The Reeler Mouse: A Translational Model of Human Neurological Conditions, or Simply a Good Tool for Better Understanding Neurodevelopment?

The first description of the Reeler mutation in mouse dates to more than fifty years ago, and later, its causative gene (reln) was discovered in mouse, and its human orthologue (RELN) was demonstrated to be causative of lissencephaly 2 (LIS2) and about 20% of the cases of autosomal-dominant lateral temporal epilepsy (ADLTE). In both human and mice, the gene encodes for a glycoprotein referred to as reelin (Reln) that plays a primary function in neuronal migration during development and synaptic stabilization in adulthood. Besides LIS2 and ADLTE, RELN and/or other genes coding for the proteins of the Reln intracellular cascade have been associated substantially to other conditions such as spinocerebellar ataxia type 7 and 37, VLDLR-associated cerebellar hypoplasia, PAFAH1B1-associated lissencephaly, autism, and schizophrenia. According to their modalities of inheritances and with significant differences among each other, these neuropsychiatric disorders can be modeled in the homozygous (reln(-/-)) or heterozygous (reln(+/-)) Reeler mouse. The worth of these mice as translational models is discussed, with focus on their construct and face validity. Description of face validity, i.e., the resemblance of phenotypes between the two species, centers onto the histological, neurochemical, and functional observations in the cerebral cortex, hippocampus, and cerebellum of Reeler mice and their human counterparts

Combined Endoscopic Stent-In-Stent Placement by Lumen-Apposing Metal Stents Through Self-Expanding Metal Stents for Simultaneous Malignant Biliary and Duodenal Obstruction

The palliation of simultaneous biliary and duodenal obstruction in patients with advanced pancreatic cancer is a clinically and technically challenging scenario. Endoscopic procedures are a valid alternative to surgical or percutaneous transhepatic biliary drainage. The availability of self-expanding metal stents (SEMSs) and lumen-apposing metal stents (LAMS) have expanded therapeutic options. We describe a case in which biliary and duodenal obstructions were treated successfully with the combined use of SEMS and LAMS devices. Endoscopic ultrasound-guided biliary drainage with the use of new LAMS and a duodenal SEMS can be a valid option in expert hands as a palliative and minimally invasive treatment for gastric outlet and biliary obstruction

A case of hemorrhagic shock due to massive upper gastrointestinal bleeding: from the differential diagnosis to the correct management

Upper Gastro-Intestinal Bleeding (UGIB) spans from minor bleeding to life-threatening events. Identification of early signs of shock, proper management of hemodynamically unstable patients, and correct risk stratification are essential for an appropriate diagnostic workup and therapy. This case reports a young man admitted to the emergency department with haematemesis. His medical history was unremarkable, without any risk factors for gastrointestinal bleeding. A few hours after admission, further episodes of haematemesis occurred, and the patient's condition rapidly deteriorated to irreversible shock. A contrast-enhanced computed tomography (CECT) revealed morphological features of chronic liver disease and oesophagal varices. The patient underwent upper gastrointestinal endoscopy, confirming oesophagal varices with massive bleeding. Although promptly applied, endoscopic hemostasis was ineffective, and the patient died twenty-four hours after admission. Based on this case, we reviewed the diagnostic and therapeutic approaches for patients with massive UGIB and provided a practical approach to this life-threatening emergency

The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age

The γ phosphorylated form of the histone H2AX (γH2AX) was described more than 40 years ago and it was demonstrated that phosphorylation of H2AX was one of the first cellular responses to DNA damage. Since then, γH2AX has been implicated in diverse cellular functions in normal and pathological cells. In the first part of this review, we will briefly describe the intervention of H2AX in the DNA damage response (DDR) and its role in some pivotal cellular events, such as regulation of cell cycle checkpoints, genomic instability, cell growth, mitosis, embryogenesis, and apoptosis. Then, in the main part of this contribution, we will discuss the involvement of γH2AX in the normal and pathological central nervous system, with particular attention to the differences in the DDR between immature and mature neurons, and to the significance of H2AX phosphorylation in neurogenesis and neuronal cell death. The emerging picture is that H2AX is a pleiotropic molecule with an array of yet not fully understood functions in the brain, from embryonic life to old age

Neuroanatomia dell'uomo. 2a Edizione

Questa seconda edizione si presenta aggiornata e arricchita di alcune significative recenti acquisizioni nel campo delle neuroscienze sperimentali e clinich

Therapeutic Potential of Allicin and Aged Garlic Extract in Alzheimer’s Disease

Garlic, Allium sativum, has long been utilized for a number of medicinal purposes around the world, and its medical benefits have been well documented. The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. Garlic and garlic extracts, especially aged garlic extracts (AGEs), are rich in bioactive compounds, with potent anti-inflammatory, antioxidant and neuroprotective activities. In light of these effects, garlic and its components have been examined in experimental models of Alzheimer’s disease (AD), the most common form of dementia without therapy, and a growing health concern in aging societies. With the aim of offering an updated overview, this paper reviews the chemical composition, metabolism and bioavailability of garlic bioactive compounds. In addition, it provides an overview of signaling mechanisms triggered by garlic derivatives, with a focus on allicin and AGE, to improve learning and memory

Disseminated Mycobacterium avium complex disease in a patient with left ventricular assist device (Heart Mate II)

Although disseminated Mycobacterium avium complex disease occurs mainly in immunocompromised hosts, especially HIV-infected patients in the last stage of the disease (AIDS), this condition is still rare in immunocompetent subjects. We report the case of a Caucasian man who received a left ventricular assist device two years before as a bridge to heart transplantation, that began to present signs and symptoms of mycobacterial infection. The diagnostic work-up we performed showed the presence of Mycobacterium intracellulare in lungs and both peripherical and bone marrow blood. Although evaluated, we found no abnormalities in the patient's immune system that can be related to mycobacterial infection. The beginning of a specific therapy made the patient slowly improve and further nuclear medicine assay (PET-TC) showed a good reduction in radio-labelled drug captation

EVALUATION OF DIFFERENT STORAGE CONDITIONS ON CHEMICAL COMPOSITION AND BIOACTIVE COMPOUNDS OF VOGHIERA GARLIC PDO

Garlic (Allium sativum L.) is considered one of the most important vegetables, with various uses throughout the world, either as a raw vegetable for culinary purposes, or as an ingredient of traditional and modern medicine, and proper storage conditions are crucial to retain the high quality of garlic bulbs and its by-products, taking into account the high importance of organosulfur and phenolic compounds1. Time/temperature storage combination is an important factor since it can affect chemical composition and consequently the final bioactivity potency of garlic. This study aims to examine different storage temperature and time/temperature combination on the chemical composition and quality of Voghiera garlic PDO (a white ecotype with long tradition in Ferrara district2). In detail we considered -3/-4°C (industrial storage) for short, medium and long times (3,6 and 9 months); -3/-4°C for 3 months and then +3/+4°C for other 3 months; +3/+4°C for 3 months (home conservation). We focused our attention on the organosulfur compounds content, phenolic compounds and related antioxidant activity since they highly contribute to the effective bioactive properties of garlic and improve the shelf-life of the product. We observed a decrease in sulfur compounds after 6 months both at -3/-4°C and +3/+4°C while phenolic compounds were stable during the storage period. To evaluate the bioactive compounds, the extracts at different time/temperature storage were administered to breast cancer cell lines and measured antioxidant and anti-inflammatory activity on macrophage RAW 264.7 cells. The results highlighted a decrease also in bioactive effect and suggested the storage at -3/-4°C to better preserve the antioxidant and bioactive property