Paromomycin

Leishmania aethiopica is the etiological agent of cutaneous leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL that can be taken forward for clinical trials. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials (n = 201), pentamidine (n = 150) and cryotherapy (n = 103). There were 20 case reports/series, with an overall poor study quality. We only identified two small and/or poor quality randomized controlled trials conducted a long time ago. There were two prospective non-randomized studies reporting on cryotherapy, antimonials and pentamidine.

Leishmaniasis is a parasitic disease transmitted through the bite of an infected phlebotomine sand fly and caused by protozoan parasites of the genus Leishmania. There is no available vaccine for leishmaniasis in human, and the current chemotherapy approaches are hampered by different clinical problems. Most of available drugs are confined to a limited number of toxic chemical compounds, which some parasite strains have evolved drug resistance against. Hence, drug discovery and production of a new anti leishmanial compound is essential. One promising strategy is using the nanoparticle delivery systems with the aim of accelerating the efficacy of the available treatments. In the present study, paromomycin sulfate (PM) was formulated in solid lipid nanoparticles (SLN) and the in vivo efficacy was investigated against Leishmania tropica in BALB/c mice model. To do so, the increase in footpad thickness was measured and real-time PCR was performed to quantify the parasite load after infectious challenge.

To ensure appropriate metabolic regulation, riboswitches must discriminate efficiently between their target ligands and chemically similar molecules that are also present in the cell. A remarkable example of efficient ligand discrimination is a synthetic neomycin-sensing riboswitch. Paromomycin, which differs from neomycin only by the substitution of a single amino group with a hydroxy group, also binds but does not flip the riboswitch. Interestingly, the solution structures of the two riboswitch-ligand complexes are virtually identical. In this work, we demonstrate that the local loss of key intermolecular interactions at the substitution site is translated through a defined network of intramolecular interactions into global changes in RNA conformational dynamics. The remarkable specificity of this riboswitch is thus based on structural dynamics rather than static structural differences. In this respect, the neomycin riboswitch is a model for many of its natural counterparts.

OBJECTIVES: Pathological disorder can disrupt the barrier integrity of the skin, thereby altering the drug delivery from topical formulations to the target site. Cutaneous leishmaniasis (CL) is an infection of the dermal layers of the skin and manifests as a variety of skin lesions from defined nodular forms to plaques and chronic ulcers. The aim of this work was to characterize the physiology and barrier integrity of the Leishmania-infected BALB/c mouse skin and how they impacted delivery of drugs into the skin.