Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice were sensitized with s.c. injection of ovalbumin (OVA) on days 1 and 8. Sensitized mice received on days 9 and 12 on the shaved dorsal surface air administration to induce the development of the air-pouches. On day 15 animals were challenged by injection of OVA into the air-pouch. Salvinorin A, administered (10 mg/kg) before each allergen exposure, significantly reduced OVA-induced LT increase in the air pouch. This effect was coupled to a reduction in cell recruitment and Th2 cytokine production. In another set of experiments, mice were sensitized with OVA and both bronchial reactivity and pulmonary inflammation were assessed. Salvinorin A abrogated bronchial hyperreactivity and interleukin (IL)-13 production, without effect on pulmonary inflammation. Indeed cell infiltration and peribronchial edema were still present following diterpenoid treatment. Similarly, pulmonary IL-4 and plasmatic IgE levels were not modulated. Conversely, Salvinorin A significantly reduced LTC4 production in the lung of sensitized mice. Finally mast cell activity was evaluated by means of toluidine blue staining. Data obtained evidenced that Salvinorin A significantly inhibited mast cell degranulation in the lung. Our study demonstrates that Salvinorin A inhibits airway hyperreactivity induced by sensitization by inhibition of LT production and mast cell degranulation. In conclusion Salvinorin A could represent a promising candidate for drug development in allergic diseases such as asthma

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

COVID-19 Infection in Autosomal Dominant Polycystic Kidney Disease and Chronic Kidney Disease Patients: Progression of Kidney Disease

Introduction: the COVID-19 pandemic has brought to light the intricate interplay between viral infections and preexisting health conditions. In the field of kidney diseases, patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Chronic Kidney Disease (CKD) face unique challenges when exposed to the SARS-CoV-2 virus. This study aims to evaluate whether SARS-CoV-2 virus infection impacts renal function differently in patients suffering from ADPKD and CKD when compared to patients suffering only from CKD. Materials and methods: clinical data from 103 patients were collected and retrospectively analyzed. We compared the renal function of ADPKD and CKD patients at two distinct time points: before COVID-19 infection (T0) and 1 year after the infection (T1). We studied also a subpopulation of 37 patients with an estimated glomerular filtration rate (eGFR) p p p p < 0.001) compared to CKD patients. Conclusion: the interplay between COVID-19 and kidney disease is complex. In CKD patients, the relationship between COVID-19 and kidney disease progression is more established, while limited studies exist on the specific impact of COVID-19 on ADPKD patients. Current evidence does not suggest that ADPKD patients are at a higher risk of SARS-CoV-2 infection; however, in our study we showed a significant worsening of the renal function among ADPKD patients, particularly those with an eGFR < 60 mL/min, in comparison to patients with only CKD after a one-year follow-up from COVID-19 infection

[Electrohydraulic intracorporeal lithotripsy in the treatment of "difficult" calculi of the common bile duct. Report of a caseload].

The Authors report their experience in 38 cases (January 1990-Septembre 1994) of "difficult" gallstone disease of the main bile duct treated with electrohydraulic intracorporeal lithotripsy. Nineteen patients were affected with giant stones of the biliary tree, 6 with multiple stones of the main bile duct, 13 with stones of one or both hepatic ducts. The approach to the biliary tree was peroral transpapillary in 16 patients and transhepatic in the remaining 22. Twenty-five patients were previously submitted to surgery of the biliary tree (13 hepaticojejunostomy, 8 choledochoduodenostony, 4 papillostomy), while 5 had required a cholecystectomy, and 6 a gastroresection according to Billroth II. In 80\% of the cases two lithotripsy sessions were enough to achieve the complete clearing of the bile duct. There was no mortality and morbidity was 5.3\%. Total clearing was obtained in 97.4\% of the cases. 6-48 months after treatment 37 patients still do not show clinical, laboratory or echographic signs of gallstone stasis or disease relapse

Beneficial effects of L-Arginine in patients hospitalized for COVID-19: New insights from a randomized clinical trial

