scholarly journals In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

2013 ◽  
Vol 57 (11) ◽  
pp. 5747-5754 ◽  
Author(s):  
Fabienne Barna ◽  
Karim Debache ◽  
Carsten A. Vock ◽  
Tatiana Küster ◽  
Andrew Hemphill
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Toxoplasma Gondii ◽  
Neospora Caninum ◽  
Ruthenium Complexes ◽  
Term Treatment ◽  
Content Type ◽  
Transmission Electron ◽  
Long Term Treatment

ABSTRACTUpon the screening of 16 antiproliferative compounds againstToxoplasma gondiiandNeospora caninum, two hydrolytically stable ruthenium complexes (compounds 16 and 18) exhibited 50% inhibitory concentrations of 18.7 and 41.1 nM (T. gondii) and 6.7 and 11.3 nM (N. caninum). To achieve parasiticidal activity with compound 16, long-term treatment (22 to 27 days at 80 to 160 nM) was required. Transmission electron microscopy demonstrated the rapid impact on and ultrastructural alterations in both parasites. These preliminary findings suggest that the potential of ruthenium-based compounds should thus be further exploited.

scholarly journals Therapeutic institutions of violence: conceptualising the biographical narratives of mental health service users/survivors accessing long term “treatment” in England

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Stephen J. Macdonald
Keyword(s):  
Mental Health ◽  
Family Members ◽  
Psychiatric Hospitals ◽  
Term Treatment ◽  
Service Users ◽  
Content Type ◽  
Criminal Violence ◽  
Long Term Treatment ◽  
Forms Of Violence

Purpose This paper aims to conceptualise the residential and psychiatric hospital as a space where criminality and social harms can emerge. Because of recent media scandals over the past 10 years concerning privately-owned hospitals, this study examines the lived experiences of service users/survivors, family members and practitioners to examine historic and contemporary encounters of distress and violence in hospital settings. Design/methodology/approach The study consists of 16 biographical accounts exploring issues of dehumanising and harmful practices, such as practices of restraint and rituals of coercive violence. A biographical methodology has been used to analyse the life stories of service users/survivors (n = 9), family members (n = 3) and professional health-care employees (n = 4). Service users/survivors in this study have experienced over 40 years of short-term and long-term periods of hospitalisation. Findings The study discovered that institutional forms of violence had changed after the deinstitutionalisation of care. Practitioners recalled comprehensive experiences of violence within historic mental hospitals, although violence that may be considered criminal appeared to disappear from hospitals after the Mental Health Act (1983). These reports of criminal violence and coercive abuse appeared to be replaced with dehumanising and harmful procedures, such as practices of restraint. Originality/value The data findings offer a unique interpretation, both historical and contemporary, of dehumanising psychiatric rituals experienced by service users/survivors, which are relevant to criminology and MAD studies. The study concludes by challenging oppressive psychiatric “harms” to promote social justice for service users/survivors currently being “treated” within the contemporary psychiatric system. The study intends to conceptualise residential and psychiatric hospitals as a space where criminality and social harms can emerge. The three aims of the study examined risk factors concerning criminality and social harms, oppressive and harmful practices within hospitals and evidence that violence occurs within these institutionalised settings. The study discovered that institutional forms of violence had changed after the deinstitutionalisation of care. These reports of violence include dehumanising attitudes, practices of restraint and coercive abuse.

scholarly journals Toxoplasma gondii Inside LLCMK2 Cells. A Study by Field Emission Scanning and Transmission Electron Microscopy

2003 ◽  
Vol 9 (S02) ◽  
pp. 232-233
Author(s):  
Rodrigo Cardoso Magno ◽  
Lorian Cobra Straker ◽  
Wanderley de Souza ◽  
Marcia Attias
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Toxoplasma Gondii ◽  
Field Emission ◽  
Transmission Electron

scholarly journals Antimicrobial Properties of a Chitosan Dextran-Based Hydrogel for Surgical Use

2011 ◽  
Vol 56 (1) ◽  
pp. 280-287 ◽  
Author(s):  
Manal A. Aziz ◽  
Jaydee D. Cabral ◽  
Heather J. L. Brooks ◽  
Stephen C. Moratti ◽  
Lyall R. Hanton
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Bacterial Species ◽  
Antimicrobial Properties ◽  
Sinus Surgery ◽  
Peptide Bonds ◽  
Content Type ◽  
E Coli ◽  
Transmission Electron

