Displaying publications 1 - 20 of 156 in total

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  1. Tan NH, Wong KY, Tan CH
    J Proteomics, 2017 03 22;157:18-32.
    PMID: 28159706 DOI: 10.1016/j.jprot.2017.01.018
    The venom proteome of Naja sputatrix (Javan spitting cobra) was elucidated through reverse-phase HPLC, nano-ESI-LCMS/MS and data mining. A total of 97 distinct protein forms belonging to 14 families were identified. The most abundant proteins are the three-finger toxins (3FTXs, 64.22%) and phospholipase A2 (PLA2, 31.24%), followed by nerve growth factors (1.82%), snake venom metalloproteinase (1.33%) and several proteins of lower abundance (<1%) including a variety of venom enzymes. At subproteome, the 3FTx is dominated by cytotoxins (48.08%), while short neurotoxins (7.89%) predominate over the long neurotoxins (0.48%) among other neurotoxins of lesser toxicity (muscarinic toxin-like proteins, 5.51% and weak neurotoxins, 2.26%). The major SNTX, CTX and PLA2 toxins were isolated with intravenous median lethal doses determined as 0.13, 1.06 and 0.50μg/g in mice, respectively. SABU, the Indonesia manufactured homologous tri-specific antivenom could neutralize the CTX and PLA2 fraction with moderate potency (potency=0.14-0.16mg toxin per ml antivenom). The SNTX, however, was very poorly neutralized with a potency level of 0.034mg/ml, indicating SNTX as the main limiting factor in antivenom neutralization. The finding helps elucidate the inferior efficacy of SABU reported in neutralizing N. sputatrix venom, and supports the call for antivenom improvement.

    BIOLOGICAL SIGNIFICANCE: The Javan spitting cobra, Naja sputatrix is by itself a unique species and should not be confused as the equatorial and the Indochinese spitting cobras. The distinction among the spitting cobras was however unclear prior to the revision of cobra systematics in the mid-90's, and results of some earlier studies are now questionable as to which species was implicated back then. The current study successfully profiled the venom proteome of authenticated N. sputatrix, and showed that the venom is made up of approximately 64% three-finger toxins (including neurotoxins and cytotoxins) and 31% phospholipases A2 by total venom proteins. The findings verified that the paralyzing components in the venom i.e. neurotoxins are predominantly the short-chain subtype (SNTX) far exceeding the long-chain subtype (LNTX) which is more abundant in the venoms of monocled cobra and Indian common cobra. The neurotoxicity of N. sputatrix venom is hence almost exclusively SNTX-driven, and effective neutralization of the SNTX is the key to early reversal of paralysis. Unfortunately, as shown through a toxin-specific assay, the immunological neutralization of the SNTX using the Indonesian antivenom (SABU) was extremely weak, implying that SABU has limited therapeutic efficacy in treating N. sputatrix envenomation clinically. From the practical standpoint, actions need to be taken at all levels from laboratory to production and policy making to ensure that the shortcoming is overcome.

