Dysregulated homeostasis of acetylcholine levels in immune cells of RR-multiple sclerosis patients

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNF alpha, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNF alpha, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis

Daily dialysis reduces pulse wave velocity in chronic hemodialysis patients

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Butyrylcholinesterase and Acetylcholinesterase polymorphisms in Multiple Sclerosis patients: Implication in peripheral inflammation

Multiple Sclerosis (MS) is an autoimmune disease, having not fully understood aetiology, and both genetic and environmental factors contribute to the pathogenesis of the disease. The cholinergic system has been indicated as a mediator of neuro-immune interactions, as well as an internal regulator of immune responses. The aim of the present research was to assess the associations between BChE and AChE genetic variations and serum cholinergic and inflammatory profiles in 102 Relapsing Remitting-MS patients and 117 healthy controls. An increased frequency of the BChE K-allele in MS patients as compared to controls was found. In addition, data showed that patients had higher BChE enzymatic activity, which is increased by the presence of the polymorphic allele and reduced amounts of circulating ACh. AChE polymorphism was significantly associated to reduced activity in both patients and controls. We propose that serum BChE and AChE activity may be used as a secondary markers to assess the role of non-neuronal cholinergic system in regulating peripheral inflammation via ACh regulation. This pilot study shed light on the role of the non-neuronal cholinergic system in immune cells to better understand MS pathogenesis. The cross-talk between the periphery and the CNS could have a new undescribed crucial role for MS, regarded as a systemic disease

Effect of heatwaves on urban sea breeze, heat island intensity, and outdoor thermo-hygrometric comfort in Rome (Italy)

The purpose of this study is to investigate the impact of heatwaves on sea breeze, urban heat island intensity, and outdoor thermo-hygrometric comfort analysing ground-based remote sensing and in-situ meteorological measurements collected in a Mediterranean coastal metropolitan area (Rome, Italy) during the summer of 2022. The dataset (01 May - 31 August 2022) has been divided into heatwaves and not-heatwaves days to highlight the distinctive features of extreme heat episodes. Furthermore, the year 2022 was compared to 2020, the latter having been characterised by temperatures in line with the last two-decades.The heatwaves do not significantly affect the onset time and the duration of sea breeze, while its cooling effect intensifies during the heatwaves. The urban heat island intensity (UHII) is evaluated by computing the hourly-averaged air temperature difference between two stations, one in the urban centre and the other in rural surroundings. Although the daily-averaged UHII does not show significant differences among the years under investigation and the subsets, marked differences can be identified in the urban heat island daily cycle. In fact, during daytime the highest temperatures are detected in rural inland areas while, at night, the city experiences higher temperatures, especially during the heatwaves. Finally, the Mediterranean outdoor comfort index suggests that a heatwave seems to be a not sufficient condition for human thermohygrometric stress, even if stronger discomfort is experienced during heatwaves

Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: A case report

Background: Pediatric tuberculous meningitis is a highly morbid, often fatal disease. Its prompt diagnosis and treat - ment saves lives, in fact delays in the initiation of therapy have been associated with high mortality rates. Case presentation: This is a case of an Italian child who was diagnosed with tuberculous meningitis after a history of a month of headache, fatigue and weight loss. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with predominance and decreased glucose concentration. Microscopy and conventional diagnostic tests to identify Myco - bacterium tuberculosis were negative, while a non classical method based on intracellular cytokine flow cytometry response of CD4 cells in cerebral spinal fluid helped us to address the diagnosis, that was subsequently confirmed by a nested polymerase chain reaction amplifying a 123 base pair fragment of the M. tuberculosis DNA. Conclusions: We diagnosed tuberculous meningitis at an early stage through an innovative immunological approach, supported by a nested polymerase chain reaction for detection of M. tuberculosis DNA. An early diagnosis is required in order to promptly initiate a therapy and to increase the patient’s surviva

ADULT DOMINANT POLYCYSTIC KIDNEY DISEASE: A PROTOTYPICAL DISEASE FOR PHARMANUTRITION INTERVENTIONS

Adult Dominant Polycystic Kidney Disease (ADPKD) is an inherited disease, associated with the development of liquid-filled cysts in the kidneys and other organs, causing renal failure. Most patients with ADPKD have mutations in either PKD1 or PKD2 genes, which encode for the two components of ion channels located in cilia and endoplasmic reticulum. These mutations cause an increase in intracellular cAMP and activate mTOR, the AMPK pathway and Jak/Stat-dependent gene transcription ultimately leading to enhanced cell proliferation and survival in cyst epithelium and to fluid release in cyst cavities. The aim of the present review is to discuss the main literature evidence suggesting that these pathologically activated transduction pathways can be targeted with an integrated pharmacological and nutritional, pharmanutrition, strategy

Effect of water contamination on the shear bond strength of self-ligating brackets

AbstractPurposeThe aim of the present study is to evaluate the effect of water contamination on the shear bond strength (SBS) and adhesive remnant index (ARI) score of self-ligating brackets.Materials and methodsOne conventional bracket and three different self-ligating brackets were bonded onto 160 bovine permanent mandibular incisors, divided randomly into 8 groups. For each type of bracket, 20 samples were bonded on dry enamel and 20 after water contamination. After 24h, all specimens were tested for SBS using an Instron Universal Testing Machine, and ARI scores were evaluated.ResultsAll groups showed clinically adequate SBSs. Quick brackets bonded onto dry enamel showed significantly higher SBSs than all other groups tested, whereas the lowest shear strength values were recorded for Step, Quick, and Damon 3MX brackets bonded onto contaminated enamel and for Damon 3MX onto dry enamel. Frequency distribution of ARI Scores showed a prevalence of ARI “2” and “3” for all the groups tested.ConclusionsWater contamination reduces the SBS of self-ligating brackets, but significant differences have been found only for Quick brackets. All groups showed a significant higher frequency of ARI Score of “2” and “3”

Integrated chemical status of the Italian marine waters sensu Descriptor 8 of the Marine Strategy Framework Directive

The European Marine Strategy Framework Directive (MSFD) required Member States to define the concept of Good Environmental Status (GES) of their marine waters in quantitative terms and to achieve it through the assessment of 11 descriptors by 2020. ISPRA (Italian Institute for Environmental Protection and Research), on behalf of the Ministry of the Environment, carried out the Initial Assessment (2012) and the evaluation of the first cycle of the MSFD (2012–2018) to understand the achievement of GES Descriptor 8 (“Contaminant concentrations are at levels that do not give rise to pollution effects”) and, now, in this second cycle of the MSFD (2018–2024), is conducting monitoring of D8C1 criterion elements (“Contaminant concentrations”). In this paper, the approach, integrating data on chemical contaminants (metals and polycyclic aromatic hydrocarbons and organochlorine compounds) in different matrices (water, sediment and biota), adopted by Italy since 2012 to study GES for the MSFD-D8C1 criterion in national marine water is described. This approach, based on the use of a dimensionless, zero-centered index, allows one to assess all regulatory contaminants as a whole. The improvements in the monitoring strategy and the GES evaluation between the Initial Assessment, the first cycle, and the beginning of the second cycle of the MSFD for the Adriatic Sea subregion are presented

Could co-infection with Anaplasma play a role in Borrelia-associated primary cutaneous marginal zone B-cell lymphomas?

6noopenopenBonin, Serena; Stinco, Giuseppe; Patriarca, Maria Martina; Trevisini, Sara; Di Meo, Nicola; Trevisan, GiustoBonin, Serena; Stinco, Giuseppe; Patriarca, Maria Martina; Trevisini, Sara; Di Meo, Nicola; Trevisan, Giust