Models and methods to study Schwann cells

Schwann cells (SCs) are fundamental components of the peripheral nervous system (PNS) of all vertebrates and play essential roles in development, maintenance, function, and regeneration of peripheral nerves. There are distinct populations of SCs including: (1) myelinating SCs that ensheath axons by a specialized plasma membrane, called myelin, which enhances the conduction of electric impulses; (2) non‐myelinating SCs, including Remak SCs, which wrap bundles of multiple axons of small caliber, and perysinaptic SCs (PSCs), associated with motor axon terminals at the neuromuscular junction (NMJ). All types of SCs contribute to PNS regeneration through striking morphological and functional changes in response to nerve injury, are affected in peripheral neuropathies and show abnormalities and a diminished plasticity during aging. Therefore, methodological approaches to study and manipulate SCs in physiological and pathophysiological conditions are crucial to expand the present knowledge on SC biology and to devise new therapeutic strategies to counteract neurodegenerative conditions and age‐derived denervation. We present here an updated overview of traditional and emerging methodologies for the study of SCs for scientists approaching this research field.     

Endogenous opioids modulate the growth of the biliary tree in the course of cholestasis

BACKGROUND & AIMS: There is poor knowledge on the factors that modulate the growth of cholangiocytes, the epithelial cell target of cholangiopathies, which are diseases leading to progressive loss of bile ducts and liver failure. Endogenous opioids are known to modulate cell growth. In the course of cholestasis, the opioidergic system is hyperactive, and in cholangiocytes a higher expression of opioid peptide messenger RNA has been described. This study aimed to verify if such events affect the cholangiocyte proliferative response to cholestasis. METHODS: The presence of the delta opioid receptor (OR), muOR, and kappaOR was evaluated. The effects on cholangiocyte proliferation of the in vitro and in vivo exposure to their selective agonists, together with the intracellular signals, were then studied. The effects of the OR antagonist naloxone on cell growth were also tested both in vivo and in vitro. RESULTS: Cholangiocytes express all 3 receptors studied. deltaOR activation strongly diminished the proliferative and functional response of cholangiocytes to cholestasis, whereas muOR resulted in a slight increase in cell growth. The deltaOR signal is mediated by the IP3/CamKIIalpha/PKCalpha pathway, which inhibits the cAMP/PKA/ERK1/2/AKT cascade. In contrast, muOR activation stimulates the cAMP/PKA/ERK1/2/AKT cascade but does not affect the IP3/CamKIIalpha/PKCalpha pathway. The blockage of endogenous opioid peptides by naloxone further enhanced cholangiocyte growth both in vivo and in vitro. CONCLUSIONS: The increase in opioid peptide synthesis in the course of cholestasis aims to limit the excessive growth of the biliary tree in the course of cholestasis by the interaction with the deltaOR expressed by cholangiocytes.     

Intermittent clamping of the hepatic pedicle in simultaneous ultrasonography-guided liver resection and colorectal resection with intestinal anastomosis: is it safe?

Purpose

In patients with colorectal cancer (CRC) and synchronous colorectal liver metastases (CRLM) potentially candidates to combined liver (LR) and colorectal resection (CRR), the extent of LR and the need of hepatic pedicle clamping (HPC) in selected cases are considered risk factors for the outcome of the intestinal anastomosis. This study aimed to determine whether intermittent HPC is predictive of anastomotic leakage (AL) and has an adverse effect on the clinical outcome in patients undergoing combined restorative CRR and LR.

Methods

One hundred six LR have been performed for CRLM in our unit from July 2005. Patients who received CRR with anastomosis and simultaneous intraoperative ultrasonography (IOUS)-guided LR/ablation for resectable CRLM were included in this study. CRR was performed first. Intermittent HPC was decided at the discretion of the liver surgeon. The perioperative outcome was evaluated according to occurrence of AL and overall postoperative morbidity and mortality.

Results

Thirty-eight patients underwent simultaneous IOUS-guided LR/ablation and CRR with intestinal anastomosis; 19 underwent intermittent HPC (group ICHPY) while 19 did not (group ICHPN); the mean?±?SD (range) duration of clamping in group ICHPY was 58.6?±?32.2 (10.0–125.0)?min. Postoperative results were similar between groups. One asymptomatic AL occurred in group ICHPY (5.2 %). Major postoperative complications were none in group ICHPY and one (5.2 %) in group ICHPN, respectively. One patient in group ICHPY died postoperatively (5.2 %).

Conclusions

This study suggests that intermittent HPC during LR is not predictive of AL and has no adverse effect on the overall clinical outcome in patients undergoing combined restorative colorectal surgery and hepatectomy for advanced CRC.     

