Displaying publications 1 - 20 of 23 in total

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  1. Pathologic activity of Plasmodium berghei prevented but not reversed by dexamethasone
    Franz DR, Lim TS, Baze WB, Arimbalam S, Lee M, Lewis GE
    Am J Trop Med Hyg, 1988 Mar;38(2):249-54.
    PMID: 3281490
    Dexamethasone has recently been shown to block the production of cachectin (implicated in the pathogenesis of cerebral malaria) if administered prior to endotoxin induction of mouse macrophages. Using the hamster cheek pouch-cerebral malaria model, we tested the hypothesis that dexamethasone is effective as a therapeutic agent in severe malaria if given before some yet undefined trigger point in the disease. Infected hamsters were treated with dexamethasone (0.7 mg/kg) daily on days 7-12, 4-12, or 1-12 post-challenge. When treatment was started on day 1, whole body oxygen consumption (used as a measure of erythrocyte transport to sites of diffusion) on day 12 was greater than (P less than 0.05) that of infected control animals, though the degree of anemia was no different in treated and untreated groups. Furthermore, treatment produced a reduction in monocyte accumulation, capillary malfunction, and monocyte/red blood cell aggregate formation observable in the cheek pouch in vivo and a similar reduction in monocyte presence, capillary pathologic change, and multifocal hemorrhage in the brain on postmortem. These data suggest that mediator(s), whose production can be blocked by pretreatment with dexamethasone, are involved in the pathogenesis of disease leading to death of the Plasmodium berghei infected hamster.
    Matched MeSH terms: Mesocricetus
  2. Lipidaemic effects of tocotrienols, tocopherols and squalene: studies in the hamster
    Khor HT, Chieng DY
    Asia Pac J Clin Nutr, 1997 Mar;6(1):36-40.
    PMID: 24394651
    Syrian Golden hamsters have been widely used as a experimental model for the investigation of the aetiology and development of atherosclerosis and cardiovascular disease. The responses of the hamster to dietary fat manipulations are in many ways similar to that observed in humans. The lipidaemic effect of a tocotrienol rich fraction (TRF) from palm oil on human trials has not been consistent. In this study, the cholesterolaemic effect of tocotrienols and tocopherols were differentiated by using pure tocotrienols (that were isolated from palm oil fatty acid distillate) and pure commercial tocopherols and squalene. A palm oil triacylglycerol fraction (POTG), free of all unsaponifiable matter, was used as the dietary fat in different feeding experiments. Tocotrienols added at 162 ppm to POTG (POTG-T3L) significantly (p<0.05) lowered serum total cholesterol (TC) level as compared to that of the POTG group; but the serum LDL-C , HDL-C and TG levels of the POTG-T3L group were not significantly lower than that of the POTG group (P>0.05). Increasing the level of tocotrienol supplementation to the diet (POTG-T3H) appeared to raise rather then reduce the serum TC, LDL-C and HDL-C levels as compared to that of POTG-T3L group. This observation that lower level of tocotrienol supplementation appeared to exhibit stronger hypocholesterolaemic effect than a higher level of tocotrienol supplementation is interesting; but its explanation is not yet forthcoming. When tocopherols were supplemented at 72 ppm to the POTG diet it was observed that the serum TC, LDL-C and HDL-C levels were all somewhat increased when compared to that of the POTG group. These results suggest that tocotrienols and tocopherols may have opposite cholesterolaemic effects in the hamster, and further experiments need to clarify the mode of action of these vitamin E isomers. In our second series of experiments the cholesterolaemic effects of tocotrienols and tocopherols were studied in the presence of squalene, a key intermediate in the cholesterol synthesis pathway and a controversial cholesterol lowering agent. Squalene added to the diet at 0.1% level significantly lowered (p<0.05) serum TC level when compared to that of the POTG group. The LDL-C, HDL-C and TG levels appeared to be lowered by the squalene supplementation also but the differences between the POTG-SQ and POTG groups were not statistically significant (P>0.05). When tocotrienols or tocopherols were added to the squalene-containing POTG diets, the serum TC and LDL-C levels were further reduced (p<0.01) when compared to that of the POTG and POTG-SQ groups. The HDL-C and TG levels were not affected by tocotrienol or tocopherol supplementation in the presence of squalene. These results indicate that in the presence of tocotrienols and squalene POTG exhibit hypocholesterolaemic action whereas tocopherols may have a hypercholesterolaemic effect in the hamster.
