Características clínicas e histopatológicas de niños peruanos con craneofaringioma

Introducción: Los craneofaringiomas son tumores benignos, de los cuales hasta el 50% ocurren en niños. Sin embargo, no hay estudios en niños peruanos. Objetivo: describir las características clínicas e histopatológicas de niños con craneofaringioma hospitalizados en el Hospital Nacional Edgardo Rebagliati Martins entre agosto de 2019 y mayo de 2021. El estudio: El diseño es transversal y la fuente de los datos fueron las historias clínicas. Se recolectó información sobre el sexo, edad, cirugías y características relacionadas a la primera cirugía de resección tumoral. Hallazgos: Incluimos 12 pacientes. El 83.3% fueron varones, al momento del diagnóstico la mediana de edad fue de 6 años y predominaron los síntomas visuales, todos tuvieron deficiencias hormonales luego de la primera cirugía de resección. Conclusión: tres recibieron radioterapia, uno desarrolló transformación maligna y otro falleció. Es necesario realizar a futuro estudios prospectivos.

Introduction: Craniopharyngiomas are benign tumors, of which up to 50% occur in children. However, there are no studies in Peruvian children. Objective : to describe the clinical and histopathological characteristics of children with craniopharyngioma hospitalized at the Edgardo Rebagliati Martins National Hospital between August 2019 and May 2021. The study: The design is cross-sectional and the data source were medical records. Information on sex, age, surgeries and characteristics related to the first tumor resection surgery were collected. Findings: We included 12 patients. 83.3% were male, at the time of diagnosis the median age was 6 years and visual symptoms predominated, all had hormonal deficiencies after the first resection surgery. Conclusions: three received radiotherapy, one developed malignant transformation and one died. Future prospective studies are necessary.

¿Neoplasia de células de Hürtle o de células oncocíticas? Denominación actual y su manejo. Reporte de caso / Hürtle cell or oncocytic cell neoplasm? Current denomination and its management. Case report

Introducción: Las células de Hürtle fueron descritas por Max Askanazy en 1898, aunque su denominación inapropiada ha permanecido en el léxico. Pueden observarse en una amplia variedad de lesiones tiroideas, desde afecciones no neoplásicas hasta francamente malignas. Caso clínico: Femenina de 62 años de edad, asmática e hipertensa controlada, alérgica al yodo y a la penicilina, quien inicia enfermedad actual 1 año previo al presentar aumento de volumen en región anterior del cuello. Ecografía tiroidea reportó glándula aumentada de tamaño, con nódulo tiroideo derecho, complejo de 4 cm; y nódulo tiroideo izquierdo, complejo de 2 cm, TI-RADS 4C. Tomografía computarizada reportó lesión ocupantne de espacio del lóbulo tiroideo derecho de 6 cm y nódulos tiroideos izquierdos de 3 y 2 cm. Pruebas tiroideas sin alteraciones. Se realizó tiroidectomía total. Diagnóstico histopatológico: adenoma de células de Hürtle. Conclusión: En la actualidad, el término correcto es neoplasia de células oncocíticas, bien sea para el adenoma o para el carcinoma. Este tipo de tumores se presenta con mayor frecuencia en mujeres de mediana edad y con un tamaño considerable al momento del diagnóstico. Es necesario establecer un protocolo de acción ante el diagnóstico presuntivo mediante punción por aspiración por aguja fina, debido a la dificultad para diferenciar entre patología benigna y maligna, con la finalidad de garantizar una conducta terapeútica adecuada(AU)

Introduction: Hürtle cells were described by Max Askanazy in 1898, although their inappropriate name has remained in the lexicon. They can be seen in a wide variety of thyroid lesions, from non-neoplastic to frankly malignant conditions. Clinical case: A 62-year-old female, asthmatic and controlled hypertensive, allergic to iodine and penicillin, who started the current disease 1 year before presenting volume increase in the anterior region of the neck. Thyroid ultrasound reported an enlarged gland, with a 4-cm complex right thyroid nodule; and left thyroid nodule, 2 cm complex, TI-RADS 4C. Computed tomography reported a 6 cm space-occupying lesion of the right thyroid lobe and 3 and 2 cm left thyroid nodules. Thyroid tests without alterations. Total thyroidectomy was performed. Histopatological diagnosis: Hürtle cell adenoma. Conclusion: Currently, the correct term is oncocytic cell neoplasm, either for adenoma or for carcinoma. This type of tumors occurs more frequently in middle-aged women and with a considerable size at the time of diagnosis. It is necessary to establish a protocol of action before the presumptive diagnosis by means of fine needle aspiration procedure, due to the difficulty to differentiate between benign and malignant pathology, with the purpose of guaranteeing an adequate therapeutic conduct(AU)

Development and characterisation of a rat model that exhibits both metabolic dysfunction and neurodegeneration seen in type 2 diabetes.

