In vivo evaluation of Aloysia triphylla britton (lemon verbena) essential oil toxicity and citral anti-Trypanosma cruzi activity.

Introducción: Existe escasa investigación en enfermedades olvidadas. Las plantas medicinales son una potencial fuente de compuestos antimicrobianos. Objetivos: Determinar la toxicidad del aceite esencial de Aloysia triphylla y la actividad del citral contra Trypanosoma cruzi en ratones. Diseño: Estudio experimental preclínico in vivo. Institución: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material: Ratones albinos. Intervenciones: La toxicidad aguda oral a dosis única fue evaluada en ratas albinas. Para la actividad tripanocida se utilizaron ratones asignados a los siguientes grupos: infectados y no tratados (G1), infectados y tratados con citral en dosis de 50, 150 y 300 mg/kg/día (G2, G3 y G4, respectivamente), infectados y tratados con benznidazol 100 mg/kg (G5) y no infectados y no tratados (G6). La parasitemia fue determinada individualmente cada 2 días por microscopia directa. En los días 14, 21 y 28 post infección, cinco ratones de cada grupo fueron sacrificados y los corazones procesados para análisis histopatológico. Principales medidas de resultados: Signos de toxicidad y mortalidad, y parasitemia. Resultados: La dosis límite de 2 000 mg/kg no provocó signos ni síntomas de toxicidad y los estudios anatomopatológicos macroscópicos y microscópicos no mostraron alteración de los órganos estudiados. La parasitemia fue reducida significativamente con la dosis de 300 mg/kg en los días 16° 18° y 20° post infección (p < 0,05). El número de nidos de amastigotes y de infiltrados inflamatorios en corazón fueron reducidos en 67,7% y 51,7%, respectivamente, con 300 mg/kg en el día 28°. Conclusiones: El aceite esencial de Aloysia triphylla es calificado como no tóxico y el citral en dosis de 300 mg/kg tuvo actividad contra Trypanosoma cruzi en ratones.Introduction: There is limited research on neglected diseases. Medicinal plants are potential sources of antimicrobial compounds. Objectives: To determine the toxicity of Aloysia triphylla essential oil and citral activity against Trypanosoma cruzi in mice. Design: Experimental study in vivo, preclinical. Setting: Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological material: Albino mice. Main outcome measures: Signs of toxicity and mortality and parasitemia. Interventions: Acute oral toxicity at single dose was evaluated in albino rats. For trypanocidal activity mice were assigned to the following groups: untreated infected (G1), infected and treated with citral at doses 50, 150 and 300 mg/kg/day (G2, G3 and G4 respectively), infected and treated with benznidazole 100 mg/kg (G5), and uninfected and untreated (G6). Parasitemia was determined individually every 2 days by direct microscopy. In days 14, 21 and 28 post infection five mice from each group were sacrificed and their hearts processed for histopathology. Results: The limit dose of 2 000 mg/kg did not cause signs or symptoms of toxicity and macro and microscopic anatomopathology did not show alterations in the organs studied. Parasitemia was significantly reduced at dose of 300 mg/kg at days 16, 18, and 20 post infection (p <0.05); the number of amastigote nests and inflammatory infiltrates in heart were reduced on day 28 by 67.7% and 51.7% respectively with 300 mg/kg. Conclusions: Aloysia triphylla essential oil is qualified as nontoxic and citral at 300 mg/kg dose had activity against Trypanosoma cruzi in mice

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Evaluación de la toxicidad del aceite esencial de Aloysia triphylla britton (cedrón) y de la actividad anti-Trypanosoma cruzi del citral, in vivo

Introduction: There is limited research on neglected diseases. Medicinal plants are potential sources of antimicrobial compounds. Objectives: To determine the toxicity of Aloysia triphylla essential oil and citral activity against Trypanosoma cruzi in mice. Design: Experimental study in vivo, preclinical. Setting: Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological material: Albino mice. Main outcome measures: Signs of toxicity and mortality and parasitemia. Interventions: Acute oral toxicity at single dose was evaluated in albino rats. For trypanocidal activity mice were assigned to the following groups: untreated infected (G1), infected and treated with citral at doses 50, 150 and 300 mg/kg/day (G2, G3 and G4 respectively), infected and treated with benznidazole 100 mg/kg (G5), and uninfected and untreated (G6). Parasitemia was determined individually every 2 days by direct microscopy. In days 14, 21 and 28 post infection five mice from each group were sacrificed and their hearts processed for histopathology. Results: The limit dose of 2 000 mg/kg did not cause signs or symptoms of toxicity and macro and microscopic anatomopathology did not show alterations in the organs studied. Parasitemia was significantly reduced at dose of 300 mg/kg at days 16, 18, and 20 post infection (p <0.05); the number of amastigote nests and inflammatory infiltrates in heart were reduced on day 28 by 67.7% and 51.7% respectively with 300 mg/kg. Conclusions: Aloysia triphylla essential oil is qualified as nontoxic and citral at 300 mg/kg dose had activity against Trypanosoma cruzi in mice.Introducción: Existe escasa investigación en enfermedades olvidadas. Las plantas medicinales son una potencial fuente de compuestos antimicrobianos. Objetivos: Determinar la toxicidad del aceite esencial de Aloysia triphylla y la actividad del citral contra Trypanosoma cruzi en ratones. Diseño: Estudio experimental preclínico in vivo. Institución: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material: Ratones albinos. Intervenciones: La toxicidad aguda oral a dosis única fue evaluada en ratas albinas. Para la actividad tripanocida se utilizaron ratones asignados a los siguientes grupos: infectados y no tratados (G1), infectados y tratados con citral en dosis de 50, 150 y 300 mg/kg/día (G2, G3 y G4, respectivamente), infectados y tratados con benznidazol 100 mg/kg (G5) y no infectados y no tratados (G6). La parasitemia fue determinada individualmente cada 2 días por microscopia directa. En los días 14, 21 y 28 post infección, cinco ratones de cada grupo fueron sacrificados y los corazones procesados para análisis histopatológico. Principales medidas de resultados: Signos de toxicidad y mortalidad, y parasitemia. Resultados: La dosis límite de 2 000 mg/kg no provocó signos ni síntomas de toxicidad y los estudios anatomopatológicos macroscópicos y microscópicos no mostraron alteración de los órganos estudiados. La parasitemia fue reducida significativamente con la dosis de 300 mg/kg en los días 16° 18° y 20° post infección (p < 0,05). El número de nidos de amastigotes y de infiltrados inflamatorios en corazón fueron reducidos en 67,7% y 51,7%, respectivamente, con 300 mg/kg en el día 28°. Conclusiones: El aceite esencial de Aloysia triphylla es calificado como no tóxico y el citral en dosis de 300 mg/kg tuvo actividad contra Trypanosoma cruzi en ratones