ABSTRACTA chitosan dextran-based (CD) hydrogel, developed for use in endoscopic sinus surgery, was tested for antimicrobial activityin vitroagainst a range of pathogenic microorganisms. The microdilution technique was used to determine minimum inhibitory, minimum bactericidal, and minimum fungicidal concentrations. In addition, the time-kill efficacy of CD hydrogel was determined for two bacterial species. Scanning and transmission electron microscopy were carried out to elucidate the antimicrobial mechanism of this compound. CD hydrogel was found to be effective againstStaphylococcus aureus,Streptococcus pyogenes,Escherichia coli, andClostridium perfringensat its surgical concentration of 50,000 mg/liter. Minimum bactericidal concentrations ranged from 2,000 to 50,000 mg/liter. Dextran aldehyde (DA) was found to be the antimicrobial component of the CD hydrogel with MBC ranging from 2,000 to 32,000 mg/liter.S. aureusappeared to be killed at a slightly faster rate thanE. coli. Candida albicansandPseudomonas aeruginosawere more resistant to CD hydrogel and DA. Scanning and transmission electron microscopy ofE. coliandS. aureusincubated with CD hydrogel and DA alone revealed morphological damage, disrupted cell walls, and loss of cytosolic contents, compatible with the proposed mode of action involving binding to cell wall proteins and disruption of peptide bonds. Motility and chemotaxis tests showedE. colito be inhibited when incubated with DA. The antibacterial activity of CD hydrogel may make it a useful postsurgical aid at other body sites, especially where there is a risk of Gram-positive infections.

Oxyhemoglobin-induced apoptosis in cultured endothelial cells

1999 ◽  
Vol 91 (3) ◽  
pp. 459-465 ◽  
Author(s):  
Kotaro Ogihara ◽  
Alexander Y. Zubkov ◽  
David H. Bernanke ◽  
Adam I. Lewis ◽  
Andrew D. Parent ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Endothelial Cells ◽  
Time Dependent ◽  
Dependent Manner ◽  
Content Type ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Transmission Electron ◽  
Fine Print

Object. Oxyhemoglobin (OxyHb) is one of the most important spasmogens for cerebral vasospasm that follows aneurysmal subarachnoid hemorrhage. The cytotoxic effect of OxyHb has been documented in endothelial and smooth-muscle cells; however, the pattern of cell death—necrosis or apoptosis—as the final stage of cell damage has not been demonstrated. This study was undertaken to determine if OxyHb induces apoptotic changes in cultured bovine aortic endothelial cells.Methods. Confluent bovine aortic endothelial cells were treated with OxyHb in a concentration- and time-dependent manner. Cell density was assayed by counting the number of cells that attached to culture dishes after exposure to OxyHb. To identify apoptotic changes, the investigators used three specific methods: DNA fragmentation (electrophoreses), the apoptotic body (transmission electron microscopy), and cleavage of poly (adenosine diphosphate ribose) polymerase (PARP [Western blotting]).Conclusions. Oxyhemoglobin decreased cell density in a concentration- and time-dependent manner. Analysis of DNA showed a pattern of internucleosomal cleavage characteristic of apoptosis (DNA ladder). Transmission electron microscopy demonstrated condensation of nuclei and apoptotic bodies in OxyHb-treated endothelial cells. Western blotting with the PARP antibody revealed that the 116-kD PARP was cleaved to the 85-kD apoptosis-related fragment. These results for the first time demonstrated that the OxyHb induces apoptosis in cultured endothelial cells.

scholarly journals Characterization of the Activities of Dinuclear Thiolato-Bridged Arene Ruthenium Complexes against Toxoplasma gondii

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Afonso P. Basto ◽  
Joachim Müller ◽  
Riccardo Rubbiani ◽  
David Stibal ◽  
Federico Giannini ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Anticancer Agents ◽  
Ribosomal Proteins ◽  
Ruthenium Complexes ◽  
Elongation Factor ◽  
Host Cells ◽  
Content Type ◽  
Transmission Electron ◽  
The Matrix

