Displaying publications 21 - 40 of 46 in total

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  1. The use of rats and mice as animal models in ex vivo bone growth and development studies
    Abubakar AA, Noordin MM, Azmi TI, Kaka U, Loqman MY
    Bone Joint Res, 2016 Dec;5(12):610-618.
    PMID: 27965220
    In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine.Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610-618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2.
  2. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice
    Ong YS, Saiful Yazan L, Ng WK, Noordin MM, Sapuan S, Foo JB, et al.
    Int J Nanomedicine, 2016 11 09;11:5905-5915.
    PMID: 27877037
    BACKGROUND: Thymoquinone (TQ), the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ.

    MATERIALS AND METHODS: The in vivo toxicity (acute and subacute toxicity) study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed.

    RESULTS: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL) was found to be 10 mg/kg/d for mice in both sexes.

    CONCLUSION: For long-term oral consumption, TQ and TQNLC at a dose of 10 mg/kg is safe in mice and does not exert any toxic effect. The results provide safety information of TQNLC, which would further help researchers in clinical use.

  3. In vitro isolation and molecular identification of reptarenavirus in Malaysia
    Abba Y, Hassim H, Hamzah H, Ibrahim OE, Ilyasu Y, Bande F, et al.
    Virus Genes, 2016 Oct;52(5):640-50.
    PMID: 27142080 DOI: 10.1007/s11262-016-1345-7
    Boid inclusion body disease (BIBD) is a viral disease of boids caused by reptarenavirus. In this study, tissue from naturally infected boid snakes were homogenized and propagated in African Monkey kidney (Vero) and rat embryonic fibroblast (REF) cells. Virus replication was determined by the presence of cytopathic effect, while viral morphology was observed using transmission electron microscopy. Viral RNA was amplified using RT-PCR with primers specific for the L-segment of reptarenavirus; similarly, quantification of viral replication was done using qPCR at 24-144 h postinfection. Viral cytopathology was characterized by cell rounding and detachment in both Vero and REF cells. The viral morphology showed round-to-pleomorphic particles ranging from 105 to 150 nm which had sand-like granules. Sanger sequencing identified four closely associated reptarenavirus species from 15 (37.5 %) of the total samples tested, and these were named as follows: reptarenavirus UPM-MY 01, 02, 03, and 04. These isolates were phylogenetically closely related to the University Helsinki virus (UHV), Boa Arenavirus NL (ROUTV; BAV), and unidentified reptarenavirus L20 (URAV-L20). Comparison of deduced amino acid sequences further confirmed identities to L-protein of UHV, L-polymerase of BAV and RNA-dependent RNA polymerase of URAV-L20. Viral replication in Vero cells increased steadily from 24 to 72 h and peaked at 144 h. This is the first study in South East Asia to isolate and characterize reptarenavirus in boid snakes with BIBD.
  4. Morinda citrifolia edible leaf extract enhanced immune response against lung cancer
    Lim SL, Goh YM, Noordin MM, Rahman HS, Othman HH, Abu Bakar NA, et al.
    Food Funct, 2016 Feb;7(2):741-51.
    PMID: 26765787 DOI: 10.1039/c5fo01475a
    Lung cancer causes 1.4 million deaths annually. In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib. Lung tumour-induced BALB/c mice were fed with 150 mg kg(-1) or 300 mg kg(-1) body weight of the leaf extract, or erlotinib (50 mg kg(-1) body-weight) for 21 days. The 300 mg kg(-1) body weight extract significantly (and dose-dependently) suppressed lung tumour growth; the extract worked more effectively than the 50 mg kg(-1) body weight erlotinib treatment. The extract significantly increased blood lymphocyte counts, and spleen tissue B cells, T cells and natural killer cells, and reduced the epidermal growth factor receptor (EGFR) which is a lung adenocarcinoma biomarker. The extract also suppressed the cyclooxygenase 2 (COX2) inflammatory markers, and enhanced the tumour suppressor gene (phosphatase and tensin homolog, PTEN). It inhibited tumour growth cellular gene (transformed mouse 3T3 cell double minute 2 (MDM2), V-raf-leukemia viral oncogene 1 (RAF1), and mechanistic target of rapamycin (MTOR)) mRNA expression in the tumours. The extract is rich in scopoletin and epicatechin, which are the main phenolic compounds. The 300 mg kg(-1)Morinda citrifolia leaf 50% ethanolic extract showed promising potential as a complementary therapeutic dietary supplement which was more effective than the 50 mg kg(-1) erlotinib in suppressing lung adenocarcinoma. Part of the mechanisms involved enhancing immune responses, suppressing proliferation and interfering with various tumour growth signalling pathways.
  5. Fulltext Antiviral Activity of Resveratrol against Human and Animal Viruses
    Abba Y, Hassim H, Hamzah H, Noordin MM
    Adv Virol, 2015;2015:184241.
    PMID: 26693226 DOI: 10.1155/2015/184241
    Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections both in vitro and in vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβ pathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.
  6. Fulltext Antihypercholesterolemic and antioxidant efficacies of zerumbone on the formation, development, and establishment of atherosclerosis in cholesterol-fed rabbits
    Hemn HO, Noordin MM, Rahman HS, Hazilawati H, Zuki A, Chartrand MS
    Drug Des Devel Ther, 2015;9:4173-208.
    PMID: 26347047 DOI: 10.2147/DDDT.S76225
    Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions.
  7. Fulltext Complete Genome Sequence of Rat Cytomegalovirus Strain ALL-03 (Malaysian Strain)
    Balakrishnan KN, Abdullah AA, Camalxaman SN, Quah YW, Abba Y, Hani H, et al.
    Genome Announc, 2015;3(3).
    PMID: 26044413 DOI: 10.1128/genomeA.00451-15
    The complete genome sequence of the ALL-03 strain of rat cytomegalovirus (RCMV) has been determined. The RCMV genome has a length of 197,958 bp and is arranged as a single unique sequence flanked by 504-bp terminal direct repeats. This strain is closely related to the English strain of RCMV in terms of genetic arrangement but differs slightly in size.
  8. Fulltext Comparative gastric morphometry of Muong indigenous and Vietnamese wild pigs
    Trang PH, Ooi PT, Zuki AB, Noordin MM
    ScientificWorldJournal, 2012;2012:894952.
    PMID: 23093914 DOI: 10.1100/2012/894952
    It is hypothesized that despite sharing a similar habitat, the Muong indigenous and Vietnamese wild pigs may reveal different gastric morphology. Due to the protective nature of procuring these pigs, a total of 12 Muong indigenous pigs and nine Vietnamese wild pigs stomach collected post mortem were analysed for selected biometric parameters and histology. The result indicated that the stomach of the Vietnamese wild pig is broader with a bigger capacity and greater proportion of proper gastric glands. Interestingly, the stomach mass correlated well with live body weight in both breeds apart from possessing similar histomorphometry of the gastric gland regions. On the other hand, the thicker (P < 0.05) submucosa in the Vietnamese wild pig is attributed to the presence of numerous loose connective tissues, abundant blood vessels, adipose tissues and nerve plexus. The appearance of lymphoid follicles underneath the tubular gastric glands in the Vietnamese wild pig exceeded that of Muong indigenous pigs. This finding suggested that the difference in feeding behavior as well as immunity. In conclusion, adaptations found in the Vietnamese wild pig indicated that this breed is equipped with a bigger and effectively functional stomach to suit its digestive physiology and immunity in the wild.
  9. Histomorphology of the stomach, proventriculus and ventriculus of the red jungle fowl
    Kadhim KK, Zuki AB, Noordin MM, Babjee SM
    Anat Histol Embryol, 2011 Jun;40(3):226-33.
    PMID: 21443757 DOI: 10.1111/j.1439-0264.2010.01058.x
    The cranial chamber (proventriculus) and caudal chamber (ventriculus) of the stomach of the Red jungle fowl (Gallus gallus spadiceus) were examined by means of light microscopy. Both chambers presented folds of the tunica mucosa lined by a simple prismatic epithelium that was positive for neutral mucin. Simple tubular glands occupied the lamina propria of both chambers; in the ventriculus of older birds, they showed a coiled base. These ventricular glands were lined by simple cuboidal cells represented by the chief cells and a few large basal cells. The luminal and tubular koilin rodlets and folds of the ventriculus were positive to periodic acid Schiff (PAS) stain. The proventricular glands were situated between the inner and outer layers of the lamina muscularis mucosae. Cells lining the tubulo-alveolar units of the proventricular glands showed a dentate appearance. Vacuoles were not observed, and the cells were negative for Alcian-PAS stain. The tunica submucosa was very thin in the proventricular wall. In the ventriculus, it was not separated from the lamina propria owing to the absence of any lamina muscularis mucosae. The tunica muscularis of the proventriculus was formed by a thick inner layer of circular smooth muscle fibres and a thin outer layer of longitudinal fibres. In addition to these layers, oblique muscle fibres formed the most internal layer of the tunica muscularis in the ventriculus.
  10. Efficacy of Nigella sativa in alleviating benzo[a]pyrene-induced immunotoxicity in broilers
    Latif IK, Karim AJ, Zuki AB, Zamri-Saad M, Niu JP, Noordin MM
    Histol Histopathol, 2011 06;26(6):699-710.
    PMID: 21472685 DOI: 10.14670/HH-26.699
    The immune response of broiler chickens exposed to intra-tracheal (i.t.) administration of benzo[a]pyrene (BaP) with and without Nigella sativa (Ns) supplementation was investigated. A total of 120 day-old chicks were divided into four groups comprising 30 birds each, into a control, Ns, BaP, and BaP+Ns group. Immune responses to Newcastle disease (ND) were evaluated by haemagglutination inhibition (HI), phytohaemagglutinin (PHA) skin test and carbon clearance assay (CCA). In most instances, there was a significant increase (p<0.05) in the ND-HI antibody titers, PHA skin-swelling response and phagocytic activity in the BaP + Ns group compared to that of the BaP group. Likewise, organ weight and indices of the spleen, bursa of Fabricius and thymus of birds from the BaP + Ns group were also higher (p<0.05) than that of the BaP group from day 1 until day 21. It is concluded that exposure to BaP may exert adverse effects on the immune system of broilers which may increase their susceptibility to disease, and Ns supplementation significantly reduces these alterations.
  11. Morphological study of the lingual papillae in the barking deer, Muntiacus muntjak
    Adnyane IK, Zuki AB, Noordin MM, Agungpriyono S
    Anat Histol Embryol, 2011 Feb;40(1):73-7.
    PMID: 21105898 DOI: 10.1111/j.1439-0264.2010.01041.x
    The morphology of the tongue of the adult barking deer, Muntiacus muntjak, was examined by light and scanning electron microscopy. The result showed that the tongue of the barking deer was elongated with a rounded apex. Four types of lingual papillae were observed: filiform, fungiform, vallate and large conical papillae. The filiform papillae represented the most numerous types of lingual papillae. The fungiform papillae were distributed among the filiform papillae on the rostral and the body portions of the tongue. Ten to thirteen vallate papillae were distributed on both sides of the lingual prominence among the large conical papillae. Histologically, both the fungiform and vallate papillae contain taste buds in the epithelial layer. The distribution and types of lingual papillae found in the barking deer are similar to those in the other species that belong to the family Cervidae.
  12. Effects of Momordica charantia on pancreatic histopathological changes associated with streptozotocin-induced diabetes in neonatal rats
    Abdollahi M, Zuki AB, Goh YM, Rezaeizadeh A, Noordin MM
    Histol Histopathol, 2011 01;26(1):13-21.
    PMID: 21117023 DOI: 10.14670/HH-26.13
    The aim of this research was to determine the effects of Momordica charantia (MC) fruit aqueous extract on pancreatic histopathological changes in neonatal STZ-induced type-II diabetic rats. Diabetes mellitus was induced in one day Sprague-Dawley neonatal rats using a single intrapretoneal injection of streptozotocin (STZ) (85 mg/kg body weight) and monitored for 12 weeks thereafter. The diabetic rats were separated into three groups, as follows: the diabetic control group (i.e. nSTZ), the diabetic group (i.e. nSTZ/M) - which was orally given 20 mg/kg of MC fruit extract, and the diabetic group (i.e. nSTZ/G) - that was treated with glibenclamide, 0.1 mg/kg for a period of four weeks. At the end of treatment, the animals were sacrificed and blood samples were collected from the saphenous vein to measure the blood glucose and serum insulin level. The pancreatic specimens were removed and processed for light microscopy, electron microscopy examination and immunohistochemical study. The results of this study showed that MC fruit aqueous extract reduced the blood glucose level as well as glibenclamide and increased the serum insulin level in the treated diabetic rats (P<0.05). The fruit extract of MC alleviated pancreatic damage and increased the number of β-cells in the diabetic treated rats (P<0.05). Our results suggest that oral feeding of MC fruit extract may have a significant role in the renewal of pancreatic β-cells in the nSTZ rats.
  13. Antihypertensive and cardiovascular effects of catechin-rich oil palm (Elaeis guineensis) leaf extract in nitric oxide-deficient rats
    Jaffri JM, Mohamed S, Rohimi N, Ahmad IN, Noordin MM, Manap YA
    J Med Food, 2011 Jul-Aug;14(7-8):775-83.
    PMID: 21631357 DOI: 10.1089/jmf.2010.1170
    Oil palm (Elaeis guineensis) leaf extract (OPLE) possesses good ex vivo vasodilation and antioxidant properties. This study evaluated the catechin-rich OPLE antioxidant, antihypertensive, and cardiovascular effects in normal and nitric oxide (NO)-deficient hypertensive rats. OPLE was administered orally (500 mg/kg of body weight/day) to normotensive Wistar rats and N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced NO-deficient hypertensive rats. OPLE significantly (P
  14. Histological study of the parotid and mandibular glands of barking deer (Muntiacus muntjak) with special reference to the distribution of carbohydrate content
    Adnyane IK, Zuki AB, Noordin MM, Agungpriyono S
    Anat Histol Embryol, 2010 Dec;39(6):516-20.
    PMID: 20682009 DOI: 10.1111/j.1439-0264.2010.01023.x
    We investigated the histology and carbohydrate content of the parotid and mandibular glands of the barking deer (Muntiacus muntjak). Three adult males were used. Paraffin wax sections of the glands were stained with haematoxylin and eosin (HE), alcian blue (AB), pH 2.5 and periodic acid Schiff (PAS). The acinar cells of the parotid gland were serous, whereas those of the mandibular gland were of the mixed type. The acini of the mandibular gland comprised serous and mucous cells with the mucous type predominating. AB and PAS staining showed high concentrations of acidic and neutral carbohydrates in the mucous cells, but not in the serous cells of the mandibular gland. These carbohydrates were also found in moderate-to-high concentrations in the secreted material in the mandibular duct lumen. However, these carbohydrates were not found in acinar cells of the parotid gland or in the serous cells of the mandibular gland. Thus, carbohydrates in the saliva of the barking deer appear to be produced mainly by the mucous cells of the mandibular glands.
  15. Fulltext Pulmonary modulation of benzo[a]pyrene-induced hemato- and hepatotoxicity in broilers
    Latif IK, Karim AJ, Zuki AB, Zamri-Saad M, Niu JP, Noordin MM
    Poult Sci, 2010 Jul;89(7):1379-88.
    PMID: 20548065 DOI: 10.3382/ps.2009-00622
    Aftermath in several air pollution episodes with high concentrations of polycyclic aromatic hydrocarbons did not significantly affect health and performance of broilers despite its renowned sensitivity to polycyclic aromatic hydrocarbons. The aim of the study was to elucidate the previous lack of response in birds exposed to such severe episodes of air pollution. Benzo[a]pyrene (BaP) was used to simulate the influence of air pollution on hematology, selected organ function, and oxidative stress in broilers. One-day-old chicks were assigned to 5 equal groups composed of a control group, tricaprylin group, and 3 groups treated with BaP (at 1.5 microg, 150 microg, or 15 mg/kg of BW). The BaP was intratracheally administered to 1-d-old chicks for 5 consecutive days. The hematology, liver and kidney function, P450 activity, and malondialdehyde level especially in the group receiving 15 mg of BaP/kg of BW demonstrated evidence of hemato- and hepatoxicity via BaP-induced oxidative stress. The deleterious effect of exposure to high concentration of BaP in broiler chickens was probably due to the anatomy of this species and the half-life of BaP. Although the effect of BaP may be transient or irreversible, pathogen challenges faced during the period of suppression may prove fatal.
  16. Tissue engineering approach to repair abdominal wall defects using cell-seeded bovine tunica vaginalis in a rabbit model
    Ayele T, Zuki AB, Noorjahan BM, Noordin MM
    J Mater Sci Mater Med, 2010 May;21(5):1721-30.
    PMID: 20135201 DOI: 10.1007/s10856-010-4007-7
    The aim of this study was to engineer skeletal muscle tissue for repair abdominal wall defects. Myoblast were seeded onto the scaffolds and cultivated in vitro for 5 days. Full thickness abdominal wall defects (3 x 4 cm) were created in 18 male New Zealand white rabbits and randomly divided into two equal groups. The defects of the first group were repaired with myoblast-seeded-bovine tunica vaginalis whereas the second group repaired with non-seeded-bovine tunica vaginalis and function as a control. Three animals were sacrificed at 7th, 14th, and 30th days of post-implantation from each group and the explanted specimens were subjected to macroscopic and microscopic analysis. In every case, seeded scaffolds have better deposition of newly formed collagen with neo-vascularisation than control group. Interestingly, multinucleated myotubes and myofibers were only detected in cell-seeded group. This study demonstrated that myoblast-seeded-bovine tunica vaginalis can be used as an effective scaffold to repair severe and large abdominal wall defects with regeneration of skeletal muscle tissue.
  17. Mineral and physichocemical characterization of cockle (Anadara granosa) shells as an alternative biomaterial for bone tissue engineering
    Hazmi AJ, Zuki AB, Noordin MM, Jalila A, Norimah Y
    Med J Malaysia, 2008 Jul;63 Suppl A:93-4.
    PMID: 19025000
    This study was conducted based on the hypothesis that mineral and physicochemical properties of cockle shells similarly resemble the properties of corals (Porites sp.). Hence, the mineral and physicochemical evaluations of cockle shells were conducted to support the aforementioned hypothesis. The results indicated that cockle shells and coral exoskeleton shared similar mineral and physicochemical properties.
  18. Effect of preservation methods on the performance of bovine pericardium graft in a rat model
    Zuki AB, Hafeez YM, Loqman MY, Noordin MM, Norimah Y
    Anat Histol Embryol, 2007 Oct;36(5):349-56.
    PMID: 17845224
    This study investigates the effect of preservation methods on the performance of bovine parietal pericardium grafts in a rat model. Mid-ventral full thickness abdominal wall defects of 3 x 2.5 cm in size were created in 90 male Sprague-Dawley rats (300-400 g), which were divided into three groups of 30 rats each. The abdominal defects of group one and two were repaired with lyophilized and glycerolized bovine pericardium grafts, while the defects of group three were repaired with expanded polytetrafluoroethylene (ePTFE) Mycro Mesh as a positive control. Another group of 30 rats underwent sham operation and was used for comparison as negative control. Each group of rats (n = 30) was divided into five subgroups (n = 6) and killed at 1, 3, 6, 9 and 18 weeks post-surgery for gross and morphological evaluations. The rats tolerated the surgical procedure well with a total mortality of 0.05%. No serious post-operative clinical complications or signs of rejection were encountered. Adhesions between the grafts and the underlying visceral organs observed in the study were mostly results of post-surgical complications. Glycerol preservation delayed degradation and replacement of the grafts, whereas lyophilization caused early resorption and replacement of the grafts. The glycerolized grafts were replaced with thick dense fibrous tissue, and the lyophilized grafts were replaced with thin loose fibrous tissue. The healing characteristic of the bovine pericardium grafts was similar to those of the sham-operated group, and quite different from those of the ePTFE Mycro Mesh. The outcome of the present study confirmed the superiority of glycerolized bovine pericardium grafts over its lyophilized counter part.
  19. Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
    Somchit N, Norshahida AR, Hasiah AH, Zuraini A, Sulaiman MR, Noordin MM
    Hum Exp Toxicol, 2004 Nov;23(11):519-25.
    PMID: 15625777
    Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.
  20. Glycerol preserved bovine pericardium for abdominal wall reconstruction: experimental study in rat model
    Hafeez YM, Zuki AB, Loqman MY, Yusof N, Asnah H, Noordin MM
    Med J Malaysia, 2004 May;59 Suppl B:117-8.
    PMID: 15468846
    The aim of this study was to evaluate bovine pericardium surgical patch in rat model. Bovine pericardial sacs collected from local abattoir were cleaned, disinfected and cut into pieces of 3 by 2.5cm and preserved in 99.5% glycerol. Full thickness abdominal wall defects of 3 by 2.5 cm were created in 30 adult male Sprague Dawley rats and repaired with glycerol preserved pieces. The rats were serially sacrificed in a group of six rats at 1,3,6,9 and 18 weeks post-surgical intervals for morphological and tensometeric study. Macroscopically, no mortality or postoperative surgical complications was encountered except slight adhesions between implanted grafts and some visceral organs in 10% of the rats. Microscopically no calcification or foreign body giant cell formation was found in the explanted grafts. The implanted grafts were replaced gradually with recipient tissue, which made mainly of dense collagenous bundles. The healing strength between the implanted grafts and the recipient abdominal wall was gradually increased with time. The results of this study showed that glycerol preserved bovine pericardium act as scaffold for transformation into living tissue without clinical complications such as that associated with prostheses.
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