5-Aminolaevulinic Acid (ALA) for the Fluorescence Detection of Bronchial Tumors

At the moment only early detection of lung cancer offers a good prognosis for the patients. Conventional white light endoscopy is mostly insufficient for early diagnosis. Therefore we developed a system of fluorescence diagnosis using 5-aminolaevulinic acid (ALA) exogeneously applied. As precursor of the heme synthesis it is metabolized to protoporphyrin IX – a red fluorescent substance. Therefore protoporphyrin IX accumulates in tumorous and premalignant tissue, and can be directly visualized by fluorescence bronchoscopy. Excitation with blue light (380–435 nm) causes a red fluorescence, which can be detected after filtering most of the blue component with the naked eye or a camera system. After earlier work with laser systems and cold light sources we now use the system D-Light AF for the fluorescence diagnosis using ALA-induced protoporphyrin IX fluorescence

Stem cells labeled with superparamagnetic iron oxide nanoparticles in a preclinical model of cerebral ischemia: a systematic review with meta-analysis

Introduction: Although there is an increase in clinical trials assessing the efficacy of cell therapy in structural and functional regeneration after stroke, there are not enough data in the literature describing the best cell type to be used, the best route, and also the best nanoparticle to analyze these stem cells in vivo. This review analyzed published data on superparamagnetic iron oxide nanoparticle (SPION)-labeled stem cells used for ischemic stroke therapy.Method: We performed a systematic review and meta-analysis of data from experiments testing the efficacy of cellular treatment with SPION versus no treatment to improve behavioral or modified neural scale outcomes in animal models of stroke by the Cochrane Collaboration and indexed in EMBASE, PubMed, and Web of Science since 2000. To test the impact of study quality and design characteristics, we used random-effects meta-regression. in addition, trim and fill were used to assess publication bias.Results: the search retrieved 258 articles. After application of the inclusion criteria, 24 reports published between January 2000 and October 2014 were selected. These 24 articles were analyzed for nanoparticle characteristics, stem cell types, and efficacy in animal models.Conclusion: This study highlights the therapeutic role of stem cells in stroke and emphasizes nanotechnology as an important tool for monitoring stem cell migration to the affected neurological locus.Instituto Israelita de Ensino e Pesquisa Albert EinsteinCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPEGHosp Israelita Albert Einstein, BR-05651901 São Paulo, BrazilUniversidade Federal de São Paulo, BR-04021001 São Paulo, SP, BrazilSanta Casa Misericordia São Paulo, BR-01221020 São Paulo, SP, BrazilUniv São Paulo, Inst Matemat & Estat, BR-05508090 São Paulo, SP, BrazilUniv São Paulo, LIM44, BR-05403000 São Paulo, SP, BrazilUniversidade Federal de São Paulo, BR-04021001 São Paulo, SP, BrazilWeb of Scienc

In-vivo kinetics of inhaled 5-Aminolevulinic acid-Induced Protoporphyrin IX fluorescence in bronchial tissue

BACKGROUND: In the diagnosis of early-stage lung cancer photosensitizer-enhanced fluorescence bronchoscopy with inhaled 5-aminolevolinic acid (5-ALA) increases sensitivity when compared to white-light bronchoscopy. This investigation was to evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the bronchial mucosa in order to define the time optimum for its application prior to bronchoscopy. METHODS: Patients with known or suspected bronchial carcinoma were randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible fluorescence bronchoscopy was performed. Macroscopically suspicious areas as well as areas with visually detected porphyrin fluorescence and normal control sites were measured spectroscopically. Biopsies for histopathology were obtained from suspicious areas as well as from adjacent normal areas. RESULTS: Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for malignant and premalignant changes (moderate dysplasia) which is almost twice as high as that of white-light bronchoscopy, whereas specificity is reduced. This is due to false-positive inflammatory lesions which also frequently show increased porphyrin fluorescence. Malignant and premalignant alterations produced fluorescence values that are up to 5 times higher than those of normal tissue. According to the pharmacokinetics of porphyrin fluorescence measured by spectroscopy, the optimum time range for 5-ALA application is 80–270 min prior to fluorescence bronchoscopy, with an optimum at 160 min. CONCLUSION: According to our results we propose inhalation of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting that this time difference provides the best tumor/normal tissue fluorescence ratio