    Matched MeSH terms: Mice, Inbred ICR
  2. Lee MHP, Tan CW, Tee HK, Ong KC, Sam IC, Chan YF
    Vaccine, 2021 03 19;39(12):1708-1720.
    PMID: 33640144 DOI: 10.1016/j.vaccine.2021.02.024
    Enterovirus A71 (EV-A71) causes hand, foot and mouth disease (HFMD) in young children. It is associated with severe neurological complications and death. This study aims to develop a live-attenuated vaccine by codon deoptimization (CD) and codon-pair deoptimization (CPD) of EV-A71. CD is generated by introducing the least preferred codons for amino acids while CPD increases the presence of underrepresented codon pairs in the specific genes. CD and CPD chimeras were generated by synonymous mutations at the VP2, VP3, VP1 and 2A gene regions, designated as XYZ. All twelve deoptimized viruses were viable with similar replication kinetics, but the plaque sizes were inversely proportional to the level of deoptimization. All the deoptimized viruses showed attenuated growth in vitro with reduced viral protein expression at 48 h and lower viral RNA at 39 °C. Six-week-old ICR mice were immunized intraperitoneally with selected CD and CPD X and XY vaccine candidates covering the VP2-VP3 and VP2-VP3-VP1 genes, respectively. All vaccine candidates elicited high anti-EV-A71 IgG levels similar to wild-type (WT) EV-A71. The CD X and CPD X vaccines produced robust neutralizing antibodies but not the CD XY and CPD XY. On lethal challenge, offspring of mice immunized with WT, CD X and CPD X were fully protected, but the CD XY- and CPD XY-vaccinated mice had delayed symptoms and eventually died. Similarly, active immunization of 1-day-old suckling mice with CD X, CPD X and CD XY vaccine candidates provided complete immune protection but CPD XY only protected 40% of the challenged mice. Histology of the muscles from CD X- and CPD X-vaccinated mice showed minimal pathology compared to extensive inflammation in the post-challenged mock-vaccinated mice. Overall, we demonstrated that the CD X and CPD X elicited good neutralizing antibodies, conferred immune protection and are promising live-attenuated vaccine candidates for EV-A71.
    Matched MeSH terms: Mice, Inbred ICR
  3. Fauzi A, Kifli N, Noor MHM, Hamzah H, Azlan A
    Open Vet J, 2024 Mar;14(3):750-758.
    PMID: 38682142 DOI: 10.5455/OVJ.2024.v14.i3.1
    BACKGROUND: Studies have reported that the phytochemical content of Mulberry (Morus alba Linn.) is influenced by the area where it grows. On the other hand, the study of the bioactivity and toxicity of mulberry leaves from Brunei Darussalam still needs to be completed. In particular, the investigation regarding the safe dose for Mulberry's application from Brunei Darussalam has yet to be studied. Hence, toxicity information must be considered even though the community has used it for generations.

    AIM: This study investigated Morus alba ethanolic leaf extract (MAE) to observe the acute toxicity in mice.

    METHODS: In particular, this study utilized 12 female Institute of Cancer Research mice, 8 weeks old, divided into 2 groups: the control group and the MAE group (2,000 mg/kg single dose). Physiology, hematology, biochemistry, and histology were analyzed during the study.

    RESULTS: The examination result indicated no mortality and behavioral changes throughout the testing period. However, the mice developed mild anemia and leukopenia, followed by decreased numbers of neutrophils, lymphocytes, and monocytes. In addition, the mice developed a mild hepatocellular injury, indicated by significant (p < 0.05) elevations of both alanine aminotransferase (ALT) and aspartate transaminase (AST). The histopathological findings of the liver were also consistent with the increment of ALT and AST, indicating mild hepatocellular necrosis through the eosinophilic cytoplasm and pyknosis (p > 0.05).

    CONCLUSION: It was evident that a single oral administration of MAE was not lethal for mice (LD50, which was higher than 2,000 mg/kg). However, the administration of high doses of MAE must be carefully considered.

