Damage to surface membrane ofSchistosoma mansoniby pristane (2,6,10,14 tetramethyl pentadecane) and other hydrophobic compounds

SummaryIntraperitoneal injection of cercariae into pristane (2, 6, 10, 14 tetramethyl pentadecane)-primed Balb/c mice led to greatly diminished numbers of portal and peritoneal worms compared with untreated mice. Schistosomula taken from the peritoneal cavity of pristane-primed mice carried globules of pristane on their surfaces, were contracted and were permeable to Trypan blue. Pristane globules bound also to adult wormsin vitroandin vivocausing rapid damage to the surface membrane. Hydrophobic compounds other than hydrocarbons either bound without causing gross damage, or did not bind to the adult worms.51Cr release studies showed that pristane had no effect on the permeability of human erythrocytes, while causing significant release from both schistosomula and adult worms. The binding of hydrocarbon globules to a variety of other parasites did not occur. The binding ofn-[1-14C]hexadecane to adultSchistosoma mansoniwas significantly decreased by extraction of the parasite with organic solvents or treatment with staphylococcal δ toxin, which interacts with phospholipids in the membrane. Possible mechanisms of damage of the parasite by the hydrocarbons are discussed.

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Schistosoma mansoni: Surface membrane stability in vitro and in vivo

Experimental Parasitology ◽

10.1016/0014-4894(86)90027-5 ◽

1986 ◽

Vol 62 (2) ◽

pp. 223-236 ◽

Cited By ~ 21

Author(s):

Andreas Ruppel ◽

Diane J. McLaren

Keyword(s):

Schistosoma Mansoni ◽

Surface Membrane ◽

Membrane Stability

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In Vitro and In Vivo Activities of Arachidonic Acid against Schistosoma mansoni and Schistosoma haematobium

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00173-10 ◽

2010 ◽

Vol 54 (8) ◽

pp. 3383-3389 ◽

Cited By ~ 38

Author(s):

Rashika El Ridi ◽

Marwa Aboueldahab ◽

Hatem Tallima ◽

Mohamed Salah ◽

Noha Mahana ◽

...

Keyword(s):

Arachidonic Acid ◽

Schistosoma Mansoni ◽

Schistosoma Haematobium ◽

Unsaturated Fatty Acids ◽

Ex Vivo ◽

Surface Membrane ◽

Calf Serum ◽

The United States

ABSTRACT The development of arachidonic acid (ARA) for treatment of schistosomiasis is an entirely novel approach based on a breakthrough discovery in schistosome biology revealing that activation of parasite tegument-bound neutral sphingomyelinase (nSMase) by unsaturated fatty acids, such as ARA, induces exposure of parasite surface membrane antigens to antibody binding and eventual attrition of developing schistosomula and adult worms. Here, we demonstrate that 5 mM ARA leads to irreversible killing of ex vivo 1-, 3-, 4-, 5-, and 6-week-old Schistosoma mansoni and 9-, 10-, and 12-week-old Schistosoma haematobium worms within 3 to 4 h, depending on the parasite age, even when the worms were maintained in up to 50% fetal calf serum. ARA-mediated worm attrition was prevented by nSMase inhibitors, such as CaCl2 and GW4869. Scanning and transmission electron microscopy revealed that ARA-mediated worm killing was associated with spine destruction, membrane blebbing, and disorganization of the apical membrane structure. ARA-mediated S. mansoni and S. haematobium worm attrition was reproduced in vivo in a series of 6 independent experiments using BALB/c or C57BL/6 mice, indicating that ARA in a pure form (Sigma) or included in infant formula (Nestle) consistently led to 40 to 80% decrease in the total worm burden. Arachidonic acid is already marketed for human use in the United States and Canada for proper development of newborns and muscle growth of athletes; thus, ARA has potential as a safe and cost-effective addition to antischistosomal therapy.

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Faculty Opinions recommendation of Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment.

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

10.3410/f.1018413.209475 ◽

2004 ◽

Author(s):

Paul J Brindley

Keyword(s):

Schistosoma Mansoni ◽

Praziquantel Treatment

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Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911521997849 ◽

2021 ◽

pp. 088391152199784

Author(s):

Loveleen Kaur ◽

Ajay Kumar Thakur ◽

Pradeep Kumar ◽

Inderbir Singh

Keyword(s):

Drug Release ◽

In Silico ◽

Ex Vivo ◽

Strong Interactions ◽

Dissolution Time ◽

Sem Images ◽

In Vivo Evaluation ◽

Release Studies

Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.

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Doxorubicin loaded magnetism nanoparticles based on cyclodextrin dendritic-graphene oxide inhibited MCF-7 cell proliferation

BioMolecular Concepts ◽

10.1515/bmc-2021-0002 ◽

2021 ◽

Vol 12 (1) ◽

pp. 8-15

Author(s):

Ainaz Mihanfar ◽

Niloufar Targhazeh ◽

Shirin Sadighparvar ◽

Saber Ghazizadeh Darband ◽

Maryam Majidinia ◽

...

Keyword(s):

Graphene Oxide ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Anticancer Drug Delivery ◽

Release Studies ◽

Anti Cancer ◽

Acidic Conditions ◽

Mcf 7

Abstract Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. In vitro release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further in vitro studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for in vitro targeting of cancer cells and suggest further studies are necessary to investigate its in vivo anti-cancer potential.

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Schistosoma mansoni: a comparative study of artificially transformed schistosomula and schistomula recoverd after cercarial penetration of isolated skin

Parasitology ◽

10.1017/s0031182000047545 ◽

1977 ◽

Vol 74 (1) ◽

pp. 73-86 ◽

Cited By ~ 81

Author(s):

Linda H. Brink ◽

Diane J. McLaren ◽

S. R. Smithers

Keyword(s):

Comparative Study ◽

Schistosoma Mansoni ◽

Amorphous Material ◽

Surface Membrane ◽

Antigenic Determinants ◽

Agglutination Reaction ◽

Rat Serum ◽

Mechanical Separation ◽

B Blood Group

A comparison was made of the ultrastructure, development and antigenic nature of the surfaces and of the viability of three types of schistosomula of Schistosoma mansoni: schistosomula formed afrer cercariae had penetrated isolated skin (SS), schistosomula produced after mechanical separation of cercarial tails from bodies (MS), and schistosomula transformed from cercariae after incubation in fresh rat serum (RS).Within 2 h of transformation, the surface membrane of all three types of schistosomula had changed from trilaminate to heptalaminate structures and SS and MS had lost their cercarial glycocalyx. Initially a dense amorphous material was demonstrated on the surfaces of RS, which was thought to be the result of an interaction between a factor in rat serum and the glycocalyx: this material was greatly reduced within 2 h of transformation. The pre-acetabular glands of SS were emptied while those of MS and RS retained their contents. Immunofluorescent studies showed that all schistosomula bound serum from mice immune to S. mansoni, but the binding was stronger with MS and RS. The mixed agglutination reaction demonstrated the presence of human A and B blood group-like antigenic determinants on approximately 30% of 3 h old SS; these determinants were not detected on MS or RS. In vitro, the development of MS and RS was similar to SS; the first schistosomula reached the ‘gut-closed’ stage by day 10; 50–70% of SS reached this stage by day 12, in contrast to only 25–50% of MS and RS. Between 28 and 45% of all schistosomula developed to maturity when injected intravenously into mice.It was concluded that the two types of artificially prepared schistosomula fultil the main criteria of transformation from cercaria to schistosomulum. Further, it is suggested that MS are the most appropriate source of material for immunochemical and physiological studies.

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