Evaluación del efecto antiulceroso del extracto acuoso y metanólico de las semillas de lupinus mutabilis sweet (tarwo, chocho) en ratas

In the present research, we have evaluated the effect of Lupinus mutabilis Sweet's seed, as watery and methanolic extracts on the gastric mucous of rats, following the Lee's method. Indometacin in doses higher than 50 mg per kg of weight causes lineal lesions, enlarging and dilatation of small intestine; partial obstruction, acute and chronic transmural granulomatous inflamation; abscess in the intestine's crypts and fibrosis. 2000 mg/kg of weight of the watery extract of the Lupinus was administered by mouth and 400 mk/kg of the methanolic extract by the same way.We use four groups of ten male rats each one with 250 g of weight approximately that were previously conditionated in our laboratory supplying food and water ad libitum. The animals were distributed in four groups in aleatory way and they received saline solution, ranitidine, watery extract of Lupinus and methanolic extract of Lupinus respectively. All substances were administered by oral route 30 minutes before to administer Indometacina to the animals that were in fast for 48 hours. Five hours later the animals were sacrificed and submitted to laparotomy in order to observe the macroscopically anti ulcerogenic effect that was evident and statistically significant with a value of p= 0,0013; microscopically was p= 0,0053.The anti ulcerogenic effect was: 57 % for Ranitidine, 60 % for watery extract of Lupinus and 40 % for methanolic extract of Lupinus; besides we could observe normalization of gastric mucous architecture and lowing of granulocites inftltration.We found that both extracts of Lupinus protected the gastric mucous from the lesions caused by Indometacina and could be an alternative for the treatment of gastroduodenal ulcer.En la presente investigación realizada con semilla de lupjnus mutabilis sweet se ha podido evaluar el efecto del extracto acuoso y del extracto metanólico sobre las lesiones producidas en la mucosa gástrica de ratas de acuerdo a la técnica de Lee. La indometacina en dosis superiores a 50 mg/Kg de peso produce lesiones lineales, engrosamiento y dilatación del intestino delgado, adhesiones, obstrucción parcial, inflamación granulomatosa transmural aguda y crónica, absceso en las criptas y fibrosis. El extracto acuoso en cocimiento, de Lupinus mutabilis Sweet fue administrado a la dosis de 2000mg/Kg de peso y el extracto metanólico a una dosis de 400mg/Kg.Se utilizaron cuatro grupos de ratas machos de aproximadamente 250g de peso a las que se les acondicionó en el Bioterio de la Facultad y se les suministró alimento y agua ad libitum. Los animales fueron distribuidos en G1: Control, G2: Ranitidina, G3: Extracto acuoso en conocimiento del Lupinus mutabilis Sweet y G4: Extracto metanólico de Lupinus mutabilis Sweet. Las sustancias fueron administradas por vía oral, previo ayuno de 48 horas, media hora antes de la Indometacina. A las cinco horas, los animales fueron sacrificados; realizándose la laparotomía para extraer el estómago y observar las lesiones producidas. Macroscópicamente apreciamos un efecto antiulceroso estadísticamente significativo según la prueba del chi cuadrado, con una probabilidad de p=0.0013 Y microscópicamente una probabilidad de p=0.0053. Para el extracto acuoso en cocimiento se obtuvo un efecto antiulceroso igual al 60%; para la Ranitidina 57% y en menor proporción para el extracto metanólico (40%), pudiendo observarse la normalización de la arquitectura de la mucosa y la atenuación de la infiltración de granulocitos. La observación fue realizada por inspección macroscópica directa y microscópica confirmándose estadísticamente la existencia de propiedades antiulcerosas para el extracto acuoso al 10% en cocimiento por 10 minutos; lo cual podría constituir una alternativa terapéutica en el tratamiento de la úlcera gastroduodenal y además la acción protectora parece ser independiente de la secreción de ácido