    Matched MeSH terms: Mice, Inbred ICR*
  4. Ahmed, QU, Radhiyah I, Siti Zaiton MS
    MyJurnal
    Leaves of Thottea dependens have been used as folk medicine in Malaysia for the treatment of
    several conditions involving pain and inflammation with accompanying pyrexia. However, there is no scientific
    evidence for its effectiveness to treat fever. Hence, the purpose of this study was to evaluate the anti-pyretic
    activity of methanol (MeOH) and aqueous (Aq) extracts of T. dependens leaves in albino mice (ICR strain).
    Matched MeSH terms: Mice, Inbred ICR
  5. Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan FH, Sithambaram S, Mohamed Mustapha N, et al.
    Sci Prog, 2021 Oct;104(4):368504211004272.
    PMID: 34886737 DOI: 10.1177/00368504211004272
    Moringa oleifera (M. oleifera) Lam belongs to the family Moringaceae. It is an important multipurpose tree that is largely distributed globally and has been used almost in every aspect of traditional medicine for the treatment of various illnesses including cancers, diabetes mellitus, asthma, arthritis, etc. This study investigated the effects of oral acute and sub-acute administration of M. oleifera hydroethanolic leaf extract (MOHE) in ICR-mice. Its major phenolic compounds were also determined. Ten (10) female, 8-week old mice were grouped into control and treatment groups for acute toxicity study. A dose of 2000 mg/kg MOHE was given once to the treatment group via oral gavage. However, for the sub-acute toxicity study, 25 mice were grouped into groups A (control), B (125 mg/kg), C (250 mg/kg), D (500 mg/kg) and E (1000 mg/kg). MOHE was given via oral gavage to groups B, C, D and E daily for 28 days. Group A received only distilled water. The mice were sacrificed at the end of the experiments and samples were collected for evaluation. The results of the chemical profiling of MOHE revealed the presence of glucomoringin, niaziminine, quercetin and kaempferol as the major compounds. The treated mice in the acute toxicity study were slightly anaemic and showed evidence of stress leukogram. Moreover, a slight increase in creatinine, significant increases in AST and CK, hepatic degeneration and necrosis, none-obstructive sinusoidal dilatation, renal tubular necrosis, interstitial nephritis and renal interstitial oedema were observed. It is concluded that the LD50 of MOHE is higher than 2000 mg/kg. However, oral administration of MOHE causes acute mild anaemia and moderate hepato-nephrotoxicity in ICR-mice. Its major phenolic compounds are glucomoringin, niaziminine, quercetin and kaempferol.
    Matched MeSH terms: Mice, Inbred ICR
  6. Yap MK, Fung SY, Tan KY, Tan NH
    Acta Trop, 2014 May;133:15-25.
    PMID: 24508616 DOI: 10.1016/j.actatropica.2014.01.014
    The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A2, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A2, three neurotoxins (two long neurotoxins and a short neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6-27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A2 are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms.
    Matched MeSH terms: Mice, Inbred ICR
  7. Jusof WH, Khan NA, Rajikin MH, Satar NA, Mustafa MF, Jusoh N, et al.
    Int J Fertil Steril, 2015 07 27;9(2):221-9.
    PMID: 26246881
    BACKGROUND: Timing of the first zygotic cleavage is an accurate predictor of embryo quality. Embryos that cleaved early (EC) have been shown to exhibit higher develop- mental viability compared to those that cleaved at a later period (LC). However, the vi- ability of EC embryos in comparison to LC embryos after vitrification is unknown. The present study aims to investigate the post-vitrification developmental viability of murine EC versus LC embryos.

    MATERIALS AND METHODS: In this experimental study, female ICR mice (6-8 weeks old) were superovulated and cohabited with fertile males for 24 hours. Afterwards, their ovi- ducts were excised and embryos harvested. Embryos at the 2-cell stage were catego- rized as EC embryos, while zygotes with two pronuclei were categorized as LC embryos. Embryos were cultured in M16 medium supplemented with 3% bovine serum albumin (BSA) in a humidified 5% CO2atmosphere. Control embryos were cultured until the blastocyst stage without vitrification. Experimental embryos at the 2-cell stage were vitri- fied for one hour using 40% v/v ethylene glycol, 18% w/v Ficoll-70 and 0.5 M sucrose as the cryoprotectant. We recorded the numbers of surviving embryos from the control and experimental groups and their development until the blastocyst stage. Results were analyzed using the chi-square test.

    RESULTS: A significantly higher proportion of EC embryos (96.7%) from the control group developed to the blastocyst stage compared with LC embryos (57.5%, P<0.0001). Similarly, in the experimental group, a significantly higher percentage of vitrified EC embryos (69.4%) reached the blastocyst stage compared to vitrified LC embryos (27.1%, P<0.0001).

    CONCLUSION: Vitrified EC embryos are more vitrification tolerant than LC embryos. Prese- lection of EC embryos may be used as a tool for selection of embryos that exhibit higher developmental competence after vitrification.