Accurate modelling type 2 diabetes and diabetic complications in rodents has proven a challenge, largely as a result of the long-time course of disease development in humans. In the present study, we aimed to develop and comprehensively characterise a new rodent model of type 2 diabetes. To do this, we fed Sprague-Dawley rats a high fat/high sugar diet (HFD) to induce obesity and dyslipidaemia. After 3 weeks, we s.c. implanted osmotic mini pumps to enable a 14 day, slow infusion of streptozotocin (STZ; lower dose = 100 mg kg-1 ; higher dose = 120 mg kg-1 ) to dose-dependently reduce pancreatic beta cell mass. After removing the mini pumps, we monitored animals for 4 months using a battery of tests to assess both metabolic and neurodegenerative changes across time. Our data demonstrate the combination of the HFD and lower dose STZ leads to induction of early-stage type 2 diabetes defined by moderate hyperglycaemia, hyperinsulinaemia and impaired glucose tolerance, at the same time as the retention of an obese phenotype. By contrast, combining the HFD and higher dose STZ leads to induction of later-stage type 2 diabetes defined by frank hyperglycaemia, hypoinsulinaemia (but not insulin depletion) and severely impaired glucose tolerance, at the same time as retaining an obese phenotype. Regardless of dose of STZ (and level of hyperglycaemia), all diabetic rats exhibited signs of peripheral neurodegeneration in the skin and muscle. Thus, this model recapitulates many of the complex metabolic disturbances seen in type 2 diabetes and provides an excellent platform for investigating the pathophysiological mechanisms that lead to diabetic complications such as peripheral neuropathy. KEY POINTS: Type 2 diabetes is a major health concern and markedly increases risk cardiovascular and neurodegenerative diseases. Accurate modelling of type 2 diabetes is a major challenge and has impeded our ability to understand the mechanisms that contribute to complications of type 2 diabetes. We have developed a method of inducing different stages of type 2 diabetes using a high fat/high sugar diet and 14 day infusion of streptozotocin to dose-dependently destroy pancreatic beta cell mass. Over 4 months, we comprehensively characterised these animals and confirmed that they develop sustained metabolic dysfunction and progressive peripheral neurodegeneration as seen in type 2 diabetes. This new model will improve our ability to investigate the pathophysiological mechanisms that link type 2 diabetes with complications such as neurodegeneration.

Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy.

Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR. Consequently, drug candidates that aim at normalizing mitochondrial function could be an attractive therapeutic approach. This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR. The model effectively mimicked type 2 diabetes over 21 weeks. During this period, visual acuity was monitored by measuring optokinetic response (OKR). Vision loss occurred 5-8 weeks after the onset of hyperglycemia. After 10 weeks of hyperglycemia, visual function was reduced by 65%. From this point, the right eyes of the animals were topically treated once daily with the test compounds. The left, untreated eye served as an internal control. Only three weeks of topical treatment significantly restored vision from 35% to 58-80%, while visual acuity of the non-treated eyes continued to deteriorate. Interestingly, the two novel SCQs restored visual acuity better than idebenone or elamipretide. This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR.

Echinacea Angustifolia DC Extract Induces Apoptosis and Cell Cycle Arrest and Synergizes with Paclitaxel in the MDA-MB-231 and MCF-7 Human Breast Cancer Cell Lines.

