in neurological patients in a clinical setting. DESIGN: Cross-sectional hospital-based registry. SETTING: Primary acute care in a neurological department of a German university hospital. PARTICIPANTS: 241patients with various neurological diseases who underwent FEES procedure. PRIMARY AND SECONDARY OUTCOME MEASURES: Dysphagia and related comorbidities. RESULTS: 267 FEES were performed in 241 patients with various neurological diagnoses. Dysphagia was diagnosed in 68.9% of the patients. In only 33.1% of the patients, appropriate oral diet was chosen prior to FEES. A relevant dysphagia occurred more often in patients with structural brain lesions (83.1% vs 65.3%, P=0.001), patients with dysphagia had a longer hospitalisation (median 18 (IQR 12-30) vs 15 days (IQR 9.75-22.75), P=0.005) and had a higher mortality (8.4% vs 1.3%, P=0.041). When the oral diet was changed, we observed a lower pneumonia rate (36% vs 50%, P=0.051) and a lower mortality (3.7% vs 11.3%, P=0.043) in comparison to no change of oral diet. A restriction of oral diet was identified more often in older patients (median 75 years (IQR 66.3-82 years) vs median 72 years (IQR 60-79 years), P=0.01) and in patients with structural brain lesions (86.8% vs 73.1%, P=0.05). CONCLUSION: On clinical investigation, dysphagia was misjudged for the majority of the patients. FEES might help to compensate this drawback, revising the diet regime in nearly 70% of the patients.

Troglitazone treatment increases protein kinase B phosphorylation in skeletal muscle of normoglycemic subjects at risk for the development of type 2 diabetes.

We investigated whether the effect of troglitazone on glucose disposal is associated with altered insulin signaling. Nondiabetic first-degree relatives of type 2 diabetic patients (age 30 +/- 2 years, BMI 30 +/- 1 kg/m(2); n = 20) were randomized in a double-blind manner to 3 months of troglitazone (200 mg/day) or placebo treatment. Before and after treatment, 3-h euglycemic-hyperinsulinemic glucose clamps (40 mU. m(-2). min(-1)) were performed, and muscle biopsies were obtained immediately before and after the clamps. In the biopsies, insulin receptor kinase (IRK) activity, insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI3K) activity, Ser(473) and Thr(308) phosphorylation of protein kinase B (PKB), and protein expression of IRS-1, IRS-2, phosphoinositol-dependent kinase-1 (PDK-1), PKB, and GLUT-4 were determined. After troglitazone treatment, insulin-stimulated glucose disposal was increased compared with pretreatment and placebo (279 +/- 37 vs. 211 +/- 26 and 200 +/- 25 mg. m(-2). min(-1); both P < 0.05). IRK and PI3K activities were not altered by troglitazone, but PKB Ser(473) phosphorylation was enhanced compared with pretreatment and placebo at the clamp insulin level (138 +/- 36 vs. 77 +/- 16 and 55 +/- 13 internal standard units; both P < 0.05) and with pretreatment at the basal level (31 +/- 9 vs. 14 +/- 4 internal standard units; P < 0.05). PKB Thr(308) phosphorylation also tended to be higher, but this was not statistically significant. Troglitazone did not alter insulin receptor number or IRS-1, IRS-2, PKB, PDK-1, or GLUT-4 protein expression. We conclude that increased PKB phosphorylation may contribute to the insulin-sensitizing effects of thiazolidinediones in human skeletal muscle.

Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes.

Cross talk between adrenergic and insulin signaling systems may represent a fundamental molecular basis of insulin resistance. We have characterized a newly established beta(3)-adrenoceptor-deficient (beta(3)-KO) brown adipocyte cell line and have used it to selectively investigate the potential role of novel-state and typical beta-adrenoceptors (beta-AR) on insulin signaling and action. The novel-state beta(1)-AR agonist CGP-12177 strongly induced uncoupling protein-1 in beta(3)-KO brown adipocytes as opposed to the beta(3)-selective agonist CL-316,243. Furthermore, CGP-12177 potently reduced insulin-induced glucose uptake and glycogen synthesis. Neither the selective beta(1)- and beta(2)-antagonists metoprolol and ICI-118,551 nor the nonselective antagonist propranolol blocked these effects. The classical beta(1)-AR agonist dobutamine and the beta(2)-AR agonist clenbuterol also considerably diminished insulin-induced glucose uptake. In contrast to CGP-12177 treatment, these negative effects were completely abrogated by metoprolol and ICI-118,551. Stimulation with CGP-12177 did not impair insulin receptor kinase activity but decreased insulin receptor substrate-1 binding to phosphatidylinositol (PI) 3-kinase and activation of protein kinase B. Thus the present study characterizes a novel cell system to selectively analyze molecular and functional interactions between novel and classical beta-adrenoceptor types with insulin action. Furthermore, it indicates insulin receptor-independent, but PI 3-kinase-dependent, potent negative effects of the novel beta(1)-adrenoceptor state on diverse biological end points of insulin action.