    Matched MeSH terms: Mice, Inbred ICR
  8. Loong SK, Mahfodz NH, Wali HA, Talib SA, Nasrah SN, Wong PF, et al.
    J Vet Med Sci, 2016 May 3;78(4):715-7.
    PMID: 26782013 DOI: 10.1292/jvms.15-0472
    Accurate identification and separation of non-classical Bordetella species is very difficult. These species have been implicated in animal infections. B. hinzii, a non-classical Bordetella, has been isolated from mice in experimental facilities recently. We isolated and characterized one non-classical Bordetella isolate from the trachea and lung of an ICR mouse. Isolate BH370 was initially identified as B. hinzii by 16S ribosomal DNA and ompA sequencing. Additionally, isolate BH370 also displayed antimicrobial sensitivity profiles similar to B. hinzii. However, analyses of nrdA sequences determined its identity as Bordetella genogroup 16. The isolation of BH370 from a healthy mouse suggests the possibility of it being a commensal. The nrdA gene was demonstrated to possess greater phylogenetic resolution as compared with 16S ribosomal DNA and ompA for the discrimination of non-classical Bordetella species.
    Matched MeSH terms: Mice, Inbred ICR
  9. Chin VK, Chuah YK, Lee TY, Nordin N, Ibraheem ZO, Zakaria ZA, et al.
    Exp Parasitol, 2020 Sep;216:107946.
    PMID: 32622941 DOI: 10.1016/j.exppara.2020.107946
    This study was aimed at investigating the involvement of Receptor for Advanced Glycation End Products (RAGE) during malaria infection and the effects of modulating RAGE on the inflammatory cytokines release and histopathological conditions of affected organs in malarial animal model. Plasmodium berghei (P. berghei) ANKA-infected ICR mice were treated with mRAGE/pAb and rmRAGE/Fc Chimera drugs from day 1 to day 4 post infection. Survival and parasitaemia levels were monitored daily. On day 5 post infection, mice were sacrificed, blood were drawn for cytokines analysis and major organs including kidney, spleen, liver, brain and lungs were extracted for histopathological analysis. RAGE levels were increased systemically during malaria infection. Positive correlation between RAGE plasma concentration and parasitaemia development was observed. Treatment with RAGE related drugs did not improve survival of malaria-infected mice. However, significant reduction on the parasitaemia levels were recorded. On the other hand, inhibition and neutralization of RAGE production during the infection significantly increased the plasma levels of interleukin (IL-4, IL-17A, IL-10 and IL-2) and reduced interferon (IFN)-γ secretion. Histopathological analysis revealed that all treated malarial mice showed a better outcome in histological assessment of affected organs (brain, liver, spleen, lungs and kidney). RAGE is involved in malaria pathogenesis and targeting RAGE could be beneficial in malaria infected host in which RAGE inhibition or neutralization increased the release of anti-inflammatory cytokines (IL-10 and IL-4) and reduce pro-inflammatory cytokine (IFNγ) which may help alleviate tissue injury and improve histopathological conditions of affected organs during the infection.
    Matched MeSH terms: Mice, Inbred ICR
  10. Pandy V, Khan Y
    Exp Anim, 2016 Nov 1;65(4):437-445.
    PMID: 27333840
    Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings.
    Matched MeSH terms: Mice, Inbred ICR
  11. Omar Farouk FN, Stott D, Vlad M
    Anim Sci J, 2011 Jun;82(3):420-7.
    PMID: 21615835 DOI: 10.1111/j.1740-0929.2010.00869.x
    This study was conducted to examine the potential for implantation and sustainable fetal development of mouse embryos cultured from the pronuclear to blastocyst stage. Pronuclear embryos from ICR mice (Harlan Sprague-Dawley) were cultured in Sydney IVF sequential media (Cook) to the blastocyst stage in medium only or co-cultured with autologous cumulus cells. We also experimented with co-culture in 100 µL drops. Drop co-culture produced blastocyst formation rates with a mean of 47.0%, which was significantly higher (P < 0.05) compared to embryos cultured in identical culture conditions except without cumulus cells at 27.3%. Blastocysts obtained in vitro in Cook medium only and co-cultured in Cook medium with cumulus cells were transferred to pseudopregnant females of ICR strain. The day of blastocyst transfer into surrogate females was designated as post-transfer of blastocyst day 1 (PT 1). The implantation and fetal development was compared to embryo transfer of in vivo derived blastocysts, which served as controls. There were no statistical differences for implantation and fetal development rates for blastocysts cultured in vitro in either Cook medium only or co-culture in Cook medium with cumulus cells compared to in vivo-derived blastocysts. The advantage of the co-culture system is in generating more blastocysts available for transfer.
    Matched MeSH terms: Mice, Inbred ICR
  12. Tan CH, Tan NH, Sim SM, Fung SY, Jayalakshmi P, Gnanathasan CA
    Toxicon, 2012 Dec 1;60(7):1259-62.
    PMID: 22975088 DOI: 10.1016/j.toxicon.2012.08.012
    Mice experimentally envenomed with Hypnale hypnale venom (1× and 1.5×LD₅₀) developed acute kidney injury (AKI) principally characterized by raised blood urea and creatinine. Prolonged blood clotting time and hemorrhage in lungs implied bleeding tendency. Pallor noted in most renal cortices was suggestive of renal ischemia secondary to consumptive coagulopathy. Intravenous infusion of Hemato polyvalent antivenom following experimental envenoming effectively prevented death and AKI in all mice, supporting its potential therapeutic use in envenoming cases.
    Matched MeSH terms: Mice, Inbred ICR
  13. Chin, V.K., Chong, W.C., Hassan, H., Zakaria, Z.A., Nordin, N., Basir, R., et al.
    JUMMEC, 2019;22(2):4-12.
    MyJurnal
    Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied.
    However, their specific association with survival and severe infection remained obscure.

