Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

Considered prevalent in many countries on five continents, especially in low-income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.     

Bilaminar Device of Poly(Lactic‐co‐Glycolic Acid)/Collagen Cultured With Adipose‐Derived Stem Cells for Dermal Regeneration

Several materials are commercially available as substitutes for skin. However, new strategies are needed to improve the treatment of skin wounds. In this study, we developed and characterized a new device consisting of poly(lactic‐co‐glycolic acid) (PLGA) and collagen associated with mesenchymal stem cells derived from human adipose tissue. To develop the bilaminar device, we initially obtained a membrane of PLGA by dissolving the copolymer in chloroform and then produced a collagen type I scaffold by freeze‐drying. The materials were characterized physically by gel permeation chromatography, scanning electron microscopy, and mass loss. Biological activity was assessed by cell proliferation assay. A preliminary study in vivo was performed with a pig model in which tissue regeneration was assessed macroscopically and histologically, the commercial device Integra being used as a control. The PLGA/collagen bilaminar material was porous, hydrolytically degradable, and compatible with skin growth. The polymer complex allowed cell adhesion and proliferation, making it a potentially useful cell carrier. In addition, the transparency of the material allowed monitoring of the lesion when the dressings were changed. Xenogeneic mesenchymal cells cultured on the device (PLGA/collagen/ASC) showed a reduced granulomatous reaction to bovine collagen, down‐regulation of α‐SMA, enhancement in the number of neoformed blood vessels, and collagen organization as compared with normal skin; the device was superior to other materials tested (PLGA/collagen and Integra) in its ability to stimulate the formation of new cutaneous tissue.     

Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface

Photocrosslinkable magnetic hydrogels are attracting great interest for tissue engineering strategies due to their versatility and multifunctionality, including their remote controllability ex vivo, thus enabling engineering complex tissue interfaces. This study reports the development of a photocrosslinkable magnetic responsive hydrogel made of methacrylated chondroitin sulfate (MA-CS) enriched with platelet lysate (PL) with tunable features, envisioning their application in tendon-to-bone interface. MA-CS coated iron-based magnetic nanoparticles were incorporated to provide magnetic responsiveness to the hydrogel. Osteogenically differentiated adipose-derived stem cells and/or tendon-derived cells were encapsulated within the hydrogel, proliferating and expressing bone- and tendon-related markers. External magnetic field (EMF) application modulated the swelling, degradation and release of PL-derived growth factors, and impacted both cell morphology and the expression and synthesis of tendon- and bone-like matrix with a more evident effect in co-cultures. Overall, the developed magnetic responsive hydrogel represents a potential cell carrier system for interfacial tissue engineering with EMF-controlled properties.     

Technological insights： Combined impedance manometry for esophageal motility testing-current results and further implications

INTRODUCTION The basic function of the esophagus is the transport of the bolus from the pharynx into the stomach. Esophageal peristalsis is based on propulsive mechanisms along the axis of the organ, generated by a latency gradient that is modulated by th…     

In vivo performance of a sol-gel glass-coated collagen

Synthetic bioactive materials offer possibilities to repair large tissue defects. It is well known that bioactivity, angiogenesis, and inflammation are key events in implant incorporation. Using glass-coated and glass-free collagen as potential bone graft substitutes, we carried out in vitro bioactivity and an in vivo angiogenesis and inflammation studies. The in vitro study showed bioactivity when the glass-coated samples were left in SBF for 5 days. This was confirmed by FTIR results, which presented P--O vibration bands characteristic of hydroxyapatite close to 1060 cm(-1) and 600 cm(-1). The in vivo response was evaluated following subcutaneous implantation of the biomaterial in the mouse dorsa. Angiogenesis, as determined by hemoglobin content extracted from implants 7 and 14 days after implantation, increased progressively in both glass-coated and glass-free collagen implants. However, vascularization was higher in the glass-coated collagen implants 14 days after implantation (mug Hb per mg wet tissue 6.0 +/- 0.3) compared with the glass-free group (1.6 +/- 0.1). The inflammatory process, determined by the levels of myeloperoxidase and N-acetylglucosaminidase, was similar for both implants. This study shows that glass-coated collagen implants hold osteogenic and angiogenic potential and may be used in clinical conditions requiring improvement of these biological processes.     

