In vitro and in vivo Assessment of Anti-Leishmanial Efficacy of Leaf, Fruit, and Fractions of Juniperus excelsa Against Axenic Amastigotes of Leishmania major and Topical Formulation in BALB/c Mice

Trifluralin, a dinitroaniline microtubule inhibitor currently in use as an herbicide, has been shown to inhibit the proliferation of Plasmodium falciparum, Trypanosoma brucei, and several species of Leishmania, in vitro. As a topical formulation, trifluralin is also effective in vivo (in BALB/c mice) against Leishmania major and Leishmania mexicana. Although trifluralin and other dinitroaniline herbicides show significant activity as antiparasitic compounds, disputed indications of potential carcinogenicity will probably limit advanced development of these substances. However, researchers have suggested that the activity of trifluralin is due to an impurity or contaminant, not to trifluralin itself. We have pursued this lead and identified the structure of the active impurity. This compound, chloralin, is 100 times more active than trifluralin. On the basis of its structure, we developed a rational structure-activity model for chloralin. Using this model, we have successfully predicted and tested active analogs in a Leishmania promastigote assay; thus, we have identified the putative mechanism of action of this class of drugs in Leishmania species. Potentially, this will allow the design of noncarcinogenic, active drugs.

Download Full-text

Safety Evaluation of Nano-Liposomal Formulation of Amphotericin B (SinaAmpholeish) in Animal Model as a Candidate for Treatment of Cutaneous Leishmaniasis

Journal of Arthropod-Borne Diseases ◽

10.18502/jad.v12i3.78 ◽

2018 ◽

Author(s):

Seyed Ebrahim Eskandari ◽

Alireza Firooz ◽

Mansour Nassiri-Kashani ◽

Mahmoud Reza Jaafari ◽

Amir Javadi ◽

...

Keyword(s):

Animal Model ◽

Cutaneous Leishmaniasis ◽

Amphotericin B ◽

Leishmania Major ◽

Skin Diseases ◽

Average Score ◽

Topical Formulation ◽

Liposomal Form

Background: Development of a topical treatment for cutaneous leishmaniasis (CL) is an important step in the improvement of lesion management. Amphotericin B (AmB) is effective against Leishmania species but it is toxic, a Nano-liposomal form of AmB with a size of about 100nm (Lip-AmB) was developed and showed to be effective against Leishmania major, and Leishmania tropica in vitro and against L. major in vivo in animal model. This study was designed to check the irritancy Draize test in rabbits and was completed in the Center for Research and Training in Skin Diseases and Leprosy, TUMS, in 2012. Methods: Twenty rabbits in 3 steps were housed individually with artificial lighting (12/12h light/dark). SinaAmpholeish cream or empty liposomes (prepared under GMP condition at Minoo Company, Tehran, Iran), was applied on a gauze patch and the patches were placed on the designated sites of the skin in the back of the rabbits. At 48 and 72h later, the erythema and oedema were checked, scored and recorded. Results: The erythema score in rabbits was 0.83+0.41 for the SinaAmpholeish and 0.5+0.55 for empty liposomes (P= 0.16). The average score for oedema was 0.67+0.52 for SinaAmpholeish and 0.33+0.52 for empty liposomes (P= 0.16). Conclusion: Based on skin irritancy reactions the topical formulation of SinaAmpholeish is safe and could be further checked in human trials.

Download Full-text

Faculty Opinions recommendation of In vitro and in vivo assessment of renal drug transporters in the disposition of mesna and dimesna.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13372017.14742134 ◽

2011 ◽

Author(s):

Peter Harvison

Keyword(s):

Drug Transporters ◽

In Vivo Assessment

Download Full-text

In vitro and in vivo assessment of biocompatibility of AZ31 alloy as biliary stents: a preclinical approach

Archives of Medical Science ◽

10.5114/aoms.2020.92675 ◽

2020 ◽

Author(s):

Yong Song ◽

Gaoping Qin ◽

Lixue Du ◽

Haitian Hu ◽

Yong Han

Keyword(s):

Az31 Alloy ◽

Biliary Stents ◽

In Vivo Assessment

Download Full-text

In vivo assessment of a single adenine mutation in 5′UTR of Endothelin-1 gene in paediatric cases with severe pulmonary hypertension: an observational study

BMC Research Notes ◽

10.1186/s13104-021-05609-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Abhishek Kumar ◽

Minati Choudhury ◽

Sakshi Dhingra Batra ◽

Kriti Sikri ◽

Anushree Gupta

Keyword(s):

Pulmonary Hypertension ◽

Congenital Heart ◽

Small Sample Size ◽

Small Sample ◽

Severe Pulmonary Hypertension ◽

Endothelin 1 ◽

Circulating Levels ◽

In Vivo Assessment

Abstract Objective Endothelin-1 plays an important role in the pathogenesis of severe pulmonary hypertension. The + 139 ‘A’, adenine insertion variant in 5′UTR of edn1 gene has been reported to be associated with increased expression of Endothelin-1 in vitro. The aim of present study was to explore the association of this variant with the circulating levels of Endothelin-1 in vivo using archived DNA and plasma samples from 38 paediatric congenital heart disease (cyanotic and acyanotic) patients with severe pulmonary hypertension. Results The plasma Endothelin-1 levels were highly varied ranging from 1.63 to75.16 pg/ml. The + 139 ‘A’ insertion variant in 5′UTR of edn1 was seen in 8 out of 38 cases with only one acyanotic sample demonstrating homozygosity of inserted ‘A’ allele at + 139 site (4A/4A genotype). The plasma Endothelin-1 levels in children with homozygous variant 3A/3A genotype were comparable in cyanotic and acyanotic groups. Lone 4A/4A acyanotic sample had ET-1 levels similar to the median value of ET-1 associated with 3A/3A genotype and was absent in cyanotic group presumably due to deleterious higher ET-1 levels. The discussed observations, limited by the small sample size, are suggestive of homozygous adenine insertion variant posing a risk in cyanotic babies with Severe Pulmonary Hypertension.

Download Full-text