    Methods: The study investigated the cytokine profiles and histopathological features of malaria in the severe
    infection and survival models by using male ICR mice and male Sprague Dawley rats respectively.

    Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after
    peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed
    mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar
    histopathological severity during peak parasitemia. The severe model produced highly elevated levels of proinflammatory
    cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the
    survival model showed low levels of TNF-α and IL-1α with high levels of IL-4.

    Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection.
    These could be a basis for immunotherapy of malaria in the future.
    Matched MeSH terms: Mice, Inbred ICR
  14. Muhammad-Azam F, Nur-Fazila SH, Ain-Fatin R, Mustapha Noordin M, Yimer N
    Vet World, 2019 Nov;12(11):1682-1688.
    PMID: 32009746 DOI: 10.14202/vetworld.2019.1682-1688
    Background and Aim: Laboratory mice are widely used as a research model to provide insights into toxicological studies of various xenobiotic. Acetaminophen (APAP) is an antipyretic and analgesic drug that is commonly known as paracetamol, an ideal hepatotoxicant to exhibit centrilobular necrosis in laboratory mice to resemble humans. However, assessment of histopathological changes between mouse strains is important to decide the optimal mouse model used in APAP toxicity study. Therefore, we aim to assess the histomorphological features of APAP-induced liver injury (AILI) in BALB/C and Institute of Cancer Research (ICR) mice.

    Materials and Methods: Twenty-five ICR mice and 20 BALB/C mice were used where five animals as control and the rest were randomly divided into four time points at 5, 10, 24 and 48 hours post-dosing (hpd). They were induced with 500 mg/kg APAP intraperitoneally. Liver sections were processed for hematoxylin-eosin staining and histopathological changes were scored based on grading methods.

    Results: Intense centrilobular damage was observed as early as 5 hpd in BALB/C as compared to ICR mice, which was observed at 10 hpd. The difference of liver injury between ICR and BALB/C mice is due to dissimilarity in the genetic line-up that related to different elimination pathways of APAP toxicity. However, at 24 hpd, the damage was markedly subsided and liver regeneration had taken place for both ICR and BALB/C groups with evidence of mitotic figures. This study showed that normal liver architecture was restored after the clearance of toxic insult.

    Conclusion: AILI was exhibited earlier in BALB/C than ICR mice but both underwent liver recovery at later time points.

