Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles

none10The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoadhesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuroblastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery.openAdriana Trapani, Lorenzo Guerra, Filomena Corbo, Stefano Castellani, Enrico Sanna, Loredana Capobianco, Anna Grazia Monteduro, Daniela Erminia Manno, Delia Mandracchia, Sante Di Gioia and Massimo ConeseTrapani, Adriana; Guerra, Lorenzo; Corbo, Filomena; Castellani, Stefano; Sanna, Enrico; Capobianco, Loredana; Monteduro, ANNA GRAZIA; Manno, Daniela Erminia; Mandracchia, Delia; Di Gioia and Massimo Conese, Sant

A population-based cohort approach to assess excess mortality due to the spread of COVID-19 in Italy, January-May 2020

Aims: To assess the impact of the COVID-19 pandemic on all-cause mortality in Italy during the first wave of the epidemic, taking into consideration the geographical heterogeneity of the spread of COVID-19. Methods: This study is a retrospective, population-based cohort study using national statistics throughout Italy. Survival analysis was applied to data aggregated by day of death, age groups, sex, and Italian administrative units (107 provinces). We applied Cox models to estimate the relative hazards (RH) of excess mortality, comparing all-cause deaths in 2020 with the expected deaths from all causes in the same time period. The RH of excess deaths was estimated in areas with a high, moderate, and low spread of COVID-19. We reported the estimate also restricting the analysis to the period of March-April 2020 (first peak of the epidemic). Results: The study population consisted of 57,204,501 individuals living in Italy as of January 1, 2020. The number of excess deaths was 36,445, which accounts for 13.4% of excess mortalities from all causes during January-May 2020 (i.e., RH = 1.134; 95% confidence interval (CI): 1.129-1.140). In the macro-area with a relatively higher spread of COVID-19 (i.e., incidence rate, IR): 450-1,610 cases per 100,000 residents), the RH of excess deaths was 1.375 (95% CI: 1.364-1.386). In the area with a relatively moderate spread of COVID-19 (i.e., IR: 150-449 cases) it was 1.049 (95% CI: 1.038-1.060). In the area with a relatively lower spread of COVID-19 (i.e., IR: 30-149 cases), it was 0.967 (95% CI: 0.959-0.976). Between March and April (peak months of the first wave of the epidemic in Italy), we estimated an excess mortality from all causes of 43.5%. The RH of all-cause mortality for increments of 500 cases per 100,000 residents was 1.352 (95% CI: 1.346-1.359), corresponding to an increase of about 35%. Conclusions: Our analysis, making use of a population-based cohort model, estimated all-cause excess mortality in Italy taking account of both time period and of COVID-19 geographical spread. The study highlights the importance of a temporal/geographic framework in analyzing the risk of COVID-19-epidemy related mortality

Ultrastructural evaluation of human metaphase II oocytes after vitrification: closed versus open devices

Objective: To compare the ultrastructural appearance of oocytes after vitrification and warming with two different devices. Design: Oocytes were examined by ultrastructural analysis after vitrification and warming with use of closed (CryoTip; Irvine Scientific, Santa Ana, CA) or open (Cryotop; Kitazato BioPharma Co., Ltd., Shizuoka, Japan) devices. Setting: Pordenone Hospital IVF Unit and Medical Morphological Research Department, University of Udine. Patient(s): Surplus oocytes from 10 patients (aged 31-39 years) undergoing assisted reproductive technologies at the Pathophysiology Unit of Human Reproduction and Sperm Bank between 2006 and 2008. Intervention(s): Oocytes with normal invertoscopic appearance underwent vitrification and warming with closed (CryoTip) or open (Cryotop) devices and were processed for transmission electron microscopy. Main Outcome Measure(s): Cryodamage extent and cell alterations in oocytes after open or closed vitrification and warming procedures and their rehydration rate. Result(s): A higher rate of complete oocyte rehydration and less-severe ultrastructural alterations were observed after vitrification and warming with the open Cryotop device. Conclusion(s): These preliminary data suggest that oocyte ultrastructure is better preserved with an open rather than closed vitrification and warming protocol

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

DOUBLE FATAL INHALATION OF DICHLOROMETHANE

1 Two cases of lethal poisoning following acute inhalation of extremely high concentrations of dichloromethane (DCM) are reported. The concentrations of the solvent found in the blood of the two subjects collected at autopsy and analysed by gas chromatography/mass spectrometry (572 and 601 mg l-1) were compatible with those measured in the air a few hours after the discovery of the bodies (up to 168,000 ppm). 2 Extensive brain and lung oedema and congestion, microhaemorrhagic changes of the stomach and congestion in other organs were observed on macroscopic and microscopic examination of both subjects. In addition, and in both cases, high but not lethal carboxyhaemoglobin (COHb) levels (30%) were found in the blood collected at autopsy. 3 Narcosis and respiratory depression due to the effect of DCM on the central nervous system (CNS) appear to have played a critical role in the death of the two men. However, biotransformation of the solvent to toxic metabolites, including carbon monoxide (via oxidative dehalogenation by the cytochrome P450-dependent mixed function oxidase system) or formaldehyde, formic acid, inorganic chloride and carbon dioxide (via the glutathione-S-transferase pathway) may have also contributed significantly to fatal toxicity. I.F. : 1.86

Freeze-all or conventional IVF? Unanswered question from unlearned lessons

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