Leishmania tropica infection, in comparison to Leishmania major, induces lower delayed type hypersensitivity in BALB/c mice

Leishmania tropica and L. major are etiologic agents of human cutaneous leishmaniasis. Delayed type hypersensitivity (DTH) is an immunologic response that has been frequently used as a correlate for protection against or sensitization to leishmania antigen. In BALB/c mice, L. tropica infection results in non-ulcerating disease, whereas L. major infection results in destructive lesions. In order to clarify the immunologic mechanisms of these 2 different outcomes, we compared the ability of these 2 leishmania species in induction of DTH response in this murine model. BALB/c mice were infected with L. major or L. tropica, and disease evolution and DTH responses were determined. The results show that the primary L. major infection can exacerbate the secondary L. major infection and is associated with DTH response. Higher doses of the primary L. major infection result in more disease exacerbation of the secondary L. major infection as well as higher DTH response. L. tropica infection induces lower DTH responses than L. major. We have previously reported that the primary L. tropica infection induces partial protection against the secondary L. major infection in BALB/c mice. Induction of lower DTH response by L. tropica suggests that the protection induced against L. major by prior L. tropica infection may be due to suppression of DTH response.     

Hydrogels Composed of Cyclodextrin Inclusion Complexes with PLGA-PEG-PLGA Triblock Copolymers as Drug Delivery Systems

Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEG-PLGA and α-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined.     

The early effects of uninephrectomy on rat kidney metabolic state using optical imaging

Uninephrectomy (UNX) is known to result in structural and metabolic changes to the remaining kidney, although it is uncertain if this alters the mitochondrial redox state and how soon such changes may occur. A custom‐designed fluorescence cryo‐imaging technique was used to quantitatively assess the effect of UNX by measuring the levels of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the remaining kidney. Kidneys were snap‐frozen 3 days following UNX, and the intrinsic fluorescence of NADH and FAD were optically acquired. The 3D images were created to characterize the NADH/FAD redox ratios (RR) of the right kidneys, which underwent UNX and the remaining kidneys 3 days following UNX. Both the NADPH‐oxidases (Nox2 and Nox4) and the mitochondria are the main sources of reactive oxygen species (ROS) production in tubular epithelial cells. Responses to the UNX were obtained in kidneys of normal Sprague Dawley (SD) rats, Dahl salt‐sensitive (SS) rats and SS rats in which NADPH‐oxidase isoform 4 (Nox4) was knocked out (SS^Nox4?/?). The results found that each of the strains exhibited similar increase in kidney weights averaging 17% after 3 days of UNX. SD and SS^Nox4?/?rats both exhibited global reductions of the RR (P < .05) with a similar tendency observed in SS rats (P < .08), indicating increased ROS production. The unexpected reduction of the RR in the remnant kidneys of SS^Nox4?/? rats indicates that mechanisms independent of H₂O₂ produced from Nox4 may be responsible for this global increase of ROS. We propose that the reduced RR was largely a consequence of enhanced mitochondrial bioenergetics due to increased tubular workload of the remaining kidney. The data indicate that mitochondria become the dominant source of increased ROS following UNX and could represent an important hypertrophic signaling mechanism.     

LAMP3 (CD208) Expression in Squamous Cell Carcinoma and Epithelial Dysplasia of the Oral Cavity and Clinicopathological Characteristics of Unfavorable Prognosis

Background:This study aimed to evaluate LAMP3 (CD208) gene expression in oral squamous cell carcinoma (OSCC) and dysplastic oral epithelium by quantitative real-time polymerase chain reaction (qPCR) and compare LAMP3 expression in different disease grades and stages.Methods:In this study, 60 OSCC and dysplastic oral epithelium samples were obtained from the Mashhad University of Medical Sciences together with their demographic and clinicopathological documents. LAMP3 expression was measured by qPCR.Results:LAMP3 expression was significantly greater in OSCC than in dysplasia samples (P=0.001), in grade III OSCC than in grades I and II, and also greater in advanced than in early OSCC disease stage (P=0.001).Conclusion:The significantly greater LAMP3 expression in OSCC than in dysplastic epithelium indicates a role for LAMP3 in carcinogenesis in oral mucosa. Our results suggest LAMP3 may be useful as an anticancer target and/or to predict disease pathogenesis in OSCC patient’s cells.Key Words: Clinicopathological, Grade, Epithelial dysplasia, LAMP3, Stage, Squamous cell carcinoma.     

Subcircuits of Deep and Superficial CA1 Place Cells Support Efficient Spatial Coding across Heterogeneous Environments

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