    Matched MeSH terms: Mice, Inbred ICR
  15. Huang YH, Lee MT, Hsueh HY, Knutson DE, Cook J, Mihovilovic MD, et al.
    Neurotherapeutics, 2023 Mar;20(2):399-418.
    PMID: 36696034 DOI: 10.1007/s13311-023-01342-y
    Ethanol has been shown to suppress essential tremor (ET) in patients at low-to-moderate doses, but its mechanism(s) of action remain unknown. One of the ET hypotheses attributes the ET tremorgenesis to the over-activated firing of inferior olivary neurons, causing synchronic rhythmic firings of cerebellar Purkinje cells. Purkinje cells, however, also receive excitatory inputs from granule cells where the α6 subunit-containing GABAA receptors (α6GABAARs) are abundantly expressed. Since ethanol is a positive allosteric modulator (PAM) of α6GABAARs, such action may mediate its anti-tremor effect. Employing the harmaline-induced ET model in male ICR mice, we evaluated the possible anti-tremor effects of ethanol and α6GABAAR-selective pyrazoloquinolinone PAMs. The burrowing activity, an indicator of well-being in rodents, was measured concurrently. Ethanol significantly and dose-dependently attenuated action tremor at non-sedative doses (0.4-2.4 g/kg, i.p.). Propranolol and α6GABAAR-selective pyrazoloquinolinones also significantly suppressed tremor activity. Neither ethanol nor propranolol, but only pyrazoloquinolinones, restored burrowing activity in harmaline-treated mice. Importantly, intra-cerebellar micro-injection of furosemide (an α6GABAAR antagonist) had a trend of blocking the effect of pyrazoloquinolinone Compound 6 or ethanol on harmaline-induced tremor. In addition, the anti-tremor effects of Compound 6 and ethanol were synergistic. These results suggest that low doses of ethanol and α6GABAAR-selective PAMs can attenuate action tremor, at least partially by modulating cerebellar α6GABAARs. Thus, α6GABAARs are potential therapeutic targets for ET, and α6GABAAR-selective PAMs may be a potential mono- or add-on therapy.
    Matched MeSH terms: Mice, Inbred ICR
  16. Tay ST, Rohani MY, Ho TM, Devi S
    PMID: 12693592
    The pathogenicity of Malaysian isolates of Orientia tsutsugamushi was investigated by a mouse virulence assay. The isolates could be differentiated as low (4 isolates), moderately (3 isolates) and highly virulent (2 isolates) based on the different responses in infected mice. No direct correlation between severity of human scrub typhus infections and virulence of the O. tsutsugamushi in mice was observed. Mice infected with virulent strains of O. tsutsugamushi showed splenomegaly, ascitis accumulation and enlargement of kidneys and livers whereas avirulent O. tsutsugamushi strains were asymptomatic and exhibited ruffled fur for a short period after infection. There was low antibody response in mice infected with isolates of low pathogenicity as compared with those of highly virulent isolates. Upon dissection of the infected mice, enlargement of mouse organs such as spleen, kidney and liver was noted. Presence of rickettsemia in mice was confirmed by the growth of O. tsutsugamushi in the L929 cells when inoculated with blood from infected mice. O. tsutsugamushi was also cultured from the peritoneal exudates of the infected mice. However, DNA of O. tsutsugamushi was only detected in the peritoneal exudates (by PCR) and blood (by cell culture) and not from other tissue samples.
    Matched MeSH terms: Mice, Inbred ICR
  17. Suresh K, Mak JW, Yong HS
    PMID: 1818401
    Matched MeSH terms: Mice, Inbred ICR/blood; Mice, Inbred ICR/immunology*
  18. Gopalsamy B, Sambasevam Y, Zulazmi NA, Chia JSM, Omar Farouk AA, Sulaiman MR, et al.
    Neurochem Res, 2019 Sep;44(9):2123-2138.
    PMID: 31376053 DOI: 10.1007/s11064-019-02850-0
    Number of ligations made in the chronic constriction injury (CCI) neuropathic pain model has raised serious concerns. We compared behavioural responses, nerve morphology and expression of pain marker, c-fos among CCI models developed with one, two, three and four ligations. The numbers of ligation(s) on sciatic nerve shows no significant difference in displaying mechanical and cold allodynia, and mechanical and thermal hyperalgesia throughout 84 days. All groups underwent similar levels of nerve degeneration post-surgery. Similar c-fos level in brain cingulate cortex, parafascicular nuclei and amygdala were observed in all CCI models compared to sham-operated group. Therefore, number of ligations does not impact intensity of pain symptoms, pathogenesis and neuronal activation. A single ligation is sufficient to develop neuropathic pain, in contrast to the established model of four ligations. This study dissects and characterises the CCI model, ascertaining a more uniform animal model to surrogate actual neuropathic pain condition.
    Matched MeSH terms: Mice, Inbred ICR*
  19. Sani MH, Taher M, Susanti D, Kek TL, Salleh MZ, Zakaria ZA
    Biol Res Nurs, 2015 Jan;17(1):68-77.
    PMID: 25504952 DOI: 10.1177/1099800414529648
    Elucidate the antinociceptive mechanisms of α-mangostin isolated from Garcinia malaccensis Linn.
    Matched MeSH terms: Mice, Inbred ICR
  20. Tan CH, Tan NH, Tan KY, Kwong KO
    Toxins (Basel), 2015 Feb;7(2):572-81.
    PMID: 25690691 DOI: 10.3390/toxins7020572
    Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa) and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii) are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV). NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking). The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4%) and H. curtus (70.4%). These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.
    Matched MeSH terms: Mice, Inbred ICR
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