Short-, mid-, and long-term complications after multisystem inflammatory syndrome in children over a 24-month follow-up period in a hospital in Lima-Peru, 2020–2022

ObjectiveTo determine the short-, mid-, and long-term complications after multisystem inflammatory syndrome in children (MIS-C) over a 24-month follow-up period in a hospital in Lima, Peru, 2020–2022, and to explore differences according to the immunomodulatory treatment received and type of SARS-CoV-2 virus circulating.MethodsAmbispective 24-month follow-up study in children <14 years of age diagnosed with MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (HNERM).ResultsA total of 62 children were admitted with MIS-C. The most common short-term complications and serious events were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV) due to respiratory failure, and shock; predominantly during the second pandemic wave (lambda predominance) and in children that received intravenous immunoglobulin (IVIG) plus a corticosteroid. Two patients died during the first wave due to MIS-C. During prospective follow-up (median of 24 months; IQR: 16.7–24), only 46.7% of patients were followed for >18–24 months. Of the total, seven (11.3%) patients were identified with some sequelae on discharge. Among the 43 remaining children, sequelae persisted in five (11.6%) cases (neurological, hematological, and skin problems). Six patients (13.9%) presented with new onset disease (hematologic, respiratory, neurological, and psychiatric disorders). One patient died due to acute leukemia during the follow-up period. None of them were admitted to the ICU or presented with MIS-C reactivation. Two patients presented persistence of coronary aneurysm until 8- and 24-month post-discharge.ConclusionIn our hospital, children with MIS-C frequently developed short-term complications and serious events during the acute phase, with less frequent complications in the mid- and long-term. More studies are required to confirm these findings

Application of hyperthermia induced by superparamagnetic iron oxide nanoparticles in glioma treatment

Gliomas are a group of heterogeneous primary central nervous system (CNS) tumors arising from the glial cells. Malignant gliomas account for a majority of malignant primary CNS tumors and are associated with high morbidity and mortality. Glioblastoma is the most frequent and malignant glioma, and despite the recent advances in diagnosis and new treatment options, its prognosis remains dismal. New opportunities for the development of effective therapies for malignant gliomas are urgently needed. Magnetic hyperthermia (MHT), which consists of heat generation in the region of the tumor through the application of magnetic nanoparticles subjected to an alternating magnetic field (AMF), has shown positive results in both preclinical and clinical assays. The aim of this review is to assess the relevance of hyperthermia induced by magnetic nanoparticles in the treatment of gliomas and to note the possible variations of the technique and its implication on the effectiveness of the treatment. We performed an electronic search in the literature from January 1990 to October 2010, in various databases, and after application of the inclusion criteria we obtained a total of 15 articles. In vitro studies and studies using animal models showed that MHT was effective in the promotion of tumor cell death and reduction of tumor mass or increase in survival. Two clinical studies showed that MHT could be applied safely and with few side effects. Some studies suggested that mechanisms of cell death, such as apoptosis, necrosis, and antitumor immune response were triggered by MHT. Based on these data, we could conclude that MHT proved to be efficient in most of the experiments, and that the improvement of the nanocomposites as well as the AMF equipment might contribute toward establishing MHT as a promising tool in the treatment of malignant gliomas

Stem cells labeled with superparamagnetic iron oxide nanoparticles in a preclinical model of cerebral ischemia: a systematic review with meta-analysis

