scholarly journals Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB/c Mice

2009 ◽  
Vol 53 (6) ◽  
pp. 2259-2265 ◽  
Author(s):  
Mahmoud R. Jaafari ◽  
Neda Bavarsad ◽  
Bibi Sedigheh Fazly Bazzaz ◽  
Afshin Samiei ◽  
Dina Soroush ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Mouse Skin ◽  
Parasite Burden ◽  
Lesion Size ◽  
Control Group ◽  
In Vitro Permeation ◽  
Significant Difference ◽  
Pm 10 ◽  
Franz Diffusion Cells

ABSTRACT The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 μg/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 μg/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.

scholarly journals MicroRNAs Expression Induces Apoptosis of Macrophages in Response to Leishmania major (MRHO/IR/75/ER): An In-Vitro and In-Vivo Study

2020 ◽  
Author(s):  
Mostafa GHOLAMREZAEI ◽  
Soheila ROUHANI ◽  
Mehdi MOHEBALI ◽  
Samira MOHAMMADI-YEGANEH ◽  
Mostafa HAJI MOLLA HOSEINI ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Parasite Load ◽  
Lesion Size ◽  
In Vivo Studies ◽  
Raw 264.7 Cells ◽  
Control Group

Background: We aimed to investigate the effect of miR-15a mimic and inhibitor of miR-155 expression on apoptosis induction in macrophages infected with Iranian strain of Leishmania major in-vitro and in-vivo. Methods: RAW 264.7 cells were infected with L. major promastigotes (MRHO/IR/75/ER), and then were treated with miRNAs. For in-vivo experiment, BALB/c mice were inoculated with L. major promastigotes, and then they were treated with miRNAs. For evaluation of miRNA therapeutic effect, in-vitro and in-vivo studies were performed using quantitative Real-time PCR, Flow cytometry, lesion size measurement, and Limiting Dilution Assay (LDA). This study was performed in Shahid Beheshti University of Medical Sciences in 2019. Results: In-vitro results of flow cytometry showed that using miR-15a mimic, miR-155 inhibitor or both of them increased apoptosis of macrophages. In in-vivo, size of lesion increased during experiment in control groups (P<0.05) while application of both miR-155 inhibitor and miR-15a mimic inhibited the increase in the size of lesions within 6 wk of experiment (P=0.85). LDA results showed that microRNA therapy could significantly decrease parasite load in mimic or inhibitor receiving groups compared to the control group (P<0.05). Conclusion: miR-155 inhibitor and miR-15a mimic in L. major infected macrophages can induce apoptosis and reduce parasite burden. Therefore, miRNA-based therapy can be proposed as new treatment for cutaneous leishmaniasis.

scholarly journals Activity of Amphotericin B-Loaded Chitosan Nanoparticles against Experimental Cutaneous Leishmaniasis

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 4002
Author(s):  
Alaa Riezk ◽  
Katrien Van Bocxlaer ◽  
Vanessa Yardley ◽  
Sudaxshina Murdan ◽  
Simon L. Croft
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Major ◽  
Chitosan Nanoparticles ◽  
Mouse Skin ◽  
Parasite Load ◽  
Lesion Size ◽  
Franz Diffusion Cells ◽  
Positively Charged

Chitosan nanoparticles have gained attention as drug delivery systems (DDS) in the medical field as they are both biodegradable and biocompatible with reported antimicrobial and anti-leishmanial activities. We investigated the application of chitosan nanoparticles as a DDS for the treatment of cutaneous leishmaniasis (CL) by preparing two types of chitosan nanoparticles: positively charged with tripolyphosphate sodium (TPP) and negatively charged with dextran sulphate. Amphotericin B (AmB) was incorporated into these nanoparticles. Both types of AmB-loaded nanoparticles demonstrated in vitro activity against Leishmania major intracellular amastigotes, with similar activity to unencapsulated AmB, but with a significant lower toxicity to KB-cells and red blood cells. In murine models of CL caused by L. major, intravenous administration of AmB-loaded chitosan-TPP nanoparticles (Size = 69 ± 8 nm, Zeta potential = 25.5 ± 1 mV, 5 mg/kg/for 10 days on alternate days) showed a significantly higher efficacy than AmBisome® (10 mg/kg/for 10 days on alternate days) in terms of reduction of lesion size and parasite load (measured by both bioluminescence and qPCR). Poor drug permeation into and through mouse skin, using Franz diffusion cells, showed that AmB-loaded chitosan nanoparticles are not appropriate candidates for topical treatment of CL.

