Niosomas encapsulados en praziquantel contra Schistosoma mansoni con sensibilidad reducida al praziquantel

Introduction: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. Objectives: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni (S. mansoni) isolate with reduced sensitivity to the drug during the intramolluscan phase. Materials and methods: Shedding snails were treated with PZQ doses of 200 mg/kg twice/week, followed by an interval of one week, and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. Results: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ-encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen’s sensitivity to PZQ, as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. A remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56% respectively) was obtained associated with a massive increase in dead eggs and complete absence of immature stages. Conclusion: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory-induced S. mansoni adult worms with reduced sensitivity to PZQ.Introducción. El praziquantel (PZQ) es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos eficaces y la falta de medidas preventivas eficaces aumentan su valor. El aumento de la prevalencia de la resistencia al PZQ bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia a PZQ mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni (S. mansoni) con sensibilidad reducida al fármaco durante la fase intramolusca. Material y métodos. Los caracoles que liberaban cercarias se trataron con dosis de PZQ de 200 mg / kg dos veces por semana, seguido de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. El éxito de inducir una sensibilidad reducida se confirmó in vitro mediante la reducción de la respuesta de las cercarias al PZQ con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. Resultados. El tratamiento oral con una dosis única de PZQ de 500 mg / kg en ratones infectados con cercarias con sensibilidad reducida a PZQ reveló una reducción no significativa (35,1%) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en PZQ inoculados por vía oral contra S. mansoni con sensibilidad reducida a PZQ permitieron reestablecer con éxito la sensibilidad del patógeno a PZQ, como lo demuestra la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a PZQ. La carga media total de gusanos fue de 1,33 ± 0,52 con una reducción estadísticamente significativa del 94,09% y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en tejido en el hígado y el intestino (97,68% y 98,56% respectivamente) asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en PZQ restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni inducidos en laboratorio con sensibilidad reducida a PZQ

A case of corticosteroid-dependent recurrent pericarditis with different response to two IL-1 blocking agents

Background: Recurrent pericarditis (RP) represents the most troublesome presentation of pericarditis and has a controversial pathogenesis that crosses infectious, auto-immune and auto-inflammatory pathways. It has been suggested that in some cases it might be an unrecognized auto-inflammatory disease. Recent studies have demonstrated that anakinra, an interleukin-1 receptor antagonist (IL-1RA), represents an effective treatment for the control of corticosteroid-dependent cases. Objectives: To describe a case of cortico-dependent recurrent pericarditis with a different response to two IL-1 blocking agents, anakinra and canakinumab. Methods: Case report Results: 11 years old boy who was admitted to our hospital because of acute precordial pain, orthopnea, fever and increased levels of acute phase reactants. Acute pericarditis was confirmed by echocardiography and a treatment with prednisone was started with prompt clinical improvement. Pericarditis recurred twice during steroid tapering (1mg/kg/day and 0.5mg/kg/day respectively). After exclusion of infectious origin, therapy with anakinra (2mg/kg/day) was established (to avoid long term steroid side effects) followed by dramatic clinical response and normalisation of laboratory findings despite tapering and discontinuation of prednisone. Treatment with anakinra was discontinued after 5 months with recurrence of pericarditis one week later. Anakinra was resumed with an excellent response. Five months later, while being in complete remission, anakinra was replaced with canakinumab (2mg/kg/dose) due to patient’s intolerance of daily injections. One week later, the patient experienced a new episode of pericarditis requiring corticotherapy. Two more relapses occured during steroid tapering, after 6 weeks and 2 months, in spite of the uptitration of canakinumab to 4mg/kg/dose. Anakinra was restarted with prompt clinical and biological remission and prednisone was discontinuated without recurrence of pericarditis. After further four weeks follow-up under anakinra alone, the pericarditis is still in remission. Conclusion: We describe a case of steroid-dependent RP with a dramatic therapeutic response to IL-1RA (anakinra) but without response to IL-1β monoclonal antibody (canakinumab). This unexpected observation could suggest that Il-1α might have a role in the pathogenesis of RP. The definitive potential usefulness of each IL-1 blocking agent requires confirmation in prospective controlled trials

Overexpression and knock-down studies highlight that a disintegrin and metalloproteinase 28 controls proliferation and migration in human prostate cancer

Prostate cancer is one of the most prevalent cancers inmen. It is critical to identify and characterize oncogenes that drive the pathogenesis of human prostate cancer. The current study builds upon previous research showing that a disintegrin and metalloproteinase (ADAM)28 is involved in the pathogenesis of numerous cancers. Our novel study used overexpression, pharmacological, and molecular approaches to investigate the biological function of ADAM28 in human prostate cancer cells,with a focus on cell proliferation andmigration. The results of this study provide important insights into the role of metalloproteinases in human prostate cancer. The expression of ADAM28 protein levels was assessed within human prostate tumors and normal adjacent tissue by immunohistochemistry. Immunocytochemistry and western blotting were used to assess ADAM28 protein expression in human prostate cancer cell lines. Functional assays were conducted to assess proliferation and migration in human prostate cancer cells in which ADAM28 protein expression or activity had been altered by overexpression, pharmacological inhibition, or by siRNA gene knockdown. The membrane bound ADAM28 was increased in human tumor biopsies and prostate cancer cell lines. Pharmacological inhibition of ADAM28 activity and/or knockdown of ADAM28 significantly reduced proliferation and migration of human prostate cancer cells, while overexpression of ADAM28 significantly increased proliferation and migration. ADAM28 is overexpressed in primary human prostate tumor biopsies, and it promotes human prostate cancer cell proliferation and migration. This study supports the notion that inhibition of ADAM28 may be a potential novel therapeutic strategy for human prostate cancer. Abbreviations: ADAM = a disintegrin and metalloproteinase, CTGF = connective tissue growth factor, DHT = dihydrotestosterone, IGF = insulin-like growth factor, IGFBP-3 = IGF binding protein-3, IL-6 = interleukin 6, RPMI = Roswell Park Memorial Institute, VEGF = vascular endothelial growth factor, VWF = von Willebrand factor

Prevalence of overweight and obesity in adults from North Africa.