BACKGROUND: Echinacea spp. displays different biological activities, such as antiviral, immunomodulatory, and anticancer activities. Currently, high sales of hydroalcoholic extracts of Echinacea have been reported; hence, the importance of studies on Echinacea. AIM: To establish the effects of Echinacea angustifolia DC extract obtained with ethyl acetate (Ea-AcOEt) in breast cancer cell lines. METHODS: Cytotoxicity, cell cycle arrest, and cell death were evaluated. Besides, the safety of the extract, as well as its effect in combination with paclitaxel were investigated. RESULTS: The echinacoside and caffeic acid content in the Ea-AcOEt extract were quantified by HPLC, and its antioxidant activity was assessed. The Ea-AcOEt extract showed cytotoxic activity on breast cancer MDA-MB-231 cells (IC50 28.18 ± 1.14 µg/ml) and MCF-7 cells (19.97 ± 2.31 µg/ml). No effect was observed in normal breast MCF-10 cells. The Ea-AcOEt extract induced cell cycle arrest in the G1 phase and caspase-mediated apoptosis. No genotoxicity was found in vitro or in vivo, and the extract showed no signs of toxicity or death at 2,000 mg/kg in rodents. In vitro, the combination of Ea-AcOEt extract and paclitaxel showed a synergistic effect on both cancer cell lines. CONCLUSION: The Ea-AcOEt extract is a potential candidate for breast cancer treatment.

Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones.

Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which largely depends on the reversible redox characteristics of the active quinone core. We recently identified 11 naphthoquinone derivatives, 1-11, from a library of SCQs that demonstrated enhanced cytoprotection and improved metabolic stability compared to the clinically used benzoquinone idebenone. Since the toxicity properties of our promising SCQs were unknown, this study developed multiplex methods and generated detailed toxicity profiles from 11 endpoint measurements using the human hepatocarcinoma cell line HepG2. Overall, the toxicity profiles were largely comparable across different assays, with simple standard assays showing increased sensitivity compared to commercial toxicity assays. Within the 11 naphthoquinones tested, the L-phenylalanine derivative 4 consistently demonstrated the lowest toxicity across all assays. The results of this study not only provide useful information about the toxicity features of SCQs but will also enable the progression of the most promising drug candidates towards their clinical use.

Absolute Blood Eosinophil Counts to Guide Inhaled Corticosteroids Therapy Among Patients with COPD: Systematic Review and Meta-analysis.

INTRODUCTION: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 recommends the use of absolute blood eosinophil count as a guide for the escalation and de-escalation of inhaled corticosteroids (ICS) in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). We evaluated the risk of moderate or severe exacerbations among patients escalating and de-escalating ICS therapy by absolute blood eosinophil thresholds in this systematic review. METHODS: Through a comprehensive literature search of Pubmed/MEDLINE, EMBASE, and clinical trial sites up to April 2019, we identified relevant studies. We used generic inverse variance method with fixed-effects estimates to compare the risk of moderate or severe exacerbations among COPD patients with elevated blood eosinophil counts exposed to inhaled corticosteroids (ICS) versus non-ICS treatments groups expressed as risk ratios. RESULTS: Ten studies (8 randomised control trials and 2 observational studies) were included, with a total of 85,059 COPD patients. In our pooled analysis, we found an overall reduction in risk of moderate or severe exacerbations in patients with absolute blood eosinophil thresholds ranging from ≥ 100 to ≥ 340 cells/µL among patients escalating ICS (RR, 0.77, 95% CI, 0.73-0.81). For studies evaluating the effects of de-escalation of ICS on moderate to severe exacerbations using blood eosinophil thresholds of ≥ 300 to ≥ 340 cells/µL had an increased risk of moderate or severe exacerbations following the de-escalation of ICS (RR, 1.66, 95% CI, 1.31-2.10). CONCLUSION: This study confirms the validity of the recommended absolute blood eosinophil count thresholds for the escalation and de-escalation of ICS among COPD patients. However, this recommendation is for COPD patients with prior exacerbations rather than among newly diagnosed COPD patients as observed in this study. COPD patients with current or past history of asthma represent a unique phenotypic group which should be further evaluated.

Evaluation of DNA/BSA Binding and Chemical Nuclease Activity of L-Tyrosine-Based Mn(III) and Fe(III) Metallo-Intercalators.

A novel class of Mn(III) and Fe(III) complexes of L-tyrosine-based ligand has been synthesized and characterized through various analytical and spectroscopic techniques. These complexes were found to exhibit efficient binding properties with the biomolecules viz. calf thymus DNA and BSA. The ability of complexes to bind with such biomolecules has been explored through absorption, emission and viscosity measurements. Based on spectroscopic techniques we can conclude that the complexes could bind to DNA via intercalation. It was observed that these complexes can cleave pBR322 DNA in gel-electrophoresis technique through oxidative mechanism. The BSA was quenched by the complexes around 340 nm adopting a mechanism of static mode. The binding constants, thermodynamic parameters and the donor to acceptor distance were calculated. Besides, molecular docking simulations were carried out for the complexes with human DNA topoisomerase and BSA protein. The docked poses are visualized to provide supportive evidence to the interaction of the synthesized complexes with DNA/BSA.

