Is Nasobiliary Tube Really Safe? A Case Report

A case of esophageal ulcer caused by nasobiliary tube is described. This tool is not routinely considered to be a cause of major complications in the literature and to our knowledge, this is the first report of this kind of complication in nasobiliary tube placement. A 72-year-old patient presented with Charcot's triad and was demonstrated to have cholangitis with multiple biliary stones in the common bile duct. Biliary drainage was achieved through endoscopic retrograde cholangiography, endoscopic sphincterotomy, biliary tree drainage and nasobiliary tube with double pigtail. The patient presented odynophagia, dysphagia and retrosternal pain 12 h after the procedure and upper endoscopy revealed a long esophageal ulcer, which was treated conservatively. This report provides corroboration of evidence that nasobiliary tube placement has potential complications related to pressure sores. In our opinion this is a possibility to consider in informed consent forms

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

A survey of clinical features of allergic rhinitis in adults

Background: Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods: The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18\u201345 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results: Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. . Conclusions: These fndings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed

Antiproliferative Effect of Plant-Derived Bioactive Compounds Endowed with Antioxidant Activity on Breast Cancer Cells

Several lines of evidence indicate that plant-derived antioxidant compounds can be used as anticancer agents to support conventional pharmacological therapy. In this context, heme-oxygenase-1 (HO-1) modulation has been proven to represent a valid approach for reducing cancer cells&rsquo; proliferation through the activation of apoptosis and ferroptosis. This study focused on three little studied HO-1 inducers (paeonol, rosolic acid and dimethoxy resveratrol) in order to evaluate their efficacy as antiproliferative compounds on breast cancer cells (MCF-7 and MDA-MB 231). Cell viability data showed an interesting selectivity of dimethoxy resveratrol (DMR) for MDA-MB 231 cells. The ineffectiveness of Ferrostatin-1 and Trolox treatment led to the exclusion of ferroptosis involvement; meanwhile, cell viability reduction was associated with caspase 3/7 activation and apoptosis. Taken together, our results suggest a potential role of DMR as an adjuvant in conventional chemotherapy for breast cancer treatment

Solid Lipid Nanoparticles Loading Idebenone Ester with Pyroglutamic Acid: In Vitro Antioxidant Activity and In Vivo Topical Efficacy

Idebenone (IDE), a strong antioxidant widely investigated for the treatment of neurodegenerative diseases and skin disorders, shows low oral and topical bioavailability due to its unfavorable physico-chemical properties. In this work, to improve IDE topical effectiveness, we explored a two-steps approach: (1) we synthesized an IDE ester (IDEPCA) with pyroglutamic acid, a molecule whose hydrating effects are well known; (2) we loaded IDEPCA into solid lipid nanocarriers (SLN). We evaluated in vitro antioxidant and anti-glycation activity and in vivo hydrating effects after topical application in human volunteers from gel vehicles of IDEPCA SLN in comparison to IDE SLN. All SLN showed good technological properties (mean particle size &lt; 25 nm, polydispersity index &lt; 0.300, good stability). The oxygen radical absorbance capacity assay showed that IDEPCA SLN and IDE SLN had similar antioxidant activity while IDEPCA SLN were more effective in the in vitro NO scavenging assay. Both IDEPCA and IDE SLN showed the same effectiveness in inhibiting the formation of advanced glycation end products. In vivo experiments pointed out a better hydrating effect of IDEPCA SLN in comparison to IDE SLN. These results suggest that the investigated approach could be a promising strategy to obtain topical formulations with increased hydrating effects

Structure-Activity Relationships and Therapeutic Potentials of 5-HT7 Receptor Ligands: An Update

Serotonin 5-HT7 receptor (5-HT7R) has been the subject of intense research efforts because of its presence in brain areas such as the hippocampus, hypothalamus, and cortex. Preclinical data link the 5-HT7R to a variety of central nervous system processes including the regulation of circadian rhythms, mood, cognition, pain processing, and mechanisms of addiction. 5-HT7R blockade has antidepressant effects and may ameliorate cognitive deficits associated with schizophrenia. 5-HT7R has been recently shown to modulate neuronal morphology, excitability, and plasticity, thus contributing to shape brain networks during development and to remodel neuronal wiring in the mature brain. Therefore, the activation of 5-HT7R has been proposed as a therapeutic approach for neurodevelopmental and neuropsychiatric disorders associated with abnormal neuronal connectivity. This Perspective celebrates the silver jubilee of the discovery of 5-HT7R by providing a survey of recent studies on the medicinal chemistry of 5-HT7R ligands and on the neuropharmacology of 5-HT7R

Antioxidant Activity and Phenolic Content of Microwave-Assisted Solanum melongena

Eggplant fruit is a very rich source of polyphenol compounds endowed with antioxidant properties. The aim of this study was to extract polyphenols from eggplant entire fruit, pulp, or skin, both fresh and dry, and compare results between conventional extraction and microwave-assisted extraction (MAE). The effects of time exposure (15, 30, 60, and 90 min) and solvent (water 100% or ethanol/water 50%) were also evaluated. The highest amount of polyphenols was found in the extract obtained from dry peeled skin treated with 50% aqueous ethanol, irradiated with microwave; this extract contained also high quantity of flavonoids and showed good antioxidant activity expressed by its capacity to scavenge superoxide anion and to inhibit lipid peroxidation

Comprehensive data on a 2D-QSAR model for Heme Oxygenase isoform 1 inhibitors

The data have been obtained from the Heme Oxygenase Database (HemeOxDB) and refined according to the 2D-QSAR requirements. These data provide information about a set of more than 380 Heme Oxygenase-1 (HO-1) inhibitors. The development of the 2D-QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together). The 2D-QSAR model regressions for HO-1 half maximal inhibitory concentration (IC50) expressed as pIC50 (pIC50=âLogIC50) are here included. The 2D-QSAR model was also employed to predict the HO-1 pIC50values of the FDA approved drugs that are herewith reported. Keywords: Heme Oxygenase, 2D-QSAR, pIC50 prediction, FDA, CORA