Study of cutaneous leishmaniasis in the State of Campeche (Yucatan Peninsula), Mexico, over a period of two years / Estudio de la leishmaniasis cutánea en el estado de Campeche (Península de Yucatán), México, por un periodo de dos años

Objective. To study cutaneous leishmaniasis (CL), in the Calakmul municipality of the Campeche State, during two years. Materials and methods. Individuals with skin lesions were evaluated. Aspirates taken from the lesions were cultured, PCR was performed to diagnose the Leishmania species. Results. The culture detected 42% of the samples. PCR diagnosed CL in 76% of the samples; of those 38% were from children and 62% from adults. 89% of the patients were infected with L. mexicana; 14.4% with Mexican strains of L. mexicana; 7% with L. braziliensis; 3.6% with L. mexicana and L. braziliensis. The most affected villages with CL were Dos Lagunas Sur with 12.3%, La Mancolona with 6.5% and La Guadalupe with 2.2% of prevalence, respectively. After the treatment with Glucantime, 96% of the patients were healed. Conclusion. CL is an important public health concern in Calakmul, and the parasite causing it belongs to Leishmania mexicana and Leishmania braziliensis complexes.

Objetivo. Estudiar la leishmaniasis cutánea en Calakmul, Campeche, México, durante dos años. Material y métodos. Se estudiaron individuos con lesiones cutáneas, se tomaron aspirados y se inocularon medios de cultivo; se realizó la técnica de PCR para identificar la especie de Leishmania. Resultados. Los cultivos detectaron 42% de las muestras. Con la PCR se amplificaron 76% de las muestras, 38% fueron tomadas de niños y 62% de adultos. En 89% de las muestras positivas se identificó Leishmania mexicana, en 14.4% cepas mexicanas de L. mexicana, en 7% L. braziliensis y en 3.6% L. mexicana y L. braziliensis. En Dos Lagunas Sur se encontró una prevalencia de 12.3%, en La Mancolona 6.5% y en La Virgen 2.2%. Del total de los pacientes, 96% se curó con Glucantime. Conclusion. La leishmaniasis cutánea es un problema de salud pública en Calakmul y las especies causantes pertenecen a los complejos Leishmania mexicana y Leishmania braziliensis.

Study of cutaneous leishmaniasis in the State of Campeche (Yucatan Peninsula), Mexico, over a period of two years.

OBJECTIVE: To study cutaneous leishmaniasis (CL), in the Calakmul municipality of the Campeche State, during two years. MATERIALS AND METHODS: Individuals with skin lesions were evaluated. Aspirates taken from the lesions were cultured, PCR was performed to diagnose the Leishmania species. RESULTS: The culture detected 42% of the samples. PCR diagnosed CL in 76% of the samples; of those 38% were from children and 62% from adults. 89% of the patients were infected with L. mexicana; 14.4% with Mexican strains of L. mexicana; 7% with L. braziliensis; 3.6% with L. mexicana and L. braziliensis. The most affected villages with CL were Dos Lagunas Sur with 12.3%, La Mancolona with 6.5% and La Guadalupe with 2.2% of prevalence, respectively. After the treatment with Glucantime, 96% of the patients were healed. CONCLUSION: CL is an important public health concern in Calakmul, and the parasite causing it belongs to Leishmania mexicana and Leishmania braziliensis complexes.

Tyr74 is essential for the formation, stability and function of Plasmodium falciparum triosephosphate isomerase dimer.

