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'Non-criteria' neurologic manifestations of antiphospholipid syndrome: a hidden kingdom to be discovered

Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH

CNS Neurol Disord Drug Targets, 2016;15(10):1253-1265.
PMID: 27658514 DOI: 10.2174/1871527315666160920122750

Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.

Matched MeSH terms: Disease Models, Animal
Fulltext (R)-Salbutamol Improves Imiquimod-Induced Psoriasis-Like Skin Dermatitis by Regulating the Th17/Tregs Balance and Glycerophospholipid Metabolism

Liu F, Wang S, Liu B, Wang Y, Tan W

Cells, 2020 02 24;9(2).
PMID: 32102363 DOI: 10.3390/cells9020511

Psoriasis is a skin disease that is characterized by a high degree of inflammation caused by immune dysfunction. (R)-salbutamol is a bronchodilator for asthma and was reported to alleviate immune system reactions in several diseases. In this study, using imiquimod (IMQ)-induced mouse psoriasis-like dermatitis model, we evaluated the therapeutic effects of (R)-salbutamol in psoriasis in vivo, and explored the metabolic pathway involved. The results showed that, compared with IMQ group, (R)-salbutamol treatment significantly ameliorated psoriasis, reversed the suppressive effects of IMQ on differentiation, extreme keratinocyte proliferation, and infiltration of inflammatory cells. Enzyme-linked immunosorbent assays (ELISA) showed that (R)-salbutamol markedly reduced the plasma levels of IL-17. Cell analysis using flow cytometry showed that (R)-salbutamol decreased the proportion of CD4+ Th17+ T cells (Th17), whereas it increased the percentage of CD25+ Foxp3+ regulatory T cells (Tregs) in the spleens. (R)-salbutamol also decreased the weight ratio of spleen to body. Furthermore, untargeted metabolomics showed that (R)-salbutamol affected three metabolic pathways, including (i) arachidonic acid metabolism, (ii) sphingolipid metabolism, and (iii) glycerophospholipid metabolism. These results demonstrated that (R)-salbutamol can alleviate IMQ-induced psoriasis through regulating Th17/Tregs cell response and glycerophospholipid metabolism. It may provide a new use of (R)-salbutamol in the management of psoriasis.

Matched MeSH terms: Disease Models, Animal
1'-Acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression

Sok SPM, Ori D, Wada A, Okude H, Kawasaki T, Momota M, et al.

Int Immunol, 2021 06 18;33(7):373-386.
PMID: 33830232 DOI: 10.1093/intimm/dxab016

The nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing (NLRP) 3 inflammasome is a multiprotein complex that triggers Caspase-1-mediated IL-1β production and pyroptosis, and its dysregulation is associated with the pathogenesis of inflammatory diseases. 1'-Acetoxychavicol acetate (ACA) is a natural compound in the rhizome of tropical ginger Alpinia species with anti-microbial, anti-allergic and anti-cancer properties. In this study, we found that ACA suppressed NLRP3 inflammasome activation in mouse bone marrow-derived macrophages and human THP-1 monocytes. ACA inhibited Caspase-1 activation and IL-1β production by NLRP3 agonists such as nigericin, monosodium urate (MSU) crystals, and ATP. Moreover, it suppressed oligomerization of the adapter molecule, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1-mediated cleavage of pyroptosis executor Gasdermin D. Mechanistically, ACA inhibited generation of mitochondrial reactive oxygen species (ROS) and prevented release of oxidized mitochondrial DNA, which trigger NLRP3 inflammasome activation. ACA also prevented NLRP3 inflammasome activation in vivo, as evidenced in the MSU crystal-induced peritonitis and dextran sodium sulfate-induced colitis mouse models accompanied by decreased Caspase-1 activation. Thus, ACA is a potent inhibitor of the NLRP3 inflammasome for prevention of NLRP3-associated inflammatory diseases.

Matched MeSH terms: Disease Models, Animal
Fulltext 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease

Xu J, Jiang H, Li J, Cheng KK, Dong J, Chen Z

PLoS One, 2015;10(4):e0119654.
PMID: 25849323 DOI: 10.1371/journal.pone.0119654

Wilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.

Matched MeSH terms: Disease Models, Animal*
Fulltext 4'-O-substitutions determine selectivity of aminoglycoside antibiotics

Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, et al.

