Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model.

A robust regimen for inducing allogeneic transplantation tolerance involves pre-emptive recipient treatment with donor splenocytes (SP) rendered apoptotic by 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide(ECDI) treatment. However, such a regimen is limited by availability of donor cells, cost of cell procurement, and regulatory hurdles associated with cell-based therapies. Nanoparticles (NP) delivering donor antigens are a promising alternative for promoting transplantation tolerance. Here, we used a B6.C-H-2bm12(bm12) to C57BL/6(B6) skin transplant model involving a defined major histocompatibility antigen mismatch to investigate design parameters of poly(lactide-co-glycolide) (PLG) NPs delivering peptides containing the donor antigen for optimizing skin allograft survival. We showed that an epitope-containing short peptide (P1) was more effective than a longer peptide (P2) at providing graft protection. Importantly, the NP and P1 complex (NP-ECDI-P1) resulted in a significant expansion of graft-infiltrating Tregs. Interestingly, in comparison to donor ECDI-SP that provided indefinite graft protection, NP-ECDI-P1 targeted different splenic phagocytes and skin allografts in these recipients harbored significantly more graft-infiltrating CD8+IFN-γ+ cells. Collectively, the current study provides initial engineering parameters for a cell-free and biocompatible NP-peptide platform for transplant immunoregulation. Moreover, it also provides guidance to future NP engineering endeavors to recapitulate the effects of donor ECDI-SP as a goal for maximizing tolerance efficacy of NP formulations.

Clinical and Parasitological Features of Patients with American Cutaneous Leishmaniasis that Did Not Respond to Treatment with Meglumine Antimoniate.

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.

Un caso de apliaación de la dermatología integral / A case of applcaation of integral dermatology / Um caso de aplicação da dermatologia ittegral

La sarcoidosis es una enfermedad granulomatosa multisistémica de etiología desconocida. Presentamos el caso de una mujer que consulta por la preocupación estética de una lesión en dorso nasal. La exploración clínica lleva a sospechar de una enfermedad granulomatosa, por lo cual se lleva a biopsia y confirmación de su patología. La sarcoidosis es un trastorno crónico, que afecta múltiples órganos, su incidencia es variable, pero es mayor en países industrializados y se presenta en su mayoría en mujeres entre 20 y 40 años de edad. De las manifestaciones sistémicas, la más frecuente es la pulmonar, mientras que la afectación cutánea oscila entre 20-35%. El diagnóstico se establece con los hallazgos clínico-radiológicos apoyados por la evidencia histopatológica de granulomas no caseificantes, aunque estos últimos no son específicos, por lo que deben excluirse otros procesos.

Sarcoidosis is a multifactorial granulomatous disease of unknown etiology. We present a case of a woman who presents with cosmetic concerns of a lesion on the dorsum of the nose. The clinical exploration raises suspicion of granulomatous disease, reason for which reason a biopsy is done confirming her pathology. Sarcoidosis is a chronic disorder that affects multiple organs. Its incidence is unknown but is more frequent in industrialized countries, and majorly affects women between 20-40 years of age. Among its multiple manifestations, pulmonary symptoms are the most frequent, meanwhile the cutaneous manifestations are only present in 20-35% of the cases. The diagnosis is made by clinical-radiographic findings associated to histopathological findings of noncaseating granulomas, even though these are not specific to the disease and other processes must be ruled out.

A sarcoidose é uma doença granulomatosa multisistêmica de etiologia desconhecida. Apresentamos o caso de uma mulher que consulta pela preocupação estética de uma lesão em dorso nasal. A exploração clínica leva a suspeitar de uma doença granulomatosa, pelo qual se leva a biopsia e confirmação de sua patologia. A sarcoidoseé um transtorno crônico, que afeta múltiplos órgãos. A sua incidênciaé variável, mas é maior em países industrializados e tempredileção porque apresenta em sua maioria nas mulheres entre 20 e 40 anos de idade. Das manifestações sistêmicas, a mais frequente é a pulmonar, por enquanto que a afetação cutânea oscila entre 20-35%. O diagnóstico se estabelece com as descobertas clínico-radiológicas apoiadas pela evidência histopatológica de granulomas não caseificantes, porémestes últimos não são específicos, pelo que devem se excluir outros processos.

Genetic and biologic characteristics of Toxoplasma gondii isolates in free-range chickens from Colombia, South America.

The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 77 free-range chickens (Gallus domesticus) from Colombia, South America was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT), and found in 32 (44.4%) of 72 chickens with titers of 1:5 in 4, 1:10 in 3, 1:20 in 1, 1:40 in 1, 1:80 in 8, 1:160 in 8, 1:320 in 3, and 1:640 or higher in 4. Hearts and brains of 31 seropositive chickens were pooled and bioassayed in mice. Tissues from 32 (16+16) seronegative chickens were pooled and fed to two, T. gondii-free cats, and tissues from nine chickens without matching sera were fed to one T. gondii-free cat. Feces of cats were examined for oocysts. T. gondii oocysts were excreted by a cat that was fed tissues of 16 seronegative chickens. T. gondii was isolated by bioassay in mice from 23 chickens with MAT titers of 1:20 or higher. All infected mice from 16 of the 23 isolates died of toxoplasmosis. Overall, 82 (81.1%) of 101 mice that became infected after inoculation with chicken tissues died of toxoplasmosis. Genotyping of these 24 isolates using polymorphisms at the SAG2 locus indicated that seven T. gondii isolates were Type I, 17 were Type III, and none was Type II. Phenotypically, T. gondii isolates from chickens from Colombia were similar to isolates from Brazil but different from the isolates from North America; most isolates from chickens from Brazil and Colombia were lethal for mice whereas isolates from North America did not kill inoculated mice. Genetically, none of the T. gondii isolates from Colombia and Brazil was SAG2 Type II, whereas most isolates from chickens from North America were Type II. This is the first report of genetic characterization of T. gondii isolates from Colombia, South America.