Therapeutic response and safety of different treatments for cutaneous leishmaniasis in patients: A retrospective cross-sectional study

Objective:To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis,received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia.Methods:This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021.Relevant information regarding sociodemographic characteristics,history of leishmaniasis,characterization of current infection,treatment received,follow-up of therapeutic response and safety was collected from the medical records.Data were analyzed with Pearson's Chi-square association tests and Mann-Whitney U test using statistical software.Results:A total of 486 clinical records of patients were analyzed,and 356 received treatment.Eight different therapeutic alternatives(systemic,local and in combination)were analyzed.The therapeutic response of the different alternatives used(except thermotherapy)was higher than 50%.Most frequent adverse events were myalgias,arthralgias and headache,and vesicles for systemic and local treatment,respectively.Conclusions:Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

Wound healing activity of Ullucus tuberosus,an Andean tuber crop

Objective:This study was designed to investigate the wound healing activity of aqueous extracts of Ullucus tuberosus(U.tuberosus) using in vitro models.Methods:Lyophilized pulp and acetone extracts of U.tuberosus were produced using ultrasound extraction.The capacity for collagenase activation was evaluated using fluorescence detection of the enzymatic activity.Then,the influence of U.tuberosus extracts on cell proliferation,cell migration and synthesis of the extracellular matrix(ECM)proteins,metalloproteinase(MMP-1) and pro-collagen was analyzed using human dermal fibroblasts in culture.Results:An increase in collagenase activity of 12% supports the utility of U.tuberosus as an agent for scar treatment.In addition,the extracts showed an increase in the proliferation and migration of human dermal fibroblasts and the production of pro-collagen and MMP-1 after treatment with U.tuberosus extracts.The increase in proliferation,migration and pro-collagen levels positively influenced the regeneration of scarless tissue during the proliferation phase,whereas the increase in MMP-1 may have favored the wound healing process during the remodeling and cellular differentiation phases.Conclusion:The results of this study show for first time that U.tuberosus is a promising candidate to support scarless tissue regeneration.

In Silico Screening of Potential Drug with Antileishmanial Activty and Validation of their Activity by in Vitro and in Vivo Studies

The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs that are currently used as anti-inflammatory and wound healing by such anti-Leishmania activity was validated by in vitro and in vivo assays. In silico analysis identified 153 compounds from which 87 were selected by data mining of DrugBank database, 22 and 44 were detected by PASS （http：//pass.cribi.unipd.it） and BLAST （http：//blast.ncbi.nlm.nih. gov/） alignment, respectively. The majority of identified drugs are used as skin protector, anti-acne, anti-ulcerative （wound healer） or anti-inflammatory and few of them had specific antileishmanial activity. The efficacy as antileishmanial was validated in vitro in 12/23 tested compounds and in all seven compounds that were evaluated in in vivo assays. Notably, this is the first report of antileishmanial activity for adapalene. In conclusion, bioinformatics tools not only can help to reduce time and cost of the drug discovery process but also may increase the chance that candidates identified in silico which have a validated antileishmanial activity by combining different biological properties.

Antagonistic Effect of Bacteria Isolated from the Digestive Tract of Lutzomyia evansi against Promastigotes of Leishmania infantum, Antimicrobial Activities and Susceptibility to Antibiotics

Lutzomyia evansi is a phlebotomine insect endemic to Colombia’s Caribbean coast and is considered the main vector of visceral and cutaneous leishmaniasis in the region. Specific studies of the direct effects generated by bacteria in the digestive tract of the insect vectors, under Leishmania infantum using in vitro models, represent a novel alternative as a control strategy for the transmission of leishmaniasis and also provide the opportunity to detect natural products or antimicrobial peptides with different biological activities. In this study, we evaluate the leishmanicidal and antimicrobial activities of Pantoea ananatis, Ochrobactrum anthropi and Enterobacter cloacae, isolated from the digestive tract of Lutzomyia evansi and the susceptibility of these bacteria to commonly used antibiotics. The antagonistic effect of Pantoea ananatis, Ochrobactrum anthropi and Enterobacter cloacae was evaluated against six species of human pathogenic bacteria and against stationary (Metacyclic-like) and exponential promastigotes (Procyclic-like) of Leishmania infantum (BCN-GFP strain) by co-culture assays for 24 hours. The activity of the bacterial isolates on Leishmania infantum promastigotes was quantified by flow cytometry. The susceptibility of the bacterial strains to clinically used antibiotics was analyzed by antibiogram. The highest percentage of inhibition was observed against exponential promastigotes with bacterial concentrations of 108 CFU/ml of Enterobacter cloacae (77.29% ± 0.6%) and Pantoea ananatis (70.17% ± 1.1%). The extracts produced by three bacterial isolates showed similar biological activity (13 mm - 22 mm inhibition halos) against all tested bacteria;however, significant differences were observed with respect to gram-positive bacteria (P < 0.003557). The most active antibacterial activity was displayed against the pathogenic bacteria Bacillus cereus. Ochrobactrum anthropi was the isolate with the highest number of antibiotic resistance patterns while Pantoea ananatis and Enterobacter cloacae showed greater susceptibility to the evaluated antibiotics. The growth inhibitory activity of exponential Leishmania infantum promastigotes shown by extracts of Enterobacter cloacae and Pantoea ananantis suggests that the presence of these bacteria in the vector intestine may affect the parasite development to metacyclic stages, infective to human hosts. This in turn confers said bacteria, a potential in controlling the transmission of Leishmania spp. that deserves to be studied in depth.