Nat Commun, 2014;5:3112.
PMID: 24473108 DOI: 10.1038/ncomms4112

Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.

Matched MeSH terms: Disease Models, Animal
Fulltext A Comparison of Culture Characteristics between Human Amniotic Mesenchymal Stem Cells and Dental Stem Cells

Yusoff NH, Alshehadat SA, Azlina A, Kannan TP, Hamid SS

Trop Life Sci Res, 2015 Apr;26(1):21-9.
PMID: 26868590 MyJurnal

In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells.

Matched MeSH terms: Models, Animal
Fulltext A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

Phyu WK, Ong KC, Wong KT

PLoS One, 2016;11(1):e0147463.
PMID: 26815859 DOI: 10.1371/journal.pone.0147463

Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

Matched MeSH terms: Disease Models, Animal
Fulltext A Review of Placenta and Umbilical Cord-Derived Stem Cells and the Immunomodulatory Basis of Their Therapeutic Potential in Bronchopulmonary Dysplasia

Chia WK, Cheah FC, Abdul Aziz NH, Kampan NC, Shuib S, Khong TY, et al.

Front Pediatr, 2021;9:615508.
PMID: 33791258 DOI: 10.3389/fped.2021.615508

Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.

Matched MeSH terms: Models, Animal
Fulltext A Review of Potential Beneficial Effects of Honey on Bone Health

Kamaruzzaman MA, Chin KY, Mohd Ramli ES

Evid Based Complement Alternat Med, 2019;2019:8543618.
PMID: 31641368 DOI: 10.1155/2019/8543618

Bone remodelling is a complex and tightly regulated process. Disruption of bone remodelling skewing towards resorption will cause osteoporosis and increase the risk of fragility fracture. Honey is a natural product containing various bioactive ingredients with health benefits, especially polyphenols. Therefore, honey may be a novel dietary supplement to prevent osteoporosis. This review aims to summarize the current evidence on the effects of honey on bone health. The evidence reported so far indicates a skeletal-beneficial effect of honey in animal models of osteoporosis. However, the number of studies on humans is limited. Honey can protect the bone via its antioxidant and anti-inflammatory properties, primarily through its polyphenol content that acts upon several signalling pathways, leading to bone anabolic and antiresorptive effects. In conclusion, honey is a potential functional food for bone health, but the dose and the bioactive contents of honey need to be verified prior to its application in humans.

Matched MeSH terms: Models, Animal
A Review on the Antinociceptive Effects of Mitragyna speciosa and Its Derivatives on Animal Model

Chin KY, Mark-Lee WF

Curr Drug Targets, 2018;19(12):1359-1365.
PMID: 28950813 DOI: 10.2174/1389450118666170925154025

Mitragyna speciosa is a tropical plant with narcotic effects. The antinociceptive effects of its crude extracts, bioactive compounds and structurally modified derivatives have been examined in rodent models. This review aims to summarize the evidence on the antinociceptive effects of M. speciosa and its derivatives and explore whether they can offer an alternative to morphine in pain management. Methanolic and alkaloid extracts of M. speciosa were shown to attenuate the nociceptive response in rodents. Mitragynine and 7-hydroxymitragynine offered better antinociceptive effects than crude extracts. Structurally modified derivatives of 7-hydroxymitragynine, such as MGM-9, MGM- 15, MGM-16, demonstrated superior antinociceptive effects compared to morphine. M. speciosa and its derivatives mainly act on the opioid receptor, but receptor subtypes specificity differs between each compound. The tolerance and adverse side effects of M. speciosa and its derivatives are similar with morphine. The affinity of MGM-9 on kappa-opioid receptor could potentially limit the effects of drug dependence. In conclusion, M speciosa derivatives can offer alternatives to morphine in controlling chronic pain. Structural modification of mitragynine and 7-hydroxymitragynine can generate compounds with higher potency and lesser side-effects. Human clinical trials are required to validate the use of these compounds in clinical setting.

