Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis

Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO) production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms) and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days) in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin) treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K). Furthermore, hypermagnesaemia, rather than magnesium (Mg) depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters. .

O uso da talidomida como terapia adjuvante na leptospirose experimental / The use of thalidomide as adjuvant therapy in experimental leptospirosis

A leptospirose é uma zoonose de importância global, causada por leptospiras patogênicas. Seu tratamento é limitado quando iniciado após quatro dias do surgimento de sintomas, portanto, novas terapias adjuvantes são necessárias. Objetivo. Testar a droga imunomoduladora talidomida como terapia adjuvante à ampicilina no modelo de tratamento tardio da leptospirose experimental em hamsters. Métodos. 60 hamsters foram infectados via intraperitoneal por Leptospirainterrogans cepa L1-130, e foram separados em grupos: nenhum tratamento (NONE), talidomida (TAL), ampicilina (AMP) e ambos (AMP-TAL)...

Leptospirosis is a zoonosis of global importance, caused by pathogenic leptospira. His treatment is limited when started after four days of onset of symptoms, increasing the risk of morbidity and mortality, so new adjuvant therapies are needed.Objectives.To test the immunomodulatory drug, thalidomide, as an adjuvant therapy to antibiotics in experimental leptospirosis. Methods. Hamsters were infected by Leptospirainterrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Thalidomide was administered via a gastric tube: 50 mg/kg in linseed oil and 2 ml/kg for three days. Ampicillin was administered intramuscularly at the rate of 100 mg/kg/bid for six days. Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). Results. Experiment 1: all hamsters from the groups AMP and AMP-TAL...