Targeting mitochondrial function to treat optic neuropathy.

Many reports have illustrated a tight connection between vision and mitochondrial function. Not only are most mitochondrial diseases associated with some form of vision impairment, many ophthalmological disorders such as glaucoma, age-related macular degeneration and diabetic retinopathy also show signs of mitochondrial dysfunction. Despite a vast amount of evidence, vision loss is still only treated symptomatically, which is only partially a consequence of resistance to acknowledge that mitochondria could be the common denominator and hence a promising therapeutic target. More importantly, clinical support of this concept is only emerging. Moreover, only a few drug candidates and treatment strategies are in development or approved that selectively aim to restore mitochondrial function. This review rationalizes the currently developed therapeutic approaches that target mitochondrial function by discussing their proposed mode(s) of action and provides an overview on their development status with regards to optic neuropathies.

Supervivencia del recién nacido que requiere ventilación mecánica artificial / Survival of the newborn who requires a mechanical ventilation

Introducción: el recién nacido enfrenta al nacer un importante desafío para poder sobrevivir fuera de su madre. Inicia la respiración aérea, la cual le permitirá obtener oxígeno del medio ambiente, requiriendo para ello el poder contar al momento de nacer con un desarrollo anatómico de vías aéreas, vasos sanguíneos pulmonares normales, adecuada estabilidad pulmonar, que se encuentra en función de la cantidad y calidad del surfactante pulmonar con que cuente el recién nacido, y la capacidad para establecer una ventilación y perfusión pulmonar adecuados. Objetivo: conocer la supervivencia del recién nacido que requiere VMA en el Hospital Carlos Manuel de Céspedes de Bayamo. Método: se realizó un estudio observacional prospectivo de los recién nacidos ventilados en el servicio de Neonatología del Hospital General Universitario Carlos Manuel de Céspedes de Bayamo, Granma en el periodo comprendido desde el 1 de enero de 2011 hasta 31 de diciembre de 2013. Resultados: la membrana hialina fue de 90 por ciento hasta el cuarto día a partir del cual decrece y 88 por ciento la bronconeumonía connatal, ambas con significación estadística, el edema pulmonar mantuvo una sobrevida de 100 por ciento relacionada con el parto por cesárea. La supervivencia global inicial fue de 98 por ciento, con descenso escalonado, observándose a partir del séptimo día una sobrevida de 40 por ciento, se encontró un riesgo relativo superior a uno en todas las variables seleccionadas. La duración de la ventilación en los neonatos ventilados vivos fue de 4,17 ± 2,92 días con relación a los que fallecieron de(AU)

Introduction: newborn faces a major challenge to survive outside his/her mother. He starts breathing, which allows getting oxygen from the environment, requiring an anatomical development of airways, normal pulmonary blood vessels, and the adequate lung stability, which is a function of the amount and quality of pulmonary surfactant of the newborn, and the ability to establish an adequate pulmonary ventilation and perfusion. Objective: to know the survival of the newborn requiring AMV in Carlos Manuel de Céspedes Hospital of Bayamo. Method: it was performed a prospective observational study of ventilated newborns in the Neonatology Service of the General University Hospital Carlos Manuel de Céspedes in Bayamo, Granma in the period of January 1st 2011 until December 31st 2013. Results:the hyaline membrane was about 90 percent until the fourth day from which it decreases and 88 percent belonged to the connatal bronchopneumonia, both with statistical significance, the pulmonary edema had a 100 percent of survival related to cesarean delivery. The initial overall survival was 98 percent with step-down, noticing on the seventh day a survival rate of 40 percent, it was found a relative risk over one in the selected variables. The duration of ventilation in ventilated neonates alive was 4.17 ± 2.92 days compared to those who died of 6.17 ± 2.57 days with statistical significance of p = 0.0001. We conclude that the survival for ventilated infants was generally good, within the study period there were 29 deceased newborns, prevailing males and caesarean delivery. Conclusions: overall survival decreases as ventilation increases for seven days or more. In newborns with gestational age between 30 and 33. 6 weeks the survival decreased from the sixth day(EU)