ABSTRACT
El uso incremental de células estromales mesenquimales (CEM) para regeneración tisular y su potencial para el manejo de enfermedades de origen inflamatorio dadas sus propiedades inmunomodulatorias, está garantizado a corto plazo. Sin embargo existe un vacío relaciona-do con los mecanismos celulares y moleculares implicados en el proceso inmunomodulatorio por parte de las CEM de gelatina de Wharton (GW). Este estudio evalúa el efecto de las CEM-GW sobre la regulación y función del fenotipo del macrófago en ambientes inflamato-rios. Se realizaron ensayos con células mononucleares de sangre periférica (PBMCs) (N=4) o con la células CD3+ (N=3), estimuladas con anti-CD3/CD28/CD2, evaluando la inhibición de la proliferación de los linfocitos en co-cultivos con CEM-GW (N=3).
Subject(s)
Wharton Jelly , MacrophagesABSTRACT
BACKGROUND: American cutaneous leishmaniasis (ACL) is a complicated disease producing about 67.000 new cases per year. The severity of the disease depends on the parasite species; however in the vast majority of cases species confirmation is not feasible. WHO suggestion for ACL produced by Leishmania braziliensis, as first line treatment, are pentavalent antimonial derivatives (Glucantime or Sodium Stibogluconate) under systemic administration. According to different authors, pentavalent antimonial derivatives as treatment for ACL show a healing rate of about 75% and reasons for treatment failure are not well known. METHODS: In order to characterise the clinical and parasitological features of patients with ACL that did not respond to Glucantime, a cross-sectional observational study was carried out in a cohort of 43 patients recruited in three of the Colombian Army National reference centers for complicated ACL. Clinical and paraclinical examination, and epidemiological and geographic information were recorded for each patient. Parasitological, histopathological and PCR infection confirmation were performed. Glucantime IC50 and in vitro infectivity for the isolated parasites were estimated. RESULTS: Predominant infecting Leishmania species corresponds to L. braziliensis (95.4%) and 35% of the parasites isolated showed a significant decrease in in vitro Glucanatime susceptibility associated with previous administration of the medicament. Lesion size and in vitro infectivity of the parasite are negatively correlated with decline in Glucantime susceptibility (Spearman: r = (-)0,548 and r = (-)0,726; respectively). CONCLUSION: A negative correlation between lesion size and parasite resistance is documented. L. braziliensis was found as the main parasite species associated to lesion of patients that underwent treatment failure or relapse. The indication of a second round of treatment in therapeutic failure of ACL, produced by L. braziliensis, with pentavalent antimonial derivatives is discussable.
Subject(s)
Antiprotozoal Agents/therapeutic use , Leishmania braziliensis/drug effects , Leishmaniasis, Cutaneous/drug therapy , Meglumine/therapeutic use , Organometallic Compounds/therapeutic use , Adult , Antiprotozoal Agents/pharmacology , Cohort Studies , Cross-Sectional Studies , Humans , Inhibitory Concentration 50 , Leishmania braziliensis/physiology , Male , Meglumine/pharmacology , Meglumine Antimoniate , Organometallic Compounds/pharmacology , Recurrence , Treatment Failure , U937 Cells , Young AdultABSTRACT
The discrimination of Leishmania species from patient samples has epidemiological and clinical relevance. In this study, different gene target PCR-restriction fragment length polymorphism (RFLP) protocols were evaluated for their robustness as Leishmania species discriminators in 61 patients with cutaneous leishmaniasis. We modified the hsp70-PCR-RFLP protocol and found it to be the most reliable protocol for species identification.