Matched MeSH terms: Disease Models, Animal
Fulltext A Systematic Review of the Protective Actions of Cat's Whiskers (Misai Kucing) on the Central Nervous System

Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF

Front Pharmacol, 2020;11:692.
PMID: 32477146 DOI: 10.3389/fphar.2020.00692

Orthosiphon stamineus (OS) or Orthosiphon aristatus var. aristatus (OAA) is commonly known as cat's whiskers or "misai kucing". It is an herbaceous shrub that is popular in many different traditional and complementary medicinal systems. Its popularity has been justified by the plethora of studies that have shown that the secondary metabolites of the plant has effects that range from anti-inflammatory and gastroprotective to anorexic and antihypertensive. As such, OS could also be a potential treatment for Central Nervous System (CNS) disorders. However, a cohesive synthesis of the protective actions of OS was lacking. This systematic review was therefore commenced to elaborate on the various protective mechanisms of OS in the CNS. The PRISMA model was used and five databases (Google Scholar, SCOPUS, SpringerLink, ScienceDirect, and PubMed) were searched with relevant keywords to finally identify four articles that met the inclusion criteria. The articles described the protective effects of OS extracts on Alzheimer's disease, epilepsy, learning and memory, oxidative stress, and neurotoxicity. All the articles found were experimental or preclinical studies on animal models or in vitro systems. The reported activities demonstrated that OS could be a potential neuroprotective agent and might improve CNS conditions like neurodegeneration, neuroinflammation, and oxidative stress.

Matched MeSH terms: Models, Animal
Fulltext A Systematic Review on Non-mammalian Models in Epilepsy Research

Johan Arief MF, Choo BKM, Yap JL, Kumari Y, Shaikh MF

Front Pharmacol, 2018;9:655.
PMID: 29997502 DOI: 10.3389/fphar.2018.00655

Epilepsy is a common neurological disorder characterized by seizures which result in distinctive neurobiological and behavioral impairments. Not much is known about the causes of epilepsy, making it difficult to devise an effective cure for epilepsy. Moreover, clinical studies involving epileptogenesis and ictogenesis cannot be conducted in humans due to ethical reasons. As a result, animal models play a crucial role in the replication of epileptic seizures. In recent years, non-mammalian models have been given a primary focus in epilepsy research due to their advantages. This systematic review aims to summarize the importance of non-mammalian models in epilepsy research, such as in the screening of anti-convulsive compounds. The reason for this review is to integrate currently available information on the use and importance of non-mammalian models in epilepsy testing to aid in the planning of future studies as well as to provide an overview of the current state of this field. A PRISMA model was utilized and PubMed, Springer, ScienceDirect and SCOPUS were searched for articles published between January 2007 and November 2017. Fifty-one articles were finalized based on the inclusion/exclusion criteria and were discussed in this review. The results of this review demonstrated the current use of non-mammalian models in epilepsy research and reaffirmed their potential to supplement the typical rodent models of epilepsy in future research into both epileptogenesis and the treatment of epilepsy. This review also revealed a preference for zebrafish and fruit flies in lieu of other non-mammalian models, which is a shortcoming that should be corrected in future studies due to the great potential of these underutilized animal models.

Matched MeSH terms: Models, Animal
Fulltext A Zebrafish Embryo as an Animal Model for the Treatment of Hyperpigmentation in Cosmetic Dermatology Medicine

Lajis AFB

Medicina (Kaunas), 2018 May 25;54(3).
PMID: 30344266 DOI: 10.3390/medicina54030035

For years, clinical studies involving human volunteers and several known pre-clinical in vivo models (i.e., mice, guinea pigs) have demonstrated their reliability in evaluating the effectiveness of a number of depigmenting agents. Although these models have great advantages, they also suffer from several drawbacks, especially involving ethical issues regarding experimentation. At present, a new depigmenting model using zebrafish has been proposed and demonstrated. The application of this model for screening and studying the depigmenting activity of many bioactive compounds has been given great attention in genetics, medicinal chemistry and even the cosmetic industry. Depigmenting studies using this model have been recognized as noteworthy approaches to investigating the antimelanogenic activity of bioactive compounds in vivo. This article details the current knowledge of zebrafish pigmentation and its reliability as a model for the screening and development of depigmenting agents. Several methods to quantify the antimelanogenic activity of bioactive compounds in this model, such as phenotype-based screening, melanin content, tyrosinase inhibitory activity, other related proteins and transcription genes, are reviewed. Depigmenting activity of several bioactive compounds which have been reported towards this model are compared in terms of their molecular structure and possible mode of actions. This includes patented materials with regard to the application of zebrafish as a depigmenting model, in order to give an insight of its intellectual value. At the end of this article, some limitations are highlighted and several recommendations are suggested for improvement of future studies.