ABSTRACT The in vitro effects of 18 dinuclear thiolato-bridged arene ruthenium complexes (1 monohiolato compound, 4 dithiolato compounds, and 13 trithiolato compounds), originally designed as anticancer agents, on the apicomplexan parasite Toxoplasma gondii grown in human foreskin fibroblast (HFF) host cells were studied. Some trithiolato compounds exhibited antiparasitic efficacy at concentrations of 250 nM and below. Among those, complex 1 and complex 2 inhibited T. gondii proliferation with 50% inhibitory concentrations (IC50s) of 34 and 62 nM, respectively, and they did not affect HFFs at dosages of 200 μM or above, resulting in selectivity indices of >23,000. The IC50s of complex 9 were 1.2 nM for T. gondii and above 5 μM for HFFs. Transmission electron microscopy detected ultrastructural alterations in the matrix of the parasite mitochondria at the early stages of treatment, followed by a more pronounced destruction of tachyzoites. However, none of the three compounds applied at 250 nM for 15 days was parasiticidal. By affinity chromatography using complex 9 coupled to epoxy-activated Sepharose followed by mass spectrometry, T. gondii translation elongation factor 1α and two ribosomal proteins, RPS18 and RPL27, were identified to be potential binding proteins. In conclusion, organometallic ruthenium complexes exhibit promising activities against Toxoplasma, and the potential mechanisms of action of these compounds as well as their prospective applications for the treatment of toxoplasmosis are discussed.

scholarly journals In Vitro Activities of MMV Malaria Box Compounds against the Apicomplexan Parasite Neospora caninum, the Causative Agent of Neosporosis in Animals

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1460
Author(s):  
Joachim Müller ◽  
Pablo A. Winzer ◽  
Kirandeep Samby ◽  
Andrew Hemphill
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Structural Changes ◽  
Neospora Caninum ◽  
Chemotherapeutic Agents ◽  
Apicomplexan Parasite ◽  
In Vivo Studies ◽  
Transmission Electron ◽  
Malaria Box ◽  
Caninum Tachyzoites

(1) Background: Neospora caninum is a major cause of abortion in cattle and represents a veterinary health problem of great economic significance. In order to identify novel chemotherapeutic agents for the treatment of neosporosis, the Medicines for Malaria Venture (MMV) Malaria Box, a unique collection of anti-malarial compounds, were screened against N. caninum tachyzoites, and the most efficient compounds were characterized in more detail. (2) Methods: A N. caninum beta-galactosidase reporter strain grown in human foreskin fibroblasts was treated with 390 compounds from the MMV Malaria Box. The IC50s of nine compounds were determined, all of which had been previously been shown to be active against another apicomplexan parasite, Theileria annulata. The effects of three of these compounds on the ultrastructure of N. caninum tachyzoites were further investigated by transmission electron microscopy at different timepoints after initiation of drug treatment. (3) Results: Five MMV Malaria Box compounds exhibited promising IC50s below 0.2 µM. The compound with the lowest IC50, namely 25 nM, was MMV665941. This compound and two others, MMV665807 and MMV009085, specifically induced distinct alterations in the tachyzoites. More specifically, aberrant structural changes were first observed in the parasite mitochondrion, and subsequently progressed to other cytoplasmic compartments of the tachyzoites. The pharmacokinetic (PK) data obtained in mice suggest that treatment with MMV665941 could be potentially useful for further in vivo studies. (4) Conclusions: We have identified five novel compounds with promising activities against N. caninum, the effects of three of these compounds were studies by transmission electron microscopy (TEM). Their modes of action are unknown and require further investigation.

scholarly journals Effects of miltefosine treatment in fibroblast cell cultures and in mice experimentally infected withNeospora caninumtachyzoites

Parasitology ◽  
2012 ◽  
Vol 139 (7) ◽  
pp. 934-944 ◽  
Author(s):  
KARIM DEBACHE ◽  
ANDREW HEMPHILL
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Treatment Group ◽  
Neospora Caninum ◽  
Fibroblast Cell ◽  
Time Span ◽  
Human Foreskin Fibroblasts ◽  
Transmission Electron ◽  
Infected Cells