Expression of MicroRNA of Macrophages Infected with Attenuated Leishmania major Parasite

2021 ◽  
Vol 16 (03) ◽  
pp. 106-110
Author(s):  
Mohammad Hossein Feiz Haddad ◽  
Hossein Rezvan ◽  
Alireza Nourian ◽  
Habib Habibpour
Keyword(s):  
Real Time ◽  
Leishmania Major ◽  
Host Cells ◽  
Control Group ◽  
Vector Borne Diseases ◽  
Intracellular Parasites ◽  
Significant Difference ◽  
Infected Cells ◽  
Vector Borne

Abstract Objective Leishmaniasis has been proposed as one of the neglected vector-borne diseases due to an obligate intracellular parasite of the genus Leishmania. MicroRNAs (miRNAs) with a length of 22-nucleotide are known as the noncoding small RNAs. MiRNAs contribute to many biological and cellular approaches. Therefore, the present study evaluated expressing mmu-miR-721, mmu-miR-294–3p, mmu-miR-155–3p, and mmu-miR-30a in murine macrophages infected with attenuated Leishmania major parasites on 3 days after infection. Methods Attenuated promastigotes have been achieved after 20 passages of Leishmania major parasites. Cell line J774A.1 (murine macrophage) has been used for in vitro experiments. The stationary phase of attenuated L. major promastigotes has been chosen to infect the cells, and then their incubation has been performed with 5% CO2 at 37°C for 3 days. The real-time polymerase chain reaction (PCR) has also been performed with SYBR Green master-mix Kit for measuring the level of mmu-miR-721, mmu-miR-294–3p, mmu-miR-30a, and mmu-miR-155-3p expression. Uninfected macrophages have been considered as a control group. Results Real-time PCR demonstrated overexpression of mmu-miR-155-3p, mmu-miR-294–3p, and, mmu-miR-721 in the infected cells with Leishmania parasites after 3 days. Results showed no statistically significant difference in the mmu-miR-30a expression between infected macrophages and the uninfected control group. Conclusion Our findings suggested the significant contribution of the alterations in the miRNA levels to the regulation of macrophage functions following the creation of intracellular parasites like Leishmania. These data could help to understand better the genes' expression in the host cells in the course of leishmaniasis.

scholarly journals Interleukin-6 Deficiency Influences Cytokine Expression in Susceptible BALB Mice Infected with Leishmania major but Does Not Alter the Outcome of Disease

2001 ◽  
Vol 69 (8) ◽  
pp. 5189-5192 ◽  
Author(s):  
Richard G. Titus ◽  
Gregory K. DeKrey ◽  
Robin V. Morris ◽  
Milena B. P. Soares
Keyword(s):  
Interleukin 6 ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Lesion Size ◽  
Cytokine Expression ◽  
Wild Type ◽  
Significant Difference ◽  
Th2 Responses

ABSTRACT Since interleukin-6 (IL-6) may promote Th2 responses, we infected BALB IL-6-deficient (IL-6−/−) mice with Leishmania major. There was not a significant difference between the courses of infection (lesion size and parasite burden) in IL-6−/− and wild-type mice, but IL-6−/−mice expressed lower levels of Th2- and Th1-associated cytokines.

scholarly journals In Vitro and In Vivo Anti-Parasitic Activity of Artemisinin Combined With Glucantime and Shark Cartilage Extract on Iranian Strain of Leishmania major (MRHO/IR/75/ER)

2021 ◽  
Vol 14 (3) ◽  
Author(s):  
Fatemeh Ghaffarifar ◽  
Soheila Molaei ◽  
Zuhair Mohammad Hassan ◽  
Mohammad Saaid Dayer ◽  
Abdolhossein Dalimi ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Human Subjects ◽  
Parasite Burden ◽  
Lesion Size ◽  
In Vivo Experiments ◽  
Parasitic Activity ◽  
Shark Cartilage ◽  
Immune System Modulation