Matched MeSH terms: Disease Models, Animal*
Fulltext A Zinc Morpholine Complex Prevents HCl/Ethanol-Induced Gastric Ulcers in a Rat Model

Salama SM, Gwaram NS, AlRashdi AS, Khalifa SA, Abdulla MA, Ali HM, et al.

Sci Rep, 2016 07 27;6:29646.
PMID: 27460157 DOI: 10.1038/srep29646

Zinc is a naturally occurring element with roles in wound healing and rescuing tissue integrity, particularly in the gastrointestinal system, where it can be detected in the mucosal and submucosal layers. Zinc chelates are known to have beneficial effects on the gastrointestinal mucosa and in cases of gastric ulcer. We synthesized complexes of zinc featuring a heterocyclic amine binding amino acids then investigated their ability to enhance the gastric self-repair. Zinc-morpholine complex, Zn(L)SCN, namely showed strong free-radical scavenging, promotion of the DNA and RNA polymerases reconstruction and suppression of cell damage. The complex's mode of action is proposed to involve hydrogen bond formation via its bis(thiocyanato-k)zinc moiety. Zn(L)SCN complex had potent effects on gastric enzymatic activity both in vitro and in vivo. The complex disrupted the ulcerative process as demonstrated by changes in the intermediate metabolites of the oxidative pathway - specifically, reduction in the MDA levels and elevation of reduced glutathione together with an attenuation of oxidative DNA damage. Additionally, Zn(L)SCN restored the gastric mucosa, inhibited the production of pro-inflammatory cytokines (IL-6, TNF and the caspases), and preserved the gastric mucous balance. Zn(L)SCN thus exhibited anti-oxidative, anti-inflammatory and anti-apoptotic activities, all of which have cytoprotective effects on the gastric lining.

Matched MeSH terms: Disease Models, Animal
A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors

Marques Da Costa ME, Zaidi S, Scoazec JY, Droit R, Lim WC, Marchais A, et al.

Commun Biol, 2023 Sep 18;6(1):949.
PMID: 37723198 DOI: 10.1038/s42003-023-05320-0

Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient's tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies.

Matched MeSH terms: Disease Models, Animal
Fulltext A comparative analysis on the binding characteristics of various mammalian albumins towards a multitherapeutic agent, pinostrobin

Feroz SR, Sumi RA, Malek SN, Tayyab S

Exp Anim, 2015;64(2):101-8.
PMID: 25519455 DOI: 10.1538/expanim.14-0053

The interaction of pinostrobin (PS), a multitherapeutic agent with serum albumins of various mammalian species namely, goat, bovine, human, porcine, rabbit, sheep and dog was investigated using fluorescence quench titration and competitive drug displacement experiments. Analysis of the intrinsic fluorescence quenching data revealed values of the association constant, K(a) in the range of 1.49 - 6.12 × 10(4) M(-1), with 1:1 binding stoichiometry. Based on the PS-albumin binding characteristics, these albumins were grouped into two classes. Ligand displacement studies using warfarin as the site I marker ligand correlated well with the binding data. Albumins from goat and bovine were found to be closely similar to human albumin on the basis of PS binding characteristics.

Matched MeSH terms: Models, Animal
A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

Ngeow WC, Atkins S, Morgan CR, Metcalfe AD, Boissonade FM, Loescher AR, et al.

Neuroscience, 2011 May 5;181:271-7.
PMID: 21377512 DOI: 10.1016/j.neuroscience.2011.02.054

We have investigated the effect of three potential scar-reducing agents applied at a sciatic nerve repair site in C57-black-6 mice. Under anaesthesia the nerve was transected, repaired using four epineurial sutures, and 100 μl of either triamcinolone acetonide (1 mg/100 μl), an interleukin-10 peptide fragment (125 ng/100 μl or 500 ng/100 μl) or mannose-6-phosphate (M6P, 200 mM or 600 mM) was injected into and around the nerve. After 6 weeks the extent of regeneration was assessed electrophysiologically by determining the ratio of the compound action potential (CAP) modulus evoked by electrical stimulation of the nerve 2 mm distal or proximal to the repair site. The conduction velocity of the fastest components in the CAP was also calculated. The percentage area of collagen staining (PAS) at the repair site was analysed using Picrosirius Red and image analysis. Comparisons were made with a placebo group (100 μl of phosphate buffered saline) and sham-operated controls. The median CAP modulus ratio in the 600 mM M6P group was 0.44, which was significantly higher than in the placebo group (0.24, P=0.012: Kruskal-Wallis test). Conduction velocities were also faster in the 600 mM M6P group (median 30 m s(-1)) than in the placebo group (median 27.8 m s(-1); P=0.0197: Kruskal-Wallis test). None of the other treated groups were significantly different from the placebo, and all had significantly lower CAP ratios than the sham controls (P<0.05). All repair groups had a significantly higher PAS for collagen than sham controls. We conclude that the administration of 600 mM mannose-6-phosphate to a nerve repair site enhances axonal regeneration.