    Matched MeSH terms: Mesocricetus
  3. Effects of administration of alpha-tocopherol and tocotrienols on serum lipids and liver HMG CoA reductase activity
    Khor HT, Ng TT
    Int J Food Sci Nutr, 2000;51 Suppl:S3-11.
    PMID: 11271854
    Male hamsters were fed on semi-synthetic diets containing commercial corn oil (CO), isolated corn oil triglycerides (COTG), COTG supplemented with 30 ppm of alpha-tocopherol (COTGTL) and COTG supplemented with 81 ppm of alpha-tocopherol (COTGTH) as the dietary lipid for 45 days. Male albino guinea pigs were fed on commercial chow pellets and treated with different dosages of tocopherol and tocotrienols intra-peritoneally for 6 consecutive days. Serum and liver were taken for analysis. Our results show that stripping corn oil of its unsaponifiable components resulted in COTG which yielded lower serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and raised high-density lipoprotein cholesterol (HDL-C) and serum triglycerides (TG) levels. These results indicate that the COTG with its fatty acids are responsible for the hypocholesterolemic effect exhibited by corn oil. However, supplementing the COTG diet with alpha-tocopherol (alpha-T) at 30 ppm significantly raised the serum TC, LDL-C and TG levels, but did not alter the HDL-C level, indicating that alpha-T is hypercholesterolemic. Supplementing the COTG diet with alpha-T at 81 ppm raised the serum TC level but to a lesser extent as compared to that obtained with 30-ppm alpha-T supplementation. The increased TC, in this case, was reflected mainly by an increased in HDL-C level as the LDL-C level was unchanged. The TG level was also raised but to a lesser extent than that obtained with a lower alpha-T supplementation. The liver HMG CoA reductase (HMGCR) activity was exhibited (56%) by the COTG as compared to CO. Supplementation of alpha-T at 30 ppm to the COTG diet resulted in further inhibition (76%) of the liver HMGCR activity. On the contrary, supplementation of alpha-T at 81 ppm to COTG diet resulted in a highly stimulatory effect (131%) on the liver HMGCR activity. Short-term studies with guinea pigs treated intra-peritoneally with alpha-T showed that at low dosage (5 mg) the HMGCR activity was inhibited by 46% whereas increasing the dosage of alpha-T to 20 mg yielded lesser inhibition (18%) as compared to that of the control. Further increase in the dosage of alpha-T to 50 mg actually resulted in 90% stimulation of the liver HMGCR activity as compared to the control. These results clearly indicate that the effect of alpha-T on HMGCR activity was dose-dependent. Treatment of the guinea pigs with 10 mg of tocotrienols (T3) resulted in 48% inhibition of the liver HMGCR activity. However, treatment with a mixture of 5 mg of alpha-T with 10 mg of T3 resulted in lesser inhibition (13%) of the liver HMGCR activity as compared to that obtained with 10 mg of T3. The above results indicate that the alpha-T is hypercholesterolemic in the hamster and its effect on liver HMGCR is dose-dependent. T3 exhibited inhibitory effect on liver HMGCR and alpha-T attenuated the inhibitory effect of T3 on liver HMGCR.
    Matched MeSH terms: Mesocricetus
  4. 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: Mesocricetus*
  5. Specific detection of Nipah virus using real-time RT-PCR (TaqMan)
    Guillaume V, Lefeuvre A, Faure C, Marianneau P, Buckland R, Lam SK, et al.
    J Virol Methods, 2004 Sep 15;120(2):229-37.
    PMID: 15288966
