Shedding light on mitochondrial outer-membrane permeabilization and membrane potential: State of the art methods and biosensors.

Membrane structural integrity is essential for optimal mitochondrial function. These organelles produce the energy needed for all vital processes, provided their outer and inner membranes are intact. This prevents the release of mitochondrial apoptogenic factors into the cytosol and ensures intact mitochondrial membrane potential (ΔΨm) to sustain ATP production. Cell death by apoptosis is generally triggered by outer mitochondrial membrane permeabilization (MOMP), tightly coupled with loss of ΔΨ m. As these two processes are essential for both mitochondrial function and cell death, researchers have devised various techniques to assess them. Here, we discuss current methods and biosensors available for detecting MOMP and measuring ΔΨ m, focusing on their advantages and limitations and discuss what new imaging tools are needed to improve our knowledge of mitochondrial function.

L-asparaginase anti-tumor activity in pancreatic cancer is dependent on its glutaminase activity and resistance is mediated by glutamine synthetase.

l-Asparaginase is a cornerstone of acute lymphoblastic leukemia (ALL) therapy since lymphoblasts lack asparagine synthetase (ASNS) and rely on extracellular asparagine availability for survival. Resistance mechanisms are associated with increased ASNS expression in ALL. However, the association between ASNS and l-Asparaginase efficacy in solid tumors remains unclear, thus limiting clinical development. Interestingly, l-Asparaginase also has a glutaminase co-activity that is crucial in pancreatic cancer where KRAS mutations activate glutamine metabolism. By developing l-Asparaginase-resistant pancreatic cancer cells and using OMICS approaches, we identified glutamine synthetase (GS) as a marker of resistance to l-Asparaginase. GS is the only enzyme able to synthesize glutamine, and its expression also correlates with l-Asparaginase efficacy in 27 human cell lines from 11 cancer indications. Finally, we further demonstrated that GS inhibition prevents cancer cell adaptation to l-Asparaginase-induced glutamine starvation. These findings could pave the way to the development of promising drug combinations to overcome l-Asparaginase resistance.

The role of liver steatosis as measured with transient elastography and transaminases on hard clinical outcomes in patients with COVID-19.

Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography [with Controlled Attenuation Parameter (CAP) measurements] was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p < 0.001). In conclusion, mild liver damage is prevalent in COVID-19 patients, but neither ALT elevation nor liver steatosis influenced hard clinical outcomes. Elevated baseline AST is a strong predictor of hard outcomes, especially in patients ⩾65 years.

Sarcoma histiocítico: presentación de un caso probable / Histiocytic sarcoma: Presentation of a probable case

El sarcoma histiocítico es un desorden de células no Langerhans extremadamente raro con un curso clínico agresivo y limitadas opciones de tratamiento. Se presenta el caso de un paciente adulto joven de género masculino, con cuadro febril prolongado, compromiso hematológico persistente, hepatoesplenomegalia y linfadenopatias generalizadas con curso clínico fatal, en quien por las características clínicas, paraclínicas y de estudios histopatológicos como de inmunohistoquímica se llegó a dicha presunción diagnostica

Histiocytic sarcoma is an extremely rare non-Langerhans cell disorder with an aggressive clinical course and limited options for therapy. We present the case of a young adult male patient, with prolonged fever, persistent hematological involvement, hepatosplenomegaly, and generalized lymphadenopathy with a fatal clinical course, in whom we arrived to this presumptive diagnosis considering the clinical, paraclinical, and histopathological characteristics, as well as immunohistochemistry

Contaminación intradomiciliaria en un sector de extrema pobreza de la comuna de La Pintana / Indoor air pollution in a zone of extreme poverty at La Pintana community, Santiago