Background: The adverse effects and increased resistance of drugs necessities the discovery of novel combination therapy. Objectives: This study aimed to examine the effects of Artemisinin plus glucantime or shark cartilage extract on the Iranian strain of Leishmania major (MRHO/IR/75/ER) in vitro and in vivo. Methods: In in vitro experiments, the effects of drugs and their combination in different concentrations (3.12 - 400 µg/mL) on the promastigotes, amastigotes, and un-infected macrophage cells were evaluated. In in vivo experiments, infected BALB/c mice were used as a cutaneous leishmaniasis model to evaluate the effects of the drugs and their combinations with different routes of administrations (namely Artemisinin: oral, ointment, and intraperitoneal; glucantime: intraperitoneal, intramuscular, intralesional, and subcutaneous; shark cartilage extract: oral) on parasite burden, lesion size, and immune system modulation. Results: The results revealed that Artemisinin and glucantime in combination with shark cartilage extract had greater effects on promastigotes than either Artemisinin or glucantime (P < 0.05), and that the combinations also had high cytotoxic effects on promastigotes and uninfected macrophages (P = 0.001). These combinations had more inhibitory effects on amastigotes and infected macrophages than promastigotes. The lesion sizes and parasite burden in the spleen decreased against the combinations of the drugs in different administrations. It was also noticed that the best combination administration route of Artemisinin and glucantime, as strong inducers of INF-γ and Th1 immune response, were ointment and IM, respectively (P < 0.05). Conclusions: The findings indicate that Artemisinin- glucantime or Artemisinin- Shark cartilage combinations are effective inhibitors of L. major. However, further clinical trials are recommended to evaluate the effects of these combinations in human subjects.

scholarly journals Topical Treatment for Cutaneous Leishmaniasis: Dermato-Pharmacokinetic Lead Optimization of Benzoxaboroles

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Katrien Van Bocxlaer ◽  
Eric Gaukel ◽  
Deirdre Hauser ◽  
Seong Hee Park ◽  
Sara Schock ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Skin Permeation ◽  
Mouse Skin ◽  
Topical Administration ◽  
Lesion Size ◽  
Drug Formulation ◽  
Content Type

ABSTRACTCutaneous leishmaniasis (CL) is caused by several species of the protozoan parasiteLeishmania, affecting an estimated 10 million people worldwide. Previously reported strategies for the development of topical CL treatments have focused primarily on drug permeation and formulation optimization as the means to increase treatment efficacy. Our approach aims to identify compounds with antileishmanial activity and properties consistent with topical administration. Of the test compounds, five benzoxaboroles showed potent activity (50% effective concentration [EC50] < 5 μM) against intracellular amastigotes of at least oneLeishmaniaspecies and acceptable activity (20 μM < EC50< 30 μM) against two more species. Benzoxaborole compounds were further prioritized on the basis of thein vitroevaluation of progression criteria related to skin permeation, such as the partition coefficient and solubility. An MDCKII-hMDR1 cell assay showed overall good permeability and no significant interaction with the P-glycoprotein transporter for all substrates except LSH002 and LSH031. The benzoxaboroles were degraded, to some extent, by skin enzymes but had stability superior to that ofpara-hydroxybenzoate compounds, which are known skin esterase substrates. Evaluation of permeation through reconstructed human epidermis showed LSH002 to be the most permeant, followed by LSH003 and LSH001. Skin disposition studies following finite drug formulation application to mouse skin demonstrated the highest permeation for LSH001, followed by LSH003 and LSH002, with a significantly larger amount of LSH001 than the other compounds being retained in skin. Finally, the efficacy of the leads (LSH001, LSH002, and LSH003) againstLeishmania majorwas testedin vivo. LSH001 suppressed lesion growth upon topical application, and LSH003 reduced the lesion size following oral administration.

The lack of effectiveness of hyperbaric oxygenation as a treatment for Leishmania major in a mouse model

2015 ◽  
Vol 60 (2) ◽  
Author(s):  
Ayelet Livneh ◽  
Ilan Youngster ◽  
Yossef El-On ◽  
Matitiahu Berkovitch ◽  
Ibrahim Abu-Kishk
Keyword(s):  
Mouse Model ◽  
Leishmania Major ◽  
Topical Therapy ◽  
Lesion Size ◽  
Control Group ◽  
Mice Model ◽  
Cutaneous Lesions ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

AbstractWe aimed to study the effectiveness of hyperbaric oxygen therapy (HOT) (100% oxygen at 2 ATA for 70 minutes each session for 20 consecutive days) on BALB/c male mice infected with Leishmania major. Fifty-one mice were assigned to six groups. Group 1 was treated with HOT from 1 day after the inoculation. In Groups 2-5, treatment began when the cutaneous lesions appeared. Group 2 received HOT only, Group 3 received topical therapy with Leshcutan only, Groups 4 and 5 received a combination of HOT and Leshcutan for 5 and 10 days respectively, and Group 6 did not receive any treatment (control group). When comparing the control group with Group 1, treatment with HOT in Group 1 did not significantly affect the time of the appearance of the lesions. In contrast, mice treated with Leshcutan demonstrated a significant difference in lesion size and spleen dimensions as compared to the rest of the mice (p<0.001). The results show that HOT treatment has no positive effect on the course of Leishmaniasis in a BALB/c mice model infected with Leishmania major. Further studies are needed with a mouse model closer to humans and with different HOT protocols.