    Nipah and Hendra viruses belong to the novel Henipavirus genus of the Paramyxoviridae family. Its zoonotic circulation in bats and recent emergence in Malaysia with fatal consequences for humans that were in close contact with infected pigs, has made the reinforcement of epidemiological and clinical surveillance systems a priority. In this study, TaqMan RT-PCR of the Nipah nucleoprotein has been developed so that Nipah virus RNA in field specimens or laboratory material can be characterized rapidly and specifically and quantitated. The linearity of the standard curve allowed quantification of 10(3) to 10(9) RNA transcripts. The sensitivity of the test was close to 1 pfu. The kinetics of Nipah virus production in Vero cells was monitored by the determination of infectious virus particles in the supernatant fluid and by quantitation of the viral RNA. Approximately, 1000 RNA molecules were detected per virion, suggesting the presence of many non-infectious particles, similar to other RNA viruses. TaqMan real-time RT-PCR failed to detect Hendra virus DNA. Importantly, the method was able to detect virus despite a similar ratio in viremic sera from hamsters infected with Nipah virus. This standardized technique is sensitive and reliable and allows rapid detection and quantitation of Nipah RNA in both field and experimental materials used for the surveillance and specific diagnosis of Nipah virus.
    Matched MeSH terms: Mesocricetus
  6. Fulltext Rapid detection of pathogenic leptospires by lyophilized reagent-based polymerase chain reaction
    Lee SV, Tai ES, Mutalib AR, Khairani-Bejo S, Bahaman AR
    Trop Biomed, 2011 Dec;28(3):497-505.
    PMID: 22433877 MyJurnal
    A simple and reliable tool for the early diagnosis of leptospirosis is urgently needed. We report the development of a lyophilized reagent-based polymerase chain reaction (PCR) assay targeting lipL32 gene, which is present only in pathogenic leptospires. To determine the effectiveness of the newly developed assay in the early diagnosis of leptospirosis, the sensitivity and specificity was evaluated. In simulated clinical samples, the assay was able to detect 10² and 10³ leptospires/ml in spiked urine and blood samples, respectively. In experimentally infected animals, leptospiral DNA could be detected in blood and lung samples as early as Day 1 post infection. This assay was also shown to be stable and remained sensitive for up to five months at ambient temperature. Hence, this lyophilized reagent-based PCR assay with high specificity, sensitivity and stability would provide a simple, rapid and reliable method in diagnosing acute leptospirosis, especially in the field of veterinary medicine.
    Matched MeSH terms: Mesocricetus
  7. Fulltext Detection of Entamoeba histolytica in experimentally induced amoebic liver abscess: comparison of three staining methods
    Ning TZ, Kin WW, Mustafa S, Ahmed A, Noordin R, Cheong TG, et al.
    Asian Pac J Trop Biomed, 2012 Jan;2(1):61-5.
    PMID: 23569836 DOI: 10.1016/S2221-1691(11)60191-3
    To compare the efficacy of three different tissue stains, namely haematoxylin and eosin (H&E), periodic-acid Schiff (PAS) and immunohistochemical (IHC) stains for detection of Entamoeba histolytica (E. histolytica) trophozoites in abscessed liver tissues of hamster.
    Matched MeSH terms: Mesocricetus
  8. Fulltext Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters
    Ch'ng WC, Stanbridge EJ, Wong KT, Ong KC, Yusoff K, Shafee N
    Virol J, 2012;9:155.
    PMID: 22877087 DOI: 10.1186/1743-422X-9-155
    Enterovirus 71 (EV71) causes severe neurological diseases resulting in high mortality in young children worldwide. Development of an effective vaccine against EV71 infection is hampered by the lack of appropriate animal models for efficacy testing of candidate vaccines. Previously, we have successfully tested the immunogenicity and protectiveness of a candidate EV71 vaccine, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP11-100) protein, in a mouse model of EV71 infection. A drawback of this system is its limited window of EV71 susceptibility period, 2 weeks after birth, leading to restricted options in the evaluation of optimal dosing regimens. To address this issue, we have assessed the NPt-VP11-100 candidate vaccine in a hamster system, which offers a 4-week susceptibility period to EV71 infection. Results obtained showed that the NPt-VP11-100 candidate vaccine stimulated excellent humoral immune response in the hamsters. Despite the high level of antibody production, they failed to neutralize EV71 viruses or protect vaccinated hamsters in viral challenge studies. Nevertheless, these findings have contributed towards a better understanding of the NPt-VP11-100 recombinant protein as a candidate vaccine in an alternative animal model system.