Plasmodium falciparum triosephosphate isomerase (PfTIM) is known to be functional only as a homodimer. Although many studies have shown that the interface Cys13 plays a major role in the stability of the dimer, a few reports have demonstrated that structurally conserved Tyr74 may be essential for the stability of PfTIM dimer. To understand the role of Tyr74, we have performed molecular dynamics (MD) simulations of monomeric and dimeric PfTIM mutated to glycine and cysteine at position 74. Simulations of the monomer revealed that mutant Tyr74Gly does not produce changes in folding and stability of the monomer. Interestingly, comparison of the flexibility of Tyr74 in the monomer and dimer revealed that this residue possesses an intrinsic restricted mobility, indicating that Tyr74 is an anchor residue required for homodimerization. Tyr74 also appears to play an important role in binding by facilitating the disorder-to-order transitions of loops 1 and 3, which allows Cys13 to form favorable interactions with loop 3 and Lys12 to be locked in a favorable position for catalysis. High-temperature MD simulations of the wild-type and Tyr74Gly PfTIM dimers showed that the aromatic moiety of Tyr74 is necessary to preserve the geometry and native contacts between loops 1 and 3 at the interface of the dimer. Disulfide cross-linking between mutant Tyr74Cys and Cys13 further revealed that Tyr74 stabilizes the geometry of loop 1 (which contains the catalytic residue Lys12) and the interactions between loops 1 and 3 via aromatic-aromatic interactions with residues Phe69, Tyr101, and Phe102. Principal component analysis showed that Tyr74 is also necessary to preserve the collective motions in the dimer that contribute to the catalytic efficiency of PfTIM dimer. We conclude that Tyr74 not only plays a role in the stability of the dimer, but also participates in the dimerization process and collective motions via coupled disorder-to-order transitions of intrinsically disordered regions, necessary for efficiency in the catalytic function of PfTIM.

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

N-allyl (NAOx) and N-propyl (NPOx) oxamates were designed as inhibitors of alpha-hydroxyacid dehydrogenase (HADH) isozyme II from Trypanosoma cruzi. The kinetic studies showed that NAOx and NPOx were competitive inhibitors of HADH-isozyme II (Ki = 72 µM, IC50 = 0.33 mM and 70 µM, IC50 = 0.32 mM, respectively). The attachment of the allylic and propylic chains to nitrogen of the competitive inhibitor oxamate (Ki = 0.91 mM, IC50 = 4.25 mM), increased 12.6 and 13-folds respectively, the affinity for T. cruzi HADH-isozyme II. NAOx and NPOx were selective inhibitors of HADH-isozyme II, because other T. cruzi dehydrogenases were not inhibited by these substances. Since HADH-isozyme II participates in the energy metabolism of T. cruzi, a trypanocidal effect can be expected with these inhibitors. However, we were not able to detect any trypanocidal activity with these oxamates. When the corresponding ethyl esters of N-allyl (Et-NAOx) and N-propyl (Et-NPOx) oxamates were tested as a possible trypanocidal prodrugs, in comparison with nifurtimox and benznidazole, the expected trypanocidal effects were obtained.

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes.

N-allyl (NAOx) and N-propyl (NPOx) oxamates were designed as inhibitors of alpha-hydroxyacid dehydrogenase (HADH) isozyme II from Trypanosoma cruzi. The kinetic studies showed that NAOx and NPOx were competitive inhibitors of HADH-isozyme II (Ki = 72 microM, IC50 = 0.33 mM and 70 microM, IC50 = 0.32 mM, respectively). The attachment of the allylic and propylic chains to nitrogen of the competitive inhibitor oxamate (Ki = 0.91 mM, IC50 = 4.25 mM), increased 12.6 and 13-folds respectively, the affinity for T. cruzi HADH-isozyme II. NAOx and NPOx were selective inhibitors of HADH-isozyme II, because other T. cruzi dehydrogenases were not inhibited by these substances. Since HADH-isozyme II participates in the energy metabolism of T. cruzi, a trypanocidal effect can be expected with these inhibitors. However, we were not able to detect any trypanocidal activity with these oxamates. When the corresponding ethyl esters of N-allyl (Et-NAOx) and N-propyl (Et-NPOx) oxamates were tested as a possible trypanocidal prodrugs, in comparison with nifurtimox and benznidazole, the expected trypanocidal effects were obtained.