Pulmonary haemorrhage as a frequent cause of death among patients with severe complicated Leptospirosis in Southern Sri Lanka.

BACKGROUND: Leptospirosis is a tropical disease associated with life threatening complications. Identifying clinical and investigation-based parameters that predict mortality and morbidity is vital to provide optimal supportive care. METHODS: We conducted an observational study in an endemic setting, in the southern Sri Lanka. Consecutive patients having complicated leptospirosis were recruited over 18 months. Clinical, investigational and treatment data were collected and the predictors of mortality were analysed. RESULTS: Out of 88 patients having complicated leptospirosis, 89% were male. Mean age was 47yrs (±16.0). Among the total major complications 94.3% had acute kidney injury, 38.6% pulmonary haemorrhages, 12.5% fulminant hepatic failure, 60.2% hemodynamic instability and 33% myocarditis. An acute significant reduction of haemoglobin (Hb) was observed in 79.4% of patients with pulmonary haemorrhage. The mean of the highest haemoglobin reduction in patients with pulmonary haemorrhage was 3.1g/dL. The presence of pulmonary haemorrhage (PH) and hemodynamic instability within first 48 hours of admission significantly predicted mortality (p<0.05) in severe leptospirosis. Additionally, within first 48 hours of admission, elevated SGOT (AST), presence of atrial fibrillation, presence of significant haemoglobin reduction, higher number of inotropes used, prolonged shock, invasive ventilation and admission to ICU significantly predicted mortality. Out of major complications during the first week after admission, pulmonary haemorrhage and fulminant hepatic failure (FHF) combination had significant adjusted odds of mortality (OR = 6.5 and 4.8, p<0.05). Six patients with severe respiratory failure due to PH underwent ECMO and four survived. The overall mortality in complicated leptospirosis was 17%. In PH and FHF, the mortality rate was higher reaching 35.4% and 54.5%, respectively. CONCLUSIONS: Within first 48 hours of admission, major complications such as pulmonary haemorrhage and haemodynamic instability and other parameters such as atrial fibrillation, acute haemoglobin reduction, elevated SGOT level could be used as early parameters predictive of mortality in severe leptospirosis. PH and FHF during the first week of admission in leptospirosis are associated with high morbidity and mortality requiring prolonged ICU care and hospitalisation. Above parameters could be used as parameters indicating severity for triaging and intensifying treatment. Using ECMO is a plausible treatment option in patients with severe pulmonary haemorrhage.

Plectranthus zeylanicus: A Rich Source of Secondary Metabolites with Antimicrobial, Disinfectant and Anti-Inflammatory Activities.

Plectranthus zeylanicus Benth is used in Sri Lankan folk medicine as a remedy for inflammatory conditions and microbial infections. Our previous investigations revealed potent 5-lipoxygenase (5-LO) inhibitory activity in lipophilic extracts of this plant, supporting its anti-inflammatory potential. In-depth studies on the antimicrobial activity have not been conducted and the bioactive ingredients remained elusive. As a continuation of our previous work, the present investigation was undertaken to evaluate the antimicrobial activity of different extracts of P. zeylanicus and to isolate and characterize bioactive secondary metabolites. Different organic extracts of this plant were analyzed for their antibacterial activity, and the most active extract, i.e., dichloromethane extract, was subjected to bioactivity-guided fractionation, which led to the isolation of 7α-acetoxy-6ß-hydroxyroyleanone. This compound displayed strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 62.5 µg/mL, and its disinfectant capacity was comparable to the potency of a commercial disinfectant. Moreover, 7α-acetoxy-6ß-hydroxyroyleanone inhibits 5-LO with IC50 values of 1.3 and 5.1 µg/mL in cell-free and cell-based assays, respectively. These findings rationalize the ethnopharmacological use of P. zeylanicus as antimicrobial and anti-inflammatory remedy.

Lipophilic extracts of Leucas zeylanica, a multi-purpose medicinal plant in the tropics, inhibit key enzymes involved in inflammation and gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Leucas zeylanica (L.) W.T. Aiton is a popular, multi-purpose medicinal plant in Sri Lanka but the pharmacological potential and the chemical profile have not been systematically investigated to understand and rationalize the reported ethnobotanical significance. AIM OF THE STUDY: The present study was undertaken to scientifically validate the traditional usage of this plant for the treatment of inflammatory conditions, gout and microbial infections. Inhibition of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)-1 and xanthine oxidase (XO) by different extracts of L. zeylanica was investigated to determine the anti-inflammatory and anti-gout activity, respectively. The antibacterial and antifungal activities were also studied and the relevant constituents in the bioactive extracts were tentatively identified. MATERIALS AND METHODS: Cell-free and/or cell-based assays were employed in order to investigate the effects of the extracts against the activity of human 5-LO, mPGES-1 and XO as well as to assess antioxidant properties. The antibacterial activity of the extracts was determined by the broth micro-dilution method against Gram positive and Gram negative bacteria including methicillin-resistant Staphylococcus aureus while the agar dilution method was employed to determine the anti-Candida activity. Gas chromatography coupled to mass spectrometric (GC-MS) analysis enabled the characterization of secondary metabolites in the extracts. RESULTS: The dichloromethane extract of L. zeylanica efficiently inhibited 5-LO activity in stimulated human neutrophils (IC50 = 5.5 µg/mL) and isolated human 5-LO and mPGES-1 (IC50 = 2.2 and 0.4 µg/mL). Potent inhibition of XO was observed by the same extract (IC50 = 47.5 µg/mL), which is the first report of XO-inhibitory activity of a Sri Lankan medicinal plant. Interestingly, significant radical scavenging activity was not observed by this extract. Only the n-hexane extract exhibited antibacterial activity against Staphylococcus aureus and Staphylococcus saprophyticus with a MIC of 250 µg/mL while the anti-Candida activity was moderate. GC-MS analysis revealed the presence of phytosterols, fatty acids, sesquiterpenes, diterpenes and several other types of secondary metabolites. CONCLUSIONS: Potent inhibition of 5-LO, mPGES-1 and XO rationalizes the ethnopharmacological use of L. zeylanica as anti-inflammatory and anti-gout remedy. Interestingly, the antimicrobial activities were not prominent, despite its wide utility as an antimicrobial medication.