    Matched MeSH terms: Mesocricetus
  9. Entamoeba histolytica antigenic protein detected in pus aspirates from patients with amoebic liver abscess
    Othman N, Mohamed Z, Yahya MM, Leow VM, Lim BH, Noordin R
    Exp Parasitol, 2013 Aug;134(4):504-10.
    PMID: 23680184 DOI: 10.1016/j.exppara.2013.05.001
    Entamoeba histolytica is a causative agent of amoebic liver abscess (ALA) and is endemic in many underdeveloped countries. We investigated antigenic E. histolytica proteins in liver abscess aspirates using proteomics approach. Pus samples were first tested by real-time PCR to confirm the presence of E. histolytica DNA and the corresponding serum samples tested for E. histolytica-specific IgG by a commercial ELISA. Proteins were extracted from three and one pool(s) of pus samples from ALA and PLA (pyogenic liver abscess) patients respectively, followed by analysis using isoelectric focussing, SDS-PAGE and Western blot. Unpurified pooled serum samples from infected hamsters and pooled human amoebic-specific IgG were used as primary antibodies. The antigenic protein band was excised from the gel, digested and analysed by MALDI-TOF/TOF and LC-MS/MS. The results using both primary antibodies showed an antigenic protein band of ∼14kDa. Based on the mass spectrum analysis, putative tyrosine kinase is the most probable identification of the antigenic band.
    Matched MeSH terms: Mesocricetus
  10. Fulltext Comparison of the pathogenicity of Nipah virus isolates from Bangladesh and Malaysia in the Syrian hamster
    DeBuysscher BL, de Wit E, Munster VJ, Scott D, Feldmann H, Prescott J
    PLoS Negl Trop Dis, 2013;7(1):e2024.
    PMID: 23342177 DOI: 10.1371/journal.pntd.0002024
    Nipah virus is a zoonotic pathogen that causes severe disease in humans. The mechanisms of pathogenesis are not well described. The first Nipah virus outbreak occurred in Malaysia, where human disease had a strong neurological component. Subsequent outbreaks have occurred in Bangladesh and India and transmission and disease processes in these outbreaks appear to be different from those of the Malaysian outbreak. Until this point, virtually all Nipah virus studies in vitro and in vivo, including vaccine and pathogenesis studies, have utilized a virus isolate from the original Malaysian outbreak (NiV-M). To investigate potential differences between NiV-M and a Nipah virus isolate from Bangladesh (NiV-B), we compared NiV-M and NiV-B infection in vitro and in vivo. In hamster kidney cells, NiV-M-infection resulted in extensive syncytia formation and cytopathic effects, whereas NiV-B-infection resulted in little to no morphological changes. In vivo, NiV-M-infected Syrian hamsters had accelerated virus replication, pathology and death when compared to NiV-B-infected animals. NiV-M infection also resulted in the activation of host immune response genes at an earlier time point. Pathogenicity was not only a result of direct effects of virus replication, but likely also had an immunopathogenic component. The differences observed between NiV-M and NiV-B pathogeneis in hamsters may relate to differences observed in human cases. Characterization of the hamster model for NiV-B infection allows for further research of the strain of Nipah virus responsible for the more recent outbreaks in humans. This model can be used to study NiV-B pathogenesis, transmission, and countermeasures that could be used to control outbreaks.
    Matched MeSH terms: Mesocricetus
  11. Fulltext Single-dose live-attenuated Nipah virus vaccines confer complete protection by eliciting antibodies directed against surface glycoproteins
    DeBuysscher BL, Scott D, Marzi A, Prescott J, Feldmann H
    Vaccine, 2014 May 07;32(22):2637-44.
    PMID: 24631094 DOI: 10.1016/j.vaccine.2014.02.087
    BACKGROUND: Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks.