The share of North African immigrants in Europe is growing continuously. In this review, we aimed to systematically analyse and describe the literature on weight status and physical activity in North African adults, both in their home country and after immigration to Europe. Existing data on North African residents and on North African immigrants in Europe were analysed by a systematic search on PUBMED. There is a wide variation among countries in the prevalence of overweight/obesity, with immigrants showing higher values. The overall results revealed a higher prevalence of overweight and obesity in females than in males in North African residents. Females also show higher levels of obesity among immigrants. In particular, literature reports indicate that 1.3-47.8% of North African residents and 3.6-49.4% of North African immigrants in adult age are overweight or obese. Physical inactivity is higher than 20% in males and 40% in females in North African residents. The highest frequency of physically inactive or lightly active people among immigrants was observed in first-generation Sudanese and Moroccans in Amsterdam (males: 57.1%; females: 74.2%), with increasing rates in second-generation females. The results underline a higher health risk in North African immigrants than in residents. Specific public health strategies should be adopted in various populations of North African origin to control the obesity epidemic

Interventional Neuroradiology: Henry Ford Hospital Experience with Nonembolization Procedures

Innovative technical developments over the past two decades have resulted in the development of a variety of useful interventional procedures for minimally invasive treatment of a variety of head and neck lesions. We have had experience with four different types of nonembolization interventional neuroradiologic procedures at Henry Ford Hospital from 1981 through 1985. Percutaneous transluminal angioplasty of six external carotid artery stenoses has been performed in five patients. Five were successful, and the artery became occluded in one patient. Intracarotid BCNU infusion was performed successfully in five patients with recurrent astrocytoma. Intraarterial streptokinase infusion was performed in one patient with acute thrombosis of an ectatic basilar artery. A traumatic carotid cavernous fistula was successfully closed by detachable silicone balloon technique

Interventional Neuroradiology: Henry Ford Hospital Experience with Transcatheter Embolization of Vascular Lesions in the Head, Neck, and Spine

Innovative developments over the past 15 years have resulted in increased sophistication and effectiveness of therapeutic neuroembolization procedures. As a result, percutaneous transcatheter embolization has assumed an increasingly important role in the management of patients with vascular lesions of the head, neck, and spine. By reducing bleeding during surgery, this technique can markedly facilitate the surgical approach to difficult vascular lesions. The technique may also be applied in cases where surgery is contraindicated. Therapeutic neuroembolization has been performed in 23 patients with vascular lesions of the head, neck, or spine at Henry Ford Hospital. Devascularization of the extraaxial blood supply was achieved in all cases, and no neurologic complications were encountered. Eighteen patients with vascular tumors of the head, neck, or spine and three patients with arteriovenous malformations (AVM) were embolized preoperatively, resulting in marked facilitation of the surgical procedures. One patient with a dural AVM and one with a spinal metastasis were embolized without surger

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

Mobile applications for obesity and weight management: current market characteristics

Mobile-Health (mHealth) is the fastest-developing eHealth sector, with over 100 000 health applications (apps) currently available. Overweight/obesity is a problem of wide public concern that is potentially treatable/preventable through mHealth. This study describes the current weight-management app-market. Five app stores (Apple, Google, Amazon, Windows and Blackberry) in UK, US, Russia, Japan and Germany, Italy, France, China, Australia and Canada were searched for keywords: 'weight', 'calorie', 'weight-loss', 'slimming', 'diet', 'dietitian' and 'overweight' in January/February 2016 using App-Annie software. The 10 most downloaded apps in the lifetime of an app were recorded. Developers' lists and the app descriptions were searched to identify any professional input with keywords 'professional', 'dietitian' and 'nutritionist'. A total of 28 905 relevant apps were identified as follows: Apple iTunes=8559 (4634, 54% paid), Google Play=1762 (597, 33.9% paid), Amazon App=13569 (4821, 35.5% paid), Windows=2419 (819, 17% paid) and Blackberry=2596 (940, 36% paid). The 28 905 identified apps focused mainly on physical activity (34%), diet (31%), and recording/monitoring of exercise, calorie intake and body weight (23%). Only 17 apps (0.05%) were developed with identifiable professional input. Apps on weight management are widely available and very popular but currently lack professional content expertise. Encouraging app development based on evidence-based online approaches would assure content quality, allowing healthcare professionals to recommend their use

Db / db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet

© 2017 Susan J. Burke et al. To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body composition, glycemia, and total body mass. To objectively compare diet-induced and genetic models of obesity, tissue analyses were conducted using mice with similar body mass. We found that adipose tissue inflammation was present in both models of obesity. In addition, distinct alterations in metabolic flexibility were evident between WD-fed mice and db/db mice. Circulating insulin levels are elevated in each model of obesity, while glucagon was increased only in the db/db mice. Although both WD-fed and db/db mice exhibited adaptive increases in islet size, the db/db mice also displayed augmented islet expression of the dedifferentiation marker Aldh1a3 and reduced nuclear presence of the transcription factor Nkx6.1. Based on the collective results put forth herein, we conclude that db/db mice capture key features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable body mass