Drug repurposing for the treatment of alveolar echinococcosis: In vitro and in vivo effects of silica nanoparticles modified with dichlorophen

Alveolar echinococcosis is a neglected parasitic zoonosis caused by the metacestode Echinococcus multilocularis, which grows as a malignant tumour-like infection in the liver of humans. Albendazole (ABZ) is the antiparasitic drug of choice for the treatment of the disease. However, its effectiveness is low, due to its poor absorption from the gastro-intestinal tract. It is also parasitostatic and in some cases produces side-effects. Therefore, an alternative to the treatment of this severe human disease is necessary. In this context, the repositioning of drugs combined with nanotechnology to improve the bioavailability of drugs emerges as a useful, fast and inexpensive tool for the treatment of neglected diseases. The in vitro and in vivo efficacy of dichlorophen (DCP), an antiparasitic agent for intestinal parasites, and silica nanoparticles modified with DCP (NP-DCP) was evaluated against E. multilocularis larval stage. Both formulations showed a time and dose-dependent in vitro effect against protoscoleces. The NP-DCP had a greater in vitro efficacy than the drug alone or ABZ. In vivo studies demonstrated that the NP-DCP (4 mg kg-1) had similar efficacy to ABZ (25 mg kg-1) and greater activity than the free DCP. Therefore, the repurposing of DCP combined with silica nanoparticles could be an alternative for the treatment of echinococcosis.Fil: Fabbri, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones en Sanidad Producción y Ambiente. - Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Investigaciones en Sanidad Producción y Ambiente; ArgentinaFil: Pensel, Patricia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones en Sanidad Producción y Ambiente. - Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Investigaciones en Sanidad Producción y Ambiente; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; ArgentinaFil: Albani, Clara Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones en Sanidad Producción y Ambiente. - Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Investigaciones en Sanidad Producción y Ambiente; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; ArgentinaFil: Arce, Valeria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; ArgentinaFil: Martire, Daniel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Elissondo, María Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones en Sanidad Producción y Ambiente. - Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Investigaciones en Sanidad Producción y Ambiente; Argentin

Skeletal status in children and adolescents with new-onset type 1 diabetes: a preliminary study based on bone densitometry and quantitative ultrasound

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality

Anthelmintic activity of Stevia aristata extract on Echinococcus granulosus: in vitro and in vivo study

Cystic echinococcosis (CE) is a worldwide zoonotic disease caused by Echinococcus granulosus, which produces long-term infections in humans and animals. Available anti-parasitic treatment against CE is mostly limited to the use of benzimidazoles, mainly albendazole (ABZ). However, it has undesirable side effects and their efficacy is about 50%. Based on the problematic described, new treatment alternatives are urgently needed. Plants from the Stevia genus (Asteraceae) are a potential source of anti-protozoal and anti-microbial compounds. The aim of the present study was to evaluate the in vitro and in vivo efficacy of the Stevia aristata dichloromethane extract against E. granulosus. Viable and free protoscoleces or cysts were treated with 100, 50, 10 and 5 μg/ml of the extract. Viability assessment using the methylene blue exclusion test and scanning electron microscopy (SEM) (for protoscoleces) or evaluation of germinal layer collapse (for cysts) was performed. CF-1 mice (n=30) infected with E. granulosus were allocated into the following experimental groups (6 months post-infection): (1) Control, (2) ABZ 25 mg/kg, every 24 h for 30 days; (3) S. aristata 50 mg/kg, every 24 h for 23 days. At the end of the treatment the weight of the cysts was recorded and samples were analysed by SEM. Protoscoleces viability decreased quickly with 100 µg/ml, reaching 0% after 20 days of treatment. After 4 days of incubation, the collapse of the germinal layer was observed in 60 ± 5.8% and 83.3 ± 12.0% of cysts treated with 50 and 100 µg/ml, respectively. Whilst ultrastructural damage was observed in the cysts obtained from S. aristata or ABZ treated mice, no significant differences in the weight of the cysts were obtained (P > 0.05). In conclusion, S. aristata treatment caused high protoscolicidal and cysticidal effects, but not significant reduction in the weight of the cysts in experimentally infected mice.Fil: Albani, Clara Maria. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Borgo, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Fabbri, Julia. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Pensel, Patricia Eugenia. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Fasciani, Lara. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Hernandez, N.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Paladini, A.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Sülsen, Valeria Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Elissondo, María Celina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaLXVI Annual Meeting of Sociedad Argentina de Investigación Clínica (SAIC); LXIX Annual Meeting of Sociedad Argentina de Inmunología (SAI); LIII Annual Meeting of Asociación Argentina de Farmacología Experimental (AAFE) y XI Annual Meeting of Asociación Argentina de Nanomedicinas (NANOMED-AR)ArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de NanomedicinasAsociación Argentina de Farmacología Experimenta