Matched MeSH terms: Disease Models, Animal
Fulltext A detailed microscopic study of the changes in the aorta of experimental model of postmenopausal rats fed with repeatedly heated palm oil

Adam SK, Das S, Jaarin K

Int J Exp Pathol, 2009 Jun;90(3):321-7.
PMID: 19563614 DOI: 10.1111/j.1365-2613.2009.00658.x

Hypercholesterolaemia, increase in lipid peroxidation and hyperhomocysteinaemia may contribute to the pathogenesis of atherosclerosis. This study was performed to examine the effects of repeatedly heated palm oil mixed with 2% cholesterol diet on atherosclerosis in oestrogen-deficient postmenopausal rats. Ovariectomy causes disruption of tunica intima layer of the rat aorta simulating a postmenopausal condition in females. Twenty-four ovariectomized female Sprague-Dawley rats were divided into four groups. The control group received 2% cholesterol diet without palm oil. A diet with 2% cholesterol content fortified with fresh, once-heated and five-times-heated palm oil was given to the other treatment groups. The rats were sacrificed at the end of 4 months of study and the aortic arch tissue was processed for histomorphometry and electron microscopy. On observation, there was disruption of the intimal layer of the ovariectomized rat aorta. There was no obvious ultrastructural change in the aorta of the rats fed with fresh palm oil. The ultrastructural changes were minimal with once-heated palm oil, in which there was a focal disruption of the endothelial layer. The focal disruption was more pronounced with five-times-heated palm oil. The results of this study show that the ingestion of fresh palm oil may have a protective effect on the aorta but such a protective action may be lost when the palm oil is repeatedly heated. The study may be clinically important for all postmenopausal women who are susceptible to atherosclerosis.

Matched MeSH terms: Disease Models, Animal
Fulltext A golden hamster model for human acute Nipah virus infection

Wong KT, Grosjean I, Brisson C, Blanquier B, Fevre-Montange M, Bernard A, et al.

Am J Pathol, 2003 Nov;163(5):2127-37.
PMID: 14578210 DOI: 10.1016/S0002-9440(10)63569-9

A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153-2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection.

Matched MeSH terms: Disease Models, Animal*
A monoclonal antibody to ameliorate central nervous system infection and improve survival in a murine model of human Enterovirus-A71 encephalomyelitis

Tan SH, Ong KC, Perera D, Wong KT

Antiviral Res, 2016 Aug;132:196-203.
PMID: 27340013 DOI: 10.1016/j.antiviral.2016.04.015

BACKGROUND: Enterovirus A71 (EV-A71) encephalomyelitis is an often fatal disease for which there is no specific treatment available. Passive immunization with a specific monoclonal antibody to EV-A71 was used on a murine model of EV-A71 encephalomyelitis to evaluate its therapeutic effectiveness before and after established central nervous system (CNS) infection.
METHODS: Mice were intraperitoneally-infected with a mouse-adapted EV-A71 strain and treated with a dose of monoclonal antibody (MAb) daily for 3 days on day 1, 2 and 3 post-infection or for 3 days on 3, 4 and 5 post-infection. Treatment effectiveness was evaluated by signs of infection and survival rate. Histopathology and qPCR analyses were performed on mice sacrificed a day after completing treatment.
RESULTS: In mock-treated mice, CNS infection was established from day 3 post-infection. All mice treated before established CNS infection, survived and recovered completely without CNS infection. All mice treated after established CNS infection survived with mild paralysis, and viral load and antigens/RNA at day 6 post-infection were significantly reduced.
CONCLUSIONS: Passive immunization with our MAb could prevent CNS infection in mice if given early before the establishment of CNS infection. It could also ameliorate established CNS infection if optimal and repeated doses were given.

Matched MeSH terms: Disease Models, Animal

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