SUMMARYMiltefosine was investigated for its activity againstNeospora caninumtachyzoitesin vitro,and was shown to inhibit the proliferation ofN. caninumtachyzoites cultured in human foreskin fibroblasts (HFF) with an IC50of 5·2μM. Treatment of infected cells with 25μM miltefosine for a period of 10 h had only a parasitostatic effect, while after 20 h of treatment parasiticidal effects were observed. This was confirmed by transmission electron microscopy ofN. caninum-infected and miltefosine-treated HFF. Administration of miltefosine toN. caninum-infected Balb/c female mice at 40 mg/kg/day for 14 days resulted in 6 out of 10 mice exhibiting weight loss, ruffled coat and apathy between days 7 and 13 post-infection. In the group that received placebo, only 2 out of 8 mice succumbed to infection, but the cerebral burden was significantly higher compared to the miltefosine treatment group. In a second experiment, the time-span of treatment was reduced to 5 days, and mice were maintained without further treatment for 4 weeks. Only 2 out of 9 mice in the miltefosine treatment group exhibited signs of disease, while 8 out of 10 mice succumbed to infection in the placebo group. These results showed that miltefosine hampered the dissemination of parasites into the CNS during experimentalN. caninuminfection in mice.

Analysis of brain biocompatibility of drug-releasing biodegradable microspheres by scanning and transmission electron microscopy

2001 ◽  
Vol 95 (3) ◽  
pp. 489-494 ◽  
Author(s):  
Joëlle Veziers ◽  
Maurice Lesourd ◽  
Christophe Jollivet ◽  
Claudia Montero-Menei ◽  
Jean-Pierre Benoit ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Brain Tissue ◽  
Neurotrophic Factors ◽  
Rat Striatum ◽  
Inert Material ◽  
Biodegradable Microspheres ◽  
Content Type ◽  
Transmission Electron ◽  
Fine Print

Object. Stereotactically guided implantation of biodegradable microspheres is a promising strategy for delivery of neurotrophic factors in a precise and spatially defined brain area. The goal in this study was to show the biocompatibility of poly(D,L,lactide-co-glycolide) microspheres with brain tissue at the ultrastructural level and to analyze the three-dimensional (3D) ultrastructure after intrastriatal implantation of these microparticles. Methods. Scanning and transmission electron microscopy were used to study the microspheres and their environment after implantation in an inert material (gelatin) and in the rat striatum. Observations were made at different time periods, ranging from 24 hours to 2 months postimplantation. Conclusions. The progressive degradation of the microspheres, with vacuolization, deformation, and shrinkage, was well visualized. This degradation was identical in microspheres implanted in the inert material and in the rat brain tissue, independent of the presence of macrophages. The studies preformed in the striatum permitted the authors to demonstrate the structural integrity of axons in contact with microspheres, confirming the biocompatibility of the polymer. Furthermore, scanning electron microscopy showed the preservation of the 3D ultrastructure of the striatum around the microparticles. These microparticles, which can be stereotactically implanted in functional areas of the brain and can release neurotrophic factors, could represent, for some indications, an alternative to gene therapy.

Human neonatal hydrocephalus

1985 ◽  
Vol 63 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Marc R. Del Bigio ◽  
J. Edward Bruni ◽  
H. Derek Fewer
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Ependymal Cells ◽  
Foramen Of Monro ◽  
Content Type ◽  
Axonal Pathology ◽  
Transmission Electron ◽  
Cell Processes ◽  
Junctional Complexes ◽  
Fine Print

✓ An infant of 43 weeks gestational age with severe congenital hydrocephalus was operated on for removal of a subependymal astrocytoma in the region of the foramen of Monro. A biopsy of periventricular tissue was taken from the lateral ventricle for examination by scanning and transmission electron microscopy. The ependyma was largely denuded, with glial cell processes forming most of the ventricular lining. Many of the attenuated ependymal cells, however, had intact junctional complexes at areas of contact with other ependymal cells. Club-shaped unipolar cells, believed to be a previously undescribed form of immature ependymal cells, were found in the ventricular lining. Cerebrospinal fluid edema was present in the neuropil up to 60 µm from the ventricular lumen, but there was no obvious axonal pathology in the tissues examined.

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