Heart Rate in Coronary Syndromes and Heart Failure

In the past 2 decades, there have been growing evidences that resting heart rate might be a marker of risk or even a risk factor for cardiovascular morbidity and mortality. This article reviews current evidences concerning the relation between heart rate and patients' outcome in different clinical settings such as acute coronary syndromes, left ventricular systolic dysfunction, and heart failure. The relationship between resting heart rate and the development of coronary artery disease, as well as all-cause and cardiovascular mortality, has been found to be strong, graded, and independent from other risk factors. Several lines of research indicate that heart rate plays an important role in the pathophysiology of atherosclerosis and in the clinical manifestations of coronary artery disease and that it is an independent prognostic factor in all coronary syndromes. The prognostic value of elevated heart rate in patients with heart failure has been tested in several clinical trials evaluating pharmacologic heart rate–lowering agents (eg, β-blockers). It is difficult to determine which percentage of the clinical benefit obtained with β-blockers is related to induced bradycardia because cardiac slowing is only one of the effects of these drugs. In the BEAUTIFUL trial, a subgroup analysis conducted in patients with resting HR more than 70 beats per minute showed that treatment with ivabradine was able to improve outcome. According to the results presented in this review, we can conclude that heart rate is a predictor of death in both stable coronary artery disease and acute coronary syndromes. Elevated heart rate is also able to negatively predict clinical outcomes in patients with heart failure. However, it is still unclear if heart rate reduction per se can improve prognosis.     

Hepatic fibrogenesis in response to chronic liver injury: novel insights on the role of cell‐to‐cell interaction and transition

Hepatic fibrosis represents the wound‐healing response process of the liver to chronic injury, independently from aetiology. Advanced liver fibrosis results in cirrhosis that can lead to liver failure, portal hypertension and hepatocellular carcinoma. Currently, no effective therapies are available for hepatic fibrosis. After the definition of hepatic stellate cells (HSCs) as the main liver extracellular matrix‐producing cells in the 1980s, the subsequent decade was dedicated to determine the role of specific cytokines and growth factors. Fibrotic progression of chronic liver diseases can be nowadays considered as a dynamic and highly integrated process of cellular response to chronic liver injury. The present review is dedicated to the novel mechanisms of cellular response to chronic liver injury leading to hepatic myofibroblasts' activation. The understanding of the cellular and molecular pathways regulating their function is crucial to counteract therapeutically the organ dysfunction caused by myofibroblasts' activation.     

The coexistence of heart failure predicts short term mortality, but not disability, in patients with acute ischemic stroke treated with thrombolysis: The Florence area Registry

BackgroundThrombolysis in ischemic stroke reduces disability but not mortality. Our aim was to evaluate the predictivity of heart failure (HF) diagnosis on 90-day mortality and disability in stroke patients undergoing thrombolysis.Material and methodsHospital records of all consecutive stroke patients treated with thrombolysis at our University Hospital were reviewed. Clinical assessment for HF and echocardiogram were available for all patients according to the thrombolysis institutional protocol. History of HF, LVEF < 40%, or BOSTON score ≥ 5 were tested as predictors.ResultsOf 130 patients (age 66 ± 14 years, 64.6% males, baseline NIHSS 15.6 ± 8.8), 17 (13.1%) had a history of HF, 16 (12.7%) a BOSTON score ≥ 5, 13 (10.9%) a LVEF < 40% and 24 (19.0%) met clinical criteria for HF diagnosis. Ninety-day mortality and incidence of disability were 16.1% and 36.1%, respectively. After adjustment for age, sex, baseline stroke severity and pre-stroke disability, LVEF < 40% and clinical diagnosis of HF were predictors of 90-day mortality, (p = 0.007 and p = 0.037, respectively).ConclusionClinical diagnosis of HF predicts mortality, but not disability, in acute stroke patients undergoing thrombolysis. Unlike anamnestic record of HF, clinical evaluation of cardiac function, with estimation of LVEF, predicts mortality.     

Parent reports of sleep/alertness problems and ADHD symptoms in a sample of obese adolescents

OBJECTIVE: Recent evidence suggests an association between obesity and Attention Deficit/Hyperactivity Disorder (ADHD) or ADHD traits. The characteristics of obese subjects with a higher probability of ADHD symptoms are still unclear. We explore the hypothesis that obese adolescents with sleep/alertness problems represent a subgroup at high risk for ADHD traits, independently from associated symptoms of anxiety/depression. The aim of this study was to assess the relationship between parent reports of sleep/alertness problems and ADHD traits in a clinical sample of obese adolescents, controlling for symptoms of anxiety/depression. METHODS: Seventy obese subjects (age range, 10-16 years) were included. The parents filled out the Sleep Disturbance Scale for Children (SDSC), the Conners Parents Rating Scale-Revised (Short Version) (CPRS-R:S), and the Child Behavior Checklist (CBCL). The ADHD Rating Scale (ADHD-RS) was completed by a child psychiatrist. RESULTS: Using multiple regression models controlling for symptoms of anxiety/depression, scores of excessive daytime sleepiness on the SDSC were significantly associated with ADHD traits on the CPRS-R:S as well as on the ADHD-RS. CONCLUSIONS: Obese adolescents described as excessively sleepy by their parents may be at higher risk of ADHD symptoms, independently from symptoms of anxiety/depression. Although the clinician may overlook a potential diagnosis of ADHD in obese adolescents described as sleepy, the results of this study suggest to systematically look for symptoms of ADHD in this subgroup of obese patients. Further studies using objective methods to assess sleep/alertness disturbances are needed to gain insight into the relationship between sleep/alertness disturbances and ADHD in obese individuals.