scholarly journals Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation

2011 ◽  
Vol 55 (4) ◽  
pp. 1661-1670 ◽  
Author(s):  
Antara Banerjee ◽  
Manjarika De ◽  
Nahid Ali
Keyword(s):  
Visceral Leishmaniasis ◽  
Combination Therapy ◽  
Low Dose ◽  
Transforming Growth Factor ◽  
Prolonged Treatment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Single Shot ◽  
Synergistic Activity ◽  
Combination Drug ◽  
Promising Alternative

ABSTRACTVisceral leishmaniasis (VL) caused by the parasiteLeishmania donovaniis a potentially fatal disease. Available limited drugs are toxic, require prolonged treatment duration, and are costly. A low-cost parenteral formulation of paromomycin sulfate (PM) has recently been approved for the treatment of VL. Monotherapy with PM runs the risk of development of resistance. Hence, efforts are needed to develop a combination therapy of PM with other drugs to shorten the duration of treatment and prolong the effective life of the drug. PM was formulated with leishmanicidal stearylamine (SA)-bearing phosphatidylcholine (PC) liposomes for low-dose therapy.In vitroandin vivoantileishmanial effects of the combination drug were determined. The immunomodulatory role of PC-SA-PM was determined using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Excluding the spleen, for which the therapeutic effect was additive, a remarkable synergistic activity toward cure and prophylaxis with a single-shot low-dose treatment with PC-SA-associated PM was achieved with BALB/c mice. PC-SA-PM showed an immunomodulatory effect on CD4+and CD8+T cells for gamma interferon (IFN-γ) production and downregulated disease-associated interleukin-10 (IL-10) and transforming growth factor β (TGF-β) to almost negligible levels. Such combination chemotherapy may provide a promising alternative for the cure of leishmaniasis, with a plausible conversion of the host immune response from a disease-promoting pattern to a Th1-biased response indicative of long-term resistance.

The Safety and Efficacy of Mupirocin Topical Spray for Burn Wound Healing in A Rat Model

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Sritharadol Rutthapol ◽  
Chunhachaichana Charisopon ◽  
Kumlungmak Sukanjana ◽  
Buatong Wilaiporn ◽  
Dechraksa Janwit ◽  
...  
Keyword(s):  
Wound Healing ◽  
Matrix Metalloproteinase ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Immunohistochemical Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Burn Wound ◽  
Safety And Efficacy ◽  
Burn Wound Healing ◽  
Tgf Β1

ABSTRACT This study evaluated the effect of mupirocin topical spray on burn wound healing in a rat model. Fifteen male Sprague Dawley rats were used to create full-thickness burns on the rat dorsum using a cylindrical stainless steel rod. The rats were topically treated with normal saline solution (NSS), mupirocin spray, ointment, and solution. The wound size and morphological evaluation were investigated by photographs and clinical criterions for wound healing. The histology was observed by hematoxylin and eosin (HandE) staining assay. The immunohistochemical study was evaluated by detection of transforming growth factor-beta 1 (TGF-β1), and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of matrix metalloproteinase-1 (MMP-9/TIMP-1) was quantified using the enzyme-linked immunosorbent assay (ELISA) assay. A complete healing was observed at 28 days in all treatments. Mupirocin formulations accelerated the wound healing faster than NSS in size. However, the clinical criteria indicated a desirable skin appearance in the mupirocin spray and ointment treated groups. The histological evaluations showed no differences between the treatments while the immunohistochemical study revealed that all treatments reduced the level of TGF-β1 over time, particularly on day 28 in the mupirocin spray and ointment treated groups. The MMP-9/TIMP-1 ratio was significantly lower in the mupirocin spray and ointment treated groups than in the NSS and mupirocin solution groups. This study shows the safety and efficacy in the use of mupirocin topical spray. The topical mupirocin spray is an alternative suitable for development as a human topical anti-infective and wound protection spray.

scholarly journals CircHYBID regulates hyaluronan metabolism in chondrocytes via hsa-miR-29b-3p/TGF-β1 axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Hong-Xing Liao ◽  
Zhi-Hui Zhang ◽  
Hui-Lin Chen ◽  
Ying-Mei Huang ◽  
Zhan-Liang Liu ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Pathological Examination ◽  
Circular Rnas ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mechanism Analysis ◽  
Gain Of Function ◽  
Qrt Pcr ◽  
Intact Cartilage ◽  
Ha Synthase ◽  
Tgf Β1

Abstract Background Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). Methods CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. Results CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.