    METHODS: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies.

    RESULTS: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection.

    CONCLUSIONS: The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management.

    Matched MeSH terms: Mesocricetus/blood
  12. Fulltext Syrian hamsters (Mesocricetus auratus) oronasally inoculated with a Nipah virus isolate from Bangladesh or Malaysia develop similar respiratory tract lesions
    Baseler L, de Wit E, Scott DP, Munster VJ, Feldmann H
    Vet Pathol, 2015 Jan;52(1):38-45.
    PMID: 25352203 DOI: 10.1177/0300985814556189
    Nipah virus is a paramyxovirus in the genus Henipavirus, which has caused outbreaks in humans in Malaysia, India, Singapore, and Bangladesh. Whereas the human cases in Malaysia were characterized mainly by neurological symptoms and a case fatality rate of ∼40%, cases in Bangladesh also exhibited respiratory disease and had a case fatality rate of ∼70%. Here, we compared the histopathologic changes in the respiratory tract of Syrian hamsters, a well-established small animal disease model for Nipah virus, inoculated oronasally with Nipah virus isolates from human cases in Malaysia and Bangladesh. The Nipah virus isolate from Bangladesh caused slightly more severe rhinitis and bronchointerstitial pneumonia 2 days after inoculation in Syrian hamsters. By day 4, differences in lesion severity could no longer be detected. Immunohistochemistry demonstrated Nipah virus antigen in the nasal cavity and pulmonary lesions; the amount of Nipah virus antigen present correlated with lesion severity. Immunohistochemistry indicated that both Nipah virus isolates exhibited endotheliotropism in small- and medium-caliber arteries and arterioles, but not in veins, in the lung. This correlated with the location of ephrin B2, the main receptor for Nipah virus, in the vasculature. In conclusion, Nipah virus isolates from outbreaks in Malaysia and Bangladesh caused a similar type and severity of respiratory tract lesions in Syrian hamsters, suggesting that the differences in human disease reported in the outbreaks in Malaysia and Bangladesh are unlikely to have been caused by intrinsic differences in these 2 virus isolates.
    Matched MeSH terms: Mesocricetus
  13. Fulltext Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters
    Baseler L, Scott DP, Saturday G, Horne E, Rosenke R, Thomas T, et al.
    PLoS Negl Trop Dis, 2016 Nov;10(11):e0005120.
    PMID: 27812087 DOI: 10.1371/journal.pntd.0005120
    BACKGROUND: Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B).

    METHODOLOGY/PRINCIPAL FINDINGS: Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi.

    CONCLUSIONS/SIGNIFICANCE: Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.

    Matched MeSH terms: Mesocricetus
  14. Gramine inhibits angiogenesis and induces apoptosis via modulation of TGF-β signalling in 7,12 dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinoma
    Ramu A, Kathiresan S, Ali Ahmed B
    Phytomedicine, 2017 Sep 15;33:69-76.
    PMID: 28887922 DOI: 10.1016/j.phymed.2017.05.008
    BACKGROUND: Transforming growth factor-β (TGF-β) and its receptors are considered as a novel target in cancer chemotherapy. Gramine, an indole alkaloid, possesses various pharmacological properties including antiproliferative and anticancer. However, the anti-angiogenic property remains unexplored.

    PURPOSE: The present study was designed to evaluate the anti-angiogenic and apoptosis induction properties of gramine through inhibiting TGF-β on DMBA induced oral squamous cell carcinoma (OSCC) in the hamster buccal pouch (HBP).

    METHODS: The effects of gramine on TGF-β signalling in DMBA induced carcinogenic events such as angiogenesis and apoptosis were analysed by studying the mRNA expression using RT-PCR, protein expression by western blot and histopathological analysis using haematoxylin and eosin (H & E) staining.

    RESULTS: Gramine significantly inhibited phosphorylation and nuclear translocation of Smad2 and Smad4 by blocking activity of the TGFβ-RII, RI and activation of inhibitory Smad7. Gramine inhibited angiogenic markers such as MMP-2, MMP-9, HIF-1α, VEGF, and VEGF-R2 as well as increased TIMP-2 expression. Furthermore, gramine induced apoptosis in DMBA induced tumour bearing animals by up regulating the pro apoptotic proteins Bax, cytochrome C, apaf-1, caspase-9 caspase-3 and PARP.

    CONCLUSION: In this study, we clearly demonstrated that gramine treatment diminishes angiogenesis and induces apoptosis in hamster buccal pouch (HBP) carcinogenesis by modulating TGF-β signals.