Abstract\ud \ud Introduction\ud Although there is an increase in clinical trials assessing the efficacy of cell therapy in structural and functional regeneration after stroke, there are not enough data in the literature describing the best cell type to be used, the best route, and also the best nanoparticle to analyze these stem cells in vivo. This review analyzed published data on superparamagnetic iron oxide nanoparticle (SPION)-labeled stem cells used for ischemic stroke therapy.\ud \ud \ud Method\ud We performed a systematic review and meta-analysis of data from experiments testing the efficacy of cellular treatment with SPION versus no treatment to improve behavioral or modified neural scale outcomes in animal models of stroke by the Cochrane Collaboration and indexed in EMBASE, PubMed, and Web of Science since 2000. To test the impact of study quality and design characteristics, we used random-effects meta-regression. In addition, trim and fill were used to assess publication bias.\ud \ud \ud Results\ud The search retrieved 258 articles. After application of the inclusion criteria, 24 reports published between January 2000 and October 2014 were selected. These 24 articles were analyzed for nanoparticle characteristics, stem cell types, and efficacy in animal models.\ud \ud \ud Conclusion\ud This study highlights the therapeutic role of stem cells in stroke and emphasizes nanotechnology as an important tool for monitoring stem cell migration to the affected neurological locus.Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE)FINEPCAPESFAPESPFAPE

Evaluación del efecto antiinflamatorio del extracto acuoso de las semillas de lupinus mutabilis sweet (tarwi, chocho), en animales de experimentación

In the investigation carried out in the seed of Lupinus mutabilis Sweet it has been possible to identify by means of a Screening Phitochemistry the present biologically active principIes in the watery extract in boiled, being determined the total alkaloids.The acute toxicity has been evaluated (LD50) so much of the watery extract as of the obtained total alkaloids of the seed.In the watery extract of the seeds the activity antiinflammatory has been evidenced (acute and subchronicle) in experimental models, being administered the Lupinus for oral route to a dose of 2000 mg/Kg of weight. The inflammation was evaluated by different techniques using the technique of Granuloma of Pouche with trementin in rats (Inflammation sub-chronicle) and inflammatory to plant with formol to 1 % and ovoalbúmina to 50% in S.S.I. in mice, following the standard techniques of the CYTED, being obtained the maximum effect of inhibition from the inflammation to the 80 minutes in comparation with the 60 minutes corresponding to the dic10fenac (30 mg/Kg) showing a percentage of inhibition of 66% in front of 100% of the standard drug. The LD50 of the watery extract in boiled for oral route it was of 3500 mg/Kg of weight and of the complete alkaloids administered for oral route it was of 600 mg/Kg.The alkaloids have been identified by TLC (Thin layer chromatography) and HPLC comparing it with standard of Spartein.En la investigación realizada en la semilla de Lupinus mutabilis Sweet se ha podido identificar mediante un Screening Fitoquímico los principios activos presentes en el extracto acuoso, determinándose los alcaloides totales.Se ha evaluado la toxicidad aguda (DL50) tanto del extracto acuoso como de los alcaloides totales obtenidos de la semilla.En el extracto acuoso de las semillas se ha evidenciado la actividad antiinflamatoria (aguda y subcrónica) en modelos experimentales, administrándose el Lupinus por vía oral a una dosis de 2000 mg/Kg de peso. La inflamación fue evaluada por diferentes técnicas utilizando la técnica de Granuloma de Pouche con trementina en ratas (Inflamación sub-crónica) y edema plantar con formol al 1 % y ovoalbúmina al 50% en S.S.I.(Inflamación aguda) en ratones, siguiendo las técnicas estándar del CYTED, obteniéndose el efecto máximo de inhibición de la inflamación a los 80 minutos en comparación con los 60 minutos corres-pon dientes al diclofenaco (30 mg/Kg) mostrando un porcentaje de inhibición de 66% frente al 100% del fármaco estándar. La DL50 del extracto acuoso por vía oral fue de 3500 mg/Kg de peso y de los alcaloides totales administrados por vía oral fue de 600 mg/Kg.Los alcaloides han sido identificados por TLC (Cromatografía en capa fina) y HPLC comparándo-10 con estándar de esparteína