We have recently demonstrated in a double-blind randomized trial the beneficial effects of L-Arginine in patients hospitalized for COVID-19. We hypothesize that one of the mechanisms underlying the favorable effects of L-Arginine is its action on inflammatory cytokines. To verify our hypothesis, we measured longitudinal plasma levels of pro-inflammatory and anti-inflammatory cytokines implied in the pathophysiology of COVID-19 in patients randomized to receive oral L-Arginine or placebo. The study was successfully completed by 169 patients. Patients in the L-Arginine arm had a reduced respiratory support evaluated at 10 and 20 days; moreover, the time to hospital discharge was significantly shorter in the L-Arginine group. The assessment of circulating cytokines revealed that L-Arginine significantly reduced the circulating levels of pro-inflammatory IL-2, IL-6, and IFN-γ and increased the levels of the anti-inflammatory IL-10. Taken together, these findings indicate that adding L-Arginine to standard therapy in COVID-19 patients markedly reduces the need of respiratory support and the duration of in-hospital stay; moreover, L-Arginine significantly regulates circulating levels of pro-inflammatory and anti-inflammatory cytokines

Malignant intestinal obstruction: Useful technical advice in self-expanding metallic stent placement

BACKGROUND: The use of endoluminal self-expanding metallic stents is an effective alternative to surgery in neoplastic gastrointestinal tract obstructions. It is often difficult to mark the proximal segment of the stricture under fluoroscopic guidance (due to patient movements or change of markers' position). PATIENTS AND METHODS: We placed Ultraflex precision colonic stent (Microvasive, Boston Scientific) in ten patients with neoplastic stricture of the rectosigmoid colon. Before placement of the delivery catheter, a radiopaque proximal marker was identified on the delivery catheter under fluoroscopic guidance. The external side of the delivery catheter was coloured (in correspondence with the radiopaque marker) with non toxic colour. After the introduction of the delivery catheter, we placed the proximal coloured marker just above the distal tumour margin under endoscopic guidance. RESULTS: The procedure was successful in relieving the obstruction in all patients, without mortality or complications. In all patients the coloured marker was identified and the stent correctly placed. CONCLUSION: The location of a coloured marker in the external side of the delivery catheter permits an accurate and correct placement of the stent, without unnecessary exposure to X-rays

Analysis of 11 trace elements in flight feathers of Italian Sparrows in southern Italy: A study of bioaccumulation through age classes, variability in three years of sampling, and relations with body condition

Trace elements have been acknowledged as one of the subtlest environmental hazards in all compartments of the total environment. Enhanced by activities in the anthroposphere, they accumulate in the atmosphere, lithosphere, and hydrosphere. Eventually, trace elements can bioaccumulate or biomagnifiy in the biosphere, with harmful effects on animals occupying higher trophic levels, including humans. Accordingly, there is great interest in assessing and monitoring trace element concentrations in the biosphere, and birds, especially passerines, have been commonly chosen as biomonitors. In this study, the concentration of 11 trace elements was measured (i.e. aluminum, chromium, manganese, iron, nickel, copper, zinc, arsenic, cadmium, barium, and lead) in flight feathers of Italian Sparrows, a common bird species hitherto not analysed in this respect. Samples were collected in an agricultural area in southern Italy, where a mosaic of natural environments, urbanized areas and industrial facilities can be found. Linear mixed modelling was applied to the analysis of flight feathers in juveniles, juvenile birds moulting to adulthood, and adults in three sampling years on 184 birds. Results are timely as they add new data to the scarce available information on Ba and As in bird feathers and showed clear bioaccumulation patterns from juveniles to adults for As, Cr, and Cd. Moreover, the modelling approach showed that the concentration of elements such as As, Cd and Cr can be variable across the years and that some elements, notably Cd and Ba, were inversely correlated with body mass and wing length, respectively, suggesting potential negative effects on bird health. Finally, when modelling bird body condition and trace elements, results showed that Cd and Ba negatively affect birds regardless of age or sampling year. Thus, the Italian Sparrow could be considered as a valuable biomonitor for trace elements in the total environment, especially for Cd and Ba