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

Santos, Cleiton Silva; Azevedo, Everton Cruz de; Soares, Luciane Marieta; Carvalho, Magda Oliveira Seixas; Santos, Andréia C.; Chagas, Adenizar Delgado das; Silva, Caroline Luane Rabelo da; Chagas, Úrsula Maira Russo; Reis, Mitermayer Galvão dos; Athanazio, Daniel Abensur

doi:10.1590/s0074-0276108042013007

Cited by 2 publications

(5 citation statements)

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“…In an in vivo study, hamsters were inoculated with L . interrogans serovar Copenhageni , and serum sodium, potassium, and magnesium concentrations were measured and compared to healthy control hamsters [ 82 ]. Serum potassium ( p < 0.05) and magnesium (day 4; p < 0.05) concentrations were significantly higher in leptospirosis-infected hamsters compared to uninfected hamsters.…”

Section: Resultsmentioning

confidence: 99%

Micronutrients and Leptospirosis: A Review of the Current Evidence

et al. 2016

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BackgroundLeptospirosis is one of the most widespread zoonoses and represents a major threat to human health. Due to the high burden of disease, limitations in diagnostics, and limited coverage and availability of effective human and veterinary vaccines, leptospirosis remains an important neglected zoonotic disease. Improved surveillance and identification of modifiable risk factors for leptospirosis are urgently needed to inform preventive interventions and reduce the risk and severity of Leptospira infection.Methodology/Principal FindingsThis review was conducted to examine the evidence that links micronutrient status and Leptospira infection. A total of 56 studies were included in this review: 28 in vitro, 17 animal, and 11 observational human studies. Findings indicated that Leptospira infection is associated with higher iron and calcium concentrations and hypomagnesemia.Conclusions/SignificanceFew prospective studies and no randomized trials have been conducted to date to examine the potential role of micronutrients in Leptospira infection. The limited literature in this area constrains our ability to make specific recommendations; however, the roles of iron, calcium, and magnesium in leptospirosis represent important areas for future research. The role of micronutrients in leptospirosis risk and severity needs to be elucidated in larger prospective human studies to inform public health interventions.

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Section: Resultsmentioning

confidence: 99%

Micronutrients and Leptospirosis: A Review of the Current Evidence

et al. 2016

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“…Regarding immunomodulation, we have previously tested N-acetylcysteine 7 and methylene blue 6 as potential adjuvants and observed no additional benefit in experimental disease when compared to ampicillin alone. In the former, study design included: treatments starting after detection of clinical signs of disease; and treatments starting six days after infection.…”

Section: Discussionmentioning

confidence: 99%

“…In the latter, survival was evaluated in a experiment with the same design of the second experiment from this study: late treatment was reproduced by starting treatments immediately after detection of the first lethal outcome. 6 It is noteworthy that even in the absence of supportive experimental data, some studies have already been performed on immunomodulation in patients with severe leptospirosis. There are anecdotal reports of clinical benefits of high doses of methyl prednisolone in patients with severe pulmonary hemorrhagic syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…5 In experimental leptospirosis, ampicillin is the most popular and standardized antibiotic treatment used by different groups in therapeutic assays. [6][7][8][9] We have previously developed a hamster model of experimental leptospirosis to reproduce the late start of antibiotic (ampicillin) therapy and to test the adjuvant effect of the antioxidant N-acetylcysteine 7 and methylene blue-an inhibitor of soluble guanylyl cyclase-downstream the action of nitric oxide synthases 6 which had no additional benefit in experimental disease. Another potential target for adjuvant therapy in leptospirosis may be the cytokine cascade related to tumor necrosis factor alpha (TNF-a) because leptospirosis seems to share the association of high levels of pro-inflammatory markers of severity and lethality with some forms of sepsis, such as meningococcemia.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 In previous studies, we developed a model of late antimicrobial treatment in the hamster model of leptospirosis to test adjuvant therapies. 6,7 In this model, late start of ampicillin results in suboptimal therapy with expected survival rates around 50%. This experimental setting tries to reproduce the common clinical practice in which patients are usually diagnosed late in the course of disease and antibiotics are started four or more days after onset of symptoms.…”

Section: Introductionmentioning

confidence: 99%

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