    Matched MeSH terms: Mesocricetus
  15. Fulltext A VLP-based vaccine provides complete protection against Nipah virus challenge following multiple-dose or single-dose vaccination schedules in a hamster model
    Walpita P, Cong Y, Jahrling PB, Rojas O, Postnikova E, Yu S, et al.
    NPJ Vaccines, 2017;2:21.
    PMID: 29263876 DOI: 10.1038/s41541-017-0023-7
    Nipah virus is a highly lethal zoonotic paramyxovirus that was first recognized in Malaysia during an outbreak in 1998. During this outbreak, Nipah virus infection caused a severe febrile neurological disease in humans who worked in close contact with infected pigs. The case fatality rate in humans was approximately 40%. Since 2001, NiV has re-emerged in Bangladesh and India where fruit bats (Pteropus spp.) have been identified as the principal reservoir of the virus. Transmission to humans is considered to be bat-to-human via food contaminated with bat saliva, or consumption of contaminated raw date palm sap, although human-to-human transmission of Nipah virus has also been documented. To date, there are no approved prophylactic options or treatment for NiV infection. In this study, we produced mammalian cell-derived native Nipah virus-like particles composed of Nipah virus G, F and M proteins for use as a novel Nipah virus vaccine. Previous studies demonstrated that the virus-like particles were structurally similar to authentic virus, functionally assembled and immunoreactive. In the studies reported here, purified Nipah virus-like particles were utilized either alone or with adjuvant to vaccinate golden Syrian hamsters with either three-dose or one-dose vaccination regimens followed by virus challenge. These studies found that Nipah virus-like particle immunization of hamsters induced significant neutralizing antibody titers and provided complete protection to all vaccinated animals following either single or three-dose vaccine schedules. These studies prove the feasibility of a virus-like particle-based vaccine for protection against Nipah virus infection.
    Matched MeSH terms: Mesocricetus
  16. Fulltext Experimental Infection of Syrian Hamsters With Aerosolized Nipah Virus
    Escaffre O, Hill T, Ikegami T, Juelich TL, Smith JK, Zhang L, et al.
    J Infect Dis, 2018 10 05;218(10):1602-1610.
    PMID: 29912426 DOI: 10.1093/infdis/jiy357
    Background: Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that can cause severe respiratory illness and encephalitis in humans. Transmission occurs through consumption of NiV-contaminated foods, and contact with NiV-infected animals or human body fluids. However, it is unclear whether aerosols derived from aforesaid sources or others also contribute to transmission, and current knowledge on NiV-induced pathogenicity after small-particle aerosol exposure is still limited.

    Methods: Infectivity, pathogenicity, and real-time dissemination of aerosolized NiV in Syrian hamsters was evaluated using NiV-Malaysia (NiV-M) and/or its recombinant expressing firefly luciferase (rNiV-FlucNP).

    Results: Both viruses had an equivalent pathogenicity in hamsters, which developed respiratory and neurological symptoms of disease, similar to using intranasal route, with no direct correlations to the dose. We showed that virus replication was predominantly initiated in the lower respiratory tract and, although delayed, also intensely in the oronasal cavity and possibly the brain, with gradual increase of signal in these regions until at least day 5-6 postinfection.

    Conclusion: Hamsters infected with small-particle aerosolized NiV undergo similar clinical manifestations of the disease as previously described using liquid inoculum, and exhibit histopathological lesions consistent with NiV patient reports. NiV droplets could therefore play a role in transmission by close contact.