Background: Indoor pollution can be an important risk factor for human health, considering that people spend more than 60 percent of their time in their houses. Aim: To investigate indoor pollution in a zone of extreme poverty in Metropolitan Santiago. Material and methods: During 24h, carbon monoxide (CO), sulfur dioxide (SO2), respirable particulate matter (PM10), polycyclic aromatic hydrocarbons absorbed in PM5, temperature and humidity, were measured in the interior of 24 houses in La Pintana, Santiago. Results: The higher pollutant concentrations were observed during hours when heating was used, in houses that used coal (mean PM10 250 µg/m3, CO 42 ppm, SO2 192 ppb) or firewood (mean PM10 489 µg/m3, CO 57 ppm, SO2 295 ppb). In all houses, polycyclic aromatic hydrocarbons were detected and they came from the interior of the house and not from external filtered air. Coal, firewood and cigarette smoke were important sources of carcinogenic and kerosene and gas were sources of non carcinogenic polycyclic aromatic hydrocarbons. Conclusions: In the houses studied, the population was exposed to an accumulation of highly toxic pollutants, caused by a lack of ventilation. A high relative humidity also contributed to the growth of biological pollutants

DOT-ELISA en el diagnóstico presuntivo de la hidatidosis humana / DOT-ELISA in the presumptive diagnosis of the human hydatidosis

Se aplicó Dot-ELISA como método de diagnóstico presuntivo de la hidatidosis humana en 1616 muestras de sangre de personas aparentemente sanas procedentes de áreas rurales de la Provincia de Linares, VII Región, Chile. Las muestras se precesaron y ensayaron en el laboratorio del Hospital Base de Linares. La reacción de hemaglutinación indirecta (RHAI) y doble difusión con pesquisa del arco 5 de Caprón (DD5) se ejecutaron en el Laboratorio de Parasitología Campus Sur, como métodos diagnósticos de referencia. Con Dot-ELISA se observaron 112 sueros positivos (7,0 por ciento), con RHAI (2,4 por ciento) y con DD5 6 (0,4 por ciento). Se usó como criterio de probable infección por hidatidosis, cuando se constató positividad a las tres reacciones serológicas, que se observó en 5 casos (0,31 or ciento). Como criterio de sospecha de probable infección hidatídica con dos reacciones serológicas, situación que se presentó en 11 casos (0,68 por ciento). En estos momentos se estudian por exámenes de imagenología los individuos con posible infección hidatídica

Evaluación de ELISA y contrainmunoelectroforesis en el diagnóstico de la neurocisticercosis humana en Chile / Evaluation of ELISA and counterimmunoelectrophoresis in human neurocysticercosis diagnosis in Chile

The aim of this work was to assess the diagnostic accuracy for neurocysticercosis of ELISA and counterimmunoelectrophoresis techniques, in sera and cerebrospinal fluid. 208 serum samples (47 coming from patients with confirmed cysticercosis) and 87 cerebrospinal fluid samples (27 coming from patients with confirmed cysticercosis) were analyzed. A crude and standardized extract of swine muscle cysticercus cellulosae was used as antigen. ELISA and counterimmunoelectrophoresis had a 100 percent specificity in cerebrospinal fluid, ELISA had a 85.1 percent sensitivity. Cross reactions were observed in sera of patients with confirmed hydatidosis. Thus, the high specificity of both techniques in cerebrospinal fluid is probably due to the low incidence of cerebral hydatidosis in Chile. It is concluded that for the diagnosis of neurocysteicersosis, antibodies against cysticercus cellulosae must be sought paralelly in serum and cerebrospinal fluid using ELISA and counterimmunoelectrophoresis

Aspectos sobre el diagnóstico inmunológico de algunas micosis oportunistas (III) / About immunologic diagnostic aspects of some opportunistic mycoses (III)

Se revisan algunos conceptos sobre antígenos micóticos y su preparación, técnicas para la detección de anticuerpos antimicóticos, técnicas para la detección de antígenos micóticos en fluidos corporales, y acerca de la utilidad del inmunodiagnóstico en las cuatro micosis oportunistas más frecuentes, a saber: candidiasis, criptococcosis, aspergilosis y zigomicosis