Prevention of Mrp2 activity impairment in ethinylestradiol-induced cholestasis by ursodeoxycholate in the rat.

Ethinylestradiol (EE) induces cholestasis by affecting bile salt-dependent and -independent fractions of the bile flow. The decrease in bile salt-independent flow is thought to be due, in part, to a reduction in the expression of the canalicular transporter Mrp2. The impact of modulation of Mrp2 function by sodium ursodeoxycholate (UDC) in EE cholestasis is unknown. We evaluated the protective effect of UDC on EE-induced impairment of Mrp2 activity in vivo and in isolated hepatocytes, by using the substrate dinitrophenyl S-glutathione (DNP-SG). EE was administered to male Wistar rats at a dose of 5 mg/kg s.c. for 5 days. UDC was coadministered with EE at a dose of 25 mg/kg b.wt. i.p. for the same period. EE alone reduced DNP-SG biliary excretion by 55% when compared with controls. Coadministration with UDC partially restored the alteration. Secretion rate of DNP-SG was decreased by 30% in isolated hepatocytes from EE-treated rats, but, contrary to in vivo results, UDC coadministration did not restore DNP-SG transport, likely as a consequence of bile salt washout resulting from the isolation procedure. As a confirmation, tauroursodeoxycholate hepatocyte preloading significantly increased Mrp2 activity. Western blotting analysis of Mrp2 indicated that EE administration significantly reduced its level in total and plasma membranes and that UDC coadministration failed to revert this alteration. In conclusion, UDC improvement in Mrp2 transport activity in vivo likely derived from a direct enhancement of Mrp2 function rather than from a restoration of its expression levels. This provides a novel mechanism explaining the beneficial effects of UDC in EE-induced cholestasis.     

Epidermal sensory organs of moles, shrew moles, and desmans: a study of the family talpidae with comments on the function and evolution of Eimer's organ

The epidermal sensory organs of members of the family Talpidae (moles, shrew-moles, and desmans) were investigated and compared to determine the range of sensory specializations and better understand how they evolved. Small domed mechanosensory organs called 'Eimer's organs' were present on the rhinarium of nearly all species of talpids, but not among the sister group of shrews (Soricidae) or other insectivore families. This suggests that the common ancestor to the talpids possessed Eimer's organs. Two species of moles from the driest habitats did not exhibit Eimer's organs - suggesting that their sensory organs degenerated in response to harsh, abrasive soil conditions. The semi-aquatic desmans uniquely possessed tiny sensory hairs interspersed with their Eimer's organs; these may act to sense water currents. Some species exhibited a subdivided, star-like, rhinarium - resembling an early embryonic stage of the star-nosed mole and providing clues to the evolution of the star. A single genera (Uropsilus) that branched off early in the evolution of the talpids had Eimer's organ-like structures but lacked some typical components. These findings fill a major gap in our knowledge of talpid sensory biology and suggest (1) how Eimer's organs evolved, (2) how the unusual appendages of the star-nosed mole evolved, (3) that the evolution of Eimer's organ is convergent with the mechanosensory push-rod of monotremes. The results also demonstrate the features that distinguish Eimer's organ from similar configurations of sensory receptors in other mammalian skin surfaces. Finally, a mechanism for Eimer's organ function in detecting object and prey specific surface features is proposed.     

The use of antioxidant compounds in the treatment of first psychotic episode: Highlights from preclinical studies

Recent evidence highlighted a pathogenetic link between redox dysregulation and the early stages of psychosis. Indeed, an increasing number of studies have pointed toward an association between oxidative stress, both at central and peripheral levels, and first psychotic episode. Moreover, basal low antioxidant capacity has been shown to directly correlate with cognitive impairment in the early onset of psychosis. In this context, the possibility to use antioxidant compounds in first psychotic episode, especially as supplementation to antipsychotic therapy, has become the focus of numerous investigations on rodents with the aim to translate data on the possible effects of antioxidant therapies to large populations of patients, with a diagnosis of the first psychotic episode. In this review, we will discuss studies, published from January 1st, 2007 to July 31st, 2017, investigating the effects of antioxidant compounds on neuropathological alterations observed in different rodent models characterized by a cluster of psychotic‐like symptoms reminiscent of what observed in human first psychotic episode. A final focus on the effective possibility to directly translate data obtained on rodents to humans will be also provided.     

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

Objectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.

Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.

Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.

Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.     

Management of respiratory complications and rehabilitation in individuals with muscular dystrophies: 1st Consensus Conference report from UILDM - Italian Muscular Dystrophy Association (Milan,January 25-26, 2019)

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals. The purpose of this work, inspired by the Italian Muscular Dystrophy Association (UILDM) is to improve management of respiratory problems necessary for the management of these patients complex. To this end, the main items that the specialist can meet in the follow-up of these pathologies have been analyzed and discussed, among which the respiratory basal evaluation, the criteria of adaptation to non-invasive ventilation, management of bronchial secretions, situations of respiratory emergency, indications for tracheostomy and the subject of advance directives of treatment (DAT).Key words: respiratory failure, muscular dystrophy, cough efficacy, spirometry, polygraphy, non-invasive ventilation, arterial blood gases, cough machine, invasive ventilation, tracheostomy, mechanical ventilation     

Surgical treatment of pleural empyema in Coronavirus disease 19 patients: the Southern Switzerland experience

We report the first surgical series of patients developing pleural empyema after severe bilateral interstitial lung disease in confirmed severe acute respiratory syndrome coronavirus 2 infection. The empyema results in a complex medical challenge that requires combination of medical therapies, mechanical ventilation and surgery. The chest drainage approach was not successful to relieve the symptomatology and to drain the excess fluid. After multidisciplinary discussion, a surgical approach was recommended. Even though decortication and pleurectomy are high-risk procedures, they must be considered as an option for pleural effusion in Coronavirus disease-positive patients. This is a life-treating condition, which can worsen the coronavirus disease manifestation and should be treated immediately to improve patient’s status and chance of recovery.