A novel mutation in the N-terminal acting-binding domain of Filamin C protein causing a distal myofibrillar myopathy

Variants in Filamin C (FLNC) gene may cause either cardiomyopathies or different myopathies. We describe a family affected by a distal myopathy with autosomal dominant inheritance. The onset of the disease was in the third decade with gait impairment due to distal leg weakness. Subsequently, the disease progressed with an involvement of proximal lower limbs and hand muscles. Muscle biopsy, performed in one subject,identified relevant myofibrillar abnormalities. We performed a target gene panel testing for myofibrillar myopathies by NGS approach which identified a novel mutation in exon 3 of FLNC gene (c.A664G:p.M222V), within the N-terminal actin-binding (ABD) domain. This variant has been identified in all affected members of the family, thus supporting its pathogenic role. Differently from previously identified variants, our family showed a predominant leg involvement and myofibrillar aggregates, thus further expanding the spectrum of Filamin C related myopathies

The “polonium in vivo” study. Polonium-210 in bronchial lavages of patients with suspected lung cancer

Few studies have reported on polonium-210, a decay breakdown product of radon-222 and lead-210, in human lungs and there has been no study in patients with suspected lung cancer. The main aim of this "Polonium in vivo" study was to evaluate polonium-210 radioactivity in bronchopulmonary systems of smoker, ex-smoker and never smoker patients with suspected lung cancer. Alpha-spectrometric analyses were performed on bronchial lavage (BL) fluids from two Italian hospitals in 2013-2016. Socio-demographic, smoking, occupational and spirometric characteristics, lung cancer confirmation and histologic type and radon-222 concentration in patients' homes were collected. Seventy BL samples from never (n = 13), former (n = 35) and current smokers (n = 22) were analyzed; polonium-210 was detected in all samples from current and former smokers and in 54% of samples from never smokers (p < 0.001; median values: 1.20, 1.43 and 0.40 mBq, respectively). Polonium-210 levels were significantly higher in COPD versus no COPD patients (median value: 3.60 vs. 0.97 mBq; p = 0.007); former and current smokers, without and with COPD, had significantly increased polonium-210 levels (p = 0.012); 96% of confirmed versus 69% of non-confirmed lung cancer patients recorded detectable polonium-210 levels (p = 0.018). A polonium-210 detectable activity was measured in BL samples from all current and former smokers. Polonium-210 in the lungs could be the result of lead-210 entrapment, which, with its half-life of 22 years, could provide a continuous emission of alpha radioactivity, even many years after quitting, thus proposing a possible explanation for the onset of lung cancer, particularly in former smokers

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

INTRODUCTION/AIMS: Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition. METHODS: We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study. Patients with facial involvement and distal or congenital myopathies were excluded, as were patients with suspected inflammatory myopathies or predominant respiratory or cardiac involvement. All patients underwent a neurological examination and nerve conduction and electromyography studies. The first step of the investigation included a screening for Pompe disease. We then evaluated the patients for myotonic dystrophy type II–related CCTG expansion and excluded patients with copy number variations in the DMD gene. Subsequently, the undiagnosed patients were investigated using a target gene panel that included 20 genes associated with isolated hyperCKemia. RESULTS: Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings. DISCUSSION: We have described our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening, and first‐line genetic investigations, followed by successive targeted sequencing panels. Both clinical signs and electromyographic abnormalities are associated with increased diagnostic yields

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients