Displaying publications 81 - 100 of 339 in total

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  1. The improvement of in vivo model (Balb/c mice) for cervical carcinogenesis using diethylstilbestrol (DES)
    Zulfahmi S, Yazan LS, Ithnin H, Armania N
    Exp. Toxicol. Pathol., 2013 Nov;65(7-8):1083-9.
    PMID: 23726752 DOI: 10.1016/j.etp.2013.04.004
    Cervical cancer is the most common gynecological cancer and one of the major causes of female cancer-related death worldwide particularly in developing countries. Thus far, there are a few in vivo models have been developed in investigating this type of cancer. In this study, we induced cervical cancer in Balb/c mice by exploiting the carcinogenic property of diestylstilbestrol (DES). The Balb/c pregnant mice were given subcutaneous (SC) injection of 67μg/kg body weight of DES on GD 13, and the mice gave birth approximately at gestation day 19-22. Female offspring were reared and the body weight was recorded once weekly. The female offspring were sacrificed at age of 5 months. Upon termination, blood was collected in a plain tube via cardiac puncture and the reproductive tracts were collected and weighed. The reproductive tract sections were stained using H&E for observation of pathological changes. The progression of disease state was monitored by measuring the level of serum interleukin (IL-6) using the Mouse IL-6 ELISA Assay Kit (BD OptEIA™, USA). All parameters were compared with Not-induced group. The outcome of this study demonstrated a significant difference in body weight gain, reproductive organ weight, diameter of cervix and the level of serum IL-6 in the Induced group as compared to the Not-induced group (P<0.05). Histopathological findings revealed the presence of adenosis only in the Induced group. It shows that DES could be employed as an agent to induce cervical carcinogenesis in animal model. In addition to that, new potential anti-cancer agents from various sources could be further evaluated using this technique.
    Matched MeSH terms: Mice, Inbred BALB C
  2. Regression of cervical intraepithelial neoplasia by zerumbone in female Balb/c mice prenatally exposed to diethylstilboestrol: involvement of mitochondria-regulated apoptosis
    Abdelwahab SI, Abdul AB, Devi N, Taha MM, Al-zubairi AS, Mohan S, et al.
    Exp. Toxicol. Pathol., 2010 Sep;62(5):461-9.
    PMID: 19581075 DOI: 10.1016/j.etp.2009.06.005
    Cervical cancer is the second most common cause of cancer death in women. We have demonstrated previously that zerumbone (ZER) has an anti-cancer effect towards human cervical cancer cells (HeLa).
    Matched MeSH terms: Mice, Inbred BALB C
  3. Fulltext Oral supplementation of L-glutathione prevents ultraviolet B-induced melanogenesis and oxidative stress in BALB/c mice
    Nagapan TS, Lim WN, Basri DF, Ghazali AR
    Exp Anim, 2019 Nov 06;68(4):541-548.
    PMID: 31243189 DOI: 10.1538/expanim.19-0017
    Dietary antioxidant supplements such as L-glutathione have gained considerable attention in dermatology and cosmeceutical fields. L-glutathione possesses antiaging, antimelanogenic, antioxidant, and anticancer properties. This study aimed to investigate the inhibitory effects of L-glutathione on melanogenesis activity and oxidative stress in ultraviolet B (UVB)-irradiated BALB/c mice. Eighteen female BALB/c mice were randomly divided into 3 groups: a control group (n=6), a group without UVB irradiation and L-glutathione administration; a UVB irradiated group (n=6), a group irradiated with a UVB dose of 250 mJ/cm2 for 3 min; and a treatment group (n=6), a group irradiated with UVB and treated with 100 mg/kg of L-glutathione by oral gavage. Treatment was given for 14 days, and UVB irradiation was given on days 9, 11, and 13. Oral L-glutathione significantly (P<0.05) reduced lipid peroxidation and elevated superoxide dismutase activity the and glutathione level. L-glutathione also inhibited melanin content and tyrosinase activity significantly (P<0.05) as compared with the UVB-irradiated group. Histopathological examination also showed that L-glutathione reduced the deposition of melanin pigment in the basal layer of the epidermis as compared with that in UVB-irradiated mice. All in all, the present study demonstrated that L-glutathione has the potential to be developed as a photoprotection agent against UVB-induced oxidative stress and melanogenesis.
    Matched MeSH terms: Mice, Inbred BALB C
  4. Toxoplasma gondii: determination of the onset of chronic infection in mice and the in vitro reactivation of brain cysts
    Chew WK, Wah MJ, Ambu S, Segarra I
    Exp Parasitol, 2012 Jan;130(1):22-5.
    PMID: 22027550 DOI: 10.1016/j.exppara.2011.10.004
    Toxoplasma gondii is an intra-cellular parasite that infects humans through vertical and horizontal transmission. The cysts remain dormant in the brain of infected humans and can reactivate in immunocompromised hosts resulting in acute toxoplasmic encephalitis which may be fatal. We determined the onset and progression of brain cysts generation in a mouse model following acute toxoplasmosis as well as the ability of brain cysts to reactivate in vitro. Male Balb/c mice, (uninfected control group, n = 10) were infected orally (study group, n = 50) with 1000 tachyzoites of T. gondii (ME49 strain) and euthanized at 1, 2, 4, 8 and 16 weeks post infection. Brain tissue was harvested, homogenized, stained and the number of brain cysts counted. Aliquots of brain homogenate with cysts were cultured in vitro with confluent Vero cells and the number of cysts and tachyzoites counted after 1 week. Brain cysts but not tachyzoites were detected at week 2 post infection and reached a plateau by week 4. In vitro Vero cells culture showed similar pattern for cysts and tachyzoites and reactivation of cyst in vitro was not influenced by the age of the brain cysts.
    Matched MeSH terms: Mice, Inbred BALB C
  5. Production of a monoclonal antibody against a mannose-binding protein of Acanthamoeba culbertsoni and its localization
    Kang AY, Park AY, Shin HJ, Khan NA, Maciver SK, Jung SY
    Exp Parasitol, 2018 Sep;192:19-24.
    PMID: 30031120 DOI: 10.1016/j.exppara.2018.07.009
    Amoebae from the genus Acanthamoeba are facultative pathogens of humans and other animals. In humans they most frequently infect the eye causing a sight threatening infection known as Acanthamoeba keratitis (AK), and also cause an often fatal encephalitis (GAE). A mannose-binding protein (MBP) has been identified as being important for Acanthamoeba infection especially in AK. This lectin has previously been characterized from Acanthamoeba castellanii as consisting of multiple 130 kDa subunits. MBP expression correlates with pathogenic potential and is expressed in a number of Acanthamoeba species. Here we report the purification of a similar lectin from Acanthamoeba culbertsoni and the production of a monoclonal antibody to it. The A. culbertsoni MBP was isolated by affinity chromatography using α-D-mannose agarose and has an apparent molecular weight of 83 kDa. The monoclonal antibody is an IgM that is useful in both western blots and immunofluorescence. We expect that this antibody will be useful in the study of the pathology of A. culbertsoni and in its identification in clinical samples.
    Matched MeSH terms: Mice, Inbred BALB C
  6. A novel synthetic analogue of ω-3 17,18-epoxyeicosatetraenoic acid activates TNF receptor-1/ASK1/JNK signaling to promote apoptosis in human breast cancer cells
    Dyari HRE, Rawling T, Chen Y, Sudarmana W, Bourget K, Dwyer JM, et al.
    FASEB J, 2017 12;31(12):5246-5257.
    PMID: 28798154 DOI: 10.1096/fj.201700033R
    A saturated analog of the cytochrome P450-mediated ω-3-17,18-epoxide of ω-3-eicosapentaenoic acid (C20E) activated apoptosis in human triple-negative MDA-MB-231 breast cancer cells. This study evaluated the apoptotic mechanism of C20E. Increased cytosolic cytochrome c expression and altered expression of pro- and antiapoptotic B-cell lymphoma-2 proteins indicated activation of the mitochondrial pathway. Caspase-3 activation by C20E was prevented by pharmacological inhibition and silencing of the JNK and p38 MAP kinases (MAPK), upstream MAPK kinases MKK4 and MKK7, and the upstream MAPK kinase kinase apoptosis signal-regulating kinase 1 (ASK1). Silencing of the death receptor TNF receptor 1 (TNFR1), but not Fas, DR4, or DR5, and the adapters TRADD and TNF receptor-associated factor 2, but not Fas-associated death domain, prevented C20E-mediated apoptosis. B-cell lymphoma-2 homology 3-interacting domain death agonist (Bid) cleavage by JNK/p38 MAPK linked the extrinsic and mitochondrial pathways of apoptosis. In further studies, an antibody against the extracellular domain of TNFR1 prevented apoptosis by TNF-α but not C20E. These findings suggest that C20E acts intracellularly at TNFR1 to activate ASK1-MKK4/7-JNK/p38 MAPK signaling and to promote Bid-dependent mitochondrial disruption and apoptosis. Inin vivostudies, tumors isolated from C20E-treated nu/nu mice carrying MDA-MB-231 xenografts showed increased TUNEL staining and decreased Ki67 staining, reflecting increased apoptosis and decreased proliferation, respectively. ω-3-Epoxy fatty acids like C20E could be incorporated into treatments for triple-negative breast cancers.-Dyari, H. R. E., Rawling, T., Chen, Y., Sudarmana, W., Bourget, K., Dwyer, J. M., Allison, S. E., Murray, M. A novel synthetic analogue of ω-3 17,18-epoxyeicosatetraenoic acid activates TNF receptor-1/ASK1/JNK signaling to promote apoptosis in human breast cancer cells.
    Matched MeSH terms: Mice, Inbred BALB C
  7. Fulltext Comparison between efficacy of allicin and fluconazole against Candida albicans in vitro and in a systemic candidiasis mouse model
    Khodavandi A, Alizadeh F, Harmal NS, Sidik SM, Othman F, Sekawi Z, et al.
    FEMS Microbiol Lett, 2011 Feb;315(2):87-93.
    PMID: 21204918 DOI: 10.1111/j.1574-6968.2010.02170.x
    The efficacy of allicin compared with fluconazole in alleviating systemic Candida albicans infections was evaluated both in vitro and in vivo through a systemic candidiasis mouse model. Determination of in vitro minimum inhibitory concentrations (MICs) for different C. albicans isolates revealed that both allicin and fluconazole showed different MICs that ranged from 0.05 to 12.5 μg mL(-1) and 0.25 to 16 μg mL(-1) , respectively. A time-kill study showed a significant effect of allicin (P<0.01) against C. albicans, comparable to that of fluconazole. Scanning electron microscopy observation revealed that, similar to fluconazole, allicin produced structural destruction of C. albicans cell surface at low MIC and lysis or puncture at high MIC concentrations. Treatment of BALB/c mice systemically infected with C. albicans showed that although the allicin treatment (at 5 mg kg(-1) day(-1) ) was slightly less efficacious than fluconazole treatment in terms of the fungal load reduction and host survival time, it was still effective against C. albicans in terms of mean survival time, which increased from 8.4 to 15.8 days. These results demonstrate the efficacy of anticandidal effects of allicin both in vitro and in an animal model of candidiasis and affirm the potential of allicin as an adjuvant therapy to fluconazole.
    Matched MeSH terms: Mice, Inbred BALB C
  8. Preliminary analysis of the antinociceptive activity of zerumbone
    Sulaiman MR, Perimal EK, Zakaria ZA, Mokhtar F, Akhtar MN, Lajis NH, et al.
    Fitoterapia, 2009 Jun;80(4):230-2.
    PMID: 19535012 DOI: 10.1016/j.fitote.2009.02.002
    We have investigated the antinociceptive activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, in acetic acid-induced abdominal writhing test and hot plate test in mice. 1 given by intraperitoneal route produced significant dose-dependent antinociceptive effect in all the test models used. In addition, the antinociceptive effect of 1 in the hot plate test was reversed by the non-selective opioid receptor antagonist naloxone, suggesting that the opioid system is involved in its analgesic mechanism of action.
    Matched MeSH terms: Mice, Inbred BALB C
  9. Evaluation of the antinociceptive activity of Ficus deltoidea aqueous extract
    Sulaiman MR, Hussain MK, Zakaria ZA, Somchit MN, Moin S, Mohamad AS, et al.
    Fitoterapia, 2008 Dec;79(7-8):557-61.
    PMID: 18672036 DOI: 10.1016/j.fitote.2008.06.005
    The aqueous extract of Ficus deltoidea leaves was evaluated for possible antinociceptive activity in three models of nociception, namely, acetic acid-induced abdominal writhing, formalin and hot plate test. The results of the present study showed that intraperitoneal administration of the F. deltoidea leaves aqueous extract at the dose of 1, 50 and 100 mg/kg, 30 min prior to pain induction produced significant dose-dependent antinociceptive effect in all the models used, which indicating the presence of both central and peripherally mediated activities. Furthermore, the antinociceptive effect of the extract in the formalin and hot plate test was reversed by the non-selective opioid receptor antagonist naloxone suggesting that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, the present results demonstrated that F. deltoidea leaves aqueous extract contains pharmacologically active constituents which possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.
    Matched MeSH terms: Mice, Inbred BALB C
  10. Antinociceptive effect of Melastoma malabathricum ethanolic extract in mice
    Sulaiman MR, Somchit MN, Israf DA, Ahmad Z, Moin S
    Fitoterapia, 2004 Dec;75(7-8):667-72.
    PMID: 15567242
    The antinociceptive effect of the ethanolic extract of Melastoma malabathricum (MME) was investigated using acetic acid-induced abdominal writhing test and hot-plate test in mice. It was demonstrated that the extract (30-300 mg/kg, i.p.) strongly and dose-dependently inhibited the acetic acid-induced writhing with an ED(50) of 100 (78-160) mg/kg i.p. It also significantly increased the response latency period to thermal stimuli. Furthermore, the nonselective opioid receptor antagonist, naloxone blocked the antinociceptive effect of the extract in both tests, suggesting that M. malabathricum may act both at peripheral and central levels.
    Matched MeSH terms: Mice, Inbred BALB C
  11. Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo
    Hashim YZ, Worthington J, Allsopp P, Ternan NG, Brown EM, McCann MJ, et al.
    Food Funct, 2014 Jul 25;5(7):1513-9.
    PMID: 24836598 DOI: 10.1039/c4fo00090k
    The decreased cancer risk associated with consumption of olive oil may be due to the presence of phenolics which can modulate pathways including apoptosis and invasion that are relevant to carcinogenesis. We have previously shown that a virgin olive oil phenolics extract (OVP) inhibited invasion of HT115 colon cancer cells in vitro. In the current study we assessed the in vitro effects of OVP (25 μg mL(-1)) on HT115 cell migration, spreading and integrin expression. Furthermore, the anti-metastatic activity of OVP - at a dose equivalent to 25 mg per kg per day for 2, 8 or 10 weeks - was assessed in a Severe Combined ImmunoDeficiency (SCID) Balb-c mouse model. After 24 h OVP did not inhibit cell migration but significantly reduced cell spreading on fibronectin (65% of control; p < 0.05) and expression of a range of α and β integrins was modulated. In vivo, OVP by gavage significantly (p < 0.05) decreased not only tumour volume but also the number of metastases in SCID Balb-c mice. Collectively, the data suggest that - possibly through modulation of integrin expression - OVP decreases invasion in vitro and also inhibits metastasis in vivo.
    Matched MeSH terms: Mice, Inbred BALB C
  12. Fulltext Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice
    Chin CY, Tan SC, Nathan S
    Front Cell Infect Microbiol, 2012;2:85.
    PMID: 22919676 DOI: 10.3389/fcimb.2012.00085
    Burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. As therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outcome. In an earlier study, we reported on the B. pseudomallei serine MprA protease, which is relatively stable over a wide pH and temperature range and digests physiological proteins. The present study was carried out to evaluate the immunogenicity and protective efficacy of the MprA as a potential vaccine candidate. In BALB/c mice immunized with recombinant MprA protease (smBpF4), a significantly high IgG titer was detectable. Isotyping studies revealed that the smBpF4-specific antibodies produced were predominantly IgG(1), proposing that immunization with smBpF4 triggered a Th2 immune response. Mice were immunized with smBpF4 and subsequently challenged with B. pseudomallei via the intraperitoneal route. Whilst control mice succumbed to the infection by day 9, smBpF4-immunized mice were protected against the lethal challenge and survived beyond 25 days post-infection. In conclusion, MprA is immunogenic in melioidosis patients whilst also eliciting a strong immune response upon bacterial challenge in mice and presents itself as a potential vaccine candidate for the treatment of melioidosis.
    Matched MeSH terms: Mice, Inbred BALB C
  13. Fulltext Induction of Protective Immunity against Toxoplasmosis in BALB/c Mice Vaccinated with Toxoplasma gondii Rhoptry-1
    Sonaimuthu P, Ching XT, Fong MY, Kalyanasundaram R, Lau YL
    Front Microbiol, 2016;7:808.
    PMID: 27303390 DOI: 10.3389/fmicb.2016.00808
    Toxoplasma gondii is the causative agent for toxoplasmosis. The rhoptry protein 1 (ROP1) is secreted by rhoptry, an apical secretory organelle of the parasite. ROP1 plays an important role in host cell invasion. In this study, the efficacy of ROP1 as a vaccine candidate against toxoplasmosis was evaluated through intramuscular or subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Briefly, a recombinant DNA plasmid (pVAX1-GFP-ROP1) was expressed in CHO cells while expression of recombinant ROP1 protein (rROP1) was carried out in Escherichia coli expression system. Immunization study involved injection of the recombinant pVAX1-ROP1 and purified rROP1 into different group of mice. Empty vector and PBS served as two different types of negative controls. Results obtained demonstrated that ROP1 is an immunogenic antigen that induced humoral immune response whereby detection of a protein band with expected size of 43 kDa was observed against vaccinated mice sera through western blot analysis. ROP1 antigen was shown to elicit cellular-mediated immunity as well whereby stimulated splenocytes with total lysate antigen (TLA) and rROP1 from pVAX1-ROP1 and rROP1-immunized mice, respectively, readily proliferated and secreted large amount of IFN-γ (712 ± 28.1 pg/ml and 1457 ± 31.19 pg/ml, respectively) and relatively low IL-4 level (94 ± 14.5 pg/ml and 186 ± 14.17 pg/ml, respectively). These phenomena suggested that Th1-favored immunity was being induced. Vaccination with ROP1 antigen was able to provide partial protection in the vaccinated mice against lethal challenge with virulent RH strain of tachyzoites. These findings proposed that the ROP1 antigen is a potential candidate for the development of vaccine against toxoplasmosis.
    Matched MeSH terms: Mice, Inbred BALB C
  14. Fulltext Evaluation of Immunoprotection Conferred by the Subunit Vaccines of GRA2 and GRA5 against Acute Toxoplasmosis in BALB/c Mice
    Ching XT, Fong MY, Lau YL
    Front Microbiol, 2016;7:609.
    PMID: 27199938 DOI: 10.3389/fmicb.2016.00609
    Toxoplasmosis is a foodborne disease caused by Toxoplasma gondii, an obligate intracellular parasite. Severe symptoms occur in the immunocompromised patients and pregnant women leading to fatality and abortions respectively. Vaccination development is essential to control the disease. The T. gondii dense granule antigen 2 and 5 (GRA2 and GRA5) have been targeted in this study because these proteins are essential to the development of parasitophorous vacuole (PV), a specialized compartment formed within the infected host cell. PV is resistance to host cell endosomes and lysosomes thereby protecting the invaded parasite. Recombinant dense granular proteins, GRA2 (rGRA2) and GRA5 (rGRA5) were cloned, expressed, and purified in Escherichia coli, BL21 (DE3) pLysS. The potential of these purified antigens as subunit vaccine candidates against toxoplasmosis were evaluated through subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Results obtained demonstrated that rGRA2 and rGRA5 elicited humoral and cellular-mediated immunity in the mice. High level of IgG antibody was produced with the isotype IgG2a/IgG1 ratio of ≈0.87 (p < 0.001). Significant increase (p < 0.05) in the level of four cytokines (IFN-γ, IL-2, IL-4, and IL-10) was obtained. The antibody and cytokine results suggest that a mix mode of Th1/Th2-immunity was elicited with predominant Th1-immune response inducing partial protection against T. gondii acute infection in BALB/c mice. Our findings indicated that both GRA2 and GRA5 are potential candidates for vaccine development against T. gondii acute infection.
    Matched MeSH terms: Mice, Inbred BALB C
  15. Fulltext Pharmacokinetics of Free Oxytetracycline and Oxytetracycline Loaded Cockle Shell Calcium Carbonate-Based Nanoparticle in BALB/c Mice
    Idris SB, Abdul Kadir A, Abdullah JFF, Ramanoon SZ, Basit MA, Abubakar MZZA
    Front Vet Sci, 2020;7:270.
    PMID: 32613011 DOI: 10.3389/fvets.2020.00270
    The development and utilization of nano-antibiotics is currently gaining attention as a possible solution to antibiotic resistance. The aim of this study was therefore to determine the pharmacokinetics of free oxytetracycline (OTC) and oxytetracycline loaded cockle shell calcium carbonate-based nanoparticle (OTC-CNP) after a single dose of intraperitoneal (IP) administration in BALB/c mice. A total of 100 female BALB/c mice divided into two groups of equal number (n = 50) were administered with 10 mg/kg OTC and OTC-CNP, respectively. Blood samples were collected before and post-administration from both groups at time 0, 5, 10, 15, and 30 min and 1, 2, 6, 24, and 48 h, and OTC plasma concentration was quantified using a validated HPLC-UV method. The pharmacokinetic parameters were analyzed using a non-compartment model. The Cmax values of OTC in OTC-CNP and free OTC treated group were 64.99 and 23.53 μg/ml, respectively. OTC was detected up to 24 h in the OTC-CNP group as against 1 h in the free OTC group following intraperitoneal administration. In the OTC-CNP group, the plasma elimination rate of OTC was slower while the half-life, the area under the curve, and the volume of the distribution were increased. In conclusion, the pharmacokinetic profile of OTC in the OTC-CNP group differs significantly from that of free OTC. However, further studies are necessary to determine the antibacterial efficacy of OTC-CNP for the treatment of bacterial diseases.
    Matched MeSH terms: Mice, Inbred BALB C
  16. The antinociceptive activity of Muntingia calabura aqueous extract and the involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in its observed activity in mice
    Zakaria ZA, Sulaiman MR, Jais AM, Somchit MN, Jayaraman KV, Balakhrisnan G, et al.
    Fundam Clin Pharmacol, 2006 Aug;20(4):365-72.
    PMID: 16867020
    The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking the dried leaves in distilled water (DH(2)O) (1 : 2; w/v) for 24 h, was prepared in concentrations of 10%, 50% and 100% that were approximately equivalent to doses of 27, 135 and 270 mg/kg, and administered subcutaneously (s.c.) 5 min after pre-treatment (s.c.) of mice with DH(2)O, L-arginine (20 mg/kg), N(G)-monomethyl-L-arginine acetate (L-NMMA; 20 mg/kg), N(G)-nitro-L-arginine methyl esters (L-NAME; 20 mg/kg), methylene blue (MB) (20 mg/kg), respectively. The AEMC was found to exhibit a concentration-dependent antinociception after pre-challenge with DH(2)O. Interestingly, pre-treatment with L-arginine was found to block significantly (P < 0.05) the AEMC antinociception but only at the highest concentration (100%) of AEMC used. On the other hand, pre-treatment with L-NAME was found to significantly (P < 0.05) enhance the low concentration but inhibit the high concentration AEMC antinociception. MB was found to significantly (P < 0.05) enhance AEMC antinociception at all concentrations used. Except for the higher concentration of AEMC used, co-treatment with L-NAME was found to insignificantly and significantly (P < 0.05) reverse the L-arginine effect when given alone or with low concentration AEMC, respectively. In addition, co-treatment with MB significantly (P < 0.05) reversed the L-arginine effect when given alone or with 10% concentration AEMC but failed to affect the activity of the rest of concentrations used. As a conclusion, this study has demonstrated the involvement of L-arginine/NO/cGMP pathway in AEMC antinociception.
    Matched MeSH terms: Mice, Inbred BALB C
  17. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently
    Lau CL, Chan ST, Selvaratanam M, Khoo HW, Lim AY, Modamio P, et al.
    Fundam Clin Pharmacol, 2015 Aug;29(4):404-16.
    PMID: 26011058 DOI: 10.1111/fcp.12126
    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.
    Matched MeSH terms: Mice, Inbred BALB C
  18. Lack of methylation on transgene leads to high level and persistent transgene expression in induced pluripotent stem cells
    Alhaji SY, Nordin N, Ngai SC, Al Abbar A, Mei L, Abdullah S
    Gene, 2020 Oct 20;758:144958.
    PMID: 32683073 DOI: 10.1016/j.gene.2020.144958
    Short-lived therapeutic gene expression in mammalian cells by DNA methylation is one of the major challenges in gene therapy. In this study, we assessed the implication of DNA methylation on the duration of GFP expression in mouse embryonic stem (ES) and mouse induced pluripotent stem (iPS) cells. The cells were transduced with lentivirus (LV) carrying green fluorescent protein (GFP) driven by either human elongation factor (EF1α) or cytomegalovirus (CMV) promoter. Transduced iPS cells exhibited higher percentage of GFP+ cells with persistent mean fluorescent intensity than transduced ES cells. Analysis on the integrated copy of transgene in the population of the transduced cells demonstrated similar copy number. However, significant increase in GFP intensity following 5-azaC treatment was observed in transduced ES cells only, suggesting the influence of DNA methylation in transgene silencing. Subsequent DNA methylation analysis showed that the promoter and the GFP region of the provirus in iPS cells had negligible methylation profile compared to transduced ES cells. Interestingly, sustained transgene expression was observed upon directed differentiation of transduced iPS cells towards CD34+ CD45+ cells. Hence, this study has shown that favourable transgene activity from lentiviral transduced iPS cells was due to the lack of methylation at the proviral regions.
    Matched MeSH terms: Mice, Inbred BALB C
  19. Fulltext Rapid detection of Haemophilus ducreyi in clinical and experimental infections using monoclonal antibody: a preliminary evaluation
    Karim QN, Finn GY, Easmon CS, Dangor Y, Dance DA, Ngeow YF, et al.
    Genitourin Med, 1989 Dec;65(6):361-5.
    PMID: 2693334
    A monoclonal antibody raised against Haemophilus ducreyi was tested for its sensitivity and specificity as an immunofluorescence (IF) reagent using simulated vaginal smears containing H. ducreyi, smears taken from skin lesions of mice infected with H. ducreyi and patients from South Africa, Thailand and Malaysia with clinically diagnosed chancroid. The IF test was more sensitive than culture or Gram staining in the simulated smears, theoretically detecting less than 4 organisms/sample. It detected H. ducreyi in 95% of the animal lesions compared with 14% detected by culture. Immunofluorescence testing identified over 90% of culture-positive cases of chancroid but also detected organisms in some culture-negative cases where clinical evidence for the diagnosis was strong. These results suggest that this antibody may provide a simple, rapid and sensitive means of detecting H. ducreyi in cases of chancroid.
    Matched MeSH terms: Mice, Inbred BALB C
  20. Histopathological effect of pterostilbene as chemoprevention in N-nitroso-tri-chloroethylurea (NTCU)-induced lung squamous cell carcinoma (SCC) mouse model
    Surien O, Ghazali AR, Masre SF
    Histol Histopathol, 2020 Oct;35(10):1159-1170.
    PMID: 32893871 DOI: 10.14670/HH-18-247
    BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, and squamous cell carcinoma (SCC) is one of the most common types of lung cancer. Chemoprevention of lung cancer has gained increasing popularity as an alternative to treatment in reducing the burden of lung cancer. Pterostilbene (PS) may be developed as a chemopreventive agent due to its pharmacological activities, such as anti-proliferative, anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of PS on the development of lung SCC in the mouse model.

    METHODS: A total of 24 seven-week-old female Balb/C mice were randomly categorised into four groups, including two control groups comprising the N-nitroso-trischloroethylurea (NTCU)-induced lung SCC and vehicle control (VC) groups and two treatment groups comprising the 10mg/kg PS (PS10) and 50mg/kg PS (PS50) groups. All lung organs were harvested at week 26 for histopathological analysis.

    RESULTS: All PS treatment groups showed chemopreventive activity by inhibiting the progression of lung SCC formation with PS10, resulting in mild hyperplasia, and PS50 was completely reversed in the normal bronchial epithelium layer compared with the VC group. PS treatment also reduced the expression of cytokeratin 5/6 in the bronchial epithelium layer. Both PS10 and PS50 significantly reduced the epithelium thickness compared to the NTCU group (p<0.05). PS is a potential chemopreventive agent against lung SCC growth by suppressing the progression of pre-malignant lesions and reducing the thickness of the bronchial epithelium.

    CONCLUSIONS: The underlying molecular mechanisms of PS in lung SCC should be further studied.

    Matched MeSH terms: Mice, Inbred BALB C
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