Nestin and vimentin colocalization affects the subcellular location of glucocorticoid receptor in cutaneous melanoma

Aims: Nestin (a neuronal stem cell/progenitor cell marker of central nervous system development), vimentin (which is ubiquitously expressed in mesenchymal cells), and the glucocorticoid receptor (GR, which is involved in the immune response, cell proliferation, and apoptosis) have been shown to interact in embryonic and undifferentiated tissues in modulating cell proliferation. The aim of this study was to analyse nestin, vimentin and GR expression in tumour tissue (melanoma), and their association with clinicopathological variables, to evaluate any effect on tumour progression. Methods and results: Immunohistochemistry, double‐label immunofluorescence and confocal laser scanning microscopy were performed on biopsy specimens of cutaneous melanoma from 81 patients. Fisher’s and Pearson’s tests showed a correlation between nestin, vimentin and subcellular GR location (P = 0.008). Their concomitant expression also correlated with Clark level and thickness (P = 0.02 and P = 0.029, respectively). Kaplan–Meier analysis revealed a poorer outcome for stage III and IV patients with associated expression of nestin, vimentin and cytoplasmic GR in tumour tissue (P = 0.02). Conclusions: These results suggest the presence in melanoma of growth mechanisms involving nestin, vimentin, and GR, similarly to that occurring in embryonic and undifferentiated cells, and may help in understanding tumour biology to provide a molecular basis for clinical therapies.     

Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series

BackgroundTo evaluate the association between COVID-19 vaccination and retinal vein occlusion (RVO).MethodsThis multicentre self-controlled case series included patients with RVO seen in five tertiary referral centres in Italy. All adults who received at least one dose of the BNT162b2, ChAdOx1 nCoV-19, mRNA-1273 or Ad26.COV2.S vaccine and had a first diagnosis of RVO between January 01, 2021, and December 31, 2021 were included. Incidence rate ratios (IRRs) of RVO were estimated using Poisson regression, comparing rates of events in a 28-day period following each dose of vaccination and in the unexposed control periods.Results210 patients were included in the study. No increased risk of RVO was observed after the first dose (1–14 days IRR: 0.87, 95% CI: 0.41–1.85; 15–28 days IRR: 1.01, 95% CI: 0.50–2.04; 1–28 days IRR: 0.94, 95% CI: 0.55–1.58) and second dose of vaccination (1–14 days IRR: 1.21, 95% CI: 0.62–2.37; 15–28 days IRR: 1.08, 95% CI: 0.53–2.20; 1–28 days IRR: 1.16, 95% CI: 0.70–1.90). No association between RVO and vaccination was found in subgroup analyses by type of vaccine, gender and age.ConclusionsThis self-controlled case series found no evidence of an association between RVO and COVID-19 vaccination.Subject terms: Retinal diseases, Epidemiology     

Detection of ∆<Superscript>9</Superscript>-tetrahydrocannabinol in exhaled breath after cannabis smoking and comparison with oral fluid

Exhaled breath is commonly used in alcohol testing, but has been recently demonstrated by scientists from Sweden, Germany, Belgium, Switzerland, and the United States to contain a large number of both volatile and non-volatile substances that can be measured using dedicated devices. ExaBreath^® is a sampling device that collects the bio-aerosol particles from the donor. Approximately 2 min exhaled breath is enough for the test. The device collects the very small bio-aerosols on a filter, which is consecutively incubated into methanol to release drugs at a laboratory. Four occasional cannabis smokers were recruited for this study. Oral fluid, collected with the Quantisal^® device, and exhaled breath were simultaneously collected up to 6 h after smoking a standard joint of cannabis. ?⁹-Tetrahydrocannabinol (THC) was tested using liquid chromatography–tandem mass spectrometry (MS/MS) or gas chromatography–MS/MS for exhaled breath and oral fluid, respectively. Linearity, precision and limit of quantification (5 pg/filter and 0.5 ng/mL for exhaled breath and oral fluid, respectively) were established. In each analytical batch, low and high controls were included. THC was identified in exhaled breath up to 6 h after smoking from all the four subjects, with concentrations in the range 15–1598 pg/filter. THC breath concentrations significantly decreased with time after smoking in all four participants. All the oral fluid specimens tested positive for THC over the 6 h of the study, with concentrations in the range 1–89 ng/mL. 11-Nor-9-carboxy-Δ⁹-tetrahydrocannabinol, the main metabolite of THC was also analysed, but was undetectable in both exhaled breath and oral fluid. This study gives further support to the possibility of using exhaled breath as a new matrix to document exposure to drugs, particularly for cannabis.     