    Matched MeSH terms: Mesocricetus
  17. Antigenic potential of a recombinant polyvalent DNA vaccine against pathogenic leptospiral infection
    Garba B, Bahaman AR, Zakaria Z, Bejo SK, Mutalib AR, Bande F, et al.
    Microb Pathog, 2018 Nov;124:136-144.
    PMID: 30138761 DOI: 10.1016/j.micpath.2018.08.028
    Leptospirosis is a serious epidemic disease caused by pathogenic Leptospira species. The disease is endemic in most tropical and sub-tropical regions of the world. Currently, there is no effective polyvalent vaccine for prevention against most of the circulating serovars. Moreover, development of an efficient leptospiral vaccine capable of stimulating cross-protective immune responses against a wide range of serovars remains a daunting challenge. This, in part, is associated with the extensive diversity and variation of leptospiral serovars from region to region. In this study, a multi-epitope DNA vaccine encoding highly immunogenic epitopes from LipL32 and LipL41 was designed using in-silico approach. The DNA encoding antigenic epitopes was constructed from conserved pathogenic Leptospira genes (LipL32 and LipL41). Immunization of golden Syrian hamsters with the multi-epitope chimeric DNA vaccine resulted in the production of both agglutinating and neutralizing antibodies as evidence by MAT and in-vitro growth inhibition tests respectively. The antibodies produced reacted against eight different serovars and significantly reduced renal colonization following in vivo challenge. The vaccine was also able to significantly reduce renal colonization which is a very important factor responsible for persistence of leptospires among susceptible and reservoir animal hosts. In conclusion, the leptospiral multi-epitope chimeric DNA vaccine can serve as a potentially effective and safe vaccine against infection with different pathogenic leptospiral serovars.
    Matched MeSH terms: Mesocricetus
  18. The hypolipidemic effects of Tamarindus indica fruit pulp extract in normal and diet-induced hypercholesterolemic hamsters are associated with altered levels of serum proteins
    Lim CY, Junit SM, Aziz AA, Jayapalan JJ, Hashim OH
    Electrophoresis, 2018 12;39(23):2965-2973.
    PMID: 30280388 DOI: 10.1002/elps.201800258
    The hypolipidemic effects of Tamarindus indica fruit pulp extract (Ti-FPE) have been earlier reported but the underlying molecular mechanisms are still uncertain. In this study, hamsters fed with Ti-FPE, both in the absence and presence of high-cholesterol diet, were shown to have significantly reduced levels of serum triglyceride, LDL-C and total cholesterol. The Ti-FPE-fed non-hypercholesterolemic hamsters also showed significant enhanced levels of serum apolipoprotein A1, antithrombin III, transferrin and vitamin D binding protein. In diet-induced hypercholesterolemic hamsters, apolipoprotein A1, antithrombin III and transferrin, which were relatively low in levels, became significantly enhanced when the hamsters were fed with Ti-FPE. These Ti-FPE-fed hypercholesterolemic hamsters also showed significant higher levels of serum vitamin D binding protein. When the different treated groups of hamsters were analyzed for the levels of the four serum proteins by ELISA, similar altered abundance were detected. Ingenuity Pathway Analysis of the Ti-FPE modulated serum proteins singled out "Lipid metabolism, molecular transport, small molecule biochemistry" as the top network. Our results suggest that the hypolipidemic effects of Ti-FPE are associated with alterations of serum proteins that are known to be cardioprotective and involved in the metabolism of lipids. The MS data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD010232.
    Matched MeSH terms: Mesocricetus
  19. Fulltext A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters
    van Doremalen N, Lambe T, Sebastian S, Bushmaker T, Fischer R, Feldmann F, et al.
    PLoS Negl Trop Dis, 2019 06;13(6):e0007462.
    PMID: 31170144 DOI: 10.1371/journal.pntd.0007462
    Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development.
    Matched MeSH terms: Mesocricetus
  20. Fulltext Establishment of an RNA polymerase II-driven reverse genetics system for Nipah virus strains from Malaysia and Bangladesh
    Griffin BD, Leung A, Chan M, Warner BM, Ranadheera C, Tierney K, et al.
    Sci Rep, 2019 08 01;9(1):11171.
    PMID: 31371748 DOI: 10.1038/s41598-019-47549-y
    Nipah virus (NiV) has emerged as a highly lethal zoonotic paramyxovirus that is capable of causing a febrile encephalitis and/or respiratory disease in humans for which no vaccines or licensed treatments are currently available. There are two genetically and geographically distinct lineages of NiV: NiV-Malaysia (NiV-M), the strain that caused the initial outbreak in Malaysia, and NiV-Bangladesh (NiV-B), the strain that has been implicated in subsequent outbreaks in India and Bangladesh. NiV-B appears to be both more lethal and have a greater propensity for person-to-person transmission than NiV-M. Here we describe the generation and characterization of stable RNA polymerase II-driven infectious cDNA clones of NiV-M and NiV-B. In vitro, reverse genetics-derived NiV-M and NiV-B were indistinguishable from a wildtype isolate of NiV-M, and both viruses were pathogenic in the Syrian hamster model of NiV infection. We also describe recombinant NiV-M and NiV-B with enhanced green fluorescent protein (EGFP) inserted between the G and L genes that enable rapid and sensitive detection of NiV infection in vitro. This panel of molecular clones will enable studies to investigate the virologic determinants of henipavirus pathogenesis, including the pathogenic differences between NiV-M and NiV-B, and the high-throughput screening of candidate therapeutics.
    Matched MeSH terms: Mesocricetus/virology
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