Comparative Study to Evaluate the Surface Detail Reproduction of Dental Stone after Immersion in Various Different Disinfectant Solutions, Under Stereomicroscope 10 X Magnification –An In-Vitro Study

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Rathika Rai ◽  
M. A. Easwaran ◽  
K. T. Dhivya
Keyword(s):  
Sodium Hypochlorite ◽  
In Vitro Study ◽  
Control Group ◽  
Immersion Method ◽  
Significant Difference ◽  
Surface Irregularities ◽  
Disinfectant Solution ◽  
Surface Detail ◽  
Group B

Aim: To evaluate the surface detail reproduction of dental stone this is immersed in different disinfectant solution and studied under stereomicroscope. Methodology: Total number of 30 specimens of dental stone (Type III) were made with measurements of 1.5cm diameter and 1cm height .This samples are divided in to 3 groups group A,B,C. were A is immersed in Distilled water which was taken as control group ;B is immersed in 2% Glutaraldehyde and C is immersed in 5%sodium hypochlorite. Each specimen were immersed in the disinfectant solution for 15 minutes and dried under room temperature for 24 hrs. After 24 hrs each specimens are studied under stereomicroscope for surface details. Result: The results showed no significant difference in the surface irregularities and porosities for a group 1 and group 2 except group 3 which showed significant increase in the porosities, surface irregularities and erosions after disinfection with 5% NaHOCl by immersion method. Conclusion: The surface detail reproduction capacity of die stone was adversely affected when 5% Sodium hypochlorite was used as disinfectant solution when compare d to control group and 2% Glutaraldehyde

Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major

2020 ◽  
Vol 20 (4) ◽  
pp. 550-555 ◽  
Author(s):  
Lima Asgharpour Sarouey ◽  
Parvaneh Rahimi-Moghaddam ◽  
Fatemeh Tabatabaie ◽  
Khadijeh Khanaliha
Keyword(s):  
Flow Cytometry ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Inhibitory Effect ◽  
Control Group ◽  
Secondary Infections ◽  
Ic50 Values ◽  
J774 Cells ◽  
Mtt Assays

: As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. Methods: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 μg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. Results: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 μg/ml and 23.73 μg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 μg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Conclusion: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.

scholarly journals Comparative Evaluation of Fracture Resistance of Endodontically Treated Teeth Restored with Resin Fiber Post and Stainless Steel Post: An In Vitro Study

2015 ◽  
Vol 03 (02) ◽  
pp. 080-084
Author(s):  
Vijay Singh ◽  
Poonam Bogra ◽  
Saurabh Gupta ◽  
Navneet Kukreja ◽  
Neha Gupta
Keyword(s):  
Stainless Steel ◽  
Fracture Resistance ◽  
Testing Machine ◽  
Compressive Force ◽  
Control Group ◽  
Fiber Post ◽  
Endodontically Treated Teeth ◽  
Group I ◽  
Significant Difference

AbstractFracture resistance of endodontically treated teeth restored with post. Aims: This study aims to compare the fracture resistance of endodontically treated teeth restored with resin fiber and stainless steel post. Commercially available prefabricated resin fiber post(Dentsply Maillefer Easy Post), prefabricated stainless steel post(Coltene/Whaledent Parapost) were used. Methods and Material: Forty five maxillary central incisors were obturated and divided into 3 groups: Control Group (Group I) without any post (n = 15), Resin Fiber Post Group (Group II) (n = 15) and Stainless Steel Post Group (Group III) (n = 15). In all Groups except control group, post space was prepared; a post was cemented, and a core build-up was provided. All the specimens were subjected to compressive force under a universal testing machine until fracture. Statistical analysis used: The results were analyzed using the variable analysis test (ANOVA). Results: One-way analysis of variance revealed significant difference among test groups. The control group demonstrated highest fracture resistance (925.2183 N), followed by the resin fiber post group (486.7265 N) and stainless steel post group (423.539N). Conclusions: Teeth restored with resin fiber post showed higher fracture resistance values than prefabricated stainless steel post.

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