Analysis of the protective potential of antigens released by Leishmania (Viannia) shawi promastigotes

Leishmania (Viannia) shawi causes cutaneous lesions in humans. Parasite antigens conferring significant protection against American tegumentar leishmaniosis (ATL) might be important for the development of effective vaccine. Therefore, this work evaluates the protective effect of antigenic fractions released by L. shawi. Antigens released by promastigotes to culture medium were concentrated and isolated by SDS-PAGE. The three main fractions LsPass1 (>75 kDa), LsPass2 (75–50 kDa) and LsPass3 (<50 kDa) were electro-eluted according with their molecular mass. Immunized BALB/c mice were challenged with L. shawi promastigotes and the course of infection monitored during 5 weeks. LsPass1-challenged mice showed no protection, however, a strong degree of protection associated to smaller lesions and high expression of IFN-γ and TNF-α by CD4⁺ T, CD8⁺ T and double negative CD4CD8 cells was achieved in LsPass3-challenged mice. Furthermore, LsPass2-challenged mice showed an intermediated degree of protection associated to high levels of IFN-γ, IL-4 and IL-10 mRNA. In spite of increased expression of IFN-γ and TNF-α, high amounts of IL-4 and IL-10 mRNA were also detected in LsPass3-challenged mice indicating a possible contribution of these cytokines for the persistence of a residual number of parasites that may be important in inducing long-lasting immunity. Therefore, LsPass3 seems to be an interesting alternative that should be considered in the development of an effective vaccine against ATL.     

From regenerative strategies to pharmacological approaches:can we fine-tune treatment for Parkinson's disease?

Parkinson's disease is the second most prevalent neurodegenerative disorder worldwide.Clinically,it is characterized by severe motor complications caused by progressive degeneration of dopaminergic neurons.Current treatment is focused on mitigating the symptoms through the administration of levodopa,rather than on preventing dopaminergic neuronal damage.Therefore,the use and development of neuroprotective/disease-modifying strategies is an absolute need that can lead to promising gains on translational research of Parkinson's disease.For instance,N-acetylcysteine,a natural compound with strong antioxidant effects,has been shown to modulate oxidative stress,preventing dopamine-induced cell death.Despite the evidence of neuroprotective and modulatory effects of this drug,as far as we know,it does not induce per se any regenerative process.Therefore,it would be of interest to combine the latter with innovative therapies that induce dopaminergic neurons repair or even differentiation,as stem cell-based strategies.Stem cells secretome has been proposed as a promising therapeutic approach for Parkinson's disease,given its ability to modulate cell viability/preservation of dopaminergic neurons.Such approach represents a shift in the paradigm,showing that cell-transplantation free therapies based on the use of stem cells secretome may represent a potential alternative for regenerative medicine of Parkinson's disease.Thus,in this review,we address the current understanding of the potential combination of stem cell free-based strategies and neuroprotective/disease-modifying strategies as a new paradigm for the treatment of central nervous system neurodegenerative diseases,like Parkinson's disease.     

Diagnosis of HIV infection on the basis of histoplasmosis‐related oral ulceration

Histoplasmosis is an endemic systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, histoplasmosis generally occurs as an opportunistic disease, with dissemination to various organs. Cutaneous involvement is observed in 38% to 85% of cases, with oral mucosal involvement in 30% to 60% of cases. This article describes the case study of a 32‐year‐old woman who presented an extensive tongue ulcer due to histoplasmosis and had the HIV infection diagnosis based on laboratory tests requested by the dentist.