Intrathecal Baclofen in Patients With Persistent Vegetative State: 2 Hypotheses

Sarà M, Pistoia F, Mura E, Onorati P, Govoni S. Intrathecal baclofen in patients with persistent vegetative state: 2 hypotheses.Sporadic cases of recovery from persistent vegetative state (PVS) after administration of intrathecal baclofen (ITB) have been reported without giving any possible explanation for its paradoxical effect. We summarize our recent findings on 5 patients with PVS treated with ITB and make some speculations on the mechanisms responsible for the observed clinical improvement. The patients developed spasticity and were judged eligible for ITB therapy. Two weeks after pump implantation, patients began to show a clinical improvement that, at the end of the 6 months' follow-up, was stable in all but 1 patient, ranging from a mere increased alertness to a full recovery of consciousness, as revealed by changes of the Coma Recovery Scale-Revised (CRS-R) score. Our findings suggest that ITB might favor a variable degree of clinical improvement. A proposal for a pharmacodynamic explanation of this effect has not been formally put forward. We hypothesize 2 possible mechanisms: first, a modulation confined to spinal cord segmental activities and to neuronal centripetal outputs reaching the cortex; and second, a modulation of sleep-wake cycles that, although present, may be dysregulated and interfere with alertness and awareness. Although our research is confined to a few subjects, it provides follow-up information by means of the CRS-R that is a validated standardized neurobehavioral instrument expressly designed for use in patients with PVS. Our observations indicate that further systematic investigation of the mechanisms and the putative clinical applications of ITB should be undertaken.     

Hürthle-cell tumors of the thyroid]

In the last 10 years 20 patients with Hürthle tumors were observed at Institute of Surgery and Oncology of Cagliari University. 17 were females and 3 males with a median age of 42 years. Tumors were malignant in 7 cases and benign in 13. A total thyroidectomy was performed in all patients with carcinoma and in 2 with adenoma because of concurrent goiter. The remaining patients were treated with a less extensive surgery. Two patients with carcinoma had a cervical node metastases at 12 and 67 months, treated by surgery (followed by radioiodine therapy in one). All patients are alive and disease free at 72 months of median follow-up. None of patients with benign adenomas recurred at 47 months of median follow-up. A longer-term follow-up is necessary in order to evaluate the benignity of adenomas.     

Interaction between naproxen and chemically modified β-cyclodextrins in the liquid and solid state

The complexation between naproxen and some chemically modified β-cyclodextrins (hydroxyethyl β-cyclodextrin with average substitution degree per anhydroglucose unit 0.6, 1.0 and 1.6; hydroxyproyl β-cyclodextrin with average substitution degree per anhydroglucose unit 0.6 and 0.9) was studied using phase-solubility analysis and molecular modelling. The amorphous carriers exhibit similar solubilizing effects and complexing abilities, which are reflected by a comparable increase in drug dissolution rate to about the same extent from equimolar blends with each chemically modified β-cyclodextrin. X-ray diffractometry and differential scanning calorimetry data indicate a role of the degree of substitution of the carrier in the decrease in crystallinity of naproxen in equimolar blends with chemically modified β-cyclodextrins.     

A resected case of advanced gastric cancer with complete remission of liver metastasis by chronic daily administration of oral etoposide and UFT]

An advanced gastric cancer with liver metastasis was treated with the combination MMC, Etoposide and UFT. Etoposide was administered orally at 25-50 mg/day to the gastric cancer patient with liver metastasis. In operative findings, there was no liver and lymphoid node metastasis. The gastric tumor diminished in size and changed its characteristics due to the chemotherapy. In 19 months, no liver nor LN metastasis was observed by CT scan. Presently, the patient feels well and receives outpatient treatment.     

Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced severe acute lung injury in rats

Lack of specific and efficient therapy leads to the high mortality rate of acute lung injury (ALI) and acute respiratory distress (ARDS). Recent evidence implies that angiotensin-converting enzyme (ACE) plays an important role in the pathogenesis of ALI. Pharmaceutical inhibitors of ACE have been used clinically for hypertension but not for ALI/ARDS yet. The objective was to study the effects of ACE inhibition with captopril on severe lung injury induced by oleic acid (OA) in rats. Oleic acid was intravenously injected into Sprague Dawley rats, followed by i.p. administration of captopril or saline control. Lung injury, endothelium damage and related molecules, and disturbance of coagulation were examined in comparison between the treated and the nontreated groups. An OA-induced ALI was featured with thickening of the alveolar septa, alveolar hemorrhage, and infiltration of inflammatory cells. Comparing with the nontreated OA group, the administration of captopril prevented the rats from OA-induced severe lungs injury, with a significantly lower lung injury score, less albumin content and infiltrated cells in the alveoli, decreased wet/dry weight ratio of the lung tissues, and improved lung function (PaO2 per fraction of inspired oxygen). Captopril also dramatically reduced the expression of intercellular adhesion molecule-1 in the lung tissue and in the circulating endothelial cells in the blood, indicating a protective effect on endothelial cells activation/damage. Moreover, captopril treatment led to a blockage of nuclear factor kappaB activation in lung tissues and to the recovery of the fibrinolytic disturbance. Thus, our data suggest that the inhibition of ACE with its clinically used inhibitor offers protective effects on ALI/ARDS, implying the potential for therapeutic option.