Use of Propentofylline in Feline Bronchial Disease: Prospective, Randomized, Positive-Controlled Study

2010 ◽  
Vol 46 (5) ◽  
pp. 318-326 ◽  
Author(s):  
Ulrike Stursberg ◽  
Isabella Zenker ◽  
Silke Hecht ◽  
Katrin Hartmann ◽  
Bianka S. Schulz
Keyword(s):  
Combination Therapy ◽  
Low Dose ◽  
Respiratory Pattern ◽  
Controlled Study ◽  
Control Group ◽  
Bronchial Disease ◽  
Observation Period

Propentofylline is a methylxanthine derivative with bronchodilating actions similar to those of theophylline. Nineteen cats with bronchial disease were enrolled in this study. All cats received a low dose of prednisolone; 10 of the cats additionally received propentofylline. Propentofylline-treated cats significantly improved in their auscultation scores, respiratory pattern scores, and radiological bronchial markings score over the observation period, and they coughed less and slept less at the end of the study. No significant changes were noted in the control group. This study provides evidence that a combination therapy with prednisolone and propentofylline in cats with bronchial disease might be superior over monotherapy with prednisolone.

scholarly journals Immunological and hematological outcomes following protracted low dose/low dose rate ionizing radiation and simulated microgravity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amber M. Paul ◽  
Eliah G. Overbey ◽  
Willian A. da Silveira ◽  
Nathaniel Szewczyk ◽  
Nina C. Nishiyama ◽  
...  
Keyword(s):  
Low Dose ◽  
Transforming Growth Factor ◽  
Expression Profiles ◽  
Transforming Growth Factor Β ◽  
Hindlimb Unloading ◽  
B Cell Differentiation ◽  
Specific Regulation ◽  
Β Receptor ◽  
Gene Orthologs ◽  
Whole Transcriptome

AbstractUsing a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) involved in signal transduction, metabolism, cell cycle, chromatin organization, and DNA repair. Although immune differentials were not changed, DEG analysis of the spleen revealed expression profiles associated with inflammation and dysregulated immune function persist to 1-week post-simulated spaceflight. Additionally, specific regulation pathways associated with human blood disease gene orthologs, such as blood pressure regulation, transforming growth factor-β receptor signaling, and B cell differentiation were noted. Collectively, this study revealed differential immune and hematological outcomes 1-week post-simulated spaceflight conditions, suggesting recovery from spaceflight is an unremitting process.

scholarly journals Canine visceral leishmaniasis in riverside communities of the Cuiabá river watershed

2019 ◽  
Vol 40 (6Supl2) ◽  
pp. 3313
Author(s):  
Valéria Régia Franco Sousa ◽  
Álvaro Felipe de Lima Ruy Dias ◽  
Juliana Yuki Rodrigues ◽  
Mariana de Medeiros Torres ◽  
Janaína Marcela Assunção Rosa Moreira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Urban Areas ◽  
Axenic Culture ◽  
Antibody Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lutzomyia Longipalpis ◽  
Cross Sectional ◽  
Mato Grosso ◽  
River Watershed

Visceral Leishmaniasis (VL) is a parasitic zoonosis expanding in Brazil. Several municipalities in the state of Mato Grosso including those on the river Cuiabá have reported the incidence of both human and canine cases and the identification of sandfly vector, Lutzomyia longipalpis and Lu. cruzi. Dogs are considered the main reservoir of Leishmania chagasi in the urban areas, hence, we devised a cross-sectional study aimed at assessing the prevalence of the infection in the dogs of riverside communities on Cuiabá River watershed by parasitological (parasitic isolation in culture), serological, and molecular methods. Of the 248 surveyed dogs, 24 were positive in enzyme linked immunosorbent assay (ELISA) or immunofluorescence antibody test (IFAT), with a prevalence of 9.7%. The riverside communities located in the town of Santo Antonio do Leverger displayed a higher prevalence of the disease than the cities of Cuiabá and Várzea Grande; however, the difference was not statistically significant (p > 0.05). Dogs born in the communities had a 3.24-fold higher risk of acquiring the infection. Promastigote were isolated in the axenic culture from the bone marrow samples and intact skin. Further, DNA of Leishmania sp. was detected in the bone marrow samples, lymph nodes, leukocyte cover, and skin of only one examined dog. These samples were sequenced and they showed 99% homology to L. infantum. To conclude, we observed a higher prevalence of infection in Riverside communities of Santo Antonio do Leverger and the confirmation of autochthony in these areas justifies the surveillance actions to minimise the risk of transmission within the riverine community itself, besides its dissemination to other areas by tourism.

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